bluuebunny/crossref_metadata_2025 huggingface dataset:
312 Associations Between Sleep Regularity and Body Mass Index: Findings from a Prospective Study of First-Year College Students
Authors: Wong Patricia , Barker David , Gredvig-Ardito Caroline , Carskadon Mary
Published: May 2021

Introduction

College students often experience irregular sleep timing, short sleep duration, and weight gain. Using data from a large, prospective study on sleep in first-year college students, we examined whether students’ sleep regularity index (SRI; Phillips et al., 2017) was associated with body mass index (BMI) and BMI change (∆BMI) during the first nine weeks of their college semester.

Methods

Analyses included data from 583 students (mean age = 18.7± 0.5 years; 59% Female; 48% non-White) who had their height and weight assessed at the start of classes (T1) and end (T2) of nine weeks. ∆BMI was calculated as the difference between T2 and T1, with a positive value indicating an increase in BMI. Throughout the semester, participants completed on-line daily sleep diaries that included bedtime, wake-time, sleep onset latency, and wake after sleep onset for the previous major sleep episode and daytime naps. Based on this data, total sleep time (TST) was calculated as time spent asleep between bedtime and wake-time, and SRI was calculated by comparing participants’ sleep/wake states across adjacent 24-hour periods. Average SRI reflects participants’ sleep regularity (0 (random) to 100 (perfect regularity)) across the study. Data were analyzed with hierarchical linear regressions that controlled for sex and average TST.

Results

Average SRI was 74.1±8.7 (range 25.7–91.6). Average BMI at T1 was 22.0±3.5; 6% of participants were underweight (BMI less than 18.5), 6% overweight (≥25 and <30) and 3% obese (≥30). Greater BMI at T1 was correlated with less ∆BMI by T2 (r=-.16, p<.001). On average, participants gained 1.8±2.4kg (range: -7.2–11.4); 6% of participants lost ≥2kg, 39% gained 2-5kg, 8% gained more than 5kg. Average TST was not significantly correlated with BMI or ∆BMI. Lower SRI was associated with greater BMI at T1 (B= -.06 [95% CI: -.09– -.02], p=.001) but less ∆BMI (B= .01 [.002–.018], p=.018).

Conclusion

We found that lower sleep-wake regularity associated with greater baseline BMI but less BMI increase during the initial transition to college. Given that the majority of our participants were normal weight young adults, our findings may indicate that sleep regularity associates with healthy growth in this population.

Support (if any)

R01MH079179, T32MH019927(P.W.)
313 Sleep Obtained by Cabin Crewmembers During a Long-haul Flight
Authors: Arsintescu Lucia , Hilditch Cassie , Glaros Zachary , Kato Kenji , Gregory Kevin , Evans Erin
Published: May 2021

Introduction

Sleep loss and circadian disruption pose a significant risk in safety-sensitive occupations. In aviation, many studies have demonstrated how inflight rest locations influence alertness and performance among pilots, but few studies have evaluated cabin crew. The purpose of the present study was to evaluate sleep outcomes among cabin crewmembers sleeping in a bunk compared to a jump seat during one long-haul route.

Methods

Thirty-one (6 male) cabin crewmembers (age M = 30, SD = +/-13) flew the same long-haul route (outbound and return) with a flight duration of 10:41 (± 0:14) hours. Participants were randomly assigned to fly on an aircraft with a bunk or a jump seat for their sleep opportunity. Participants wore an Actiwatch (Phillips-Respironics Spectrum) throughout the entire study and completed a sleep diary at bedtime and upon waking. During flight they completed a nap diary entering the start time of the inflight sleep (if any) and the duration.

Results

Sixty-five flights (32 outbound and 33 return) were included in the analyses. Seventy-seven percent of the flights had a bunk and 23% had a jump seat. Crewmembers obtained M = 146.46 (± 67.20) minutes of rest out of which they slept M = 125.33 (± 64.91) minutes in the bunk. While using the jump seat, crewmembers obtained M = 169.53 (± 133.30) minutes of rest out of which they slept M = 142.92 (± 149.72) minutes. When crewmembers slept in the bunk, sleep latency was shorter (M = 13.69 ± 12.64 minutes) and efficiency was better (M = 76.16 ± 16.09 %) compared to the jump seat (sleep onset: M = 16.77 ± 13.89 minutes; sleep efficiency: M = 60.64 ± 17.42 %).

Conclusion

We found that cabin crewmembers slept for longer time when they used the jump seat. They fell asleep faster and their sleep efficiency was better when using the bunk compared to the jump seat. Further research is needed to understand how sleep quality and subsequent performance are influenced by sleep opportunity in a bunk compared to a jump seat.

Support (if any)

NASA Airspace Operations and Safety Program, System-Wide Safety Project.
315 Athlete Sleep and Mental Health: Differences by Gender, Race, and Ethnicity
Authors: Huskey Alisa , Kim Kelly , Emert Sarah , Auerbach Alex , Webb Rachel , Skog Michelle , Grandner Michael , Taylor Daniel
Published: May 2021

Introduction

Sleep is important for athletic and academic performance, injury risk and recovery, and physical and mental health. However, athletes commonly have poor and insufficient sleep, which may be worsened by their inflexible schedules, stress, traveling, and timing of competition. To date, little is known about the relationship between sleep problems and risk for mental health problems in college student athletes. Almost nothing is known about gender, racial and ethnic sleep disparities in this group. The current study aimed to examine the cross-sectional relationships between sleep disorder symptoms and mental health symptoms, further examining differences by gender, race, and ethnicity.

