bluuebunny/crossref_metadata_2025 huggingface dataset:
276 The Actigpatch: validation of a novel adhesive monitor against PSG and wrist-actigraphy
Authors: Saletin Jared , McGeary John , Carskadon Mary
Published: May 2021

Introduction

Wrist actigraphy is a gold-standard method for estimating sleep patterns in the field. Actigraphy adherence is limited when participants remove the device for daily activities (e.g., showers, exercise). Here we evaluate the validity of a novel water-resistant wearable, the “Actigpatch,” compared to polysomnography and traditional actigraphy.

Methods

Seven adults (4F; aged 22-54 years [m: 31.1±13.1]) slept in the laboratory for a total of 33 nights. Participants wore a Micro Motionlogger actigraphy (Ambulatory Monitoring Inc., Ardley, NY) on the non-dominant wrist and the Actigpatch—a 0.5in2 circuit board enclosed in a water-resistant adhesive (Circadian Positioning Systems, Newport, RI)—on the triceps. Both devices recorded tri-axial accelerometry, with sleep-wake estimates produced in 1-minute epochs (Sadeh algorithm). Simultaneous PSG data were reduced to 1-minute resolution favoring wake, keeping with recent recommendations. We computed epoch-by-epoch confusion matrices and derived 2 validation parameters: sensitivity (e.g., ability to detect sleep) and specificity (e.g., ability to detect wake). Finally, we compared total sleep time estimates (TST) to evaluate the bias of each device. Nested mixed models (nights within individuals) compared device performance.

Results

The Actigpatch demonstrated high sensitivity (.95; 95%CI: [.92 .98]) and specificity (.89; [.86, .91]) against polysomnography. Similar sensitivity (.96; [.94, .99]) and specificity (.84; [.78 .91]) were found comparing the Actigpatch to the Motionlogger. Comparing the devices’ validity with PSG, sensitivity was not statistically different between the Actigpatch and Motionlogger (b=.0041, t=0.56; p=.58); however, the Motionlogger demonstrated higher specificity (.95; [.92, .97]) compared to the Actigpatch (b=0.065, t=4.69; p<.001). To that end, TST estimates were longer (p=.016) for the Actigpatch (449min; [428, 471] relative to the Motionlogger (438min; [416, 459]).

Conclusion

These data indicate that the adhesive “Actigpatch” is as sensitive to detect polysomnographic-confirmed sleep as a common research-grade actigraph. The Actigpatch may be less capable of detecting wake episodes. Unlike traditional actigraphs, the Actigpatch can be worn continuously for 3 weeks without risk of water or impact damage. Participants are not responsible for remembering to wear the device. Field studies, or studies in populations struggling with adherence (e.g., children) may benefit from wearable monitors such as the Actigpatch.

Support (if any)

R01AA025593, Circadian Positioning Systems
279 WACSAW: A Statistical and Individually Adaptive Method to Determine Sleep and Wakefulness from Activity
Authors: Vandegriffe Austin , Samaranayake V A , Thimgan Matthew
Published: May 2021

Introduction

Technological innovations have broadened the type and amount of activity data that can be captured in the home and under normal living conditions. Yet, converting naturalistic activity patterns into sleep and wakefulness states has remained a challenge. Despite the successes of current algorithms, they do not fill all actigraphy needs. We have developed a novel statistical approach to determine sleep and wakefulness times, called the Wasserstein Algorithm for Classifying Sleep and Wakefulness (WACSAW), and validated the algorithm in a small cohort of healthy participants.

Methods

WACSAW functional routines: 1) Conversion of the triaxial movement data into a univariate time series; 2) Construction of a Wasserstein weighted sum (WSS) time series by measuring the Wasserstein distance between equidistant distributions of movement data before and after the time-point of interest; 3) Segmenting the time series by identifying changepoints based on the behavior of the WSS series; 4) Merging segments deemed similar by the Levene test; 5) Comparing segments by optimal transport methodology to determine the difference from a flat, invariant distribution at zero. The resulting histogram can be used to determine sleep and wakefulness parameters around a threshold determined for each individual based on histogram properties. To validate the algorithm, participants wore the GENEActiv and a commercial grade actigraphy watch for 48 hours. The accuracy of WACSAW was compared to a detailed activity log and benchmarked against the results of the output from commercial wrist actigraph.

Results

WACSAW performed with an average accuracy, sensitivity, and specificity of >95% compared to detailed activity logs in 10 healthy-sleeping individuals of mixed sexes and ages. We then compared WACSAW’s performance against a common wrist-worn, commercial sleep monitor. WACSAW outperformed the commercial grade system in each participant compared to activity logs and the variability between subjects was cut substantially.

Conclusion

The performance of WACSAW demonstrates good results in a small test cohort. In addition, WACSAW is 1) open-source, 2) individually adaptive, 3) indicates individual reliability, 4) based on the activity data stream, and 5) requires little human intervention. WACSAW is worthy of validating against polysomnography and in patients with sleep disorders to determine its overall effectiveness.

Support (if any):
289 Rack curtains improve sailors’ sleeping conditions in berthing compartments of the United States Navy (USN) ships
Authors: Matsangas Panagiotis , Shattuck Nita , Clifton Heather
Published: May 2021

Introduction

Ambient light is one of the primary factors affecting sailor sleep in berthing compartments on USN ships. Each “rack” (i.e., bunk) has a curtain, however, intended only for privacy. Current rack curtain specifications do not address light-blocking properties. We assessed the effects of replacing existing, standard rack curtains with enhanced rack curtains that provide superior light-blocking in the sleeping environment.

