bluuebunny/crossref_metadata_2025 huggingface dataset:
059 Daridorexant: A dual, equipotent, and insurmountable antagonist of both orexin-1 and orexin-2 receptors
Authors: Grandjean Celia Mueller , Kiry Manon , Vaillant Catherine , Nayler Oliver , Gatfield John
Published: May 2021

Introduction

The orexin neuropeptide–receptor system is a central sleep and wake regulator in the brain. The two orexin receptor subtypes, OX1R and OX2R, are expressed either alone or together in all major wake-promoting brain areas. OX1R and OX2R activation by orexins causes elevation of intracellular calcium, which enhances synaptic transmission in secondary, monoaminergic wake- and arousal-promoting neurotransmitter circuits. Orexin receptor antagonists represent a novel and specific treatment of insomnia, which is different from classical therapy that more broadly inhibits brain activity via GABAA activation. Here we describe the molecular pharmacology of daridorexant, an orexin receptor antagonist which has proven highly effective in improving sleep and daytime functioning in insomnia patients.

Methods

Orexin-A(OxA)-induced calcium release assays in OX1R- and OX2R-expressing recombinant cell lines were applied to measure the antagonistic potency and kinetic properties of daridorexant in functional assays. Whole-cell competitive binding assays, using an orthosteric tracer were employed to determine the Ki of daridorexant. Comparisons were made with suvorexant and lemborexant.

Results

In OxA-induced calcium release assays with 2-h pre-incubation time, daridorexant displayed apparent Kb values of 0.5 nM (OX1R) and 0.8 nM (OX2R) with insurmountable antagonism on both receptors, demonstrating equipotent and highly effective functional inhibition of both receptor subtypes. On-target residence times of daridorexant (37oC) expressed as receptor occupancy half-lives (ROt1/2) were 4 min (OX1R) and 8 min (OX2R). In binding assays, daridorexant behaved as highly potent orthosteric antagonist. Also suvorexant behaved as dual insurmountable antagonist at OX1R/OX2R (appKb=0.7nM/1.0nM; ROt1/2=9 min/6 min) and as potent orthosteric antagonist in binding assays. Interestingly, lemborexant displayed a different interaction profile at OX1R/OX2R (appKb=13nM/0.4nM, ROt1/2<2min/<2min), i.e. it behaved as preferential OX2R antagonist with a very short on-target residence time and little insurmountability.

Conclusion

Daridorexant displays the desired target interaction profile of a dual, equipotent, and insurmountable antagonist of both OX1R and OX2R, which ensures equally efficient inhibition of both arousal-/wake-promoting receptor subtypes. Daridorexant′s on-target residence times are long enough to cause insurmountable inhibition, but short enough to avoid pharmacodynamic effects after drug elimination.

Support (if any)

Funded by Idorsia Pharmaceuticals Ltd.
066 Noradrenaline and acetylcholine inhibit sleep-promoting neurons of ventrolateral preoptic area through a local GABAergic circuit
Authors: De Luca Roberto , Nardone Stefano , Zhu Lin , Arrigoni Elda
Published: May 2021

Introduction

The ventrolateral preoptic (VLPO) nucleus is a key area involved in the initiation and maintenance of sleep. During wakefulness, sleep-promoting galanin neurons in the VLPO are directly inhibited by arousal signals including noradrenaline and acetylcholine. We have found that while these neurotransmitters directly inhibit VLPO galanin neurons, they also activate GABAergic neurons in the VLPO that do not express galanin. We propose that when activated by monoaminergic and cholinergic inputs, these local VLPO GABAergic neurons provide an additional inhibition of the VLPO galanin sleep-promoting neurons. We tested this model in brain slices in mice.

Methods

We studied VLPO galanin neurons in mouse brain slices using patch-clamp recordings. We recorded from fluorescently labeled VLPO galanin neurons following the injection of a cre-dependent AAV encoding for mCherry, into the VLPO of Gal-cre mice. For the optogenetic studies we expressed channelrhodopsin-2 (ChR-2) in VLPO VGAT neurons and mCherry in galanin neurons by injecting a flp-dependent and a cre-dependent AAV encoding respectively for ChR2 and mCherry into the VLPO of VGAT-flp::Gal-cre mice. We photo-stimulated local GABAergic neurons and recorded from labeled VLPO galanin neurons. Noradrenaline, carbachol and receptor antagonists were bath-applied.

Results

Noradrenaline and carbachol inhibited VLPO galanin neurons by alpha-2 and muscarinic receptors and these effects were maintained in the presence of tetrodotoxin (TTX) indicating, as previously proposed, a direct inhibitory effect of noradrenaline and carbachol on VLPO galanin neurons. In addition, both noradrenaline and carbachol increased the frequency of spontaneous inhibitory post-synaptic currents (sIPSCs) of VLPO galanin neurons, suggesting an additional inhibitory action on VLPO galanin neurons. Finally, optogenetic stimulation of local VLPO GABAergic neurons produced short latency, TTX-resistant, opto-evoked IPSCs in VLPO galanin neurons. Both noradrenaline and carbachol increased the amplitude of these opto-evoked IPSCs by the activation of alpha-1 and muscarinic receptors.