Methods

Student athletes (N = 1033) from four universities within the Pacific Athletic Conference (PAC-12) were surveyed using previously-validated mental health questionnaires. Since few individuals self-identified as Asian, American Indian/Alaskan Native, Native Hawaiian/Pacific Islander, or “Other,” the race variable was recoded into three groups: White, Black, and Other Underrepresented groups. Gender, race, and ethnicity differences on Athlete Sleep Screening Questionnaire (ASSQ) total scores were examined using a three separate MANOVAs. Next, sleep-disorder symptoms were classified as clinically relevant (n=174) or not (n=733) based on established cutoff values on the ASSQ. Gender and sleep disorder differences on mental health total scores were examined using a MANOVA.

Results

Women athletes reported significantly worse sleep disorder symptoms as a whole. In addition, Black athletes had worse sleep disorder symptoms. There was a trend for women with sleep problems to have higher PC-PTSD scores than women without sleep problems. In addition, athletes in the Other Underrepresented race group with sleep problems also had greater depression, PTSD, and psychotic symptom severity than White or Black student athletes. There was also a trend for Hispanic athletes with sleep disorder symptoms to have greater ADHD symptom severity.

Conclusion

To further examine individual differences in specific components of sleep symptoms, sleep duration, insomnia symptoms, medication, quality will be reported in the poster presentation. Future studies are needed to understand whether frequency and chronicity of athletic and external stressors, explain elevations in sleep and other psychiatrics symptoms in student athletes.

Support (if any)

This project was funded by a PAC-12, Mental Health Coordinating Unit Grant.
316 Comorbidities among medically diagnosed insomnia patients: A MarketScan database study
Authors: Zhong Wenjun , Liu Xinyue , Mott Katrina , Qureshi Zaina
Published: May 2021

Introduction

A large proportion of patients with insomnia frequently suffer from comorbid medical conditions. Literature on the relationship between insomnia and associated comorbidities is severely limited due to challenges of generalizability, focus on a specific comorbidity and concerns of information biases. We conducted a comprehensive secondary database analysis to describe comorbidities among medically diagnosed insomnia patients.

Methods

All patients in the MarketScan database in 2018 with a full year of enrollment were included. Insomnia patients were identified using ICD-10-CM diagnosis codes (at least 2 outpatient claims or 1 inpatient claim of insomnia in 2018), along with their comorbidities recorded in that year. The frequencies of comorbidities among patients with insomnia were estimated. For comorbidities with prevalence > 1%, we further grouped them when appropriate to reduce the number of comorbidities.

Results

Among 20,209,292 enrollees, 259,035 (1.3%) had insomnia in 2018. Patients with insomnia had a median of 2 (IQR: 1–3) insomnia claims. The mean age of these insomnia patients was 49.3 years (std: 15.7), most of them were female (62.5%). About 172 comorbidities with >1% were found in this patient population, and 35 comorbidities had a frequency greater than 10%. The common comorbidities among these insomnia patients included 1): common physical disorders among middle aged and older adults: hyperlipidemia (39%), hypertension (39%), skin diseases (37%), back pain 35%; 2):common mental health disorders such as anxiety disorder (41%), depression (28%); and 3): other diseases such as GERD and thyroid diseases also had high frequencies among insomnia patients (18% and 18.7%, respectively).

Conclusion

Using claims data, we provided a quantitative assessment of comorbidities among patients with medically diagnosed insomnia. These results could help clinicians become aware of the most frequently occurring comorbidities and assist in integrating management of the insomnia.

Support (if any):
319 Validation of the Insomnia Severity Index Short-Form for Identifying Insomnia Disorder in Young Adult Cancer Survivors
Authors: Chevalier Lydia , Michaud Alexis , Zhou Eric , Chang Grace , Recklitis Christopher
Published: May 2021

Introduction

Insomnia is a common and impairing late effect experienced by many young adult cancer survivors (YACS). Although routine evaluation of sleep disorders in cancer survivors is recommended, lack of consensus on appropriate screening measures contributes to under-identification and under-treatment of these disorders in YACS. As screening measures are ideally as brief as possible while maintaining validity, we sought to validate the recently published three-item Insomnia Severity Index Short-Form (ISI-SF) in YACS.

Methods

250 YACS completed the ISI and the Structured Clinical Interview for the DSM-5 (SCID-5). The ISI-SF was created by summing three ISI items: distress (item #6), interference (item #7), and satisfaction (item #4). In receiver operating characteristic (ROC) analyses, area under the curve (AUC) was calculated to compare discrimination on the ISI-SF to two criteria: the full-scale ISI using a cutoff of ≥8 recently validated in this sample, and the SCID-5 insomnia module. Consistent with previous research, we specified a priori that a cut-off score on the ISI-SF with sensitivity ≥.85 and specificity ≥.75 would be acceptable.

Results

The ISI-SF had excellent discrimination when compared to the full-scale ISI (AUC = .97) and a cut-off score of ≥4 met criteria with a sensitivity of 97% and specificity of 86%. The ISI-SF had good discrimination when compared to the SCID-5 (AUC = .88), but none of the cut-off scores met a priori criteria for sensitivity and specificity. A cut-off score of ≥4 came closest with a sensitivity of 94% and specificity of 70%.

Conclusion

Although the ISI-SF did not meet sensitivity and specificity criteria for a stand-alone screening measure when compared to a diagnostic interview, it demonstrated utility as the first step in a two-step screening procedure. Specifically, the high sensitivity of the ≥4 ISI-F cut-off score is well-suited to accurately screening out YACS who do not need insomnia services; as a second screen, the SCID-5 insomnia module could be administered only to those elevated on the ISI-SF in order to identify false positives cases before making referrals for insomnia specialists.

Support (if any)

National Cancer Institute (1R21CA223832), Swim Across America
322 Comparisons of clinical and polysomnographic characteristics between negative and positive sleep state misperception in insomnia
Authors: Yoon Gahui , Lee Mi Hyun , Oh Seong Min , Choi Jae-won , Lee Yu Jin
Published: May 2021

Introduction

Most of insomnia patients tend to underestimate their sleep duration and quality. In current study, we classified insomnia patients into negative sleep state misperception (NSSM) group and positive sleep state misperception (PSSM) group according to difference between subjective and objective sleep duration. We compared clinical and polysomnographic characteristics between two groups.