Methods

Longitudinal (~2 weeks), naturalistic observation of sailors (N=52; 41 enlisted personnel) on a USN destroyer during deployment. The standard curtain was used for one week followed by one week with the enhanced light-blocking curtain. Sleep-related attributes (Epworth Sleepiness Scale–ESS, Insomnia Severity Index–ISI, Pittsburgh Sleep Quality Index–PSQI) were assessed at the end of each week. Actigraphy and rack temperature data (both inside and outside the rack) were collected throughout the study. Results are presented as median±median absolute deviation.

Results

Participants slept on average 6.8±1.0 hours/day. ESS scores improved with decreases from 9.0±3.0 with standard curtains to 7.0±3.0 with the enhanced curtains (p=0.020). Sailors with normal daytime sleepiness improved from 33 (63.5%) with standard curtains to 40 (76.9%) with the enhanced curtains. ISI scores decreased from 11.0±3.0 to 8.0±2.0 in the two conditions (p<0.001). The number of Sailors with ISI scores ≥15 decreased from 11 (21.2%) with standard curtains to 8 (13.5%) with the enhanced curtains (p=0.103). PSQI scores (8.0±2.0), however, did not change between the control and the intervention periods (p=0.527). Preliminary analysis showed that, compared to outside the rack, temperature inside the rack was slightly warmer on average with new curtains (~1 °F; p=0.096).

Conclusion

Our results suggest that the enhanced curtains reduced average daytime sleepiness and severity of insomnia symptoms. A greater difference in rack temperature with the enhanced curtains was observed; however, this may be attributed to the ship sailing in southern latitudes during the intervention period. Ongoing analysis will provide more insight on the utility of the enhanced curtains and their efficacy in improving sleeping conditions.

Support (if any)

Supported by the Naval Medical Research Center’s Advanced Medical Development Program, the US Navy 21st Century Sailor Office, and the US Navy OPNAV N1.
291 A Pilot Study of Light Management in the US Navy
Authors: Shattuck Nita , Matsangas Panagiotis
Published: May 2021

Introduction

Exposure to light at appropriate times can improve alertness and mood; however, light can also interfere with sleep if exposure occurs before bedtime. Therefore, light management is important for sailor well-being and operational performance. One approach to administer light in field settings is to use personal wearable devices. This pilot study assessed the challenges in using the blue-light blocking goggles (BLBG) and light emitting goggles (LEG) for crewmembers of a US Navy ship while underway.

Methods

Longitudinal (~2 weeks) assessment of sailors (N=18) during deployment. Sailors completed a questionnaire asking whether they used the devices, reasons (if any) they may have had for not using the devices, what they liked/did not like about the devices, and whether wearing the devices made a difference in terms of fatigue, alertness, ability to fall asleep, and reported sleep quality.

Results

Sailors reported that the LEGs seemed to increase alertness (n=8) and helped wake up faster (n=5), but the devices were bulky/heavy (n=9), too bright (n=4), and made it difficult to see in dim light (n=2). The reported reasons for not using the devices include: the devices were heavy/uncomfortable (n=5), they caused eye strain (n=4), and the LEGs interfered with sailor ability to see while on watch (n=3). Also, wearing the LEGs made sailors feel less tired (71%) and more alert (59%). Sailors reported that the BLBGs kept them drowsy before bed (n=3) and reduced eye strain (n=5). Sailors complained, however, that BLBGs were bulky/inconvenient (n=3). When not wearing the BLBGs, it was because the devices were easy to forget (n=2), sailors had to work after their shift (n=2), and other reasons (n=3). Wearing the BLBGs during watch made falling asleep easier (47%) and improved sleep quality (47%).

Conclusion

This study provided valuable insight regarding the use of personal wearable light management devices in field settings. Even though not conclusive, our results are promising. We will continue assessing the utility of such devices with a goal of improving sailor well-being and operational performance.

Support (if any)

Supported by the Naval Medical Research Center’s Advanced Medical Development Program, the US Navy 21st Century Sailor Office, and the US Navy OPNAV N1.
292 Rest Schemes and Inflight Sleep Duration on Long Range and Ultra-Long Range Commercial Airline Routes
Authors: Rempe Michael , Rasmussen Ian , Belenky Gregory , Lamp Amanda
Published: May 2021

Introduction

Pilots flying long range (LR; 8-16 hour) and ultra-long range (ULR; 16+ hour on 10% of trips) commercial airline routes use a variety of work/rest schedules during flights, resulting in a wide distribution of total inflight sleep time (TIFS) amounts. Since sleep is a strong predictor of performance, it is important to quantify TIFS and determine rest scheme patterns that optimize sleep opportunity and subsequent alertness and performance. Here we report rest schemes for pilots on LR and ULR routes and longer TIFS values than previously reported. These rest schemes can serve as templates to increase TIFS and improve pilot performance, particularly on ULR routes.

Methods

427 commercial airline pilots provided data for this sub-study that was part of a larger study on Fatigue Risk Management System (FRMS) routes. Inflight sleep timing and duration were measured on 3 LR and 5 ULR routes. Inflight sleep times were self-reported in a sleep/work logbook and verified using actigraphy.

Results

Most outbound and inbound landing crews took one break during the second half of the flight (average LR TIFS=4.0 hr; average ULR TIFS=4.9 hr), while most outbound and inbound relief crews consequently took one break during the first half of the flight (average LR TIFS=3.5 hr; average ULR TIFS=4.5 hr). However, three of the five ULR routes used more complex split rest schemes for landing and relief crews, primarily on outbound flights (average TIFS=5.0 hr). Across all routes and both crews, the maximum average TIFS reached ~6 hours.

