bluuebunny/crossref_metadata_2025_split huggingface dataset:
0204 Sleep Irregularity Is Associated with Increased Risk of Hypertension: Data From Over Two Million Nights
Authors: Scott Hannah , Lechat Bastien , Reynolds Amy , Lovato Nicole , Escourrou Pierre , Catcheside Peter , Eckert Danny 
Published: May 2022

Abstract

Introduction
Sleep irregularity has been associated with worse cardio-metabolic health compared to regular sleep, but prior studies have been limited in sample size and have assessed sleep irregularity by actigraphy or questionnaires over a relatively short duration (~ 14 days). The current study investigated associations between sleep regularity and hypertension in a large, global sample over multiple months.

Methods
Data from 12,300 participants (aged 18-90 years) who used an under-mattress sleep device and a portable blood pressure monitor between July 2020 and March 2021 were included in this study. Sleep duration regularity was assessed as the standard deviation via device-assessed total sleep time. Sleep timing regularity was assessed as the standard deviation in sleep onset time and in sleep midpoint. Logistic regressions controlling for age, sex, BMI, and mean total sleep time were conducted to investigate potential associations between sleep regularity and hypertension.

Results
Participants were typically middle-aged (Mean ± SD; 50 ± 12 years) and predominantly male (12% females). Each participant had ~180 nights of recordings and ~70 blood pressure entries. There were 2,499 cases of hypertension defined as SBP&gt;140 and/or DBP &gt;90mmHg (20% of the sample). Across total sleep time quartiles, high sleep duration irregularity was consistently associated with a 9 to 15% increase in hypertension risk. A 38-minute increase in sleep midpoint irregularity was associated with an 11% (1.11 [1.03, 1.20]) increase in hypertension risk, independent of mean total sleep time and mean sleep midpoint. Similarly, a ~31-minute increase in sleep onset time irregularity was associated with a 29% increased risk of hypertension (1.29 [1.18, 1.42]).

Conclusion
These novel findings provide insight into the potential important impact of sleep irregularity on cardiovascular health. Further assessment of day-to-day fluctuations in sleep duration and timing for potential effects on next-day blood pressure and other cardiovascular health outcomes are warranted.

Support (If Any)
This was an unfunded investigator-initiated study. De-identified data were provided by Withings for unrestricted investigator-led analysis. PE serves as a consultant for Withings.
0214 Effects of Simulated Night-Shiftwork Induced Circadian Misalignment on the Human Plasma Metabolome
Authors: Kubicki Michelle , McHill Andrew , Melanson Edward , Reisdorph Nichole , Wright Kenneth , Depner Christopher 
Published: May 2022

Abstract

Introduction
Circadian misalignment occurs when behaviors such as food intake and sleep happen at inappropriate endogenous circadian times, is common among shift-workers, and is a risk factor for cardiometabolic disease. Identifying mechanisms underlying adverse cardiometabolic risk linked to circadian misalignment could help develop new countermeasure strategies to mitigate health consequences of shiftwork. Thus, we analyzed 24-hour profiles of plasma metabolites during circadian alignment and misalignment in a night-shiftwork protocol.

Methods
14 healthy adults (6M/8F), aged 26.4±1.2y (mean±SD), completed a 6 day in-laboratory simulated night-shiftwork study. The protocol comprised 2 baseline days (circadian alignment) followed by a transition day to shiftwork, and then 2 simulated night-shiftwork days (circadian misalignment). Participants consumed energy-balanced diets throughout the protocol, starting 3 days prior to laboratory admission. Plasma was collected every 4h during circadian alignment and misalignment conditions and was analyzed via untargeted metabolomics (liquid chromatography/mass-spectrometry). A model selection approach (best fit) with circadian and behavioral cosine models identified metabolites influenced by circadian (central circadian clock measured via dim-light melatonin onset) versus behavioral cycles (food intake/sleep).