Methods

Objective sleep measures using nocturnal polysomnography (nPSG) and subjective measures including Pittsburgh Sleep Quality Index (PSQI), Beck Depression Inventory (BDI) and subjective questionnaire at the morning after overnight nPSG of 150 insomnia patients were reviewed. The questionnaire included subjective total sleep time (subjective TST), subjective sleep latency (subjective SL). Additionally, TST/SL discrepancy was calculated by subtracting objective variables of nPSG from the morning subjective questionnaire. We calculated misperception index (MI) using the following method; MI=(objective TST-subjective TST)/objective TST. According to MI value, insomnia patients were classified into NSSM (MI>0, n=115), and PSSM (MI<0, n=35) groups.

Results

There were no significant differences in nPSG parameters, except N3 sleep (%); the PSSM group had significantly higher N3 sleep than NSSM group (p=0.002). On the subjective measures, the NSSM group had significantly higher PSQI score (p<0.001), longer subjective SL (p=0.001) and higher SL discrepancy (p=0.001). In the NSSM group, MI showed positive correlations with N1 sleep proportion (r=0.250, p=0.011), PSQI (r=0.250, p=0.011), BDI (r=0.211, p=0.032), subjective SL (r=0.441, p<0.001) and SL discrepancy (r=0.453, p<0.001). Meanwhile, there were no significant correlations of MI with subjective measures in PSSM group. In the multiple regression analysis, MI was related with SL discrepancy and BDI (R2=0.216, p=0.004) in NSSM group. For belonging the PSSM group, associated factors were N3 sleep (OR=1.075, p=0.001), PSQI (OR=0.813, p=0.002) and SL discrepancy (OR=0.956, p<0.001) on binary logistic regression analysis.

Conclusion

In the NSSM group, MI was related with high SL discrepancy and depressive mood. High N3 sleep, low PSQI score, and low SL discrepancy were associated factors in the PSSM group. Perception of sleep should be properly evaluated and managed, since they vary with different characteristics of sleep state misperception.

Support (if any)

This study was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF-2018R1D1A1B07049704).
323 Is daytime napping a risk factor for persistent insomnia symptoms?
Authors: Pereira Rui , Hartescu Iuliana , Morgan Kevin , Jackson Robin , Ellis Jason , Morales Knashawn , Perlis Michael
Published: May 2021

Introduction

Napping, episodes of short daytime sleep separated from the main sleep period, can compensate for the detrimental effects of inadequate night-time sleep or, as ‘siestas’, may form an integral part of personal sleep-wake schedules. Napping may also precipitate or perpetuate insomnia symptoms through the erosion of homeostatic sleep pressure at night. Using longitudinal data, these analyses were designed to evaluate links between daytime napping styles and the incidence of persistent insomnia symptoms, in a sample of middle aged and older adult good sleepers at baseline.

Methods

567 participants (65% female; >35 years old) were sub-sampled from the NITES cohort (Perlis et al, 2019). All were self-rated good sleepers, reporting typical sleep latencies (5 nights/week) and WASO durations of = 1 nap/baseline period) or habitual (>= 2 naps/week). ‘Persistent insomnia symptoms’ cases reported sleep initiation and/or maintenance complaints on >= 3 nights/week for at least two consecutive weeks. Relationships between nap categories and the incidence of persistent insomnia symptoms arising in months 4–12 of the study were assessed in logistic regression models adjusted for age, gender, employment status and depression. Risk is expressed as the odds ratio (OR) with 95% confidence interval (CI).

Results

Prevalence rates for ever/habitual napping were 57% and 10%. Unemployed status and aged 50+ significantly increased habitual nap probability. The 1-year incidence of persistent insomnia symptoms was 5.6%. In logistic regression models, ‘ever’ napping was associated with an almost 3-fold increase in the risk of developing persistent insomnia symptoms (OR=2.994; 95% CI 1.244–6.969; p=.014). When the logistic regression model was rerun with habitual napping, the risk attenuated substantially (OR = 1.4, 95% CI .592–3.163; p=.463).

Conclusion

These results suggest that napping patterns serve as a marker for insomnia symptom development, with haphazard non-habitual napping patterns associated with significantly greater risk.

Support (if any)

RP: Loughborough University doctoral studentship; MP: K24AG055602 & R01AG041783 (NITES).
325 Stress-Induced Physiological Profiles Among Different Phenotype Insomniacs
Authors: Huang Ya-Chuan , Lee Hsin-Chien , Yang Chien-Ming
Published: May 2021

Introduction

Stress reactivity and autonomic nervous system (ANS) dysregulation have been suggested to be the pathophysiology of insomnia. Based on the finding PSG-measured short sleep duration was associated with higher morbidity of metabolic and cardiovascular disease. Vgontzas and Fernandez-Mandoza (2013) proposed that objective sleep duration is a biomarker for insomnia phenotypes. The phenotype with short objective sleep duration is associated with increased stress-related physiological hyperarousal. The present study aims to test this hypothesis by comparing the stress-induced cardiovascular reactivity between insomnia patients with short and long objective sleep durations.

Methods

27 insomnia patients (age mean 34.48 ±12.87, Male: Female= 6:21) without comorbidity of psychiatric, medical or sleep disorders participated in this study. They went through one night of 8-hour PSG recording and were divided into two groups by their total sleep time with a cutoff of 6 hours. Nine participants were in short sleep duration group and 18 in longer sleep duration group. Psychophysiological reactivity profile, as recorded with EKG, skin conductance (SC), body temperature (BT), blood volume pulse (BVP), respiration rate (RR), was measured under three conditions: baseline resting state, arithmetic word problems solving, and recovery resting state.

