bluuebunny/crossref_metadata_2025 huggingface dataset:
0385 Children, Adolescents, and Their providers: the Narcolepsy Assessment Partnership (CATNAP™) Pediatric Narcolepsy Registry: Baseline Demographics
Authors: Macfadden Wayne , Leary Eileen , Gwadry-Sridhar Femida , Owens Judith
Published: May 2022

Introduction

Limited information is available on the natural history, presentation, and management of pediatric narcolepsy. CATNAP™ is a retrospective/prospective, longitudinal, multicenter, web-based pediatric narcolepsy registry (NCT04899947). The primary objectives are to improve understanding of the natural history of pediatric narcolepsy, characterize symptom presentation and diagnosis, and understand treatment practices and outcomes.

Methods

Eligible children/adolescents (<18 years) had confirmed narcolepsy. Using web-based portals, patients, caregivers, and clinicians completed an initial survey on sociodemographic characteristics; diagnostic, medical, and treatment history; comorbidities; and disease progression.

Results

Patient/caregiver-reported interim baseline data are included (N=25 patients; mean±SD age: 15.6±2.9 years; 52.0% female; 60.0% White; 64.0% narcolepsy type 1 [NT1]; 28.0% narcolepsy type 2; mean±SD age at narcolepsy diagnosis: 11.0±4.0 years). At narcolepsy diagnosis, the percentages of participants who were <10, 10 to 15, and ≥16 years of age were 36.0%, 52.0%, and 12.0%, respectively. Symptoms at first diagnosis included excessive daytime sleepiness (EDS; 96.0%), cataplexy (64.0%), disrupted sleep (64.0%), vivid dreams (52.0%), and nightmares (40.0%). Comorbid psychiatric disorders were present in 36.0% of participants and included anxiety disorder (20.0%), depression (16.0%), attention-deficit/hyperactivity disorder (ADHD; 12.0%), and panic attacks (8.0%). Misdiagnosis of narcolepsy was reported in 32.0% of participants; alternative diagnoses included anxiety disorder, ADHD, sleep apnea (all 8.0%), and obsessive-compulsive disorder (4.0%). Physician specialties that confirmed narcolepsy diagnosis included neurologists and pediatricians (each 24.0%), pulmonologists (16.0%), pediatric neurologists (12.0%), general practitioners/internists (8.0%), and endocrinologists (4.0%). In participants with NT1 (n=16), warning symptoms for cataplexy were reported by 43.8% and included a sense that cataplexy was imminent without physical symptoms, a sense that time had somewhat suspended, fear/fright, and a feeling of warmness (all 6.3%). At diagnosis, the number of cataplexy episodes per day in order of frequency was 2 (37.5%), 3 (25.0%), 4 (18.8%), and 1 (12.5%). Current medications for narcolepsy included stimulants (60.0%), wake-promoting agents (40.0%), sodium oxybate (32.0%), serotonin-norepinephrine reuptake inhibitors (16.0%), and selective serotonin reuptake inhibitors (8.0%).

Conclusion

Interim baseline data from CATNAP provide valuable information on the experience and management of pediatric narcolepsy that will facilitate education of patients and caregivers, inform clinical decision-making, and potentially improve treatment strategies.

Support (If Any)

Jazz Pharmaceuticals.
0387 Weight Changes During Treatment With Lower-Sodium Oxybate in a Phase 3 Clinical Study in Patients With Idiopathic Hypersomnia
Authors: Dauvilliers Yves , Chandler Patricia , Hickey Luke , Chen Abby , Steininger Teresa , Foldvary-Schaefer Nancy
Published: May 2022

Introduction

Treatment with sodium oxybate (SXB) has been associated with weight loss in patients with narcolepsy. Lower-sodium oxybate (LXB) contains the same active moiety as SXB, with 92% less sodium, and is approved in the United States for the treatment of idiopathic hypersomnia in adults. This analysis assessed weight changes during LXB treatment in a phase 3 clinical study (NCT03533114).

Methods

Participants 18–75 years of age with idiopathic hypersomnia (treatment naive or taking an alerting agent [with or without SXB] at study entry) began LXB treatment in a 10- to 14-week, open-label, optimized treatment and titration period. After a 2-week stable-dose period (SDP) on their optimized dose of LXB, participants were randomized (1:1) to LXB or placebo for a 2-week, double-blind, randomized withdrawal period, followed by a 24-week open-label extension (OLE).

Results

Study participants (N=154) had a mean (SD) age of 40.3 (13.7) years; baseline mean (SD) weight was 76.9 (18.6) kg, and baseline mean (SD) body mass index (BMI) was 27.1 (5.9) kg/m2. At baseline, 1.3% (2/154) of participants were underweight (BMI <18.5 kg/m2), 40.3% (62/154) of participants had a normal weight (BMI 18.5 to <25 kg/m2), 33.8% (52/154) were overweight (BMI 25 to <30 kg/m2), and 24.7% (38/154) were obese (BMI ≥30 kg/m2). At the end of the SDP, 28.7% (31/108) of participants had weight loss ≥5%. Mean (SD) change in weight at the end of the SDP (n=108) was −2.5 (4.1) kg. Mean (SD) decreases in weight at the end of SDP were numerically greater in participants with higher baseline BMI (normal baseline BMI, −1.8 [3.0] kg; overweight baseline BMI, −2.8 [3.1] kg; obese baseline BMI, −3.2 [5.9] kg).

Conclusion

In this phase 3 clinical trial, adults with idiopathic hypersomnia treated with LXB experienced weight loss, including weight loss ≥5% in 28.7% of participants. Mean weight loss was greater in participants with a higher baseline BMI.