Results
5,171 metabolites were detected with average abundance of 424 (~8%) changing between conditions (false discovery rate (FDR)&lt;0.05). 380 metabolites had significant (FDR&lt;0.05) 24-h time-of-day patterns. Of these 380 metabolites, 248 had 24-h time-of-day patterns during circadian alignment, 283 had 24-h time-of-day patterns during misalignment, and 141 had 24-h time-of-day patterns during both conditions. Of the metabolites with 24-h time-of-day patterns in both conditions, 50 were circadian-influenced (e.g., arachidinoyl-serine) and 91 were behaviorally-influenced (e.g., propionylcarnitine).

Conclusion
Almost twice as many metabolites were influenced by the behavioral versus circadian cycle suggesting altered timing of behaviors like food intake and sleep have a significant impact on 24-h time-of-patterns in the human plasma metabolome. For example, propionylcarnitine is involved in energy metabolism and likely reflects 24h time-of-day patterns altered by food intake. Alternatively, arachidinoyl-serine was circadian influenced, is involved in vasodilation, and thus may contribute to circadian regulation of blood pressure. Further understanding circadian and behavioral regulation of the metabolome could have application in identifying mechanisms of physiological dysregulation and targets for intervention to mitigate health consequences of circadian misalignment.

Support (If Any)
NIH-DK092624, NIH-TR001082, NIH-DK048520, NIH-HL132150, NIH-HL145099, NIH-DK111161
0219 Interplay of School Days and Free Days with Sleep Midpoint on the Association of Visceral Adiposity with Blood Pressure in Adolescents
Authors: Morales-Ghinaglia Natasha , Larsen Michael , Calhoun Susan , He Fan , Liao Jason , Vgontzas Alexandros , Bixler Edward , Liao Duanping , Fernandez-Mendoza Julio 
Published: May 2022

Abstract

Introduction
The circadian timing of sleep, including its variability, has emerged as an important contributor to obesity and cardiovascular health, such as elevated blood pressure. Adolescence is a particularly vulnerable period for circadian misalignment, which may express differently if youth are in school or on free-days. We examined whether deviations in sleep midpoint increase the impact of visceral adiposity on elevated blood pressure in adolescents as a function of being entrained to school or not.

Methods
We analyzed cross-sectional data from the Penn State Child Cohort follow-up study, a random population-based sample of 303 adolescents (16.2 ± 2.2 y; 47.5% female; 21.5% minority). Actigraphy-measured sleep midpoint was calculated as the midpoint (zeroed to midnight) of the sleep period for weekdays (5-nights) and weekends (2-nights). Actigraphy-measured sleep regularity was calculated as the intra-individual standard deviation of the 5-night weekdays sleep midpoint. Visceral adipose tissue (VAT) was measured via dual-energy X-ray absorptiometry scan. Systolic (SBP) and diastolic (DBP) blood pressure was measured three times in the seated position. Multivariable linear regression models were stratified by “in school” and “on break” to test sleep midpoint and sleep regularity as effect modifiers of VAT on SBP/DBP levels. Analyses were adjusted for sex, race/ethnicity, age, actigraphy-measured sleep duration and polysomnography-measured apnea/hypopnea index.

Results
When participants were studied while “in school”, significant interactions were found between VAT and weekdays sleep midpoint on SBP (p-interaction=0.027) and DBP (p-interaction=0.046), so that the later the sleep midpoint on school days, the greater the association of VAT with SBP/DBP. When participants were studied while “on break”, a significant interaction was found between VAT and weekdays sleep regularity on SBP (p-interaction=0.039), so that the higher the sleep irregularity on weekdays, the greater the association of VAT with SBP. No other significant interactions were found.

Conclusion
A delayed and an irregular sleep midpoint during school days and during breaks, respectively, best identified those adolescents with greater cardiovascular risk associated with visceral obesity. These data suggest that not only the circadian timing of sleep contributes to adverse cardiovascular outcomes but its distinct biomarkers require measurement under different entrainment conditions in adolescents.