Conclusion

Our results demonstrate that noradrenaline and acetylcholine inhibit VLPO galanin neurons directly and indirectly. Both noradrenaline and acetylcholine increase GABAergic afferent inputs to VLPO galanin neurons by activating local GABAergic neurons. We propose that during wakefulness this feedforward inhibition provides additional inhibition of VLPO galanin sleep-promoting neurons.

Support (if any)

NS091126 and HL149630
084 Does Alignment between the Timing of Sleep and Circadian Rhythm Predict Behavioral Decision Making?
Authors: Hisler Garrett , Dickinson David , Hasler Brant
Published: May 2021

Introduction

Cognitive performance and decision making have been shown to suffer under conditions of misalignment between circadian preference and time-of-assessment; however, little is known about how misalignment between the timing of sleep and circadian rhythm impacts decision making. To this end, this study captured naturally occurring degrees of alignment between the timing of sleep and the circadian rhythm (i.e., alignment of sleep-wake timing with circadian phase) to examine if greater misalignment predicts worse behavioral decision making.

Methods

Over the course of two weeks, 32 participants (18–22 years of age; 61% female; 69% White) continuously wore actigraphs and completed two overnight in-lab visits (Thursday and Sunday) in which both dim light melatonin onset (DLMO) and behavioral decision-making (risk taking, framing, and strategic reasoning tasks) were assessed. Sleep-wake timing was assessed by actigraphic midsleep from the two nights prior to each in-lab visit. Alignment was operationalized as the interval between DLMO and average midsleep. Multilevel modeling was used to predict performance on decision making tasks from circadian alignment during each in-lab visit; nonlinear associations were also examined.

Results

Misalignment characterized by shorter time between DLMO and midsleep predicted decision-making in a curvilinear fashion (i.e., squared misalignment term predicted performance). Specifically, shorter time between DLMO and midsleep predicted greater risk-taking under conditions of potential loss (B = .10, p = .04), but less risk-taking under conditions of potential reward (B = -.14, p = .04) in a curvilinear fashion. Misalignment did not predict decision-making in the framing and strategic reasoning tasks.

Conclusion

Findings suggest that naturally occurring degrees of misalignment between the timing of sleep and the circadian rhythm may impact risky decision-making, further extending accumulating evidence that sleep/circadian factors are tied to risk-taking preferences. Future studies will need to replicate findings and experimentally probe whether manipulating alignment influences risky decision making.

Support (if any)

R21AA023209; R01DA044143
095 Steering Wheel Angle Excursions as a Measure of Fatigue-Related Driver Performance Impairment
Authors: Muck Rachael , Van Dongen Hans
Published: May 2021

Introduction

Fatigue from sleep loss and circadian misalignment causes automobile driving performance impairment. Metrics based on steering wheel angle, which is straightforward to measure, could be used to quantify this impairment. As the tail of the distribution of steering wheel angles (absolute magnitude of deviation from center) increases with fatigue, we investigated whether driving performance impairment could be quantified based on the prevalence of steering wheel excursions beyond a given angle threshold. We used data from two published laboratory studies of simulated shift work, in which fatigue remained low during day shifts but increased across time awake during night shifts.

Methods

N=37 healthy adults (ages 26.8±5.2y; 25 men) were assigned to a simulated night shift schedule (awake 20:00-10:00) or day shift schedule (awake 08:00-22:00; study 1 only). After an adaptation period, participants underwent two 5-day shift cycles with an intervening rest period. Driving performance was measured on a high-fidelity simulator during adaptation (data not used) and four times at 3h intervals during each shift day. Every drive involved 30min driving at 55mph, including ten 0.5mi uneventful straightaways being considered here. Steering wheel angle was measured at 72Hz (study 1) or 60Hz (study 2). A total of 1,471 drives (31,394,498 angle measurements) were available for analysis.

Results

We investigated angle thresholds across 0.01-0.25rad in 0.01rad intervals and counted the corresponding number of threshold excursions in each drive for each participant. For study 1, we applied mixed-effects ANOVA with fixed effects for condition and time awake, and their interaction, and determined the local effect size for interaction. A 0.03rad (1.7°) threshold yielded the greatest effect size, f²=0.031 (small). For this threshold, we repeated the analysis using the data from both studies, controlling for study. The interaction was significant (F[3,1428]=13.23, p<0.001), showing low driving impairment across time awake during day shifts but increasing impairment across time awake during night shifts.

Conclusion

The prevalence of steering wheel excursions beyond a 1.7° angle threshold yielded sensitivity to fatigue-related driving performance impairment during simulated night shifts. Further research will extend our results to driving through curves and with greater fatigue levels.

Support (if any)

FMCSA DTMC75-07-D-00006
123 Detrimental effects of acute sleep deprivation on perceptual metacognition
Authors: Bigica Marco , Jiang Chunxiang , D’Onofrio Ilenia , Liu Zhishan , Song Chen
Published: May 2021

Introduction

Sleep deprivation (SD) impairs cognitive performance but its impact on metacognition – i.e. the ability to introspect about cognitive performance – is less clear. A few studies have assessed metacognitive accuracy after acute sleep deprivation in tasks of executive functions and found no impairments. However, whether SD has no influence on metacognition of other cognitive domains such as perception has not been investigated. In this study, we examined how metacognitive accuracy in perceptual decision tasks is affected by 32 hours of sustained wakefulness.

