bluuebunny/crossref_metadata_2025 huggingface dataset:
493 Weight Loss With FT218, a Once-Nightly Sodium Oxybate Formulation for the Treatment of Narcolepsy: Post Hoc Analysis From REST-ON
Authors: Morse Anne Marie , Roy Asim , Dubow Jordan , Seiden David , Bogan Richard
Published: May 2021

Introduction

Patients with narcolepsy are more likely to be obese compared with healthy controls. FT218 is an investigational once-nightly sodium oxybate formulation for the treatment of narcolepsy. Here, we report on changes in weight-related clinical values with FT218 treatment in patients with narcolepsy.

Methods

This was a randomized, double-blind, placebo-controlled multicenter study in patients with narcolepsy ≥16 years old. Patients were not excluded based on baseline weight or body mass index (BMI). Patients were randomized 1:1 to receive FT218 or matching placebo: 4.5 g/night for 1 week, 6.0 g/night for 2 weeks, 7.5 g/night for 5 weeks, and 9.0 g/night for 5 weeks (maximum treatment duration, 13 weeks). Weight and BMI were measured at baseline and study end. LS mean difference in BMI between FT218 and placebo was analyzed using analysis of covariance.

Results

A total of 107 patients received FT218 and 105 patients received placebo. At baseline, mean (SD) weight was 81.2 (20.8) kg in the FT218 treatment group and 82.1 (22.5) kg in the placebo treatment group. At end of study (week 13), mean (SD) weight was 80.9 (21.9) kg in the FT218 treatment group and 82.25 (21.6) in the placebo treatment group. At week 13, mean (SD) change in weight from baseline was –1.29 (3.6) kg for FT218 and 0.19 (2.6) kg for placebo; 17.5% of patients receiving FT218 vs 3.8% of patients receiving placebo had ≥5% weight loss. At baseline, mean (SD) BMI was 28.1 (7.8) kg/m2 in the FT218 treatment group and 28.2 (6.6) kg/m2 in the placebo treatment group. At study end (week 13), LS mean (SE) change from baseline in BMI was ‒0.51 (0.13) kg/m2 for patients receiving FT218 and 0.08 (0.13) kg/m2 for patients receiving placebo (LS mean difference [95% CI], ‒0.59 [‒0.95 to ‒0.23]; P=0.001). FT218 was generally well tolerated.

Conclusion

Patients receiving FT218 experienced a significantly greater decrease in weight and BMI vs placebo. These results suggest that treatment with once-nightly FT218 may provide weight-related benefit for patients with narcolepsy and comorbid weight gain.

Support (if any)

Avadel Pharmaceuticals
495 Efficacy of Lower-Sodium Oxybate on Idiopathic Hypersomnia, Measured by the Idiopathic Hypersomnia Severity Scale
Authors: Foldvary-Schaefer Nancy , Arnulf Isabelle , Šonka Karel , Chandler Patricia , Chen Abby , Chen Dan , Dauvilliers Yves
Published: May 2021

Introduction

Idiopathic hypersomnia (IH) is a rare central hypersomnolence disorder with no approved treatment, characterized by excessive daytime sleepiness, prolonged sleep time, and sleep inertia. The Idiopathic Hypersomnia Severity Scale (IHSS) is a 14-item, self-reported questionnaire that assesses severity of IH symptoms, including symptoms related to night/inertia (component I) and day/performance (component II). Individual IHSS items measure symptom frequency, intensity, and consequences using 3- or 4-point Likert scales, yielding a total score (range, 0–50), comprising component I (range, 0–16) and component II (range, 0–34). Higher scores indicate worse symptoms. In a recent clinical trial of the efficacy and safety of lower-sodium oxybate (LXB; Xywav™) for the treatment of IH, the IHSS was a key efficacy measure.

Methods

Eligible participants 18–75 years of age with IH began LXB treatment with an open-label treatment titration and optimization period (OLTTOP; 10–14 weeks), followed by a 2-week stable-dose period (SDP). Participants were randomized to placebo or continued LXB treatment during a 2-week, double-blind, randomized withdrawal period (DBRWP). The IHSS was completed at baseline, during OLTTOP (weeks 1, 4, and 8), and at the end of OLTTOP, SDP, and DBRWP. Change in IHSS total score from SDP to DBRWP was a key secondary endpoint.

Results

The efficacy population included 115 participants (mean±SD age, 41±14 years; 71% female). At baseline and the end of SDP, respectively, mean±SD IHSS scores were 31.6±8.3 and 15.3±8.5 for total score, 10.3±3.6 and 5.4±2.8 for component I (night/inertia), and 21.2±5.8 and 9.9±6.5 for component II (day/performance). Worsening from SDP to DBRWP was observed in patients randomized to placebo compared with LXB in IHSS total scores (estimated median difference [95% CI], −12.0 [−15.0, −8.0]; significant P<0.0001), component I scores (LS mean difference [95% CI], −3.9 [−4.9, −2.9]; nominal P<0.0001), and component II scores (LS mean difference [95% CI], −7.8 [−9.6, −5.9]; nominal P<0.0001). Results on all individual IHSS items reflected an improvement with LXB treatment over time during OLTTOP, which remained consistent during SDP.