Support (If Any)
National Institutes of Health (R01HL136587, UL1TR000127)
0254 Association of Slow Wave Activity and Odds Ratio Product with Internalizing and Externalizing Problems in Children and Adolescents
Authors: Fernandez-Mendoza Julio , Ricci Anna , He Fan , Calhoun Susan , Fang Jidong , Younes Magdy , Vgontzas Alexandros , Liao Duanping , Bixler Edward 
Published: May 2022

Abstract

Introduction
The association of metrics of sleep microstructure with internalizing and externalizing problems in youth has remained elusive. While one study found increased frontal slow wave activity (SWA) in depressed adolescents, there is lack of evidence for a relationship between dimensional measures of behavior and metrics of sleep depth/intensity. We examined the association between two measures of sleep depth/intensity, slow wave activity (SWA) and odds ratio product (ORP), with internalizing and externalizing problems in children and adolescents.

Methods
We calculated SWA and ORP during non-rapid eye movement (NREM) sleep at central, frontal and fronto-occipital derivations in 639 children (5-12y, median 9y) and 418 adolescents (12-23y, median 16y) from the Penn State Child Cohort via in-lab polysomnography. ORP provides a standardized measure of NREM sleep depth, while ORP-9 (average ORP in the 9-seconds following NREM arousals) provides a metric of arousability. SWA (0.4-4Hz) absolute power (µV2) was determined during NREM sleep. Internalizing and externalizing problems were assessed on Achenbach’s Behavior Checklist by parent (subjects≤17y) or self-report (subjects≥18y). For each scale, T-scores with a mean of 50 and standard deviation of 10 were obtained following standardized scoring. Multivariable-adjusted linear regression models examined the association between SWA/ORP and clinical outcomes.

Results
At ages 5-12, fronto-occipital SWA was negatively associated with externalizing behaviors (p=0.05), while fronto-occipital and frontal ORP, and frontal ORP-9 were positively associated with internalizing symptoms (all p&lt;0.01). At ages 12-23, central SWA was negatively associated with internalizing symptoms (p=0.05), while central (p=0.05) and frontal (p=0.03) ORP and central ORP-9 (p=0.03) were positively associated with externalizing behaviors.

Conclusion
Reductions in SWA in childhood or adolescence are associated with developmentally appropriate behavioral problems, as depression/anxiety are more prevalent in adolescence. In contrast to SWA, increased ORP (lighter sleep) and ORP-9 (greater arousability) are associated with more anxiety/depression in childhood, yet more externalizing behaviors in adolescence. These distinct associations, such as SWA with externalizing behaviors and ORP with internalizing symptoms during childhood, may reflect how SWA captures local/synaptic control, while ORP global/state control, of sleep depth, making both sleep EEG biomarkers important from a developmental standpoint.

Support (If Any)
National Institutes of Health (R01MH118308, UL1TR000127)
0365 Evaluation of Sleep Medicine Fellowship Program Websites
Authors: Shenoy Shanti , Akberzie Wahida , Gutierrez Jeremy S Landeo , Guerrero Christopher R Leon , Karroum Elias G 
Published: May 2022

Abstract

Introduction
Fellowship program websites often serve as the initial resource applicants use to learn about programs. Websites have likely become even more important due to social distancing mandates related to the on-going Covid-19 pandemic. In this study, we evaluated the websites of sleep medicine fellowship programs and analyzed the comprehensiveness of their content.

Methods
Sleep medicine fellowship programs in the United States (US) for the 2021 match cycle were identified using the Electronic Residency Application Service (ERAS) directory and the Fellowship and Residency Electronic Interactive database (FREIDA). Twenty-two prespecified website content criteria related to education, recruitment, and compensation were evaluated. Programs’ website comprehensiveness was compared based on geographic location (Northeast/Midwest/South/West); type of programs (Community/University); programs matching status (Complete/Partial or No matching status); core specialty (Internal medicine/Other specialties); and program size (based on number of sleep fellows).

Results
A total of 78 US sleep fellowship program’ websites were evaluated. Most (80.8%) had a direct functional link to ERAS or FREIDA websites. The percentage of sleep medicine fellowship program’ websites reporting each of the twenty-two-criterion was highly variable (range: 2.6%-98.7%). The percentage of overall website comprehensiveness among sleep medicine fellowship programs was 56.8%±16.5% (range:13.6%-90.9%). There was a significantly higher educational website content comprehensiveness for the Internal medicine compared to other specialties-based sleep programs (p = 0.002). There were no significant association between the overall, educational, recruitment, and compensation website content comprehensiveness of sleep programs and their US region location, type of affiliation, matching status, or program size.