Support (If Any)

Jazz Pharmaceuticals.
0395 Effectiveness and Treatment Optimization Among Participants With Narcolepsy Switching From Sodium Oxybate to Lower-Sodium Oxybate: Interim Data From the SEGUE Study
Authors: Leary Eileen , Kirby Todd , Skowronski Roman , Xu Kevin , Pfister Craig , Macfadden Wayne
Published: May 2022

Introduction

Lower-sodium oxybate (LXB) contains 92% less sodium than sodium oxybate (SXB) and is approved for treating cataplexy or excessive daytime sleepiness in patients with narcolepsy (≥7 years of age) and for treating idiopathic hypersomnia in adults. The SEGUE study examines safety, tolerability, effectiveness, and treatment optimization in participants with narcolepsy transitioning from SXB to LXB.

Methods

Eligible participants in this ongoing, multicenter, open-label study are adults with narcolepsy type 1 or 2 who are on a stable dose (maximum 9 g/night; no single dose >6 g) and regimen (once, twice, or thrice nightly) of SXB. After 2 weeks on a stable SXB dose/regimen (baseline period), participants switch to the same dose/regimen of LXB (intervention period; 6 weeks). If needed, LXB dose/regimen is titrated to optimize efficacy/tolerability. Assessments include the Patient Global Impression of Change (PGIc), a forced preference questionnaire (FPQ), and an ease of switching medication scale (EOSMS; all collected at end of treatment/early discontinuation). An interim analysis (first 24 participants to complete the study) is reported.

Results

A majority of participants were female (54%) and White (92%); mean (SD) age was 45.5 (16.20) years. Starting and ending (end of treatment/early discontinuation) median total nightly doses of LXB were both 9.0 g. Most participants took LXB twice nightly (88% at both time points). Twenty-two participants completed the transition period; mean (SD) time to optimized dose was 1.4 (1.56) days, and median (range) number of changes in dose/regimen was 0.0 (0, 1). At end of treatment/early discontinuation, most participants reported improvement (very much/much/minimal; 57%) or no change (43%) in narcolepsy symptoms on the PGIc, preferred LXB over SXB on the FPQ (86%), and reported that the transition to LXB was easy (easy/extremely easy/not difficult at all) on the EOSMS (91%).

Conclusion

Participants with narcolepsy switched from SXB to LXB with minimal modifications of dose/regimen and reported that the transition process was easy. Efficacy of oxybate treatment was maintained or improved, and most participants preferred LXB over SXB.

Support (If Any)

Jazz Pharmaceuticals.
0398 Is Increased Serum Prolactin Associated with Excessive Daytime Sleepiness? A Proof-of-Concept Analysis
Authors: Mogavero Maria , Cosentino Filomena , Lanuzza Bartolo , Tripodi Mariangela , Lanza Giuseppe , Aricò Debora , DelRosso Lourdes , Pizza Fabio , Plazzi Giuseppe , Ferri Raffaele
Published: May 2022

Introduction

With this study we aimed to: 1) identify subjects with hyperprolactinemia in a clinical sample of patients; 2) compare the neurologic, psychiatric, and sleep conditions found in patients subgrouped by excessive daytime sleepiness (EDS) and hyperprolactinemia; 3) identify patients with hyperprolactinemia and EDS not supported by the presence of any other neurologic, psychiatric, or sleep disorder, or substance/medication use.

Methods

A retrospective chart review of inpatients was carried out in order to identify all patients in whom the prolactin (PRL) serum levels were determined. A total of 130 subjects were retrieved: 55 had increased levels of PRL while the remaining 75 participants had normal PRL levels.

Results

EDS was reported by 32 (58.2%) participants with increased PRL and 34 (45.3%) with normal PRL. Obstructive sleep apnea or other sleep or neurologic/psychiatric conditions could explain EDS in all participants with normal PRL. Among subjects with increased PRL, eight had no other neurologic/psychiatric or sleep disorder (or drug) potentially causing EDS; these participants, at polysomnography, had time in bed, sleep period time, and total sleep time longer than those with EDS associated to another condition.

Conclusion

These findings can be considered as a preliminary indication of a role of hyperprolactinemia in EDS and represent a basis for future controlled studies able to test in a reliable, objective, and methodologically more appropriate way this hypothesis.

Support (If Any)

This study was partially supported by a fund from the Italian Ministry of Health “Ricerca Corrente” (RC n. 2764026) (Drs. Cosentino, Aricò, Lanuzza, Lanza, Tripodi, and Ferri)
0400 Sleep Onset REM Period (SOREMP); Beyond the Diagnostic Marker
Authors: Honda Makoto , Ito Wakako
Published: May 2022

Introduction

Shortened mean sleep latency and multiple Sleep Onset REM Period (SOREMP) on MSLT has been used as a characteristic marker for narcolepsy and incorporated in all editions of International Classification of Sleep Disorders. Epidemiologic studies have shown that SOREMP could occur in general population especially those with sleep insufficiency and shift work. However the physiological meaning of SOREMP besides the diagnostic marker is not well clarified. We searched for subjective and objective sleep variables independently associated with the number of SOREMPs.

Methods

Participants were 769 consecutive sleepy patients or controls who gave written informed consent and underwent PSG followed by MSLT in Seiwa Hosiptal or Koishikawa Tokyo Hospital from October 2014 to November 2021. We excluded those with obvious nocturnal sleep disturbances (AHI≥10, PLMI≥15), with medication affecting sleep and with severe first-night effect at the time of PSG. We analyzed data from resultant 580 participants (male/female=312/268, age 25.3±8.4 years old, BMI 21.6±3.3). They were subdivided into 4 groups according to the number of SOREMPs on MSLT (used as ordinal scale). Subjects with 3 or more SOREMPs were merged into one group to increase number enough for statistical analyses. We dichotomized participants into narcolepsy type 1 (NT1) (n=50) and others (n=530) to adjust the effect of NT1 diagnosis. Epworth Sleepiness Scale (ESS) as well as conventional sleep variables on PSG and MSLT were compared by ANOVA and variables associated with the number of SOREMPs were further analyzed by regression analyses to determine the independent association after adjustment of covariates (age, sex, BMI and dichotomized diagnosis).