Methods

14 participants (3 males, aged 20-32) repeated four visual psychophysical tasks (orientation discrimination, two-flicker fusion, vernier acuity and a novel face/house discrimination in noise) at regular intervals during 32 hours of sustained wakefulness and once after 8 hours recovery sleep. In each task, we concurrently measured quantitative indices of perceptual threshold, confidence rating and metacognitive accuracy (i.e. how well confidence ratings discriminate correct vs incorrect perceptual judgements).

Results

We observed a gradual increase of perceptual threshold in all tasks with increased time awake. Furthermore, metacognitive accuracy gradually decreased during sustained wakefulness in all tasks. Specifically, the decrease in metacognitive accuracy was driven by over-estimated confidence in trials when participants made incorrect perceptual judgements. After recovery sleep, perceptual thresholds were reset to baseline for all tasks, while metacognitive accuracy was reset to baseline for the orientation discrimination and two-flicker fusion tasks only.

Conclusion

We showed that sustained wakefulness up to 32 hours increasingly impairs metacognitive accuracy in perceptual decision tasks. These results are consistent across different perceptual tasks, but are in contrast to previous studies showing preserved metacognition of executive functions after SD. Overall, this suggests that the fundamental mechanisms of perceptual metacognition may be similarly affected by sleep deprivation, but that SD selectively impacts different domains of metacognition, such as perceptual metacognition and metacognition of executive functions.

Support (if any)

MB - Cardiff University PhD Funding CS - Wellcome Trust 209192/Z/17/Z
167 Food Insecurity and Cardiometabolic Risks in Urban American Indian/Alaska Native (AI/AN) Youth: The Role of Sleep Health
Authors: Dong Lu , D’Amico Elizabeth , Dickerson Daniel , Brown Ryan , Palimaru Alina , Johnson Carrie , Troxel Wendy
Published: May 2021

Introduction

American Indian/Alaska Native (AI/AN) individuals experience significant health disparities, including poor sleep health and cardiometabolic disease, and these risks emerge early in life. Food insecurity (lack of consistent access to healthy foods) is an important social determinant of health, and AI/AN people are one of the highest risk groups for experiencing food insecurity. Yet, little is known about how food insecurity contributes to health outcomes in urban AI/AN youth. This is the first study to examine the association between food insecurity and sleep (both self-reported sleep disturbance and a composite index of sleep health) and cardiometabolic outcomes in urban AI/AN youth, and whether sleep may be an indirect path between food insecurity and cardiometabolic outcomes.

Methods

Participants were 142 urban AI/AN youth (mean age = 14, 58% female, 53% living in single-parent households). The Child Food Security Survey Module assessed food insecurity. Sleep disturbance was measured using the School Sleep Health Survey. A multi-dimensional sleep health composite was derived using questionnaire measures (i.e., satisfaction, alertness) and actigraphy-derived indices (i.e., duration, efficiency, regularity, timing). Cardiometabolic measures included body mass index (BMI), blood pressure, glycosylated hemoglobin (HbA1c), waist circumference, cholesterol, and triglycerides. Covariates were sex and age, and single-parent household.

Results

Greater food insecurity was significantly associated with greater BMI (b = 0.12, p = 0.015), higher systolic blood pressure (b = 0.93, p = 0.03), and greater sleep disturbance (b = 1.49, p < .001), and marginally associated with poorer sleep health via the sleep health composite (b = -0.09, p = 0.08). Food insecurity was not associated with any other cardiometabolic outcomes. There was a significant indirect path from greater food insecurity to greater waist circumference through lower sleep health composite score (0.11, 95% bootstrapping CI: [0.01, 0.30]).

Conclusion

Food insecurity is an important social determinant of sleep and cardiometabolic health. This is the first study of these associations in urban AI/AN youth. Sleep health may be an important, modifiable intervention target to mitigate the negative impact of food insecurity and reduce cardiometabolic risks in this vulnerable population.

Support (if any)

NIMHD R01MD012190
184 Racial awareness and insufficient sleep
Authors: Grigsby-Toussaint Diana , Shin Jong Cheol
Published: May 2021

Introduction

Population-based studies are needed to fully disentangle persistent racial and ethnic disparities in sleep health in the US. In this study, we examine whether the frequency of self-reflection on racial identify influences insufficient sleep among US adults.

Methods

The 2010 Behavioral Risk Factor Analysis Surveillance System (BRFSS) was used as the primary data source to explore the relationship between self-reflection of racial identity and insufficient sleep. Data was limited to states administering the “Reactions to Race Module,” which included Georgia, Kentucky, and Rhode Island (N=7,085). Frequency of self-reflection of race was assessed using the question “How often do you think about your race? Would you say never, once a year, once a month, once a week, once a day, once an hour, or constantly?” Insufficient sleep was determined using the item, “During the past 30 days, for about how many days have you felt you did not get enough rest or sleep?” Multivariate regression analyses were performed while controlling for age, sex, education, income, marital status, and poor mental and physical health.