Conclusion

Our results indicate that pilots on average are sleeping inflight more than previous studies demonstrated. Additionally, we found that crews on some ULR flights used more complicated rest schemes, but still generally preferred 2 or 3 breaks. These findings have implications for airline procedures and aviation policies by showing that pilots may be sleeping longer than originally expected on LR and ULR flights. Recommending rest schemes that allow for the greatest inflight sleep opportunity may provide the best chance for inflight recuperation, especially before the Top of Descent critical phase of flight.

Support (if any)

United Airlines
295 Impacts of travel distance and travel direction on back-to-back games in the National Basketball Association (NBA)
Authors: Charest Jonathan , Samuels Charles , Bastien Célyne , Lawson Doug , Grandner Michael
Published: May 2021

Introduction

Travel fatigue and circadian disruptions are known factors that can hinder performance in professional athletes. The present exploratory study focused on investigating the impact of travel distance and direction on back-to-back games over the 2013–2020 seasons in the National Basketball Association (NBA).

Methods

Data from away and home games of back-to-back sequences, in two different cities, from the 2013 to 2020 seasons in the National Basketball Association were included in this study. Information from every selected game was retrieved from the official website of the NBA (www.nba.com). The outcomes were based on winning percentage with additional covariates including the direction of travel (eastward or westward) and the distance travelled (0-500km – 501-1000km – 1001-1500km – 1501km and more). If a team played both games of a back-to-back sequence on the road, they were considered Away-Away; if a team played the first game of a back-to-back sequence at home they were considered Home-Away; if a team played the first game of a back-to-back sequence on the road they were considered Away-Home.

Results

The sequence Away-Home significantly increases the likelihood of winning compared to the Away-Away and Home-Away sequences 54.4% (95%CI: 54.4,54.5); 39.2% (95%CI: 37.2,41.2), and 36.8%, (95%CI: 36.7,36.8), respectively. Following a road game, when teams travel back home, every additional 500km reduces the likelihood of winning by approximately 4% (p = 0.038). Finally, after withdrawing the Away-Home sequence, travelling eastward significantly increases the chance of winning (p = 0.024) compared to westward travel but has no significant impact on the probability of winning compared to neutral time zone travel (p = 0.091).

Conclusion

The accumulation of travel fatigue and the chronic circadian desynchronization that occurs over the NBA season can acutely disturb sleep and recovery. It appears that tailored sleep and recovery strategies need to be dynamically developed throughout the season to overcome the different challenges of the NBA schedule.

Support (if any):
297 The Relationship Between Sleep and Objectively Measured Sedentary Behavior in Adults with Desk Jobs
Authors: Egeler Mara , Kubala Andrew , Perera Subashan , Patel Sanjay , Hall Martica , Jakicic John , Gibbs Bethany Barone , Kline Christopher
Published: May 2021

Introduction

Both poor sleep and sedentary behavior lead to negative health outcomes. While some previous studies have observed an association between poor sleep and greater sedentary behavior, few studies have assessed this relationship using an objective measure of sedentary behavior. We examined the association of both self-reported and objectively-measured sleep with objectively-measured sedentary behavior.

Methods

In a secondary analysis of baseline data from an ongoing clinical trial, the present analysis included 157 physically inactive adults with elevated blood pressure (120–159 mmHg systolic or 90–99 diastolic) and desk jobs (82.8% white, 65.6% female, age 45.5±12.0). To assess sedentary behavior, participants wore an accelerometer/inclinometer (activPAL3 micro) on the upper thigh continuously for 7 days. Variables included total sedentary time, prolonged sedentary time (≥30 minute bouts), and sit-to-stand transitions; these were averaged across all waking hours as well as the workday. To assess sleep, participants completed the Pittsburgh Sleep Quality Index (PSQI) and a subsample (n=57) wore an Actiwatch Spectrum for 7 nights. Variables examined included the PSQI global score, actigraphy-based total sleep time (TST) and sleep efficiency (SE). Linear regression examined associations between sleep and sedentary behavior, with adjustments for age, gender, race, body mass index, and activPAL3 wear time.

Results

Participants had (mean±standard deviation) 11.1±1.5 hours sedentary time per day, with 6.3±2.0 occurring in ≥30 minute bouts, and 51.3±13.4 sit-to-stand transitions. During the workday, participants had 6.6±1.3 hours sedentary time with 3.8±1.7 occurring in ≥30 minute bouts and 27.2±11.2 sit-to-stand transitions. PSQI global score was 4.9±2.9; 32.5% were classified as poor sleepers. Actigraphic TST was 6.7±0.8 hours, with SE of 85.4±6.3%.Greater SE was associated with less sit-to-stand transitions during the workday (β=-0.36, p=0.01) and during the full day (β=-0.37, p=0.01). Subjective sleep quality and actigraphic TST were not associated with sedentary behavior.

Conclusion

We did not find a cross-sectional association between sedentary behavior and sleep in insufficiently active adults, potentially due to restricted range of sedentary behavior and physical activity in the sample. The association between greater sleep efficiency with fewer sit-to-stand transitions is counterintuitive and warrants further exploration.

