bluuebunny/crossref_metadata_2025_split huggingface dataset:
476 Sleep-Disordered Breathing is More Predictive than Obesity of Increased Left Ventricular Mass Index in Bariatric Surgery Patients
Authors: Usama Muhammad , Wang Lu , Jin Jian , Milinovich Alex , Aylor Joan , Kaw Roop , Kashyap Sangeeta , Cetin Derrick , Aminian Ali , Kempke Nancy , Mehra Reena , Aboussouan Loutfi 
Published: May 2021

Abstract

Introduction
Obesity and obstructive sleep apnea (OSA) are associated with left ventricular hypertrophy and increased cardiovascular risk. Alternatively, the “obesity paradox” describes an improved prognosis from heart failure in obesity, though potentially attributable to confounding/bias. We sought to determine the contributions of obesity and sleep-disordered breathing (SDB) to left ventricular function and morphology in bariatric surgery candidates.

Methods
Patients undergoing polysomnography prior to bariatric surgery from 2011–2018 had demographic (age, gender, race), anthropometric (body mass index [BMI], neck circumference), comorbidities (atrial fibrillation, coronary artery disease, diabetes, hypertension, hyperlipidemia), echocardiographic and sleep-disordered breathing (apnea-hypopnea index [AHI], peak end-tidal CO2 [etCO2]) variables retrospectively examined. The echocardiographic visit closest to polysomnogram within two years was selected with missing values filled by available values within 6 months. Linear regression assessed the relationship of BMI, AHI, and etCO2 with left ventricular mass index (LVMI) after adjustment of demographics and comorbidities. Echocardiographic measures were logarithm transformed before regression analysis. Coefficients and 95% confidence intervals (CI) were calculated by exponential transformation. The analysis was performed based on an overall significance level of 0.05 using SAS software (version 9.4, Cary, NC).

Results
The total of 832 patients had 24% males, mean age 48.8±12, 60% white, and BMI:49.4±9.5kg/m2. Ejection fraction (%) was 60.0±7.0, and LVMI (g/m2): 80.9±23.7. In adjusted models, LVMI decreased by 2.1% for each 5kg/m2 increase in BMI (coefficient=0.979, 95%CI 0.961–0.997, p=0.022) and increased by 4.3% for each 5 mmHg increase in etCO2 (coefficient=1.043, 95%CI 1.013–1.073, p=0.005). Without adjustment, patients with AHI ≥ 5 had 15.3% higher LVMI than non-OSA group (coefficient=1.153, 95%CI 1.034–1.286, p=0.011) and moderate/severe OSA was associated with a 7.6% higher LVMI than those with AHI&lt;15 (coefficient 1.076, 95%CI 1.003–1.153, p=0.040), but not statistically significant after adjustment.

Conclusion
In obese patients, nocturnal hypoventilation rather than obesity may have adverse influences on left ventricular morphology. Future studies should focus on clarifying whether obesity is truly protective in terms of LV mass, i.e. reflective of paradox versus a product of bias. The potential benefit of identifying/treating SDB in bariatric surgery candidates to mitigate cardiovascular risk also deserves further investigation.

Support (if any)
Cleveland Clinic Transformative Resource Neuroscience Award
479 The association of QTc and QT Variability with Severity of Sleep Disordered Breathing
Authors: Patel Salma , Zareba Wojciech , Couderc Jean-Philippe , Xia Xiaojuan , Woosley Raymond , Patel Imran , Combs Daniel , Mashaqi Saif , Parthasarathy Sairam 
Published: May 2021

Abstract

Introduction
The apneas and hypopneas that characterize sleep-disordered breathing (SDB) are associated with QTc prolongation and increased QT variability. There have been mixed results as to whether QTc and QT variability increase with increasing SDB severity. This study assesses whether QTc prolongation and QT variability are likely to increase with increasing severity of SDB in a large multi-center cohort.

Methods
200 subjects with no SDB and approximately 600 with three levels of SDB (mild, moderate, severe) were randomly selected from the Sleep Heart Health study and matched by age, gender and BMI. SDB was defined as an apnea/hypopnea index ≥5. Respiratory and electrocardiograms (ECG) signals from polysomnography studies were analyzed. Bazett’s heart rate correction was used to calculate QTc. QT variability was measured as standard deviation of QT intervals (SDQT) and short-term interval QT variability (STVQT), at 5-minute intervals. Subjects were excluded if there were missing data or low-quality ECG.