Results: Results

Across the sample, participants reported an average of 8.95+/- 10.06 days of insufficient sleep per month. Participants from Georgia reported the highest number of days of insufficient sleep (9.83+/- 10.51) followed by Kentucky (8.64+/- 9.94) and Rhode Island (8.38+/- 9.67) (p<0.05). After controling for age, sex, education, income, employment, and marital status, individuals reporting any self-reflection on their race were more likely to report insufficient sleep within a 30-day period (Beta=0.026, 95% CI [0.062, 1.02], p=0.027).

Conclusion: Conclusion

In a sample of US adults, self-reflection of race adversely impacted sleep quality. More studies are needed to fully explore the mechanisms underpinning this association.

Support (if any):
242 Sufficient sleep attenuates the impact of COVID-19 pandemic on executive function decline in late adolescents and young adults
Authors: Ji Xiaopeng , Saylor Jennifer
Published: May 2021

Introduction

Executive function (EF), which shows continued development into early adulthood, is essential to build resilience to cope with COVID-19-related social and environmental changes. However, how sleep interacts with the pandemic on affecting EF remains unclear, particularly among late adolescents and young adults. This study examined (1) the impact of COVID-19 pandemic on sleep and EF and (2) whether sleep moderated pandemic-related changes in EF among young people aged 18-21 years old.

Methods

Between April and May 2020, university students with baseline data on sleep and EF (Spring and Fall semesters in 2019) available were invited to this follow-up study. Sleep duration, mid-sleep times, social jetlag (the difference between mid-sleep times on weekdays and weekends) and sleep latency were assessed using 7-day sleep diaries. Participants also completed the Pittsburgh Sleep Quality Index (PSQI), the Morningness/Eveningness Questionnaire, and the Behavior Rating Inventory of Executive function which yielded Global Executive Composite (GEC) scores. Paired t-test and multilevel random-effects models (STATA 16.0) estimated the associations. Covariates in multilevel models included age, sex, race, family income, parental education, COVID status, and health behaviors.

Results

Forty participants (19.25±1.12 years old) had paired data before and during COVID-19 pandemic. Participants slept 24 min longer (t= -2.07, p=0.03) but had increased sleep latency (t=-1.83, p=0.07) during the pandemic compared to pre-COVID baseline. Mid-sleep times shifted 40 min later (t= -3.22, p=0.003) during the pandemic. In multilevel models, GEC scores increased during pandemic (b=3.15, p=0.03) versus baseline, suggesting decreased executive function. Sleep duration (β=-4.72, p=0.03) significantly interacted with assessment time (before/during COVID-19), with increasing sleep duration attenuating the decline in EF during pandemic versus baseline. Although there was no interaction with COVID-19 pandemic, poor sleep quality (PSQI>5) was independently associated with decreased EF (B=4.69, p=0.02). Other sleep variables were not associated with EF nor moderators.

Conclusion

Compared with pre-COVID-19 baseline, young people report longer sleep duration, later sleep phase, increased sleep latency, and worse executive function during the pandemic. Sufficient sleep represents a resilience factor against executive function decline during this unprecedented crisis.

Support (if any)

No
244 Physical fitness attenuates the deleterious association of sleep apnea with gray matter volume in the Wisconsin Sleep Cohort Study
Authors: Edmunds Kyle , Hagen Erika , Gaitán Julian , Barnet Jodi , Driscoll Ira , Lose Sarah , Motovylyak Alice , Okonkwo Ozioma , Peppard Paul
Published: May 2021

Introduction

Recent evidence has illustrated that gray matter (GM) atrophy, a diagnostic hallmark of Alzheimer’s disease (AD), may be influenced by psychosocial risk modifiers such as physical exercise and sleep. Cardiorespiratory fitness, a measure of oxygen delivery and utilization during exercise, is positively associated with both sleep quality and gray matter volume in brain areas associated with age-related cognitive decline, such as the hippocampus. In contrast, sleep apnea has been linked to global and regional gray matter atrophy, which is thought to be driven in-part by the incomplete modulation of cardiovascular and respiratory control during sleep. This study examines whether cardiorespiratory fitness modifies the deleterious relationship between sleep apnea and GM volume in a sample of non-demented older participants from the Wisconsin Sleep Cohort (WSC).

Methods

Using data from a subset of WSC participants (n=129, 51% female, mean [range] age at baseline=68 [49-85] years), cardiorespiratory fitness was estimated using a Non-Exercise CardioRespiratory Fitness Measure (NECRFM; based on age, sex, BMI, self-reported physical activity, and resting heart rate). Sleep apnea severity was measured by overnight polysomnography and characterized by the base 10 logarithm of the apnea-hypopnea index, log10(AHI+1). We assembled cross-sectional linear models of MRI-measured total GM volume using NECRFM and log10(AHI+1) as predictors while controlling for age, sex, BMI, education, and hypertension. Regional volumetric changes in the hippocampus and amygdala were assessed using analogous linear models, adjusting both outcome volumetrics for total intracranial volume.

Results

While the interaction between fitness and apnea severity was not significant (p=0.50), results stratified at the median NECRFM illustrated that among the less fit individuals, higher log10(AHI+1) was associated with a significant reduction in total GM volume (B(SE)=-0.06 (0.02); p=0.007); this relationship was not significant among those who were more fit (B(SE)=-0.03 (0.02); p=0.11). There were no significant effects in the hippocampus or amygdala.