Support (if any)

This study was funded by National Institutes of Health (NIH) grants R01HL134809 and R01HL147610.
300 The Use of Sleep Aids in Young Athletes and Non-Athletes: An Exploratory Study
Authors: Caron Jean-François , Godin Roxanne , Gaudreault Pascale , Roy Jonathan , Forest Geneviève
Published: May 2021

Introduction

Studies have shown that sleep in adolescents is characterized by sleep disturbances. Many teens resort to prescribed or nonprescribed medication to alleviate their sleep difficulties. Research suggests that sport and physical activity may be protective factors regarding sleep. The aims of the present study were to investigate the use of sleep aids among young athletes and non-athletes, and to identify possible factors associated with prescribed and nonprescribed sleep aids

Methods

35 young athletes (14.6±0.7 years old; 54.3 % males) and 30 young non-athletes (15.1±0.7 years old; 16.7% males) completed questions on sleep aids, the Academic Motivation Scale, the anxiety and depression scales of the Beck Youth Inventory-II, and the Multidimensional Self-Esteem Questionnaire, at the beginning, middle, and end of the school year. Mean scores for the school year were computed for amotivation in school, intrinsic academic motivation of accomplishment, self-esteem, anxiety symptoms, and depressive symptoms. Teens were each categorized as user or non-user if they had or had not used sleep aids during the school year. First, comparison of sleep aids usage between groups were done using a Chi-square test. Then, both groups of athletes and non-athletes were combined. Amotivation, intrinsic motivation, self-esteem, and anxiety and depressive symptoms were compared between users and non-users using paired t-tests

Results

Results show that young non-athletes report using sleep aids more often than young athletes (X2(1,N=65)=5.205, p=.023). Indeed, 65.2% non-athletes compared to 34.8% athletes reported using sleep aids during school year. Users represent 35.4% of the total sample. T-tests showed that users have a significantly higher amotivation score (t(65)=-2.010, p=.049), more anxiety symptoms (t(65)=-2,480, p=.016), and more depressive symptoms (t(65)=-2,126, p=.037) than non-users.

Conclusion

These results show a high prevalence of prescribed and nonprescribed sleep aids usage in teens. Our results also suggest that sleep aids in young adolescents is associated with mental health problems and academic motivation issues. On the other hand, our results support that sport and physical activity may have a protective role regarding sleep. This highlights the importance to promote sport participation among adolescents.

Support (if any)

n/a
305 Subjective sleep predicts Cadet performance during U.S. Army Reserve Officer Training Corps Advanced Camp
Authors: Carlsson Kajsa , Mickelson Carolyn , Choynowski Jake , Mantua Janna , Devine Jaime , Sowden Walter , Mckeon Ashlee
Published: May 2021

Introduction

U.S. Army Reserve Officer Training Corps (ROTC) Advanced Camp (AC) is a 29-day training that assesses military skills and leadership potential in college students training to become Commissioned Officers (i.e. Cadets). Military trainings are widely known to disrupt normative sleep. Additionally, operational sleep disruption is linked to performance decrements. This study examined the ability for objective and subjective sleep during ROTC AC to predict Cadet performance.

Methods

One hundred and fifty-nine ROTC Cadets (age 22.06±2.49 years; 76.1% male) wore an actiwatch device continuously for 29 days during AC. Paper surveys administered at the end of AC captured subjective sleep metrics during the training. ROTC instructors evaluated Cadet performance and provided scores of overall class rank and summary performance. Multiple and ordinal linear regressions assessed the predicative utility of subjective (sleep duration [SD]; Global score [Global] from the Pittsburgh Sleep Quality Index) and objective (Total Sleep Time [TST]; Sleep Efficiency [SE]; Sleep Latency Onset [SOL]; Wake After Sleep Onset [WASO] from actigraphy) sleep on performance.

Results

The interaction of SD and Global, when controlling for age and gender, significantly predicted increased Cadet rank, F(4,153) = 3.09, p = 0.018. Models testing the prediction of SD and Global on summary performance score were non-significant. Further, regressing of both Cadet rank and summary performance individually on objective sleep metrics, when controlling for age and gender, resulted in non-significant findings.

Conclusion

Subjective and objective sleep showed no significant individual predictive utility on performance. However, the combined subjective model significantly predicted that Cadets who slept worse (lower SD; higher Global) during AC received a lower rank at the end of the training. These findings suggest there may be a unique combined predictive utility of subjective sleep on performance when compared to the predictive power of individual variables. Therefore, subjective sleep may be better for predicting operational performance than objective sleep. Future analyses will refine these models and examine how performance on individual AC events may be influenced by sleep. Support for this study came from the Military Operational Medicine Research Program (MOMRP) of the United States Army Medical Research and Development Command (USAMRDC).

Support (if any):
324 Naturalistic Characterization of Sleep in Chronic Insomnia Using a Non-Contact Sleep Measurement Device
Authors: Hansen Devon , Peterson Mary , Raymann Roy , Van Dongen Hans , Watson Nathaniel
Published: May 2021

Introduction

Individuals with insomnia report poor sleep quality and non-restorative sleep, and often exhibit irregular sleep patterns over days and weeks. First night effects and logistical challenges make it difficult to measure these sleep characteristics in the laboratory. Also, sensitivity to sleep disruption from obtrusive measurement devices confounds sleep measurements in people with insomnia in their naturalistic setting. Non-contact sleep measurement devices have the potential to address these issues and enable ecologically valid, longitudinal characterization of sleep in individuals with insomnia. Here we use a non-contact device – the SleepScore Max (SleepScore Labs) – to assess the sleep of individuals with chronic insomnia, compared to healthy sleeper controls, in their home setting.