Results

Both groups showed similar stress physiological response with increased heart rate (HR) and SC, nearly equivalent BT and BVP, and decreased RR when solving arithmetic problems, and opposite reaction during recovery resting state. Mann-Whitney U test comparing the changes from baseline resting state on all the psychophysiological measures between two phenotypes of insomnia showed no significant differences: stress-induced heart-rate (U=106, p=.119.) recovery heart-rate (U=44, p=.095), stress-induced skin conductance (U=104.5, p=.132),recovery skin conductance (U=51.5, p=.198), stress-induced body temperature (U=79, p=.897),recovery body temperature (U=60.5, p=.418), stress-induced blood volume pulse amplitude (U=77, p=1.0), and recovery blood volume pulse amplitude (U=69, p=.735), stress-induced respiration rate (U=76, p =.696), and recovery respiration rate (U=85, p=.658).

Conclusion

Our results indicate that the insomnia phenotypes with short and long objective sleep duration are not different in their stress-induced physiological responses. Future studies are needed to confirm these results and to explore other mechanisms for the increased metabolic and cardiovascular disease risk in insomnia patients with short objective sleep duration.

Support (if any):
329 High Prevalence of Sleep Difficulties and Low Rate of Seeking Professional Help in Polish Population
Authors: Gustavsson Katarzyna , Wichniak Adam
Published: May 2021

Introduction

The number of people suffering from sleep disorders is on the rise. Insomnia is a complex issue with an impact on numerous aspects on everyday functioning. At the same time it is highly dependent on an individual’s lifestyle and untreated episodic sleep issues may lead to chronić insomnia. The aim of the present study was to assess complaints regarding sleep difficulties among men and women in Poland, as well as their severity and whether it leads to seeking treatment.

Methods

Data was gathered as a part of an online-based nationwide campaign on insomnia, which included a survey assessing sleep quality. The survey was developed for the purpose of this study. Statistical analysis included Chi-Square and Mann-Whitney tests as well as Spearman’s correlations.

Results

Responses were obtained from 3807 individuals – 2616 (68.7%) women and 1191 (31.3%) men. Sleep issues with the highest prevalence were sleep maintenance difficulties reported by 62.8% of the respondents, snoring among 61.2%, sleep initiation difficulties (sleep latency of over 30 minutes) among 55.6%, daytime sleepiness among 49.5%, and symptoms of Restless Leg Syndrome among 45.1%. Out of the participants who reported at least one sleep issue, the rate of having been to a professional consultation was 20.8% - 22.8% among women and 16.4% among men.

Conclusion

Even though the prevalence of different sleep troubles was very high, it did not correspond to the rate of seeking professional help. The vast majority of both men and women who experienced sleep difficulties had never consulted with a specialist regarding their sleep quality. There is a great need for psychoeducation of the general public on sleep as a vital component of health and on benefits of professional help.

Support (if any)

This study was supported by an unrestricted educational grant by Polfarmex. The funding source had no role in the design and conduct of the study, collection, management and analysis of the data, or preparation of the abstract. The authors declare no other conflicts of interest.
331 Adverse Childhood Experience and Sleep Quality in Adulthood
Authors: Bakour Chighaf , Desch Jill , Mansuri Fahad , Schwartz Skai W
Published: May 2021

Introduction

Poor sleep quality, a risk factor for many negative health outcomes, may result from physical or emotional disturbance including chronic stress. Adverse childhood experiences (ACEs) have been linked with chronic stress, and may therefore be associated with poor sleep quality in adulthood. This study examines the longitudinal association between specific ACEs and the number of ACEs and sleep quality in adulthood.

Methods

Using data from the National Longitudinal Study of Adolescent to Adult Health, we examined the association between ACEs and trouble falling asleep or staying asleep (rarely or never, sometimes, frequently) in waves 1 (age 12–18), 4 (age 24–32), and 5 (age 33–43). We examined ten ACEs (physical, sexual, or emotional abuse; neglect; parental death, incarceration, alcoholism, divorce or separation; foster home placement; poverty; and exposure to community violence) and the number of ACEs (0, 1, 2–3, 4+), using weighted logistic regression to calculate odds ratios and confidence intervals for each of the ACEs and ACE score and each of the outcomes after adjusting for relevant confounders.

Results

The analysis included 12,768 participants, 75.3% of whom experienced at least one ACE, including 14.7% who experienced 4 or more. Physical and emotional abuse were associated with frequent sleep complaints at waves 1, 4, and 5. Sexual abuse, neglect and community violence were associated with frequent complaints in two waves, while parental alcoholism, parental incarceration, and foster home placement were associated with frequent complaints in one wave. The number of ACEs experienced showed a dose-response association with frequent sleep complaints in wave 1 ([1 ACE: aOR=2.12 (1.16, 3.9), 2–3 ACEs: aOR=2.86 (1.70, 4.82), 4+ ACEs: aOR=4.17 (2.33, 7.48)], wave 4 [1 ACE: aOR=1.02 (0.77, 1.36); 2–3 ACEs: aOR= 1.66 (1.30, 2.10); 4+ ACEs: aOR=2.68 (1.99, 3.61) and in wave 5 [1 ACE: aOR=1.22 (0.93, 1.60)), 2–3 ACEs: aOR=1.42 (1.11, 1.81), 4+ ACEs: aOR=1.88 (1.40, 2.53)]

Conclusion

Certain adverse childhood experiences such as physical, sexual, and emotional abuse and neglect have a lasting impact on sleep quality in adulthood, highlighting the need to mitigate their impact to prevent negative health outcomes associated with poor sleep quality

Support (if any):
333 Associations Between Insomnia and Health Correlates in Nurses
Authors: Nagy Samantha , Dietch Jessica , Slavish Danica , Messman Brett , Ruggero Camilo , Kelly Kimberly , Taylor Daniel
Published: May 2021

Introduction

Insomnia, shiftwork (i.e., circadian rhythm disruptions) and insufficient sleep are common among nurses and healthcare workers. Each of these sleep problems can contribute to physical (e.g., inflammation, musculoskeletal pain, cardiovascular disease and heart rate variability, indigestion, and menstrual cycle irregularity) and mental (e.g., depression, anxiety, suicidality) health problems as well as daytime fatigue and sleepiness among nurses and may contribute to burnout and job change.