Conclusion

These results support the efficacy of LXB for the treatment of IH symptoms, as assessed with the IHSS.

Support (if any)

Jazz Pharmaceuticals
504 Assessment of the Clinical Benefits of Pitolisant on Excessive Daytime Sleepiness and Cataplexy in Adults With Narcolepsy
Authors: Meskill Gerard , Davis Craig , Zarycranski Donna , Doliba Markiyan , Schwartz Jean-Charles , Dayno Jeffrey
Published: May 2021

Introduction

When evaluating results of randomized, placebo-controlled trials, the clinical impact of a treatment can be assessed using number needed to treat (NNT; number of patients that need to be treated to achieve a specific outcome for one person) and effect size (magnitude of drug–placebo difference on outcome measures). Lower NNTs indicate a more robust effect; NNT <10 is generally considered to represent a meaningful between-treatment difference. This analysis evaluated NNTs and effect sizes for pitolisant in the treatment of excessive daytime sleepiness (EDS) and cataplexy, using data from 7- or 8-week, randomized, placebo-controlled studies.

Methods

Patients in both studies experienced EDS at study baseline (Epworth Sleepiness Scale [ESS] score ≥14 in HARMONY-1 and ≥12 in HARMONY-CTP); patients in HARMONY-CTP also experienced ≥3 cataplexy attacks/week. Pitolisant was titrated over a 3-week period to a maximum potential dose of 35.6 mg/day, after which the dose remained stable. End-of-treatment assessments occurred at Week 8 in HARMONY-1 and Week 7 in HARMONY-CTP. Treatment response was defined for EDS based on ESS score reduction (≥3-point decrease from baseline or final score ≤10) and for cataplexy as ≥50% reduction from baseline to stable-dose period in the weekly rate of cataplexy (WRC). NNTs were calculated as the inverse of the drug–placebo difference in response rates. Effect sizes for change from baseline in mean ESS score and WRC were calculated using Cohens’ d. Missing values were imputed using a last-observation-carried-forward approach.

Results

Treatment response for EDS was observed in HARMONY-1 (pitolisant, n=31; placebo, n=30) in 67.7% of pitolisant-treated versus 43.3% of placebo-treated patients (NNT=5) and in HARMONY-CTP (pitolisant, n=54, placebo, n=51) in 68.6% versus 34.0% of patients, respectively (NNT=3). In HARMONY-CTP, treatment response for cataplexy was observed in 66.7% of pitolisant-treated patients versus 25.5% of placebo-treated patients (NNT=3). Effect sizes were 0.61 (HARMONY-1) and 0.86 (HARMONY-CTP) based on ESS change scores, and 0.86 (HARMONY-CTP) based on change in WRC.

Conclusion

The low NNTs and large effect sizes observed in this analysis provide further evidence that pitolisant produces meaningful clinical benefits in the treatment of EDS and cataplexy in adults with narcolepsy.

Support (if any)

Bioprojet Pharma and Harmony Biosciences, LLC.
506 Samelisant: Baseline Characteristics from a Phase 2 Study Evaluating Efficacy and Safety in Patients with Narcolepsy
Authors: Nirogi Ramakrishna , Ravula Jyothsna , Jayarajan Pradeep , Jetta Satish , Bhyrapuneni Gopinadh , Benade Vijay , Shinde Anil , Goyal Vinod
Published: May 2021

Introduction

histamine H3 receptor (H3R) antagonists/ inverse agonists increase histaminergic neurotransmission and offer a therapeutic option for the treatment of narcolepsy. Samelisant (SUVN-G3031) is a potent and selective H3R inverse agonist exhibited selectivity over 70 other targets. Samelisant showed wake-promoting and anticataplectic effects in orexin knockout mice suggesting its potential therapeutic utility in the treatment of EDS and cataplexy associated with narcolepsy. Safety and tolerability studies in animals and healthy humans suggested a favorable risk/benefit profile.

Methods

The current study is a 2 week treatment, multicenter, double-blind, placebo controlled, parallel-group study in patients with Narcolepsy with or without Cataplexy. Eligibility criteria include age between 18 to 50 years old, an ESS score of ≥ 12; and mean MWT time of < 12 minutes and a confirm diagnosis of narcolepsy as per ICSD-3. Further, the randomization will be stratified according to type of narcolepsy (Type-1 or Type-2). Each subject will receive either placebo or study drug once daily for 2 weeks in a fixed ratio of 1:1:1. The primary efficacy endpoint is change in maintenance of wakefulness test (MWT) score from baseline to week 2. Key secondary endpoints include change from baseline to week 2 in ESS and an improvement in CGI-S scores. Safety will be monitored by medical monitor and by an independent data safety monitoring committee. Baseline clinical and demographic data for the currently enrolled study is summarized descriptively. Since the study is blinded, a breakdown of baseline characteristics by treatment group will not be available until after completion.