Conclusion

These results indicate that cardiovascular fitness may attenuate the effect of severe sleep apnea on GM volume in older adults, supporting the protective role of cardiovascular fitness in aging brain health.

Support (if any)

This work was supported by United States National Institutes of Health grants R01AG058680, R01HL62252, 1R01AG036838, 1UL1RR025011, and R01AG062167.
265 Blue Light Filtering Laptop and Tablet Screen Protectors Used After Sunset Improve Sleep
Authors: Rus Holly , Danoff-Burg Sharon , Weaver Morgan , Rodriguez Rodolfo , Raymann Roy
Published: May 2021

Introduction

Light exposure at night is associated with altered sleep behavior and impaired sleep satisfaction, in part due to suppressing the release of melatonin. According to a National Sleep Foundation poll, 90% of people report using electronic devices within an hour of bed at least a few times per week. This study aimed to examine how use of EyeJust, a blue light filtering screen protector applied to laptops and tablet devices, impacted sleep.

Methods

A within subjects, pre-post intervention design was implemented. Adults (n=24) who self-reported regular blue light exposure after sunset and eye strain participated in a 6-week study (3 weeks of baseline followed by 3 weeks of product use). Intervention consisted of the use of blue light filtering screen protectors on iOS devices used after sunset. Sleep was measured objectively each night using SleepScore Max and by self-report. Participants also reported level of eye strain each night. Multilevel regression and paired t-tests were used to test for statistical significance.

Results

Across participants (75% female; age 21-50, avg. 37), there were 850 nights of sleep measured. When measured pre-post, many aspects of perceived sleep improved when using the screen protectors: sleepiness at bedtime, falling asleep in the preferred amount of time, ability to sleep through the night, feeling rested in the morning, sleep quality, and satisfaction with sleep (ps<.05). When measured daily, improvement was seen in eye strain, perceived time to fall asleep, perceived awakenings, and time spent awake at night (ps<.05). Objective sleep improvement was found in a subgroup of younger adults (age 21-35). They spent more time in bed (p=.03) and slept longer (6 hours, 40 minutes on average during baseline vs. 6 hours, 50 minutes during intervention; p=.04). This subgroup also had more REM sleep as reflected by a 2% increase in MindScore (measure of REM sleep; p=.04)

Conclusion

Using blue light filtering screen protectors helped improve sleep, measured by self-report and objectively, especially among younger adults. This intervention may help reduce the negative impact electronic devices have on sleep.

Support (if any)

EyeJust
273 Automatic sleep staging with photoplethysmography and accelerometer in a community-based population
Authors: Lee Pei-Lin , Ting Nettie , Lin Yu-Cheng , Chiu Hung-Chih , Liu Yu-Ting , Ku Bo-Wen
Published: May 2021

Introduction

The study aims to validate the automatic sleep staging system (ASSS) with photoplethysmography (PPG) and accelerometers embedded in smart watches in community-based population

Methods

75 healthy subjects were randomly recruited form 304 staffs in an industrial firm who volunteered for this study. A four-stage classifier was designed based on Linear Discriminant Analysis using PPG and accelerometers. To better validate the system performance, the leave-one-out approach was applied in this study. The performance of ASSS was assessed with the epoch-by-epoch and whole-night agreement for sleep staging against manual scoring of overnight polysomnography.

Results

The mean agreement of four stages across all subjects was 61.1% (95% CI, 58.9-63.2) with kappa 0.55 (0.52-0.58). The mean agreement for wake, light sleep (LS), deep sleep (DS), and REM was 53.4%, 84.1%, 40.3%, 75.6%, respectively. The whole-night agreement was good-excellent (Intra-class correlation coefficient, 0.74 to 0.84) for total sleep time, sleep efficiency, wake after sleep onset, and duration of wake and REM. The agreement was fair for sleep onset and LS duration, but poor for DS duration.

Conclusion

Our result showed that PPG and accelerometers based smart watches have proper validity for automatic sleep staging in the community-based population.

Support (if any)

“Center for electronics technology integration (NTU-107L900502, 108L900502, 109-2314-B-002-252)” from the Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan; MediaTek Inc (201802034 RIPD).
278 Understanding Perspectives on Artificial Intelligence Technologies for Sleep Self-Management
Authors: Kearns William , Laine Megan , Oh Esther , Thompson Hilaire , Demiris George
Published: May 2021

Introduction

Until recently, understanding one’s sleep activity relied on technology only available in sleep labs with data analyzed by experts. Transitioning this technology from the lab to natural environments results in noisy data. Fortunately, advances in signal processing through Artificial Intelligence (AI) have made these technologies accessible to consumers. This study seeks to provide recommendations that address user preferences and concerns related to sleep self-management devices and software that leverage AI, as they have the potential to increase both the quantity and quality of sleep data available to researchers.