Methods

As part of a larger study, 13 individuals with chronic insomnia (ages 25-60y, 7 males) and 8 healthy sleeper controls (ages 21-46y, 6 females) participated in an at-home sleep monitoring study. Enrollment criteria included an age range of 18-65y and, for the insomnia group, ICSD-3 criteria for chronic insomnia with no other clinically relevant illness. Participants used the non-contact sleep measurement device to record their sleep periods each night for 8 weeks. Sleep measurements were analyzed for group differences in both means (characterizing sleep overall) and within-subject standard deviations (characterizing sleep variability across nights), using mixed-effects regression controlling for systematic between-subject differences.

Results

Based on the non-contact sleep measurements, individuals with chronic insomnia exhibited greater variability in bedtime, time in bed, total sleep time, sleep latency, total wake time across time in bed, wakefulness after sleep onset, sleep interruptions, and estimated light sleep, compared to healthy sleeper controls (all F>5.7, P<0.05). No significant differences were found for group averages and for variability in estimated deep and REM sleep.

Conclusion

In this group of individuals with chronic insomnia, a non-contact device used to characterize sleep naturalistically captured enhanced variability across nights in multiple aspects of sleep stereotypical of sleep disturbances in chronic insomnia, differentiating the sample statistically significantly from healthy sleeper controls.

Support (if any)

NIH grant KL2TR002317; research devices provided by SleepScore Labs.
337 A Multicenter Open-label Pilot Study Evaluating Next-Dose Transition From Zolpidem to Lemborexant: Analysis of Female Subgroup
Authors: Ahmad Maha , Malhotra Manoj , Amchin Jess , Kumar Dinesh , Perdomo Carlos , Atkins Norman , Moline Margaret
Published: May 2021

Introduction

Dosing paradigms for transitioning patients to lemborexant (LEM) from zolpidem (ZOL: immediate [IR] or extended-release [ER]) were examined in E2006-A001-312 (Study 312; NCT04009577), an open-label pilot study. Given insomnia prevalence in women, post hoc analyses in female subjects were conducted.

Methods

Study 312 included: 3-week Screening Period (subjects continued ZOL); 2-week Titration Period (TITR); 12-week Extension Period (EXT); 4-week Follow-up. Adults with insomnia taking ZOL-IR or ZOL-ER intermittently (3–4 nights/week) or frequently (≥5 nights/week) were enrolled. Subjects with intermittent, or one week each of intermittent and frequent ZOL use, were assigned to Cohort-1 and started TITR with LEM 5mg (LEM5). Frequent ZOL users (Cohort-2) were randomized 1:1 to LEM5 (Cohort-2A) or LEM 10mg (LEM10; Cohort-2B). Subjects who transitioned to LEM could opt into EXT. Subjects could change LEM dose during TITR (only once) and during EXT. The primary endpoint was the proportion of subjects who transitioned to LEM at end of TITR. Treatment-emergent adverse events (TEAEs) were assessed by dose at time of TEAE.

Results

Overall, 35 subjects were female and 29/35 (82.9%) transitioned to LEM. In Cohort-1, 7 subjects began TITR; all transitioned to LEM (5 subjects ended TITR on LEM5; 2 ended on LEM10). In Cohort-2A, 14 subjects began TITR with LEM5; 12/14 (85.7%) transitioned (6 subjects each ended TITR on LEM5 or LEM10). In Cohort-2B, 14 subjects began TITR with LEM10; 10/14 (71.4%) transitioned to LEM (3 subjects ended TITR on LEM5 and 7 on LEM10). All 29 transitioned subjects opted into EXT, and 27/29 (93.1%) completed the study. Based on modal dose (most frequent dose taken during TITR and EXT combined) groups, median time to first dose change during EXT was 14.5 and 17.0 days for LEM5 and LEM10, respectively. Overall, most TEAEs were mild/moderate in severity. Across TITR and EXT, more TEAEs occurred with LEM10 than with LEM5; the most common TEAEs were somnolence (n=3) and abnormal dreams (n=3).

Conclusion

Most female subjects successfully transitioned from intermittent or frequent ZOL-IR/ZOL-ER use to LEM and completed the study. LEM was generally well tolerated. The safety profile was consistent with that observed in Phase 3 studies.

Support (if any)

Eisai Inc.
343 A benefit-risk assessment of daridorexant for the treatment of insomnia using patient preference data from two phase 3 trials
Authors: Heidenreich Sebastian , Phillips-Beyer Andrea , Ross Melissa , Chua Gin Nie , Fietze Ingo , Mayleben David
Published: May 2021

Introduction

The efficacy and safety of daridorexant, a dual orexin receptor antagonist intended to treat insomnia, was demonstrated in two placebo-controlled phase III trials. Both pivotal trials included instruments for eliciting treatment preferences of enrolled patients, to interpret the trial findings from their perspective using a patient-centered benefit-risk assessment (pBRA).

Methods

Digital ethnographies and qualitative interviews with insomnia patients informed the design of a discrete choice experiment (DCE). The DCE was pre-tested in qualitative and quantitative pilots before inclusion in the trials. Within the DCE, patients were asked to make trade-offs between seven outcomes (“time to fall asleep,” “total time asleep,” “daytime functioning,” “likelihood of daytime dizziness/grogginess,” “likelihood of abnormal thoughts and behavioural changes,” “likelihood of falls in the night,” and “treatment withdrawal”). The preference data were analysed using a mixed logit (MXL) model that accounted for preference heterogeneity. Relative attribute importance (RAI) and maximum acceptable risk (MAR) of abnormal thoughts and behavioral changes were obtained from the MXL. A pBRA combined elicited preferences with collected clinical trial data to predict preferences for daridorexant over placebo. Sensitivity analysis accounted for uncertainty in both clinical outcomes and preferences.