Methods

Participants (N=458) were nurses recruited for a parent study, “Sleep and Vaccine Response in Nurses (SAV-RN)” (Taylor & Kelly: R01AI128359-01). Most identified as female (90.5%), White/Caucasian (77.2%), and non-Hispanic (88.6%) with an average age of 39.03 (SD = 11.07). Participants completed baseline measures online via Qualtrics survey. The Sleep Condition Indicator (SCI; Espie et al., 2014) was used to identify a probable diagnosis of insomnia (score of ≤16 = Insomnia; endorsement of each of the primary DSM-5 criteria on the measure). In addition, a checklist of current major health conditions (high blood pressure, sleep apnea, GI issues, HIV/AIDS, cancer, etc.) was also completed. A Chi square test of Independence was conducted using SPSS to determine if insomnia detected by the SCI was associated with reported health conditions.

Results

At baseline, 25.4% of nurses had a probable insomnia diagnosis. Insomnia was associated with a greater likelihood of diagnosed sleep apnea, cancer (all types), high blood pressure, chronic pain, gastrointestinal problems, an autoimmune disease, and/or an endocrine problem at Month 11 of the study (all ps <.05). Data cleaning is ongoing, but similar analyses will be presented examining shift work sleep disorder and insufficient sleep (i.e., average < 6hrs per night) as individual and simultaneous predictors of physical and mental health at baseline and change from baseline to Month 11 (if available).

Conclusion

These results help to identify associations between insomnia and health conditions in nurses and may contribute to future research that supports evidence-based intervention and prevention strategies for this population. While evidence-based interventions for sleep disturbances and insomnia exist (CBT-I), accessibility and feasibility of scaling such interventions to reach the nursing community at large remains challenging.

Support (if any):
334 36 Month Surveillance Confirms Favorable Safety Profile of a Novel Continuous Release and Absorption Melatonin Delivery System
Authors: Corsino Patrick , Brodner David , Zeitzoff Linda
Published: May 2021

Introduction

The cumulative long-term effects of sleep loss have been associated with a wide range of damaging health consequences. There is a medical need for novel, non-pharmacological sleep aid alternatives. The ideal sleep solution would allow sleep to occur with normal sleep architecture and without causing dependence or daytime somnolence. Melatonin with its soporific effects and benign safety profile has been shown to be an effective sleep aid to decrease sleep onset latency, increase total sleep time and improve overall sleep quality. The novel, well tolerated CRA-melatonin, with the unique design of its delivery system, was shown in a randomized, crossover, pharmacokinetic (PK) study versus the leading marketed melatonin to achieve quick uptake and then continuous release and absorption for up to 7 hours. The REMfresh Safety Update at 36 months (REMSU36), a real world safety surveillance analysis was conducted to confirm the previously observed safety profile of CRA-melatonin.

Methods

An independent call center with pharmacovigilance-trained health care personnel, was retained to receive and record customer questions, product issues and adverse events (AEs). The data collection was conducted from March 9, 2017 to March 9, 2020. An estimated 981,735 adults used CRA-melatonin during the surveillance period.

Results

There were no serious AEs reported. Eighty-one (81) non-serious AEs were recorded, resulting in a 0.008% event reporting rate. The two most frequent AEs were headaches (7) and dizziness (5), which are also known comorbidities of chronic sleeplessness.

Conclusion

CRA-melatonin with its extended 7 hour PK profile may be an effective, well tolerated baseline therapy to improve sleep in adults These results, in a real world setting, support the previous reports of safety and tolerability of melatonin, as well as observed in the CRA-melatonin PK study.

Support (if any):
336 Effect of Lemborexant Versus Placebo and Zolpidem on REM Sleep by Quarter Night Intervals in Older Adults with Insomnia Disorder
Authors: Zammit Gary , Roth Thomas , Kumar Dinesh , Perdomo Carlos , Atkins Norman , Moline Margaret
Published: May 2021

Introduction

Effects of the dual orexin receptor antagonist lemborexant (LEM) on sleep architecture in adults ≥55y with insomnia disorder were assessed in Study E2006-G000-304 (Study 304; SUNRISE-1; NCT02783729). These post hoc analyses of Study 304 examined the acute effect of LEM on REM pressure (REM latency [REM-L] and REM by quarter of the night [QoN]).

Methods

This study was a 1mo, randomized, double-blind, placebo- and active-controlled (zolpidem tartrate extended-release 6.25mg [ZOL]) study of LEM (5mg, LEM5; 10mg, LEM10). Subjects received placebo (n=208), ZOL (n=263), LEM5 (n=266), or LEM10 (n=269). Two nights of PSGs were recorded at baseline, first 2 (N1/2), and last 2 (N29/30) treatment nights.