Results
Seven hundred and seventy-one subjects (age 68±10 years, 51% female, 92% Caucasian) were included. One hundred and sixty-five subjects had no SDB, 235 mild, 195 moderate and 176 had severe SDB. The mean (SD) QTc was 422(29), 411(26), 419 (34) and 418 (36) ms for the no SDB, mild, moderate, and severe SDB groups, respectively (p=0.017). The mean (SD) STVQT was 7 (9), 11 (16), 8 (9) and 9 (11) for the no SDB, mild, moderate severe SDB groups, respectively (p=&lt;0.001). The mean (SD) STVQT was 3 (2), 4 (4), 4 (3) and 4(4) for the no SDB, mild, moderate severe SDB groups, respectively (p=&lt;0.001). There was no statistically linear relationship between QT prolongation or QT variability and SBD severity.

Conclusion
QTc duration and QT variability were not increased with SDB severity.

Support (if any)
American Academy of Sleep Medicine Foundation (203-JF-18), National Institutes of Health (HL126140), University of Arizona Health Sciences Career Development Award (5299903), and University of Arizona Faculty Seed Grant (5833261)
483 Neuroanatomical and Neurofunctional Correlates of Unexplained Excessive Daytime Sleepiness
Authors: Cook Jesse , Plante David 
Published: May 2021

Abstract

Introduction
Excessive daytime sleepiness (EDS) frequently presents as a secondary symptom, but some experience EDS in the absence of an explanatory medical condition, psychiatric illness, sleep disorder, or medication/substance use. The neurobiology underlying unexplained EDS (uEDS) is poorly understood, which contributes to the existing limitations in uEDS classification, assessment, and treatment. This investigation was designed to identify potential neuroanatomical and neurofunctional correlates of uEDS.

Methods
Data were acquired from the open-access Stockholm Sleepy Brain (SSB) Project, which included either young (20–30 years old) or older (65–75 years old) adults. SSB criteria ruled out common EDS explanations. A uEDS sample (N = 18; Percentage Female = 33%; Percentage Young = 33%) was established using Epworth Sleepiness Scale (ESS) ≥ 11. Age-and-sex matched controls without EDS (noEDS) were identified. T1-weighted MRI and resting-state fMRI (rs-fMRI) data were compiled for each subject, as well as depression, anxiety, and global health self-ratings. Processing pipelines were performed on T1-weighted and rs-fMRI data. Neuroanatomical analyses compared groups using voxel-based morphometry and across gray matter (GM), white matter (WM), and cerebral spinal fluid volume. Threshold free cluster enhancement was used across all neuroanatomical comparisons. For neurofunctional analyses, seed-based connectivity analysis was performed with a seed placed in the left hemisphere of the medial prefrontal cortex (MNI coordinates: 2 -46 12). Fischer Z-transformed functional connectivity maps were compared across groups. Depression, anxiety, and global health scores were included as covariates and corrections were applied for multiple comparisons, across all analyses.

Results
Group characteristics were comparable, except for ESS. Significantly increased GM volume (middle occipital gyrus and precuneus) was associated with uEDS, relative to noEDS. Robust, bilateral increases in WM matter (thalamus, cerebellum, and middle frontal gyrus) were observed for uEDS, relative to noEDS. No significant group differences were observed in rs-fMRI.

Conclusion
Significant neuroanatomical alterations were associated with uEDS that included increases in both GM and WM. These findings converge on previous research associating anatomical differences within the default mode network with uEDS. Future research using more sensitive quantitative measures of WM is warranted.

Support (if any)
This project was supported by a National Institute Nursing Research grant (NR018288).
484 Solriamfetol Titration & AdministRaTion (START): Physician titration strategies in a hypothetical patient with narcolepsy
Authors: Singh Haramandeep , Hyman Danielle , Parks Gregory , Chen Abby , Baldys Beth , Ito Diane , Thorpy Michael 
Published: May 2021

Abstract

Introduction
Solriamfetol (Sunosi®), a dopamine/norepinephrine reuptake inhibitor, is approved (US and EU) to treat excessive daytime sleepiness (EDS) in adults with narcolepsy (75–150 mg/day) or obstructive sleep apnea (OSA) (37.5–150 mg/day). Patient characteristics, comorbidities, and other EDS medications can influence treatment strategies. To understand factors physicians consider when initiating solriamfetol, this study analyzed titration strategies for a hypothetical patient.

Methods
This virtual, descriptive, cross-sectional, qualitative survey enrolled US-based physicians treating patients with EDS due to OSA and/or narcolepsy. Responses to 4 open-ended questions regarding a hypothetical patient were recorded. Patient scenario: 32-year-old woman with narcolepsy (Epworth Sleepiness Scale score=8) using an amphetamine stimulant (35 mg/day) and sodium oxybate (6 g/night) for 6 months and occasionally experiencing non-use-limiting but bothersome adverse events (AEs) with the stimulant. Content analysis of the recordings identified themes in the responses; a trained linguist captured language choices/patterns.