Results

Patients valued all seven outcomes (p < 0.05), but considered improving daytime functioning (RAI = 33.7%) and avoiding treatment withdrawal (RAI = 27.5%) as most important. Patients were also willing to accept an additional 18.8% risk (p-value < 0.001) of abnormal thoughts and behavioral changes for an improvement in daytime functioning from difficulty functioning to restricted functioning. The pBRA suggested that both daridorexant 50 mg and 25 mg were significantly preferred (p-value < 0.001) over placebo, and 50 mg was significantly preferred (p-value < 0.001) over 25 mg, even after accounting for uncertainty in clinical outcomes and preferences.

Conclusion

All seven outcomes included in the DCE were valued by patients, but improving daytime functioning and avoiding severe treatment withdrawal was considered as most important. Daridorexant 50 mg and 25 mg were found to be significantly preferred over placebo, suggesting a positive benefit-risk balance of both doses. Overall, the preference data allowed for an innovative interpretation of the trial data from patients’ perspective.

Support (if any):
345 Preliminary efficacy of CBT-I for psychosis in a Veteran sample
Authors: Howell Mary Katherine , Klingaman Elizabeth A
Published: May 2021

Introduction

Sleep dysfunction is pervasive in people with psychosis. Insomnia worsens psychotic symptoms and functioning, though treating insomnia can improve functioning. Cognitive Behavioral Therapy for Insomnia (CBT-I) is an effective treatment, but there has been limited research on CBT-I in persons with psychosis. There is mounting evidence that sleep disturbances in people with psychiatric disorders do not improve with treatment of psychiatric illness. The present study 1) developed empirical guidelines for tailoring CBT-I to the needs of people with psychosis and insomnia; 2) conducted a preliminary efficacy study of CBT-I with these novel guidelines for psychosis; and 3) utilized objective and subjective insomnia and functional measures.

Methods

Novel psychosis guidelines were developed in response to illness-related, environmental, and practical challenges for engaging in traditional components of CBT-I, identified via a series of 25 qualitative interviews and an uncontrolled acceptability trial. A preliminary efficacy study of CBT-I with novel psychosis guidelines was conducted against an active treatment comparison group. Forty-seven Veterans with insomnia and co-occurring psychotic-spectrum disorder completed sleep measures, including the Insomnia Severity Index (ISI), at baseline, post-treatment, and 3-month follow-up.

Results

Psychosis guidelines for CBT-I included supporting integrated care (e.g., with case managers, prescribers, etc.), simplifying instructions on all treatment materials, reminder handouts, reality testing with sleep-related experiences, cognitive restructuring guidance for common sleep-related cognitions held by people with psychosis, techniques for use during psychotic experiences at bedtime. At post-treatment and follow-up, there was a large effect of CBT-I on ISI scores (d = 1.00, 1.18, respectively). Further, a clinically significant reduction in mean ISI score of participants was observed in the CBT-I condition (> 6), but not in the control condition. Participants in the CBT-I group reported reductions in daily functional impairment due to sleep problems (from 89% to 50%), while the control group reported a slight increase in functional impairment (from 86% to 88%).

Conclusion

CBT-I delivered with guidelines for psychosis should be further investigated with a larger randomized controlled trial over a longer time period of 6 months.

Support (if any)

Time on this project was supported by the U.S. Department of Veterans Affairs, Rehabilitation Research and Development Service-1IK2RX001836, PI: Elizabeth A. Klingaman.
348 Absence of Withdrawal Symptoms and Rebound Insomnia Upon Discontinuation of Daridorexant in Patients with Insomnia
Authors: Leger Damien , Fietze Ingo , Pain Scott , Kinter Dalma Seboek , Flamion Bruno , Mignot Emmanuel
Published: May 2021

Introduction

Abrupt discontinuation of sleep medications in patients with insomnia often causes withdrawal symptoms and rebound insomnia. In a Phase 3 program evaluating efficacy and safety of daridorexant on sleep and daytime functioning in patients with insomnia during 3 months of treatment, the risks of withdrawal symptoms and rebound insomnia were evaluated at treatment cessation.

Methods

In two randomized, double-blind, 3-month trials, adult (18–64 years) and elderly (≥65) patients with insomnia were assigned (1:1:1) to receive oral daridorexant 25mg, 50mg or placebo (Trial-1, NCT03545191) or 10mg, 25mg or placebo (Trial-2, NCT03575104) every evening. Each trial included a 7-day, single-blind, placebo run-out period following double-blind treatment to evaluate withdrawal symptoms and rebound insomnia. Withdrawal effects were assessed by the change in Benzodiazepine Withdrawal Symptom Questionnaire (BWSQ) total score, from last assessment on double-blind treatment to end of placebo run-out, and occurrence of relevant adverse events (AEs). Rebound insomnia was assessed objectively by change in wake-after-sleep-onset (WASO) and latency-to-persistent sleep (LPS), from baseline to first night of placebo run-out, and by subjective total-sleep-time (sTST), from baseline to end of run-out (mean of 7-days). Analyses included all patients who received ≥1 dose of placebo run-out treatment (Trial-1: N=852; Trial-2: N=851).