Results

Number of SOREMPs on MSLT was positively associated with ESS score (p=0.010), Total Sleep Time (TST) (p=0.03), REM %TST(p<0.001), and negatively associated with Sleep Latency (p<0.01), REM Latency (p<0.001), MSLT mean Sleep Latency (p<0.001) and MSLT REM Latency (p<0.001) and subjective sleep latency on PSG night.

Conclusion

Our data indicate that the number of SOREMPs have physiological significance besides narcolepsy diagnosis. More SOREMPs reflects higher sleep propensity and REM propensity as well as subjective sleepiness. The number of SOREMPs can be a marker reflecting one aspect of sleepiness. Our study will also contribute to better understand the meaning of SOREMP in diagnostic criteria of central disorders of hypersomnolence.

Support (If Any)

This study was partly supported by JSPS KAKENHI Grant Number JP21H02856.
0402 Efficacy of FT218, a Once-Nightly Sodium Oxybate Formulation, in Patients With Narcolepsy: Post-hoc Sensitivity Analyses From the REST-ON Trial
Authors: Kushida Clete , Roth Thomas , Thorpy Michael , Seiden David , Dubow Jordan , Gudeman Jennifer
Published: May 2022

Introduction

In REST-ON, once-nightly sodium oxybate (ON-SXB; FT218) achieved significant improvement (P<0.001) vs placebo for all coprimary endpoints: Maintenance of Wakefulness test (MWT) mean sleep latency, Clinical Global Impression of Improvement (CGI-I) rating, and weekly number of cataplexy attacks (NCA).

Methods

Individuals aged ≥16 years were randomized 1:1 to receive ON-SXB (1 week, 4.5 g; 2 weeks, 6 g; 5 weeks, 7.5 g; 5 weeks, 9 g) or placebo. Post-hoc sensitivity analyses were conducted with methods to handle missing data: completer population; placebo-based multiple imputation (MI) with missing not at random assumption; analysis of covariance (ANCOVA); and tipping point-based MI of worsening values until P>0.05.

Results

Completers (ON-SXB, n=69; placebo, n=79) showed significant improvement (P<0.001) with 6, 7.5, and 9 g ON-SXB vs placebo on all coprimary endpoints; with 9-g dose, mean (95% CI) differences vs placebo were 6.0 min (3.3–8.7) on MWT and –6.6 (–9.6 to –3.6) in NCA; 72.3% and 31.6%, respectively (odds ratio [OR], 5.7 [95% CI: 2.8–11.6]), were CGI-I responders. All ON-SXB doses achieved significant improvement (P<0.001) vs placebo on all coprimary endpoints with placebo-based MI and ANCOVA. With placebo-based MI, mean (95% CI) differences vs placebo (9-g dose) were 5.4 min (2.8–8.0) on MWT and –6.4 (–11.3 to –3.7) in NCA; 63.0% and 28.5%, respectively (OR, 4.3 [95% CI: 2.3–8.0]), were CGI-I responders. With ANCOVA, mean (95% CI) differences vs placebo (9-g dose) were 6.0 min (3.6–8.5) on MWT and –6.4 (–9.0 to –3.8) in NCA; CGI-I rating difference was –1.0 (–1.3 to –0.7). With MWT tipping point MI, between-treatment differences lost significance with worsening of 7.0, 5.2, and 4.3 min from baseline for 6, 7.5, and 9 g, respectively (implausible for 7.5- and 9-g doses). When withdrawals from ON-SXB were imputed as “not improved,” CGI-I remained significant (all 3 doses, P<0.001). Mean NCA remained significant for all 3 doses vs placebo with worsening trajectories imputed; positive results were not tipped over with plausible values.

Conclusion

These results support the robustness of the primary efficacy data for ON-SXB for narcolepsy treatment.

Support (If Any)

Avadel Pharmaceuticals
0418 Use of Actigraphy for the Optimization of the Diagnosis and Treatment of Hypersomnia
Authors: Chen Brian , Wang Lu , Mehra Reena , Shah Vaishal
Published: May 2022

Introduction

Actigraphy and sleep logs are used prior to Mean Sleep Latency Test (MSLT) testing to effectively interpret MSLT. Inaccuracies in sleep logs may inadvertently mask insufficient sleep, thereby resulting in a false positive MSLT. We evaluate the use of actigraphy in comparison to patient-reported sleep logs in the diagnosis and treatment of hypersomnia.

Methods

Retrospective analysis of n=56 patients (average age 39±16.8 years, 19.5% male) who underwent evaluation for hypersomnia with actigraphy, sleep diary, polysomnogram (PSG), and MSLT in 2021 at the Cleveland Clinic was completed. Data was collected from the electronic medical record, actigraphy and polysomnography softwares. Positive MSLT (MSL) was defined as ≤8min. Average total sleep time (TST) from actigraphy and sleep logs were divided into three different time points; inadequate TSTs were defined at ≤8hours and ≤7hours, and invalid TST at ≤6hours. Paired t-test was used to compare TST from actigraphy and sleep diary. Receiver operating characteristic (ROC) analysis was performed to investigate the discrimination of MSLT(≤8min) by total sleep time from actigraphy and sleep logs using area under curve (AUC).

Results

Mean TST did not have a statistically significant difference between actigraphy and sleep logs (7.8±1.3 hours vs. 8.0±1.5 hours, p=0.53). However, on sub-analysis, out of 20 people who reported >8hours average TST on sleep logs, 11 were objectively found to have ≤8hours of average TST on actigraphy (55%). Of the 34 who reported >7hours TST on sleep logs, 8 had ≤7hours on actigraphy (24%). Of the 41 who reported >6hours TST on sleep logs, 1 had ≤6hours on actigraphy (2%). On MSLT, the average MSL was 12.7±5.1min, with 20% of patients with times ≤8min. Actigraphy performs better than sleep logs in discriminating MSL ≤8min (AUC 0.67 vs. 0.61).