Conclusion
Website content comprehensiveness amongst sleep fellowship programs in the US is variable with a lower educational content on website pages of non-internal medicine-based sleep programs. Improvement in website content of sleep medicine programs is a potentially easy way for programs to improve fellow recruitment, and more importantly, allow prospective sleep fellow applicants to make a more informed decision with regards to program selection.

Support (If Any)
This study was not funded.
0369 Sleep Education for the Nurse Practitioner: Nurse Practitioner Student Focus Group Findings
Authors: Watach Alexa , McPhillips Miranda , Saconi Bruno , Lang-Gallagher Rebecca , Lyons M Melanie , Renz Susan , Rosen Ilene , Sawyer Amy 
Published: May 2022

Abstract

Introduction
Primary care nurse practitioners (NPs) receive little to no sleep education in graduate programs despite being first-line providers for patients presenting with sleep-related symptoms. Sleep curriculum has been consistently identified as a gap in nursing education and confirmed in recent survey studies of nurses and NPs.

Methods
Qualitative descriptive study to explore NP students’ reactions to an asynchronous, case-based sleep e-learning program. Data were collected as part of a larger pre-/post-study assessing the program. Six asynchronous online modules were offered to a cohort of primary care NP students in a single academic institution’s master’s degree in primary care nursing program. At the end of the course, students were invited to participate in one-hour, online, focus group sessions. Directed content analysis, guided by the Kirkpatrick training evaluation model, was used to analyze the qualitative data to understand NP students’ experience with the program and elicit their perspectives about sleep education.

Results
Participants in the course (N=67) were predominantly female (88%) and ≤35 years old (81%). Twenty-four students participated in the focus group sessions. Two overarching themes emerged, including positive reactions to (1) course design and (2) course content. Students reported the case-based scenarios and quizzes enhanced their learning and kept them engaged, noted the user-friendly format, and appreciated that the course was asynchronous. After completing the modules, students recognized they had a previous knowledge gap related to sleep and perceived the information they received to be relevant to their practice/patient population and to their own personal health/wellbeing. Students also discussed their intentions to incorporate sleep assessments into practice.

Conclusion
Given the increasing sleep health needs of the population and the growing shortages of sleep providers, there is a critical need to ensure NP’s have the proper education to recognize and identify implications of poor and disordered sleep in their patients. In this study, NP students enthusiastically embraced sleep education, identified knowledge gain, and had intentions to apply their learned skills in practice highlighting the feasibility of increasing curricular exposure to sleep medicine.

Support (If Any)
The work reported herein was supported by National Institutes of Health (R25HL120874 Rosen, PI).
0388 Dosing and Reasons for Transitioning From Sodium Oxybate to Lower-Sodium Oxybate in People With Narcolepsy: Data From the Real-World TENOR Study
Authors: Husain Aatif , Leary Eileen , Fuller Douglas , Macfadden Wayne , Whalen Marisa , Bae Charles , Zee Phyllis 
Published: May 2022

Abstract

Introduction
Lower-sodium oxybate (LXB) contains 92% less sodium than sodium oxybate (SXB) and is approved for treating cataplexy or excessive daytime sleepiness in patients with narcolepsy (aged ≥7 years) and for treating idiopathic hypersomnia in adults. The Transition Experience of persons with Narcolepsy taking Oxybate in the Real-world (TENOR) study examines the impact of transitioning from SXB to LXB in a real-world setting.

Methods
TENOR is a patient-centric, prospective, observational, noninterventional, virtual-format study (NCT04803786). Eligible participants include US adults with narcolepsy (type 1 or 2) transitioning from SXB to LXB within the previous/upcoming 7 days. Longitudinal data are collected for 21 weeks post-transition. These analyses include data collected at initiation of LXB treatment from all qualifying participants.