Methods

We assigned adult participants (N=25) with Pittsburgh Sleep Quality Index scores ≥ 5 (indicating low sleep quality) to one of four focus group sessions based on their self-reported prior use of sleep technologies. After a short demonstration, the moderator solicited participant feedback on devices and software in each of the following four categories: • headbands (Beddr, Dreem 2, Muse S) • sleep tracking mats (Withings) • snoring detectors (Smart Nora) • mobile applications (Sleep Cycle Alarm Clock, Sleep Score, Do I Snore, Sleep Rate)

Results

Participants anticipated discomfort from wearing headbands and placing snoring detectors under their pillow, although a subset of participants indicated that they would be willing to sacrifice comfort in exchange for improved accuracy. Conversely, participants were interested in sleep tracking pads since they could passively collect sleep data without additional burden. Similarly, participants viewed mobile applications positively due to their ability to collect sleep data from a nightstand rather than being attached to the participant; however, there were concerns about remembering to activate these applications.

Conclusion

Based on these results, we recommend using sleep tracking mats to collect patient-generated sleep data due to their ease of use and relative comfort, the main concerns related to lab-based sleep study participation. As a passive sensor, these require the least setup and support consistent data collection. Other devices run the risk of participants forgetting to use the device or becoming removed during the night resulting in missing data. By leveraging these existing technologies for remote sleep studies, researchers can increase recruitment and accessibility to promote sleep research participant diversity.

Support (if any):
353 A Direct-to-Patient Mailing about Sedative-Hypnotics and Online CBT-I: Participant Reported Use of Study Materials
Authors: Mak Selene , Ulmer Christi , Kaufman Chritopher , Alessi Cathy , Martin Jennifer , Smith Jason , Mitchell Michael , Josephson Karen , McCarthy Michaela , Lum Hillary , Fung Constance
Published: May 2021

Introduction

Cognitive behavioral therapy for insomnia (CBT-I) is recommended as first-line treatment for chronic insomnia disorder for all adults. Older adults are often prescribed sedative-hypnotics (e.g., benzodiazepine receptor agonists, BRAs) for insomnia, despite observational studies showing these medications increase risk of falls, fractures, and cognitive decline. In an ongoing randomized controlled trial, we are testing “Sleep EducatioN Information Sent Directly to Patients (SEND),” a novel program combining direct-to-patient mailing with information about access to an online CBT-I resource, compared to a similarly structured control condition. In the current study, we surveyed participants in both groups to examine their self-reported use of intervention or control materials.

Methods

In the larger trial, 1,672 Veteran participants (aged >=65 years, receiving care from a Colorado VA facility, and prescribed a BRA) were randomized to receive the SEND intervention brochure with information on how to access a free, anonymous online CBT-I resource (n=836) or control condition brochure with information about general sleep education (n=836). Six months after the initial brochure mailing, all participants were mailed a blinded survey querying participants’ recollection and use of the mailed materials. We used chi-squared tests to compare survey responses for SEND versus control groups.

Results

354 surveys were returned by study participants (overall response rate: 21%; SEND: 172 [20%], control: 182 [22%]). Respondents were 94% male with mean age 71.7 years (no difference between groups). In the SEND group, 97 (56%) reported receiving the brochure, 18 (10%) visited the website, and 14 (8%) discussed the brochure with their provider. No significant differences between groups were observed in the number of participants who reported receiving the brochure (chi2=2.96, p=.085); visiting the website (chi2=0.0253, p=.874); or discussing the brochure with their provider (chi2=1.91, p=.167).

Conclusion

At 6-months follow-up, over half of participants recalled receiving a mailing about sedative-hypnotics. A modest number reported visiting the online CBT-I program and a similar number discussed the materials with their healthcare provider. Similar results between groups suggest successful blinding of the intervention and control participants. If successful, the SEND intervention may provide a low-touch, low-cost approach to address BRA over-use in some older adults.

Support (if any):
426 Clinical Validation of A.I. Analysis of Photoplethysmogram (PPG) Based Sleep-Wake Staging, Total Sleep Time, and Respiratory Rate
Authors: Watson Nathaniel , Fernandez Chris , Rusk Sam , Nygate Yoav , Turkington Fred , Mortara Justin
Published: May 2021

Introduction

The Photoplesthymogram (PPG) raw waveform is the basis for both the pulse rate and oximetry during polysomnography (PSG) and Home Sleep Apnea Tests (HSAT). The PPG has also recently become ubiquitous as a basis of continuous measurement for the most widely adopted consumer sleep technologies, particularly smart watches. In this study, we clinically validate AI performance for interoperable, PPG-based epoch-by-epoch Sleep-Wake staging (PPG-SW), Total Sleep Time (PPG-TST), and Respiratory Rate (PPG-RR), when compared to 1) PSG-based panel scoring by technologists (RPSGTs) and 2) PSG-based AI scoring (EEG-SW, EEG-TST, Effort Belt-RR).

Methods

We applied stratified random sampling with proportionate allocation to a database of N>10,000 retrospective PSGs. We controlled for: 1) Obstructive sleep apnea severity, 2) Sleepiness, 3) Medical diagnoses including sleep, psychiatric, neurologic, neurodevelopmental, cardiac, pulmonary, metabolic disorders, 4) Medications including benzodiazepines, antidepressants, stimulants, opiates, sedative-hypnotics, 5) Demographics including sex, age, BMI, weight, and height, to establish representative adult (N=100) PSG studies from which PPG samples were obtained. Double blinded scoring was prospectively collected for each PSG by 3 experienced RPSGTs randomized from a pool of 6 scorers. RR was established by mode when two scorers agreed on RR value and median otherwise.