Results
Twenty-six physicians (neurologists, n=7 [27%]; internists/family practitioners, n=7 [27%]; pulmonologists, n=6 [23%]; psychiatrists, n=5 [19%]; otolaryngologists, n=1 [4%]) representing 781 patients on stable solriamfetol doses participated; 19 (73%) were board-certified in sleep disorders. Physicians had been treating narcolepsy a mean 15.7±6.6 years. Most (21 [81%]) thought the patient appropriate for solriamfetol, 3 (12%) thought not appropriate, and 2 (8%) thought appropriateness depended on other factors. Sixteen physicians (62%) suggested adjusting her stimulant, 3 (12%) the stimulant and sodium oxybate, and 1 (4%) neither. Nineteen (73%) would titrate solriamfetol per the label, with 13 (50%) aiming for 75 mg/day and 8 (31%) for 150 mg/day. Physicians emphasized stopping the stimulant before starting solriamfetol: 10 (39%) would taper down before starting solriamfetol, 7 (27%) while starting solriamfetol, and 1 (4%) while aiming to eventually switch; 8 (31%) would discontinue abruptly. Nineteen physicians (73%) would not change their approach if the stimulant dose were 60 mg/day. Most clinicians would change their approach if AEs occurred while starting solriamfetol by taking a slower or more gradual approach, while some would titrate off the stimulant more aggressively.

Conclusion
Physicians considered existing medications and potential AEs in their titration strategy when initiating solriamfetol.

Support (if any)
Jazz Pharmaceuticals
489 Pivotal Phase 3 Study of FT218, a Once-Nightly Sodium Oxybate Formulation, in Patients With Narcolepsy: REST-ON Primary Results
Authors: Kushida Clete , Shapiro Colin , Roth Thomas , Thorpy Michael , Rosenberg Russell , Corser Bruce , Ajayi Akinyemi , Dubow Jordan , Seiden David , Dauvilliers Yves 
Published: May 2021

Abstract

Introduction
Sodium oxybate (SO) is an effective treatment for patients with narcolepsy; however, currently available SO formulations require twice-nightly dosing. The purpose of this study was to evaluate efficacy and safety of FT218, an investigational once-nightly controlled-release SO formulation, for the treatment of excessive daytime sleepiness and cataplexy in patients with narcolepsy types 1 (NT1) and 2 (NT2).

Methods
This was a randomized, double-blind, placebo-controlled, multicenter study in patients with narcolepsy ≥16 years old. Patients were randomized 1:1 to receive FT218 or matching placebo: 4.5 g/night for 1 week, 6.0 g/night for 2 weeks, 7.5 g/night for 5 weeks, and 9.0 g/night for 5 weeks (maximum treatment duration, 13 weeks). Coprimary endpoints were mean sleep latency (minutes) on maintenance of wakefulness test (MWT), Clinical Global Impression-Improvement (CGI-I) of sleepiness, and weekly number of cataplexy attacks (NCAs; NT1 only).

Results
A total of 212 patients were randomized and received study treatment (FT218, n=107; placebo, n=105). FT218 showed significant (P&lt;0.001) improvement vs placebo in mean sleep latency on MWT for all evaluated doses; LS mean difference (minutes) between FT218 and placebo was 6.13 at 9.0 g (week 13), 6.21 at 7.5 g (week 8), and 4.98 at 6.0 g (week 3). A higher proportion of patients receiving FT218 were much/very much improved on CGI-I vs placebo (72% vs 31.6% at 9.0 g; 62.6% vs 22.8% at 7.5 g; and 40.1% vs 6.1% at 6.0 g; all P&lt;0.001). LS mean difference between FT218 and placebo in mean weekly NCAs was significant (P&lt;0.001) for all doses: −6.65 at 9.0 g, −6.27 at 7.5 g, and −4.83 at 6.0 g. The most common adverse reactions were nausea, vomiting, headache, dizziness, enuresis, and decreased appetite.

Conclusion
All evaluated doses of FT218 showed significant improvement vs placebo in mean sleep latency on MWT, CGI-I, and weekly NCAs. FT218 was generally well tolerated and the most common adverse events were consistent with known side effects of SO.