Results

No increase in mean BSWQ score from last assessment on double-blind treatment to end of placebo run-out was reported (Trial-1: 25mg, -0.6±2.3; 50mg, -0.6±2.3; placebo, -0.7±2.3; Trial-2: 10mg, -0.5±2.6; 25mg, -0.4±1.9; placebo, -0.4±1.4). No patients had a BWSQ score >20 at end of run-out. No AEs suggestive of withdrawal symptoms were reported. Mean WASO and LPS values (min) decreased from baseline to placebo run-out (WASO Trial-1: 25mg, -8.6±55.5; 50mg, -2.5±52.4; placebo, -20.4±45.8; Trial-2: 10mg, -11.6±58.3; 25mg, -5.1±57.9; placebo, -26.2±53.5; LPS Trial-1: 25mg, -17.2±56.7; 50mg, -15.0±55.8; placebo, -27.8±47.2; Trial-2: 10mg, -17.3±67.2; 25mg, -10.3±67.3; placebo, -18.3±63.8) while sTST values (min) increased (Trial-1: 25mg, 43.3±53.8; 50mg, 42.9±59.6; placebo, 42.3±52.7; Trial-2: 10mg, 43.3±52.9; 25mg, 46.8±55.4; placebo, 42.3±53.8) indicating absence of rebound effects.

Conclusion

Treatment with daridorexant for up to 3-months was not associated with any evidence of drug withdrawal or rebound insomnia upon abrupt discontinuation, indicating no safety concerns for patients should treatment be stopped.

Support (if any)

Funded by Idorsia Pharmaceuticals Ltd.
354 Trends in the Drug-Sparing Effects for Benzodiazepines and Prescription Opioids among Insomnia Patients on Suvorexant in the US
Authors: Kale Hrishikesh , Khandker Rezaul , Shah Ruchit , Botteman Marc , Meng Weilin , Jootun Murvin , Qureshi Zaina
Published: May 2021

Introduction

Use of benzodiazepines to treat insomnia has been associated with serious side effects and abuse potential. Insomnia patients are at high risk of opioid abuse and better sleep patterns may help to reduce opioid use. This study examined the trend in the use of benzodiazepines and prescription opioids before and after initiation of suvorexant in insomnia patients.

Methods

The study analyzed 2015–2019, Optum Clinformatics Data Mart. Insomnia patients, identified using ICD-9/10 codes and prescribed suvorexant were included. The study included incident (newly diagnosed) and prevalent cohorts of insomnia patients. The proportion of patients on benzodiazepines or prescription opioids were calculated for 12 monthly intervals before (pre-period) and after initiation of suvorexant (post-period). Interrupted time series (ITS) analysis was conducted to assess trends for use of benzodiazepine or prescription opioids over time.

Results

A total of 5,939 patients from the incident insomnia cohort and 18,920 from the prevalent cohort were included. For the incident cohort, mean age was 64.47 (SD: 15.48), 63% were females, 71% had Medicare Advantage coverage, 59% had Charlson comorbidity index score (CCI) ≥ 1, 27% had an anxiety disorder and 16% had substance abuse disorder. Prevalent insomnia cohort was similar but had higher CCI. Results from ITS suggested that at the beginning of the pre-period, 28% of incident insomnia patients used either opioids or benzodiazepines with the rate of use in the pre-period increasing by 0.11% per month. In the post-period, the rate of use decreased by 0.33% per month. About 26% patients used benzodiazepines or opioids at 12-month after suvorexant initiation. In the absence of suvorexant, this proportion would have been 31%. Similar findings were observed for the prevalent insomnia cohort. A larger decrease was observed for opioid use than benzodiazepines.

Conclusion

The rate of benzodiazepines or prescription opioid use decreased over time after the initiation of suvorexant. Suvorexant has the potential to reduce the use of opioids and benzodiazepines among insomnia patients. Further research is needed to confirm these findings.

Support (if any)

This study was sponsored by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
355 Predictors of Longitudinal Sleep Outcomes in a Statewide Randomized Trial of Telephone Cognitive Behavioral Therapy for Insomnia
Authors: McCurry Susan , Pike Kenneth , Von Korff Michael , Morin Charles , Vitiello Michael
Published: May 2021

Introduction

We examined the relationship between treatment process measures and 12-month insomnia outcomes from a large clinical trial of telephone-delivered CBT-I.

Methods

A statewide sample of 327 Kaiser Permanente Washington members aged 60+ with OA, Insomnia Severity Index (ISI) scores of 11+ and Brief Pain Inventory scores of 9+ were randomized to six sessions of individual telephone-delivered cognitive-behavior therapy for insomnia (CBT-I) vs. education-only control. Participants rated their perceptions of treatment credibility and perceived effectiveness on a 7-point Likert scale after session 1 and at 2-month post-test. They also completed the Sleep Hygiene Index (SHI), the 8-item Sleep Problem Acceptance Questionnaire (SPAQ), and the 8-item Chronic Pain Acceptance Questionnaire (CPAQ) at baseline, post-treatment, and 12 months. Insomnia outcome was measured using the ISI.

Results

Participants (mean age=70.2 years [SD=6.81], 74.6% female, 87.8% with sleep problems for over 1 year) were randomized to the two treatment arms. Regression analyses controlling for baseline age, opioid use, depression, pain, and ISI showed that lower 12-month ISI scores were associated with CBT-I group membership and lower baseline ISI (both p<.001), higher session 1 ratings of treatment credibility (p=.004), higher baseline CPAQ activity engagement (AE) subscale scores (p=.04), and lower baseline SPAQ AE scores (p=.016) when predictors were simultaneously entered. Lower 12-month ISI scores were also associated with post-test ratings of treatment perceived effectiveness (p=.004) and higher SPAQ AE (p=.038) scores. Improvements on the SHI at post-test were significantly associated with lower 12-month ISI scores when variables were entered singly into regression models, but not when all predictors were entered simultaneously. SPAQ and CPAQ sleep and pain willingness subscale scores were not significantly related to ISI outcomes in any model.