Results

Baseline REM-L (minutes) was similar across treatments (98.4–101.4). Significant decreases from baseline in REM-L were observed for LEM5 (−42.6 [53.9]) and LEM10 (−49.6[52.9]) vs placebo (−6.9[54.5]) and ZOL (0.2[54.2]) on N1/2 (all P<0.0001). No difference was observed for ZOL vs placebo. Baseline REM (minutes) for each QoN was similar across treatments. In Q1, mean(SD) REM (minutes) on N1/2 was 16.5(9.7), 19.7(10.5), 10.3(8.2), and 8.5(7.6) for LEM5, LEM10, placebo, and ZOL, respectively. The difference was significant for LEM5 and LEM10 vs placebo and ZOL (all P<0.0001), and ZOL vs placebo (P<0.05). In Q2, mean(SD) REM on N1/2 was 19.2(9.4), 21.6(10.0), 17.9(8.9), and 17.2(9.3) for LEM5, LEM10, placebo, and ZOL, respectively. The difference was significant for LEM10 vs placebo (P<0.0001) and for LEM5 and LEM10 vs ZOL (P<0.01, P<0.0001, respectively). No difference was observed for ZOL vs placebo. In Q3, mean(SD) REM on N1/2 was 23.3(10.3), 25.9(9.7), 20.8(9.4), and 22.8(9.9) for LEM5, LEM10, placebo, and ZOL, respectively. The difference was significant for LEM5, LEM10, and ZOL vs placebo (P<0.01, P<0.0001, P<0.05, respectively) and LEM10 vs ZOL (P<0.001). In Q4, mean (SD) REM on N1/2 was 23.8(9.4), 26.1(11.0), 21.6(10.9), and 22.5(10.1) for LEM5, LEM10, placebo, and ZOL, respectively. The differences were significant for LEM5 and LEM10 vs placebo (P<0.05, P<0.0001, respectively), and for LEM10 vs ZOL (P<0.0001). Generally, similar findings were noted at N29/30; these data will be reported.

Conclusion

LEM, but not ZOL, acutely increases REM pressure as evidenced by REM latency and REM duration per quarter.

Support (if any)

Eisai Inc.
338 How Much Improvement in the Insomnia Severity Index Is Associated With a Positive Impact of A Patient’s Insomnia Medication?
Authors: Lenderking William , Savva Yulia , Chabot Isabelle , Meier Genevieve , Yardley Jane , Moline Margaret
Published: May 2021

Introduction

In Phase 3 Study 304 (SUNRISE-1; NCT02783729) and Study 303 (SUNRISE-2; NCT02952820), lemborexant (LEM) provided significant benefit versus placebo on sleep diary-based sleep onset/maintenance outcomes over 1mo and 6mo, respectively, in subjects with insomnia disorder. Both studies included the Insomnia Severity Index (ISI) and the Patient Global Impression–Insomnia version (PGI-I). On the PGI-I scale, subjects assess positive, neutral or negative treatment impact on falling asleep, overall benefit on sleep, and total sleep time. Using an anchor-based approach, ratings were compared with mean changes in ISI scores from baseline to evaluate what would be considered a responder definition on the ISI.

Methods

Study 304 was a 1mo, randomized, double-blind, placebo- and active-controlled, parallel-group study in female (age ≥55y) and male (age ≥65y) subjects (n=1006); subjects received placebo, LEM 5mg, LEM 10mg, or zolpidem tartrate extended-release. Study 303 was a 12mo, randomized, double-blind study in subjects age ≥18y (n=950). Subjects received placebo, LEM 5mg, or LEM 10mg for 6mo. Data from both studies were pooled for the first month of treatment across all treatment groups. A modified ISI total score (ISI-ts) was used based on a confirmatory factor analysis that showed no incremental value to including Question 5 (How NOTICEABLE to others do you think your sleep problem is in terms of impairing the quality of your life?).

Results

The ‘Overall Sleep’ PGI-I item demonstrated that mean [SD] changes from baseline in ISI-ts decreased more in association with self-reported positive effects (−8.15 [4.98]) than for neutral (−3.59 [3.37]) or negative effects (−1.67 [2.91]) at Day 31/Month 1. For PGI-I Item ‘Time to Fall Asleep,’ mean (SD) changes from baseline in ISI-ts were −7.49 (5.10) for positive, −4.54 (4.13) for neutral, and −2.94 (4.04) for negative effects at Day 31/Month 1. For PGI-I Item ‘Total Sleep Time’ mean (SD) changes from baseline in ISI-ts were −8.15 (5.04) for positive, −3.74 (3.23) for neutral, and −2.40 (3.49) for negative effects at Day 31/Month 1.

Conclusion

Results of this anchor-based approach using the PGI-I suggest that the responder definition for ISI-ts, using the modified ISI, should be approximately −8 points.

Support (if any)

Eisai Inc.
342 CBT-I Has Sustained Effects on Insomnia Versus Heart-Failure Self-Management Education among Adults with Chronic Heart Failure
Authors: Redeker Nancy , Bessette Andrew , Breazeale Stephen , Conley Samantha , Hollenbeak Christopher , Hwang Youri , Iannacco Joanne , Jacoby Daniel , Kelly-Hauser Jessica , Linsky Sarah , Moemeka Lesa , Nwanaji-Enwerem Uzoji , O’Connell Meghan , Yaggi Henry , Jeon Sangchoon
Published: May 2021

Introduction

Insomnia is common among adults with chronic heart failure (HF), often not explained by sleep apnea (SA), and associated with daytime symptoms and poor daytime function. The purpose of this randomized controlled trial was to evaluate the sustained effects of cognitive behavioral therapy for insomnia (CBT-I) on insomnia severity and sleep characteristics over 6 months among adults with stable chronic HF.

Methods

We included adults with HF who had at least mild insomnia [Insomnia Severity Index (ISI) > 8] and no more than mild SA or SA treated with continuous positive airway pressure. We randomized in groups to 8 weeks of group CBT-I (Healthy Sleep: HS) [4 group sessions + calls on alternate weeks] or attention control (Healthy Hearts: HH) [HF self-management education + brief sleep hygiene] in the same format. We administered the ISI, the Pittsburgh Sleep Quality Index (PSQI), the Dysfunctional Beliefs & Attitudes about Sleep Scale (DBAS), and the Sleep Disturbance Questionnaire (SDQ) at baseline (T0), 2 weeks after treatment ended (T1) and at 6 months (T2). Statistical analysis included descriptive statistics and mixed effects models with random intercepts and slopes.