Results
The analyses included 85 participants with confirmed narcolepsy (type 1, n=45; type 2, n=40). Mean (SD) age was 40.3 (13.0) years; most participants were female (73%) and White (87%) and took ≥1 concomitant medication for narcolepsy at baseline in addition to SXB (79%, with 38% taking 1 concomitant medication, 33% taking 2, and 8% taking ≥3). Mean (SD) time on current SXB regimen was 57.8 (52.1) months. Almost all (96%) participants took SXB twice nightly. After transitioning, 98% of participants took LXB twice nightly. Mean (SD) total nightly SXB (n=85) and starting LXB (n=84) doses at baseline were 7.7 (1.5) g and 7.7 (1.5) g, respectively; SXB-LXB dose conversions at baseline were gram-for-gram in 87% of participants. The most common total nightly LXB dose was &gt;7.5 g (56%), followed by &gt;6.0 to ≤7.5 g (21%), &gt;4.5 to ≤6.0 g (15%), and ≤4.5 g (7%). Participant-reported reasons for transitioning to LXB (multiple selections allowed) included lower sodium content for long-term health (93%), physician recommendation (47%), to avoid cardiovascular issues (39%), to avoid side effects (31%), to improve control of narcolepsy symptoms (18%), and other (14%).

Conclusion
The majority of participants transitioned from SXB to LXB using a gram-for-gram dose conversion. The most common reason cited for switching was for long-term health due to the lower sodium content of LXB.

Support (If Any)
Jazz Pharmaceuticals.
0391 Physician Perspective on Idiopathic Hypersomnia: Awareness, Diagnosis, and Impact on Patients
Authors: Whalen Marisa , Roy Bailey , Steininger Teresa , Dronamraju Nalina , Enson Daniel 
Published: May 2022

Abstract

Introduction
Idiopathic hypersomnia is a debilitating central disorder of hypersomnolence characterized by excessive daytime sleepiness, severe sleep inertia, and prolonged nighttime sleep. Awareness of idiopathic hypersomnia among physicians and the general public is believed to be low, and diagnosis may be delayed by years.

Methods
US physicians completed an online survey (February 5–12, 2021) assessing familiarity with idiopathic hypersomnia and understanding of the diagnostic process and impact on patients’ lives. Eligible physicians had been in practice for ≥2 years and had treated ≥2 patients for idiopathic hypersomnia and ≥2 patients for narcolepsy.

Results
There were 305 respondents, including 62 primary care physicians (PCPs), 67 neurologists, 82 psychiatrists, 90 pulmonologists, and 4 sleep specialists. Most were male (73%), White (58%), and 35–54 years of age (62%); mean years in practice was 16.6, and median number of patients with idiopathic hypersomnia was 30. Overall, 48% of physicians reported being extremely familiar with idiopathic hypersomnia (PCPs, 29%; neurologists, 60%; psychiatrists, 34%; pulmonologists, 62%), and 64% agreed that most healthcare providers have an insufficient understanding of idiopathic hypersomnia. Fewer than half (46%) considered the diagnostic process for idiopathic hypersomnia to be clear (strongly/somewhat agree), a lower proportion compared with other sleep disorders (93% for obstructive sleep apnea, 76% for restless legs syndrome, 72% for narcolepsy type 1, and 67% for narcolepsy type 2). Most considered the diagnostic process to be challenging (strongly agree, 40%; somewhat agree, 47%; neither agree nor disagree, 9%; somewhat disagree, 4%; strongly disagree, 1%) and agreed that patients with idiopathic hypersomnia are often misdiagnosed (strongly/somewhat agree, 90%) and that the negative impact of idiopathic hypersomnia is underestimated (strongly/somewhat agree, 92%). Estimated years to diagnosis of idiopathic hypersomnia were 0–1 (11%), 1–2 (32%), 2–5 (39%), 5–10 (15%), and 10+ (2%). Most considered idiopathic hypersomnia to be both a daytime wakefulness disorder and a nighttime sleep disorder (64%).

Conclusion
The survey findings highlight the need for more healthcare provider education and increased understanding of idiopathic hypersomnia, its diagnosis, and its impact on patients’ lives.

Support (If Any)
Jazz Pharmaceuticals, with participation of the Hypersomnia Foundation.