Conclusion

People with less severe baseline insomnia levels who received telephone-delivered CBT-I were more likely to have lower 12-month ISI scores. Participant perceptions of treatment credibility and effectiveness, and engagement in life activities despite pain and sleep symptoms were also associated with long-term improvements in insomnia, but willingness to experience sleep and pain symptoms were not contributing factors.

Support (if any)

This work was supported by PHS grant 5R01AG053221.
371 Insomnia and Metacognitive abilities: a new treatment target?
Authors: Sforza Marco , Scarpellino Alessandro , Salibba Andrea , Galbiati Andrea , Zucconi Marco , Casoni Francesca , Ferini-Strambi Luigi , Castronovo Vincenza
Published: May 2021

Introduction

Metacognition is defined as the ability to reflect on one’s mental state. Literature showed that dysfunctional metacognitive activity (such as worry and rumination) plays an important role in insomnia genesis and maintenance. The aim of this study is (i) to evaluate metacognition differences between insomnia disorders (ID) patients and good sleepers (GS)and (ii) to assess Cognitive-Behavioral Therapy for Insomnia (CBT-I) effectiveness on both insomnia and metacognitive abilities.

Methods

We compared 27 GS (Insomnia Severity Index, ISI<10) (63.0% female, mean age 33±13.7yrs) and 27 ID patients (51.9% female, mean age 46.4±13.7yrs) evaluated both by ISI and Metacognition Insomnia Questionnaire (MCQ-I). ID patients underwent 7-session of group CBT-I and were evaluated pre- (T0) and post- (T1) treatment.

Results

GS and ID patients differed in MCQ-I total score (GS=105.6±20.5 vs ID= 138.1±26.2). All ID patients’ scores were above the clinical cutoff of 110. ID patients showed significant improvements both at ISI (T0=14.67±4.67 vs T1=7.07±4.37, p<0.001) and Sleep Diary parameters (T0 vs T1, p<0.05) as sleep latency, wake after sleep onset and sleep efficiency at T1. ID patients also showed an improvement of MCQ-I scores at T1, nevertheless, maintaining MCQ-I the mean score above the clinical cutoff level (MCQ-I_T0=138.1±26.2 vs MCQ-I_T1=123.7±28.6; p<0.05). Indeed, 29.6% of ID patients maintained equal or worse MCQ-I score at T1 compared to T0; 63% of ID patients still had a MCQ-I score above the clinical cutoff at T1.

Conclusion

CBT-I results effective on insomnia symptoms. Metacognitive dysfunctions appears to be a core feature in ID patients compared to good sleepers. Although the score reduction was significant after CBT-I, metacognitive dysfunction did not show remission after treatment possibly indicating the need of a specific intervention on this aspect. Metacognitive dysfunction in ID needs to be further investigated and may represent a new treatment target, in order to improve CBT-I effectiveness.

Support (if any)

None
374 Cognitive Behavioral Therapy with Exercise in Adults with Insomnia and Short Sleep: Daytime Function Outcomes from a Pilot Study
Authors: Kubala Andrew , Egeler Mara , Buysse Daniel , Hall Martica , Barinas-Mitchell Emma , Kline Christopher
Published: May 2021

Introduction

Cognitive behavioral therapy for insomnia (CBT-I) is efficacious, but there is mixed evidence as to whether improvement is blunted in adults with insomnia and short sleep duration. Exercise training can reduce physiologic hyperarousal and may increase homeostatic sleep drive, which could potentiate CBT-I treatment effects. This pilot study explored changes in self-reported outcomes from a CBT-I intervention augmented by exercise training in a sample of adults with insomnia and objective short sleep duration.

Methods

Eight adults (50% female, 62.5% white) with insomnia disorder and short sleep duration (mean actigraphic TST <6.5 hr) completed a 12-week single-arm trial. Participants self-administered the online “Sleep Healthy Using the Internet” (SHUT-I) CBT-I program with additional staff guidance while completing a supervised exercise program (EX; 150 min/wk of moderate-intensity aerobic exercise and 2 days/wk of strength training). Participants completed assessments of self-reported sleep and daytime function pre- and post-intervention, including the Insomnia Severity Index (ISI), Flinders Fatigue Scale (FFS), Ford Insomnia Response to Stress Test (FIRST), Perceived Stress Scale (PSS), and Epworth Sleepiness Scale (ESS). Differences between timepoints were analyzed using paired t-tests and Cohen’s d effect size calculations.

Results

Insomnia severity significantly decreased after the intervention (ISI: p<0.001, d=2.99), with 75% reporting post-intervention ISI ≤ 7. Likewise, fatigue significantly decreased after the intervention (FFS: p=0.032, d=0.95). Symptoms of stress-related sleep reactivity and stress were also reduced (FIRST: p=0.012, d=1.19; PSS: p=0.014, d=1.14). Though nonsignificant, large reductions in sleepiness were additionally observed (ESS: p=0.058, d=0.80).

Conclusion

In this pilot trial among patients with insomnia and short sleep duration, online CBT-I plus a supervised exercise program resulted in a significant reduction in insomnia severity. The intervention also produced large and meaningful reductions in fatigue and stress, which are common daytime impairments in patients with insomnia. Future research should attempt to disentangle the independent contributions of CBT-I and exercise on outcomes in this population.

Support (if any)

NIH: K23HL118318