Results

AI EEG-SW demonstrated 96%/94%/95% Sensitivity/Specificity/Accuracy compared to 2/3 majority PSG staging, and AI PPG-SW demonstrated 90%/89%/90% Sensitivity/Specificity/Accuracy compared to the same PSG panel. AI EEG-TST achieved a Pearson Correlation Coefficient (R-value) of 0.968 and AI PPG-TST achieved 0.873 R-value compared to 2/3 majority PSG-TST. When compared to the RR panel consensus in N=282 one-minute RR scoring epochs of PSG, AI Effort Belt-RR performance was <= 2 breaths-per-minute (brpm) in 93.6% of epochs with an average difference of 0.992 brpm, and AI PPG-RR performance was <= 2 brpm in 92.2% of epochs with an average difference of 0.996 brpm.

Conclusion

The study shows interoperable AI analysis performs robustly in evaluating PPG-based epoch-by-epoch sleep-wake stages, total sleep time, and respiratory rate, demonstrating state-of-art accuracy when compared to a prospective, double-blinded PSG scoring panel. This work has implications for consumer sleep technology, HSAT accuracy, inpatient sleep monitoring, and may support the growth of HSATs by increasing total sleep time accuracy and reliability.

Support (if any):
473 Effectiveness of tailored peer-based sleep health education and social support in increasing home-based OSA screening among blacks
Authors: Jean-Louis Giardin , Seixas Azizi , Rogers April , Blanc Judite , Jin Peng , Ravenell Joseph , Ogedegbe Olugbenga
Published: May 2021

Introduction

Our Sleep Disparity Workgroup has investigated several approaches to reducing sleep health disparities. In the METSO trial, we observed phone-delivered sleep education addressing impediments to OSA care among blacks was successful in increasing OSA evaluation. We found in the TASHE trial web-based sleep education significantly increased OSA self-efficacy among blacks. In the present RCT, we examined the role of congruent peer sleep educators and social support (PEERS-ED) in navigating blacks seeking OSA care.

Methods

In the two study arms RCT, we ascertained PEERS-ED’s effectiveness in increasing OSA screening among 317 blacks at OSA risk (intervention=159 and control=158); the average age was 47±12.9 years, 41% were male. OSA risk was assessed with the ARES questionnaire, administered in barbershops, and places of worship. Data also included assessment of beliefs and attitude (DBAS), apnea knowledge (AKT), apnea beliefs (ABS), readiness to change, anxiety, depression, and social support. Participants in the intervention arm received quality-controlled, culturally and linguistically tailored OSA education by trained PEERS during a 6-month period. The present analysis focused on the PEERS-ED effectiveness in increasing physician-recommended home-based OSA screening. Analysis also considered the role of psychosocial factors in adherence to OSA screening. Analyses were performed using the R-studio software.

Results

Results showed no significant differences in baseline demographic and clinical measures contrasting patients in the arms. The adherence rates for OSA screening between the intervention and control arms were 45.9% and 45.6%, respectively. The average DBAS and ABS scores were significantly greater among blacks who had home-based screening (DBAS: 6.0±1.8 vs. 4.9±2.2; p=0.024 and ABS: 77.0±7.1 vs 73.2±7.4; p=0.041). Other measures did not show significant differences between patients who had OSA screening versus those who did not. We observed those who screened were likely to experience greater level of social support (8.23±2.36 vs 7.31±2.35; p=0.063).

Conclusion

Our previous METSO trial demonstrated tailored OSA education is critical to increase adherence to recommended OSA care. While delivery of health information is generally associated with enhanced adherence to medical care, results of the present RCT favored an important role of peer-based social support leading to behavioral change towards receipt of OSA care.

Support (if any)

K07AG052685, R01MD007716, R01HL142066, K01HL135452, R01HL152453
477 Association between Nocturnal Hypoxemic Burden and Glucose Metabolism
Authors: Thanaviratananich Sikawat , Cheng Hao , Chirakalwasan Naricha , Reutrakul Sirimon
Published: May 2021

Introduction

To evaluate the association between a novel integrated event-based and hypoxemia-based parameter of polysomnography (PSG), hypoxemic load or HL100, and fasting blood glucose (FBG) and hemoglobin A1c (HbA1c) levels.

Methods

Adult patients, who underwent an in-lab PSG at University of Iowa Hospitals and Clinics with FBG or HbA1c levels were included. Event-based parameter and hypoxemia-based parameter data were derived. HL100, defined as an integrated area of desaturation under 100% oxygen saturation curve during the total sleep time divided by the total sleep time, was calculated by Python software version 3.8.5. Demographic data and glycemic parameters within 1 year prior to PSG(FBG and HbA1c) were retrieved from chart review Spearman correlation analysis and stepwise backward regression analysis were performed to determine independent predictors of FBG and HbA1c levels.

Results

Of the 467 patients underwent an in-lab PSG, 385 had FBG levels and 239 had HbA1c levels. All event-based and hypoxemia-based parameter; including HL100, were significantly correlated to FBG and HbA1c levels. Stepwise backward regression analyses, adjusting for age, sex, body mass index and diabetes status, revealed that log HL100 was significantly related to FBG (B=20.8, p=0.015), and log oxygen desaturation index was found related to HbA1c levels (B=0.273, p=0.037). Other parameters (e.g. apnea hypopnea index, minimum oxygen saturation) were not independently associated with glycemic parameters.