Support (if any)
Avadel Pharmaceuticals.
491 Efficacy of FT218, a Once-Nightly Sodium Oxybate Formulation, by Narcolepsy Subtype: A Post Hoc Analysis From the REST-ON Study
Authors: Roy Asim , Morse Anne Marie , Dubow Jordan , Seiden David , Bogan Richard 
Published: May 2021

Abstract

Introduction
FT218 is an investigational, once-nightly, controlled-release formulation of sodium oxybate for the treatment of narcolepsy. The purpose of this post hoc analysis of the REST-ON study was to evaluate the effect of FT218 on measures of excessive daytime sleepiness (EDS) in patients with narcolepsy subtypes 1 (NT1) and 2 (NT2).

Methods
This was a randomized, double-blind, placebo-controlled, multicenter study in patients with narcolepsy ≥16 years old. Patients were stratified by narcolepsy subtypes and randomized 1:1 to receive FT218 or matching placebo: 4.5 g/night for 1 week, 6.0 g/night for 2 weeks, 7.5 g/night for 5 weeks, and 9.0 g/night for 5 weeks (maximum treatment duration, 13 weeks). Assessments of EDS included mean sleep latency (minutes) on maintenance of wakefulness test (MWT) and Clinical Global Impression-Improvement (CGI-I) in sleepiness.

Results
A total of 190 patients were included in the modified intent-to-treat population (NT1: FT218, n=72; placebo, n=73; NT2: FT218, n=21, placebo, n=24). Patients with NT1 or NT2 receiving FT218 had significant improvement in MWT. LS mean difference in mean sleep latency (minutes) vs placebo for NT1 was 5.97 for 9.0 g (week 13), 7.02 for 7.5 g (week 8), and 4.89 for 6.0 g (week 3; all P&lt;0.001), and for NT2, 6.27 for 9.0 g (P=0.020), 4.01 for 7.5 g (P=0.162), and 5.33 for 6.0 g (P=0.020). A higher proportion of NT1 patients receiving FT218 had significant improvement on CGI-I vs placebo (9.0 g: 75.5% vs 35.9%; 7.5 g: 66.9% vs 27.9%; 6.0 g: 39.9% vs 7.8%; all P&lt;0.001). A higher number of NT2 patients receiving FT218 were consistently rated as much/very much improved vs placebo, based on descriptive statistics. FT218 was generally well tolerated.

Conclusion
FT218 had similar efficacy on EDS at evaluated doses in NT1 and NT2, with improvement in MWT and CGI-I greater than placebo. FT218 may provide effective treatment for EDS in patients with narcolepsy, with or without cataplexy.

Support (if any)
Avadel Pharmaceuticals.
496 Do Patients and Healthcare Providers Have Similar Perceptions of Available Narcolepsy Educational Materials and Treatment Options?
Authors: Patterson Mark 
Published: May 2021

Abstract

Introduction
Studies have shown that patients typically retain &lt;50% of the information communicated to them by their healthcare providers. This lack of retention can lead to serious problems and misunderstandings regarding the condition, its treatment, and course. The goal of this study was to compare the information sleep specialists report providing to patients with the materials narcolepsy patients recall receiving.

Methods
Deidentified on-line surveys were submitted to active members of the American Academy of Sleep Medicine and to patients with narcolepsy Type 1 (NT1) and Type 2 (NT2) via the cloud-based software service company SurveyMonkey. These patients were recruited from the private Facebook group ‘Doctors and Narcoleptic Patients’.

Results
Results were received from a total of 75 patients (68% NT1, 29% NT2, 3% uncertain type; mean time since diagnosis: 11 years) and 18 sleep specialists (mean time in practice: 22 years). Physicians reported that their practices provided written material about narcolepsy to patients 69% of the time. By contrast, only 32% of patients recall receiving written information. Regarding treatment options, the groups reported variable results, with 94% of doctors/86% of patients discussing modafinil/armodafinil, 89% of providers/68% of patients communicating about amphetamines/methylphenidate, and 83% of physicians/47% of patients considering sodium oxybate. Additionally, only 56% of physicians were aware of narcolepsy patient advocacy organizations.

Conclusion
With the ready availability of social media and the exchange of oft inaccurate medical information, it is essential that physicians supply their patients with accurate up-to-date materials, especially following the diagnosis of a life-altering condition such as narcolepsy. This study suggests that there is a mismatch between the information which physicians believe they are providing and the materials the patients recall receiving. In addition to the medical care sleep specialists provide, patients and their families frequently rely on support from condition-specific organizations. Health care providers should be aware of the local and national organizations and supply their patients with contact information in an effort to provide a more holistic approach to medical care. Efforts are necessary to educate physicians about their patients’ needs for on-going care, distinct from that provided solely in the clinical setting.
Support (if any):
497 Clinical Presentation Prior to Idiopathic Hypersomnia Diagnosis Among US Adults: A Retrospective, Real-World Claims Analysis
Authors: Saad Ragy , Ben-Joseph Rami , Prince Patricia , Stack Catharine , Bujanover Shay , Taylor Ben 
Published: May 2021

Abstract

Introduction
Idiopathic hypersomnia (IH) is a rare, serious central hypersomnolence disorder for which there are no FDA-approved medications available. A retrospective study was conducted to characterize newly diagnosed patients with IH in the United States. Here, we report morbidity and comorbidity claims prior to IH diagnosis.