Conclusion

Actigraphy is more objective than sleep logs and thus less prone to human recall errors. This study demonstrates the utility of actigraphy in the validation of the MSLT and in the accurate diagnosis of disorders of hypersomnia. In the future, our continued collection of an actigraphy and sleep log database will allow for more detailed analyses including consideration of the influence of medications on these findings.

Support (If Any)
0425 New onset insomnia following COVID-19 infection
Authors: Viereck Matthew , Javaheri Sogol
Published: May 2022

Introduction

Post-COVID neuropsychiatric symptoms have a significant impact on morbidity following COVID-19 infection. We present three patients without a prior history of insomnia symptoms who developed new-onset and chronic insomnia following infection with COVID-19.

Methods

Retrospective chart review was performed on three patients who presented to an ambulatory sleep clinic with complaints of new onset insomnia following COVID-19 infection.

Results

Three patients without a history of prior insomnia developed difficulty initiating or maintaining sleep during or following COVID-19 infection. Patient 1 developed symptoms of insomnia 2 weeks after recovery from COVID-19 infection. Symptoms improved after 5 months with a combination of hydroxyzine and cognitive behavioral therapy for insomnia (CBTi). Patient 2 developed insomnia at the same time as COVID-19 infection and symptoms consisted of sleep onset and maintenance insomnia.Hydroxyzine and trazodone were ineffective. Symptoms improved with zolpidem and CBTi. Patient 3 had a more severe course of COVID-19 infection requiring management in the intensive care unit that coincided with onset of insomnia. He presented to sleep clinic with new insomnia complaints but was also found to have moderate obstructive sleep apnea and periodic limb movements on polysomnography and prior history of restless legs. The patient was treated with a combination of positive airway pressure therapy and a dopamine agonist with plans to follow up to reassess severity of insomnia at future visit.

Conclusion

Three patients without a prior history of insomnia developed insomnia following infection with COVID-19. Management included a combination of CBTi and pharmacotherapy as well as treatment of underlying sleep disorders (OSA, RLS) when applicable. Further work is needed to understand the prevalence of new onset insomnia in patients following COVID-19 infection and best therapeutic approaches in this unique population.

Support (If Any)
0429 Insomnia vs Poor Sleep: Characteristics of Sleep Complaints in a Social Media Sample
Authors: Glidewell Robert , Okun Michele
Published: May 2022

Introduction

There is a tendency for individuals to interpret sleep difficulties as "poor sleep" rather than insomnia. This occurs even though when many individuals describe their symptoms, they often describe symptoms of insomnia. Indeed, they reject the label of insomnia as applying to their specific sleep difficulties. Misinterpreting chronic insomnia as simply "poor sleep" may prevent or delay treatment seeking behavior and thereby prolong/worsen associated negative outcomes. Little is known about the sleep characteristics and rate of chronic insomnia in individuals who interpret their sleep disturbance as “poor sleep.”

Methods

44,439 individuals age 30+ were shown an advertisement on social media with the prompt, "Poor sleep is annoying but insomnia is a serious issue. Take this free 1-minute quiz to learn the difference between insomnia and poor sleep." 1533 clicked on the ad to view the quiz and 468 completed the quiz. We included 449 responses in the current analysis. Nineteen were excluded as no insomnia symptoms were endorsed. The quiz queried DSM-V chronic insomnia diagnostic criteria. After completing the survey, the website supplied respondents with automated feedback and education about their responses.

Results

The quiz did not collect demographic information. However, those who clicked on the ad were 84% female and 87% age 55+. Sixty-nine percent (n=310) of responses met full diagnostic criteria. Reasons for not meeting diagnostic criteria were 13% (n=59) no sleep dissatisfaction, 10% (n=45) symptom frequency <3 nights/week, 6% (n=25) symptom duration <3 months, 7% (n=31) denied daytime symptoms, and 5% (n-21) inadequate opportunity for sleep. 54% (n=244) endorsed short sleep duration (<6 hours) despite adequate opportunity for sleep.

Conclusion

Of community members responding to the advertisement, over 2/3 met full diagnostic criteria for chronic insomnia and over 50% appear to have the more severe phenotype of insomnia with short sleep duration. Formal study of subjective sleep disturbance interpretation may help develop effective methods for communicating with insomnia sufferers who may minimize or not recognize the seriousness of their sleep disturbance.

Support (If Any)

None
0434 The Relationship between Spirituality and Insomnia in Military Soldiers
Authors: Nunez-Cruz Nayeli , Miller Katherine , Brownlow Janeese , Klingaman Elizabeth , Gehrman Philip
Published: May 2022

Introduction

Insomnia is prevalent among military soldiers and contributes to poor physical and mental health outcomes. Spirituality has been found to mitigate mental and physical health complaints; however, there is a dearth of research on its relationship with insomnia, particularly among military soldiers. Therefore, this study examined the associations between spirituality, religiosity, and insomnia in a sample of Army soldiers.

Methods

Data were acquired from the All Army Study of the Army Study to Assess Risk and Resilience in Servicemembers (STARRS; N=21,449; mean age= 28.6; 88.24% male). Participants completed the Brief Insomnia Questionnaire, and current insomnia status was determined by DSM-5 criteria. They also completed questions on religious affiliation, how often they attend religious services, and how religious or spiritual they consider themselves on a 4-point scale (1-Very to 4-Not at all). Chi-Square analyses were used to assess the magnitude of relationships.

Results

A total of 19.45% of this sample had insomnia. Self-reported religious affiliation was more common in those without insomnia (73.5%) than those with insomnia (69.9%; p<.0001). Self-reported spirituality and religiosity were associated with lower rates of insomnia (p<.0001; p<.0001). However, insomnia was associated with higher rates of regular attendance of religious services (29.8% vs. 26.0%; p<.0001).

Conclusion

In this sample of Army servicemembers, insomnia was less prevalent among those with a religious affiliation and those with regular attendance at religious services. In contrast, individuals with insomnia reported themselves to be less religious or spiritual compared to those without insomnia. These findings underline the importance of further research to understand whether spirituality provides any protective effects against insomnia.