Conclusion

HL100 showed a significant positive correlation with FBG and HbA1c levels and only log HL100 was an independent predictor for FBG levels. This might imply that any degree of desaturation below 100% could result in adverse glucose metabolism. HL100 might be useful for interpretation of sleep studies, risk stratification and patient management purposes in the future.

Support (if any):
503 Cardio-Vascular Burden of Narcolepsy Disease (CV-BOND): a Real-World Evidence Study
Authors: Ben-Joseph Rami , Saad Ragy , Dabrowski Elizabeth , Taylor Ben , Gallucci Sophia , Somers Virend
Published: May 2021

Introduction

Narcolepsy is a rare, lifelong disorder that requires long-term treatment and is associated with multiple comorbidities, including cardiovascular conditions. Many available treatments have cardiovascular-related warnings and precautions in their labels. The objective of this study was to estimate the incidence of cardiovascular comorbidities in adult patients with a narcolepsy diagnosis in the US.

Methods

Claims from IBM® MarketScan®, an administrative claims database, between January 2014 and June 2019 were analyzed. Eligible patients were ≥18 years and had continuous medical and prescription coverage (gaps <30 days allowed). The narcolepsy cohort was defined by ≥2 outpatient claims containing a diagnosis of narcolepsy type 1 or type 2 on separate days and no more than 6 months apart, with ≥1 non-diagnostic office-visit. Non-narcolepsy patients were matched 3:1 to narcolepsy patients by calendar date of cohort entry, age, gender, US geographic region, and insurance type. Each incidence calculation required a 6 month wash-out period prior to cohort entry. Differences between cohorts were evaluated using a Cox proportional hazard model adjusted for age, gender, region, insurance type, and relevant morbidities/comorbidities and medications in the baseline period.

Results

Of 54,239,110 adults in the database, 12,816 and 38,441 were included in the narcolepsy and matched non-narcolepsy cohort. Approximately 67% were female patients and mean age was approximately 38 years in both cohorts. Incidence rates (per 1,000 person-years) for newly recorded cardiovascular comorbidities or events in narcolepsy/non-narcolepsy were: CVD without hypertension (13.29/7.99), MACE+ (11.75/6.86), heart failure (5.72/3.41), stroke (4.28/2.17), ischemic stroke (3.69/1.91), edema (9.84/4.22), and a composite of stroke, atrial fibrillation, and edema (17.73/8.88).

Conclusion

Physicians should consider the increased cardiovascular risk when considering risk modification strategies and treatment options for narcolepsy patients. Further research is needed to understand treatment-specific risks.

Support (if any)

Jazz Pharmaceuticals
536 Is mothers’ perceived pressure associated with infant sleep-related parenting practices?
Authors: Lannes Émilie M , Kenny Samantha , Burdayron Rebecca , Dubois-Comtois Karine , Beliveau Marie-Julie , Pennestri Marie-Helene
Published: May 2021

Introduction

Studies suggest that feeling pressure about parenting practices is related to higher levels of stress. However, little is known about the pressure mothers feel about infant sleep-related parenting practices. This is surprising, considering that mothers are often exposed to contradictory information about infant sleep. This exploratory study aimed to 1) identify the proportion of mothers of 6-month-old infants who report feeling pressure about their sleep-related parenting practices and 2) assess the relationships between demographic factors and perceived pressure, and between parenting practices and perceived pressure.

Methods

Fifty-four mothers of 6-month-old infants completed a demographic questionnaire and the Sleep Practices Questionnaire (SPQ). Mothers were asked, “Have you ever felt pressure about your parenting choices and practices related to your child’s sleep?”. Responses ranged from never to always. Linear regressions were conducted to assess the concurrent associations between demographic factors (maternal age, maternal education, parity) and perceived pressure, and between sleep-related parenting practices (feeding method, frequency of bed-sharing, picking up or not picking up the infant when he/she cries at night) and perceived pressure.

Results

Analyses revealed that 5.6% of mothers reported feeling pressure constantly, 20.4% reported feeling pressure quite often, 46.3% reported feeling pressure sometimes, and about a quarter (27.7%) reported feeling pressure rarely or never. Lower maternal education and breastfeeding were associated with feeling more pressure about sleep-related parenting practices (p < .05). Furthermore, mothers reporting that they (or their partner) pick up their infant when he/she cries at night were more likely to report feeling pressure (p < .01). Maternal age, parity, and frequency of bed-sharing were not associated with feeling pressure (p > .05).

Conclusion

The majority of mothers (72.3%) in our sample reported feeling pressure about their sleep-related parenting practices at least sometimes, suggesting that this experience is quite common. Lower maternal education, breastfeeding, and picking up the infant to comfort him/her during the night were associated with higher perceived pressure. Future studies should examine feelings of pressure about sleep-related parenting practices in larger samples of mothers and investigate whether fathers share similar concerns. Moreover, identifying the potential sources of these feelings would represent an interesting clinical avenue.

Support (if any)

SSHRC, FRQS