Results

The sample include 175 participants (HS: N = 91; 62 + 13 years; 58% Male; 15% Black; 68% NY Heart Class II-III) (HH: N = 84; 64 + 12.5 years; 56% Male; 17% Black; 70% NY Heart Class II-III). There was no significant difference at baseline in demographic characteristics or the mean ISI [HS: 15.3 (4.5); HH: 14.4 (4.5)], but a greater percentage in the HS group had clinical/moderate-severe insomnia (ISI > 15) (HS: 60.4% vs. HH: 47%). The CBT-I intervention (HS) was associated with significant improvement in insomnia severity (ISI: p = .001), sleep quality (PSQI: p = .002), and sleep-related cognitions (DBAS: p = .0006; SDQ: p = .0138), and a modest effect on self-reported sleep duration (46 vs. 20 mins, p = .054), but no effect on sleep efficiency. At 6 months, 12.9% of the HS group, compared with 24.9% of the HH group had clinical insomnia.

Conclusion

CBT-I has sustained effects on insomnia, sleep-quality, and sleep-related cognitions in people with HF.

Support (if any)

R01NR01691 (NSR, PI)
344 Daridorexant Improves Total Sleep Time (TST) in Insomnia Patients Without Altering the Proportion of Sleep Stages
Authors: Zammit Gary , Mayleben David , Fietze Ingo , Pain Scott , Kinter Dalma Seboek , Gimona Alberto , Dauvilliers Yves
Published: May 2021

Introduction

Daridorexant, a new dual orexin receptor antagonist, improved sleep parameters and daytime functioning in two pivotal Phase 3 trials in patients with insomnia (Trial-1, NCT03545191; Trial-2, NCT03575104); polysomnography data were collected at multiple timepoints from >1,800 patients. We report the effects of daridorexant on TST and sleep stages from both trials.

Methods

Eligible patients with insomnia (according to DSM-5) were randomized (1:1:1) in Trial-1 (N=930) to daridorexant 25mg, 50mg, or placebo and in Trial-2 (N=924) to daridorexant 10mg, 25mg, or placebo. Oral treatment was administered each night during a 3-month double-blind treatment period. Assessment of TST and sleep stages (non-rapid eye movement [NREM, N]1, N2, N3, REM), measured by polysomnography in sleep laboratory, was performed on two consecutive nights during single-blind placebo run-in (baseline) and Months 1 and 3 (M1 and M3) of double-blind treatment. Change from baseline in TST and sleep stages were exploratory endpoints in both trials. Data for M3 (mean ± standard deviation) are presented as change from baseline.

Results

Daridorexant dose-dependently increased TST(minutes) from baseline to M3, more than placebo, in Trial-1 (25mg, 55±56; 50mg, 61±53; placebo, 40±56) and Trial-2 (10mg, 37±57; 25mg, 50±53; placebo, 35±56). In both trials, sleep stage proportions were preserved from baseline to M3, with no relevant changes in any group. Baseline time spent in each sleep stage (% of TST) was consistent across groups in both trials (range across treatment groups in both trials: N1:11–13; N2:55–57; N3:11–14; REM:19–20). In Trial-1 (25mg/50mg/placebo), the change from baseline to M3 in % of TST spent in N1(-0.3±4.7/-0.2±5/0.1±5), N2(2±8/1±7/1±7), N3(-2±6/-2±6/-2±6), and REM(1±6/1±5/1±5) was low and numerically similar across treatments. In Trial-2, the change from baseline to M3 in % of TST spent in each sleep stage was consistent with Trial-1, with no effect of dose. Mean changes from baseline (% of TST) for each sleep stage appeared to be independent from increasing TST. Data for 25mg were consistent between trials.

Conclusion

Daridorexant at any dose, and each more than placebo, increased TST in a dose-dependent manner without affecting the proportion of all sleep stages in patients with insomnia.

Support (if any)

Funded by Idorsia Pharmaceuticals Ltd.
346 Semi-Individualized Acupuncture for Insomnia Disorder: A Randomized Sham-Controlled Trial
Authors: Yeung Jerry Wing-Fai , Yu Branda Yee-Man , Yuen John , Ho Janice , Chung Ka-Fai , Zhang Zhang-Jin , Mak Deejay Suen-Yui , Suen Lorna Kwai-Ping , Ho Lai Ming
Published: May 2021

Introduction

Acupuncture is an alternative treatment for improving sleep quality and the effectiveness is thought to be optimized with an individualized approach resembling real practice. However, existing evidence is limited by methodological shortcomings due to blinding issues, standardized measures, and diagnostic procedures. It was of the present study’s interest to examine the efficacy and safety of semi-individualized acupuncture treatment on insomnia.

Methods

Adults with DSM-5 insomnia disorder (n = 140) were randomized with 1:1 allocation to a 4-week intervention traditional acupuncture (TA) or validated non-invasive sham acupuncture (SA). The selection of acupoints was semi-individualized by the acupuncturist. As the primary outcome, the sleep efficiency (SE) by sleep diary was assessed at baseline, 1-week posttreatment, and 5-week posttreatment. Other sleep parameters derived from sleep diary, the wrist-actigraphy-derived sleep parameters, insomnia symptom severity, anxiety, and depressive symptoms, as well as the health-related quality of life, were also evaluated.

Results

Although linear mixed-effect model revealed both groups did not attain significant difference in sleep-diary-derived SE and other outcome measures (all P > 0.05), TA promising effect on improving insomnia symptom (within-group effect size, d = 1.13 & 1.30 at 1-week & 5-week posttreatment respectively) and also a higher proportion of subjects achieved SE ≥ 85% compared with SA (55.6% versus 36.4% at week 9, P = 0.03). Besides, subjects in TA group reported significantly greater improvement in both the total sleep time (TST) derived from sleep diary and actigraph than those in the SA group at 1-week posttreatment (difference in mean changes from baseline: sleep diary = 22.0 min, p = 0.01; actigraphy =18.8 min, P = 0.02) but not 5-week posttreatment.