Support (If Any)

This publication is based on public use data from Army STARRS (Inter-university Consortium for Political and Social Research, University of Michigan-http://doi.org/10.3886/ICPSR35197-v1), funded by U.S. NIMH-U01MH087981. KEM’s time was supported by the U.S Department of Veterans Affairs, Veterans Health Administration (Clinical Science Research and Development Service – IK2 CX001874). EAK’s time was supported by the U.S Department of Veterans Affairs, Rehabilitation Research and Development Service – 1IK2 RX001836.
0435 The Relationship Between Pathogen Avoidance and Insomnia Symptoms: Results from a Longitudinal Study Conducted During the COVID-19 Pandemic
Authors: Walker Jamie , Makhanova Anastasia , Egeler Mara , Vargas Ivan
Published: May 2022

Introduction

Pathogen avoidance has intensified during the past two years because of fear related to the high transmissibility of SARS-CoV-2. This trend aligns with previous research that found increases in pathogen avoidance as a result of impaired immune system functioning, such as in the case of autoimmune disease. Another link to compromised immunity is the presence of insomnia symptoms, which may interfere with a healthy immune response to pathogens. It is not clear, however, if insomnia could be an immuno-compromising factor that leads to a compensatory increase in pathogen avoidance. Therefore, the purpose of the present study was to explore the relationship between situational pathogen avoidance and insomnia symptoms during the COVID-19 pandemic.

Methods

A national online survey was conducted at two time points: April-June 2020 (baseline) and January-March 2021 (follow-up). Insomnia symptoms were assessed using the Insomnia Severity Index (ISI). Affective, cognitive, and behavioral responses that comprise pathogen avoidance psychology, especially as it pertains to avoidance of potentially pathogenic social stimuli, were assessed with the Situational Pathogen Avoidance (SPA) scale.

Results

2,980 adults (mean age = 47 years) completed both surveys. Overall, the means on the SPA scale at both time points were higher than previously published norms (mean at both timepoints = 5.4), suggesting that average pathogen avoidance increased since the onset of the pandemic. The mean differences in the SPA scale varied by insomnia symptoms (at both time points), with participants who endorsed clinically elevated insomnia (ISI >14) reporting higher pathogen avoidance (baseline, F(1,2972) =10.4, p = 0.001; follow-up, F(1,2918) =26.6, p < 0.001).The mean differences in the SPA scale by insomnia were greater at follow-up compared to baseline (mean difference at baseline = 0.19; mean difference at follow-up = 0.33). This suggests that, compared to the initial months of the pandemic (Apr–June 2020), the relationship between insomnia and situational pathogen avoidance was stronger post-pandemic peak (Jan–Mar 2021).

Conclusion

Our findings suggest that there is a positive correlation between insomnia symptoms and situational pathogen avoidance. Furthermore, results indicated that this relationship became stronger as the pandemic went on.

Support (If Any)

K23HL141581 (PI: Vargas); R25HL10544 (PI: Jean-Louis); K24AG055602 (PI: Perlis)
0437 Psychometric Evaluation of the Insomnia Severity Index in Nurses
Authors: Emert Sarah , Nagy Samantha , Dietch Jessica , Taylor Daniel
Published: May 2022

Introduction

This secondary analysis was conducted to examine the psychometric properties of the Insomnia Severity Index (ISI) in a sample of non-shift working nurses. Insomnia is a common sleep disorder and has been linked to poor physical, psychological, and cognitive outcomes and increased accidents. Unique features of this sample (e.g., long shifts, patient care, quick emergency response) create a need for population-specific validation of the commonly used ISI. Study I assessed convergent and discriminant validity between the ISI, sleep diary, and other sleep and psychosocial measures. Study II assessed the test-retest validity of the ISI.

Methods

Participants (N = 289) were nurses from two regional hospitals in north Texas recruited for a parent study (268 females, M age = 40.67 years; SD = 11.03; 79.9% White) who completed daily sleep diaries and sleep and mental health screeners at four timepoints. Shift workers and participants who did not complete the ISI at baseline were excluded from the analysis.

Results

The ISI had medium to large correlations with measures intended to establish convergent validity including sleep onset latency (r = .41), wake time after sleep onset (r = .40), sleep efficiency (r = -.45), sleep quality (r = .66), and sleep related impairment (r = .67). Examination of ISI items and analogous sleep diary parameters showed small to large correlations (rs = .13-.53). The ISI had small to large correlations with measures intended to establish discriminant validity including nightmares (r = .25), circadian preference (r = -.26), shiftwork-related disorders (r = .09) and PTSD (r = .36), depression (r = .69), anxiety (r = .51), and perceived stress (r = .43). The ISI demonstrated good test-retest reliability from baseline to 1-month (ICC = .88), 6-month (ICC = .77), and 11-month follow up (ICC = .74).

Conclusion

The ISI demonstrated good psychometric properties and is a psychometrically strong measure for the assessment of insomnia severity in nurses. Overlap with psychological symptoms suggests caution while interpreting these constructs.

Support (If Any)

This study was supported by a grant from the National Institute of Allergy and Infectious Diseases, Grant/Award Number: R01AI128359-01.
0440 Subjective Sleep Outcomes with Lemborexant Among Subjects with Insomnia and Clinically Meaningful Decreases on the Insomnia Severity Index
Authors: Roth Thomas , Moline Margaret , Pinner Kate , Yardley Jane , Pappadopulos Elizabeth , Malhotra Manoj
Published: May 2022

Introduction

Lemborexant (LEM) is a dual orexin receptor antagonist approved in multiple countries for the treatment of adults with insomnia. In Study 303 (NCT02952820), LEM provided significant benefit on sleep outcomes including patient-reported (subjective) sleep onset latency (sSOL) and wake after sleep onset (sWASO) versus placebo (PBO). This post-hoc analysis assessed these measures in Insomnia Severity Index (ISI) responders, defined as subjects with clinically meaningful reductions (≥7 points) in ISI total scores (ISI-TS).