Methods
Claims from the IBM® MarketScan® database were analyzed between January 2014 and September 2019. The general population cohort included all adults with ≥12 months of continuous enrollment. From this population, a cohort with newly diagnosed IH was identified, defined as ≥2 claims with an IH diagnosis code ≥1 day and ≤180 days apart, and without an IH diagnosis in the 12 months prior to cohort entry. Patients without continuous medical/prescription coverage (enrollment gaps &gt;30 days) in the 12 months prior to cohort entry were excluded. Claims with diagnoses for select morbid/comorbid conditions were identified from 12 months prior to cohort entry for the IH and general population cohorts and summarized using descriptive statistics. A sensitivity analysis was conducted on IH patients with the diagnosis code recorded in the primary position (“primary IH”) on the claims to understand the effects of applying a more specific definition of IH.

Results
Of the general population cohort (N=32,948,986; mean age, 42 years; 52% female), 4,980 (0.015%) newly diagnosed IH patients were identified (mean age, 43 years; 67% female). Sleep-related morbidities in the 12 months prior to cohort entry included narcolepsy type 2 (17%/0.1%) and hypersomnia (10%/0.2%) for the IH/general population cohorts, respectively. Common comorbidities were sleep apnea (50%/4%), mood disorders (32%/8%), depressive disorders (31%/7%), anxiety disorders (31%/9%), hyperlipidemia (30%/20%), headache/migraine (24%/7%), diabetes or use of diabetes/obesity medication (20%/12%), hypertension (15%/10%), and cardiovascular disease (14%/8%) for the IH/general population cohorts, respectively. Common morbidities/comorbidities for the primary IH cohort (n=2,205) were generally similar to the overall IH population.

Conclusion
Compared with the general MarketScan® population, morbidities/comorbidities were more common for IH patients across all conditions analyzed, including sleep disorders and psychiatric, cardiometabolic, and cardiovascular disease. With cardiovascular risk factors common upon diagnosis of IH, therapies that do not increase cardiovascular risk are warranted.

Support (if any)
Jazz Pharmaceuticals
501 Clinical PK of XW10172 for Once Nightly Therapy in Patients with Narcolepsy or Sleep Disorders in Neurodegenerative Diseases
Authors: Canafax Daniel , Xiang William , Xiang Jia-Ning 
Published: May 2021

Abstract

Introduction
Patients with narcolepsy and patients with sleep disorders secondary to neurodegenerative diseases have been shown to respond to oxybate. To overcome the limitations of current oxybate therapies, we designed XW10172, a new chemical entity and GABA-B agonist with no sodium or other cation content and for once nightly dosing. The objectives of two clinical studies were to assess the XW10172 pharmacokinetics (PK), pharmacodynamics (PD) and safety/tolerability in normal study participants.

Methods
Two XW10172 studies in healthy participants assessed ascending single and multiple doses, comparison to sodium oxybate in immediate release (IR) and extended release (ER) formulations. PK parameters were calculated from concentration vs. time data. Safety and tolerability were assessed by monitoring adverse events, laboratory tests, and vital signs.

Results
To date, 84 study participants received XW10172 and the PK from single and multiple dose administration showed doses of 0.1 to 7.25 g had a mean oxybate half-life range of 0.5 to 1.3 hours. Oxybate levels from the drug were about 6-fold higher than XW10172 levels. Oxybate PK from XW10172 (IR) was the same as from equal molar doses of sodium oxybate. XW10172 (ER) formulations showed delayed Tmax with extended oxybate exposure compatible with single nightly dose therapy. PK-PD assessment of somnolence, the desired pharmacologic effect, showed a concentration-effect relationship (Cmax p=0.0004, AUC p&lt;0.0001). XW10172 was generally well tolerated and adverse events were those known to be associated with oxybate.

Conclusion
These data support progression of XW10172 (ER) in further clinical development studies to assess this once nightly GABA-B agonist therapy for the treatment of patients with various sleep disorders.

Support (if any)
XWPharma