Conclusion

This study is the first to evaluate the effect of the TCM-theory-based individualized acupuncture on sleep using a sham-control design. A 4-week semi-individualized acupuncture is able to significantly increase total sleep time with few adverse events.

Support (if any)

Research Grants Council of Hong Kong, Early Career Scheme (Project no.: 25101017)
347 Daridorexant is Safe and Improves Both Sleep and Daytime Functioning in Elderly Patients with Insomnia
Authors: Fietze Ingo , Bassetti Claudio , Mayleben David , Gimona Alberto , Pain Scott , Kinter Dalma Seboek
Published: May 2021

Introduction

Insomnia affects elderly more than younger adults, and comorbidities more prevalent in elderly populations can add to symptom burden and reduce therapeutic options. Drugs that improve insomnia symptoms with limited safety risks are needed to treat this patient group. We report elderly subgroup analyses from a Phase-3 registration trial with daridorexant.

Methods

In this multi-center, double-blind trial (NCT03545191), adult (18–64y) and elderly (≥65y) patients with insomnia were randomized (1:1:1) to receive oral daridorexant 25mg, 50mg or placebo every evening for 3 months. Month 3 endpoints were: change from baseline in polysomnography-measured wake-after-sleep-onset (WASO) and latency-to-persistent-sleep (LPS) (both primary endpoints), subjective total sleep time (sTST), and daytime functioning (Insomnia Daytime Symptoms and Impacts Questionnaire [IDSIQ] – sleepiness domain; with a lower score indicating improved daytime functioning). Safety endpoints included treatment emergent adverse events (TEAE), AEs of special interest (AESI; symptoms related to excessive daytime sleepiness or complex sleep behavior, and suicidal ideation/self-injury) and withdrawal effects upon treatment cessation (assessed by the Benzodiazepine Withdrawal Symptom Questionnaire total score and relevant AEs).

Results

Of the 930 patients randomized, 364 (39.1%) were ≥65y: daridorexant 25mg (n=121), 50mg (n=121) and placebo (n=122). In this subgroup, at Month 3, the placebo-corrected least-square mean of change from baseline [95%CL] for daridorexant 25mg and 50mg were: WASO -17.0[-27.0,-7.0] and -19.6[-29.5,-9.7] mins; LPS -7.8[-15.2,-0.4] and -14.9[-22.3,-7.5] mins; sTST 18.7[4.1,33.2] and 30.6[16.1,45.2] mins; IDSIQ sleepiness domain -0.6[-2.2,0.9] and -2.6[-4.1,-1.0], all respectively. TEAEs were reported in 32.2%, 35.3%, and 31.1% of patients ≥65y in the 25mg, 50mg and placebo groups, respectively. Falls (n=1,1,4 for 25mg, 50mg, placebo, respectively) and dizziness (n=4,1,1), both of particular interest in elderly, were least frequent in the 50mg group. Compared to placebo, somnolence was as frequent for 50mg daridorexant (n=6,1,1) while fatigue was more frequent in both daridorexant groups (n=4,3,1); incidence did not appear dose-related. AESI, of mild intensity, were reported in 2 patients ≥65y (one in each daridorexant group). There was no evidence of withdrawal symptoms.

Conclusion

Daridorexant is efficacious in the elderly population for improvements in sleep and daytime functioning. No safety concerns in this vulnerable population were identified at either dose.

Support (if any)

Funded by Idorsia Pharmaceuticals Ltd.
356 Examining Use and Beliefs about Sleep Medications in a Sample of Older Adults: The Role of Hypnotic Dependency
Authors: Tully Isabelle , Simpson Norah , Dietch Jessica , Tutek Joshua , Manber Rachel
Published: May 2021

Introduction

Prevalence of insomnia and prescription of sleep medications increases in older adults and is associated with heightened risk of falls, cognitive and psychomotor detriments, and exacerbation of pre-existing conditions. The present study aimed to characterize beliefs about sleep and sleep medications, hypnotic self-efficacy, and hypnotic dependence in a sample of older adults with insomnia disorder.

Methods

Adults 50 years and older (N = 141) who met DSM-5 criteria for insomnia disorder were enrolled in the RCT of the Effectiveness of Stepped-Care Sleep Therapy In General Practice (RESTING) study. At baseline, participants completed the Beliefs about Medications Questionnaire (BMQ; subscales assess the belief that hypnotics are necessary and concern regarding consequences of use), Insomnia Severity Index (ISI), Dysfunctional Beliefs and Attitudes about Sleep Scale (DBAS), Pre-Sleep Arousal Scale (PSAS), and the Patient Health Questionnaire-4 (PHQ-4). Participants taking prescription sleep medications (n = 54) also reported if they had sedative hypnotic reduction goals and completed the Sleep Medications Dependency Scale and Hypnotic Self-Efficacy Scale.

Results

Those taking prescription sleep medications reported greater belief in the necessity of sedative hypnotics (p < .001, d = 1.69) and greater anxiety and depression (p = .005, d = .57) than those not taking prescription medications; groups did not differ significantly on the BMQ concern subscale, ISI, DBAS, or PSAS. 70.4% of participants using prescription sleep medications endorsed decrease in sedative hypnotic use as a treatment goal. Dependency on sleep medications, but not hypnotic self-efficacy, was greater in those with this goal (p = .003, d = .94). Higher levels of hypnotic dependence were associated with both greater concern (r = .40, p = .003) and belief in the necessity of sleep medications (r = .48, p < .001).

Conclusion

Our findings indicate that many treatment-seeking older adults with insomnia disorder take prescription sleep medications. They tend to believe in the necessity of sleep medications for controlling sleep disruption, but also identify medication reduction as a treatment goal, even if endorsing dependence on hypnotics. This highlights the importance of disseminating non-medication treatments that address both insomnia and reduction of sedative hypnotic use.

Support (if any)

1R01AG057500