Methods

Study 303 was a 12-month, PBO-controlled (first 6mo), randomized, double-blind, phase 3 study in subjects with ISI-TS ≥15 (moderate to severe insomnia). Subjects (n=949; Full Analysis Set [FAS]) received LEM (5mg [LEM5]; 10mg [LEM10]) or PBO for 6mo. Changes from baseline (CFB) in sSOL (min) and sWASO (min) at 6mo were analyzed in ISI responders from the FAS and in subjects with severe insomnia (baseline ISI-TS ≥22), using mixed-effect model repeated measurement analysis.

Results

At 6mo, 175 (LEM5), 151 (LEM10), and 124 (PBO) subjects were ISI responders; of these, 46 (LEM5), 48 (LEM10) and 29 (PBO) had severe insomnia. CFB in the FAS in median sSOL was significantly greater with LEM5 (−21.8) and LEM10 (−28.2) versus PBO (−11.4; both P<0.001). ISI responders also had significantly greater decreases in sSOL with LEM (LEM5: −26.7, P<0.01; LEM10: −32.6, P<0.001) than PBO (−18.0). In ISI responders from the severe insomnia subgroup, greater CFB in median sSOL was observed with LEM10 (−41.4) than with PBO (−32.1; P>0.05), but not with LEM5 (−32.9, P>0.05).Least-squares mean (standard error) CFB in sWASO in the FAS was −46.8(3.7) with LEM5 (P<0.001), −42.0(3.7) with LEM10 (P<0.05), versus −29.3(3.6) with PBO. In ISI responders, CFB in sWASO was greater with LEM10 (−52.7[4.0], P>0.05) and significantly greater with LEM5 (−58.9[3.8], P<0.01) versus PBO (−43.6[4.4]). In ISI responders from the severe insomnia subgroup, greater CFB was observed with LEM5 (−91.6[9.5]) versus PBO (−70.2[11.1]); P>0.05); CFB with LEM10 (−71.4[9.0]) was similar to PBO.

Conclusion

ISI responders including those from the severe insomnia subgroup reported greater CFB in sSOL and sWASO than the FAS that was somewhat dose dependent. LEM generally showed benefit versus PBO.

Support (If Any)

Eisai Inc.
0443 Life Values Expressed by Female Veterans Engaged in an Acceptance and Commitment-based Behavioral Therapy for Primary Insomnia
Authors: Saldaña Kathryn , Revolorio Kaddy , Carlson Gwendolyn , Culver Najwa , Kay Morgan , McGowen Sarah Kate , Song Yeonsu , Martin Jennifer
Published: May 2022

Introduction

Women Veterans disproportionately suffer from insomnia, which negatively impacts health and overall quality of life. Insomnia can result in fewer value-based choices and less engagement in meaningful life activities. This study sought to identify common life values expressed by women Veterans engaged in an acceptance-and commitment-based behavioral therapy for primary insomnia.

Methods

74 female-identifying Veterans (mean age=48.3 years; 47.3% non-Hispanic White, 28.4% Black/African American, 23.0% Hispanic/Latina, 12.2% American Indian/Alaska Native, 5.4% Asian American and 9.5% Other) who met DSM-5 diagnostic criteria for Insomnia disorder were randomly assigned to an acceptance-based behavioral treatment for insomnia called Acceptance of the Behavioral Changes to treat insomnia (ABC-I; compared to a similarly structured group receiving CBT-I). Women in the ABC-I group received 5 weekly, 60-minute sessions containing key components of sleep restriction, stimulus control, and sleep hygiene. In place of traditional cognitive therapy exercises, we incorporated essential components of Acceptance and Commitment Therapy (ACT), such as the identification of values. Outcome measures included qualitative responses of values identified by participants. Qualitative responses were coded by three separate raters who coded participant stated values into five categories: Work/Education, Relationships, Personal Care/Health, Leisure, and Pets.

Results

The three independent coders reached 100% agreement after independent coding and adjudication. The five categories are listed in order of frequency of response: 1) Relationships (n =68); 2) Personal Care/Health (n =51); 3) Work/Education (n =46); 4) Pets (n =12) and; 5) Leisure (n =5).

Conclusion

The current study showed that personal and social relationships are of high importance to women Veterans undergoing behavioral treatment for insomnia, followed by personal care and health, which includes spirituality/religion, and physical and mental health. Findings indicate that incorporating outcomes of insomnia treatment trials that assess relationship quality may prove important in future studies of women Veterans with sleep disorders. Further, identifying common shared values among women Veterans is an important first step in developing and adapting treatments for insomnia that help to improve quality of life.

Support (If Any)

VA HSR&D IIR 13-058-2 and RCS-20-191, NIH K24 HL143055; VA GLAHS GRECC
0448 Self-care trajectories and sleep characteristics in people with heart failure and insomnia
Authors: Conley Samantha , Jeon Sangchoon , OConnell Meghan , Redeker Nancy
Published: May 2022

Introduction

Sleep disturbance is common among people with heart failure (HF) and associated with poor self-care. The purpose of this study, a secondary analysis of data from a randomized controlled trial of the sustained effects of cognitive behavioral therapy for insomnia compared to HF self-management, was to examine the extent to which these interventions improved HF self-care trajectories and the associations between changes in sleep and self-care trajectories.

Methods

We measured changes in self-care maintenance (daily activities), management (symptom management), and confidence (self-efficacy), components of self-care (SC: Self-care of Heart Failure Index) and self-reported sleep characteristics [Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), daytime sleepiness (PROMIS Sleep Impairment)] at baseline and 3, 6, and 12 months post-intervention. We used group-based trajectory modeling to identify self-care trajectories and generalized linear models to identify the associations between changes in sleep and SC trajectories.

Results

We included 175 participants [N = 91 HS; age M = 63 years (12.9); n = 110 (57.1%) male; n = 133 (76.0%) White]. At baseline, SC maintenance, management, and confidence were poor overall [M = 66.3 (16.4); 53.4 (23.8); 68.1 (20.3), respectively]. We identified four self-care trajectories. Class A (poor SC maintenance & management; moderate confidence: N = 47, 26.9%); Class B (low self-care management & confidence, moderate maintenance: N = 68, 38.9%): Class C (high maintenance & management, low confidence; N = 42, 24.0%); Class D (high on all SC: N = 18, 10.3%). There was no significant difference in changes in self-care over time between HS and HH, but both groups improved at 3 and 6 months on self-care maintenance, and self-care management improved at 12 months over baseline (p < .05). Participants in all classes improved on insomnia severity and sleepiness (p< .05) over time.

Conclusion

We found that insomnia and sleepiness improved even those with poor self-care suggesting that adequate HF SC may not be needed to improve insomnia. Future research is needed to determine if a combination of HF self-management and CBT-I improves SC trajectories in this population.

Support (If Any)

R01NR016191 and P20NR014126
0449 Correlations Between Sleep Parameters and ISI Total Score in Subjects with Moderate to Severe Insomnia Treated with Lemborexant
Authors: Moline Margaret , Roth Thomas , Pinner Kate , Yardley Jane , Pappadopulos Elizabeth , Malhotra Manoj
Published: May 2022

Introduction

Lemborexant (LEM) is a dual orexin receptor antagonist (DORA) approved in multiple countries for the treatment of adults with insomnia. In Study 303 (NCT02952820), LEM provided significant benefit on subject-reported sleep measures versus placebo (PBO). This post hoc analysis investigated whether changes from baseline in sleep parameters with LEM are correlated with insomnia disorder severity.

Methods

Study 303 was a randomized, double-blind, PBO-controlled (first 6mo [Period 1]), phase 3 study. During Period 1, subjects received LEM 5mg (LEM5), LEM 10mg (LEM10), or PBO. During Period 2 (second 6mo), LEM subjects continued their assigned dose and PBO subjects were rerandomized to LEM5 or LEM10 (rerandomized subjects not reported here). The correlation between changes in subject-reported sleep parameters (sleep onset latency [sSOL], wake after sleep onset [sWASO], sleep efficiency [sSE], total sleep time [sTST]) and insomnia disorder severity, as assessed by the Insomnia Severity Index total score (ISI-TS) were evaluated in the Full Analysis Set (FAS; ISI-TS ≥15) and in a subgroup of subjects with severe (ISI-TS ≥22 at baseline) insomnia over 12mo for LEM and over 6mo for PBO.

Results

Among 949 (PBO=318; LEM5=316; LEM10=315) subjects, 223 (PBO=65; LEM5=84; LEM10=74) had severe insomnia at baseline. Within each sleep parameter and severity group, baseline values were similar across treatments. Overall, strong to very strong correlations were observed between changes from baseline in sleep parameters and decrease in ISI-TS, regardless of treatment, as determined by correlation coefficients for sSOL (LEM5=0.973 [P=0.0053]; LEM10=0.997 [P=0.0002]; PBO=0.844 [P=0.361]), sSE (LEM5=–0.937 [P=0.0188]; LEM10=–0.992 [P=0.0008]; PBO=–0.950 [P=0.2018]), sWASO (LEM5=0.937 [P=0.0187]; LEM10=0.996 [P=0.0003]; PBO=0.979 [P=0.1299]), and sTST (LEM5=–0.876 [P=0.0515]; LEM10=–0.974 [P=0.0050]; PBO=–0.933 [P=0.2346]). Strong to very strong correlations were also observed in subjects with severe insomnia: sSOL (LEM5=0.818 [P=0.0904]; LEM10=0.823 [P=0.0868]; PBO=0.828 [P=0.3788]), sSE (LEM5=–0.860 [P=0.0616]; LEM10=–0.975 [P=0.0048]; PBO=–0.961 [P=0.1792]), sWASO (LEM5=0.871 [P=0.0544]; LEM10=0.936 [P=0.0194]; PBO=0.875 [P=0.3213]), and sTST (LEM5=–0.843 [P=0.0729]; LEM10=–0.969 [P=0.0095]; PBO=–0.974 [P=0.1449]).

Conclusion

Across the study period, changes from baseline in reported nocturnal sleep parameters correlated with reductions in severity of insomnia disorder regardless of insomnia severity at baseline.

Support (If Any)

Eisai Inc.
0455 The Insomnia Daytime Symptoms and Impacts Questionnaire: An Analysis of Clinically Meaningful Change Using Phase 3 Clinical Trial Data
Authors: Phillips-Beyer Andrea , Kawata Ariane , Kleinman Leah , Kinter Dalma Seboek
Published: May 2022

Introduction

The Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ) is a new validated patientreported outcome (PRO) instrument evaluating daytime functioning in people with insomnia. It comprises 14 items grouped into 3 domains: Alert/Cognition, Mood, and Sleepiness. To further explore the ability of the IDSIQ to capture clinically meaningful changes in daytime functioning resulting from treatment, we estimated withinsubject changes in IDSIQ scores using phase 3 trial data.

Methods

A randomized double-blind placebocontrolled trial of daridorexant in adults with insomnia (NCT03545191), in which subjects completed the IDSIQ daily during treatment, provided data for blinded analyses. Spearman correlations were calculated for changes in IDSIQ scores and potential anchors: Insomnia Severity Index, Patient Global Assessment of Disease Severity, Patient Global Impression of Severity, and Patient Global Impression of Change, applying a prespecified threshold of 0.30 (moderate association). Anchor-based analyses of weekly average IDSIQ total and domain scores were used to estimate responder definitions (RDs). The various RD estimates were triangulated to identify values where they converged. Distribution-based and receiver operating characteristic analyses calculated standard error of measurement (SEM), 0.5 standard deviation (SD), and Youden’s index as supportive evidence for anchor-based RD estimates.

Results

The analysis included 930 subjects (18-88 years). Score change correlations for the potential anchors and IDSIQ at month 1 (0.36–0.44) and month 3 (0.45–0.57) were all >0.30. Triangulation of mean IDSIQ score changes in subjects with clinically relevant improvement on the different anchors supported RD thresholds for clinically meaningful change of 17 points for the IDSIQ total score, 9 points for the Alert/Cognition domain, 4 points for the Mood domain, and 4 points for the Sleepiness domain. SEM and 0.5 SD values were within the ranges of anchor-based IDSIQ score changes, and Youden’s index was maximized or near-maximized when the RD estimates were used as thresholds for identifying responders based on the anchors.

Conclusion

The IDSIQ is sensitive to changes in patients who experience daytime impacts of insomnia and can be used to assess treatment efficacy on daytime functioning in patients with insomnia.

Support (If Any)

This work was funded by Idorsia Pharmaceuticals Ltd.
0459 The First Step of a Triaged Stepped-Care Delivery of CBTI: A Preliminary Report from the RESTING Study
Authors: Manber Rachel , Kim Jane , Simpson Norah , Tully Isabelle , Tutek Joshua , Dietch Jessica , Gumport Niki , Rosas Lisa , Zulmann Donna , Palaniappan Latha
Published: May 2022

Introduction

Both online and therapist-led cognitive behavioral therapy for insomnia (CBTI) are effective. However, little is known about the optimal combination and sequence to maximize both access and effectiveness. The RESTING study is a randomized controlled trial assessing the effectiveness of a triaged stepped care approach (STEPPPED-CARE) to delivering CBTI that utilizes a simple five-item Checklist to determine which patients should start treatment with online versus therapist-led CBTI.

Methods

Adults 50 years and older (N=222; age = 63.1 (SD=8.2); 74% female) with insomnia disorder who met the study’s broad eligibility criteria were randomized to STEPPED-CARE (N=112) or to ONLINE-ONLY CBTI (N=110). Participants in the STEPPED-CARE arm who responded yes to any Checklist item (Checklist Yes) received therapist-led CBTI (N=61); the rest (Checklist NO) received the online CBTI program Sleepio (N=62). All participants in the ONLINE-ONLY arm received Sleepio. Randomization was stratified by Checklist (Yes/No). We used mixed effects models with an Arm by Checklist by Time interaction to determine the effect of STEPPED-CARE on insomnia severity two months after randomization, using the Insomnia Severity Index (ISI).

Results

A mixed effects model revealed an Arm by Checklist by Time interaction (p=0.013). Post-hoc analyses within stratum revealed that within the Checklist Yes stratum, participants assigned to STEPPED-CARE (all received therapist-led treatment) experienced significantly greater reduction in ISI (from 16.2 (SD=1.2) to 11.6 (SD=2.1)) than those assigned to ONLINE-ONLY (from 16.2 (SD=1.2) to 13.7 (SD=1.4); p=0.007, d=0.22). Among those in the Checklist No stratum, there was no Arm difference in ISI change. The combined mean ISI in the Checklist No group was 14.8 (0.8) at baseline and 11.2 (0.8) at 2 months. Overall, remission of insomnia (ISI<8) was attained by 23% of those in STEPPED-CARE and 15% of those assigned to ONLINE-ONLY.

Conclusion

Results support the efficacy of the first step of a triaged stepped care approach to CBTI among middle age and older adults with insomnia disorder. Given minimal exclusion criteria, results from the current trial are generalizable to individuals with comorbidities and those who use hypnotics, offering a way to triage patients to digital or therapist-led CBTI effectively and efficiently.

Support (If Any)

R01AG057500
0461 Does “TIB” Differentiate Between Good Sleepers and Subjects That Develop Acute or Chronic Insomnia? A 2nd Analyses
Authors: Perlis Michael , Morales Knashawn , Grandner Michael , Posner Donn , Vargas Ivan , Seewald Mark , Muench Alexandria , Boyle Julia , Ellis Jason
Published: May 2022

Introduction

According to the 3P model of insomnia, the variable that mediates the transition from acute to chronic insomnia is “sleep extension” (the behavioral tendency to expand sleep opportunity to compensate for sleep loss). Recently, this proposition was prospectively evaluated by assessing how Time-in-Bed (TIB) varied, week-by-week, relative to the incidence of acute insomnia in four groups, those that: maintained good sleep (GS,n=911), recovered good sleep (AI-REC,n=244); had persistent poor sleep (AI-PPS,n=65); and developed chronic insomnia (AI-CI,n=23)). Significant differences for pre-to-post acute insomnia TIB were not detected for the insomnia groups (as compared to one another or as compared to GSs). The observed trends suggested that the increases in TIB observed were minor (< 15 min overall, at 2 weeks, and at 12 weeks post AI). In the present analysis, a more granular evaluation was undertaken to assess whether sleep extension occurs on the nights following poor sleep bouts.

Methods

The same data set and subject groups were modeled for TIB occurring on the night following a poor night’s sleep (≥ 30 min for SL or WASO or EMA) for the post-acute insomnia interval (by weekday and weekend). Linear mixed effects model was used to account for up to 1 year of repeated nights per subject.

Results

During the weekdays, the groups did not differ with respect to TIB following a poor nights’ sleep. On average, the four groups (including good sleepers) did not vary TIB by more than 5 minutes. During the weekends, all four groups tended to restrict TIB. In this instance, AI-CI subjects restricted TIB the least (AI-CI -17.2[5.11]; (GS -25.7[SE 1.58]; AI-PPS -27.6[6.1]; AI-REC -32.3[1.9].

Conclusion

As with the prior analysis, the transition to CI does not appear to be triggered by sleep extension. In the present analysis there is some evidence to support the notion that AI-CI subjects restrict TIB less. This counterintuitive finding needs to be further evaluated taking into account sleep timing. That is, time-to-bed and time-out-of-bed may vary (show the attempt to extend sleep opportunity) while TIB does not change appreciably (owing to limitations in sleep ability [plasticity]).

Support (If Any)

Support: R01AG041783;K24AG055602;R01AT003332