Results

As of data cutoff date of Dec 20, 2020, a total of 54 subjects were completed in the study. The median age of subjects was 30 years (range: 18 - 50 years) with mean BMI of 28.6 (range: 18.3 - 43.1 kg/m2). Overall, 74% of subjects were female and 83% were Caucasian. Mean (SD) baseline values of MWT and ESS are 5.65 (3.5) and 16.7 (2.5), respectively.

Conclusion

Baseline characteristics are consistent with the general narcolepsy population. The study is currently enrolling the subjects with Narcolepsy with or without Cataplexy, and the Data readout is expected in the second half of 2021.

Support (if any):
509 Health-Related Quality of Life in Narcolepsy: A Systematic Review and Meta-Analysis
Authors: Tadrous Ragy , O’Rourke Deirdre , Broderick Julie , Mockler David
Published: May 2021

Introduction

Narcolepsy is a neurological condition that has been associated with considerable detriment to daily life including impaired quality of life, occupational and academic difficulties and adversely affected social and personal relationships. To date, there has been no systematic analysis of the literature regarding health-related quality of life (HRQoL) in Narcolepsy. This systematic review aimed to examine the impact of narcolepsy on HRQoL, measured through standardised HRQoL questionnaires such as the Short Form 36 (SF36).

Methods

Medline, Embase, Cinahl and Web of Science were searched for studies which investigated HRQoL in adults with narcolepsy. Studies were reviewed independently by two reviewers, and a random-effects meta-analysis was performed. The methodological quality of the included studies was assessed using a modified version of the Joanna Briggs Institute Checklist for Analytical Cross Sectional Studies tool. The impact of study variables and characteristics on HRQoL was assessed using Spearman’s Correlation analyses with adjusted r2 values.

Results

A total of 30 studies were eligible for inclusion in the review. Additionally, meta-analyses were conducted for the SF36 and the EQ5D. The SF36 meta-analysis identified that the pooled mean scores for the Physical Component Summary (45.91) were less affected than the Mental Component Summary (42.98). The HRQoL of people with narcolepsy was compared to general population norms (US, UK, France and Norway) and to people with chronic diseases including multiple sclerosis, diabetes, and epilepsy.

Conclusion

People with narcolepsy report significant impairments in HRQoL when compared to the general population and other chronic health conditions including epilepsy, multiple sclerosis, diabetes and hypertension, especially concerning their mental wellbeing. Further research is warranted to identify the longitudinal effects of narcolepsy on HRQoL and to develop a narcolepsy-specific HRQoL tool.

Support (if any)

This review was completed as part of Mr Ragy Tadrous’ Master of Science (MSc) degree in Trinity College Dublin. This degree was co-sponsored by the Physiotherapy Department in St. James’s Hospital, Dublin.
512 Confirmatory Factor Analysis of the Sleep Inertia Questionnaire in a Clinical Sample with Sleep Disorders
Authors: Puzino Kristina , Calhoun Susan , Harvey Allison , Fernandez-Mendoza Julio
Published: May 2021

Introduction

The Sleep Inertia Questionnaire (SIQ) was developed and validated in patients with mood disorders to evaluate difficulties with becoming fully awake after nighttime sleep or daytime naps in a multidimensional manner. However, few data are available regarding its psychometric properties in clinical samples with sleep disorders.

Methods

211 patients (43.0±16.4 years old, 68% female, 17% minority) evaluated at the Behavioral Sleep Medicine (BSM) program of Penn State Health Sleep Research & Treatment Center completed the SIQ. All patients were diagnosed using ICSD-3 criteria, with 111 receiving a diagnosis of chronic insomnia disorder (CID), 48 of a central disorder of hypersomnolence (CDH), and 52 of other sleep disorders (OSD). Structural equation modelling was used to conduct confirmatory factor analysis (CFA) of the SIQ.

Results

CFA supported four SIQ dimensions of “physiological”, “cognitive”, “emotional” and “response to” (RSI) sleep inertia with adequate goodness-of-fit (TLI=0.90, CFI=0.91, GFI=0.85, RMSEA=0.08). Internal consistency was high (α=0.94), including that of its dimensions (physiological α=0.89, cognitive α=0.94, emotional α=0.67, RSI α=0.78). Dimension inter-correlations were moderate to high (r=0.42–0.93, p<0.01), indicating good construct validity. Convergent validity showed moderate correlations with Epworth sleepiness scale (ESS) scores (r=0.38) and large correlations with Flinders fatigue scale (FFS) scores (r=0.65). Criterion validity showed significantly (p<0.01) higher scores in subjects with CDH (69.0±16.6) as compared to those with CID (54.4±18.3) or OSD (58.5±20.0). A SIQ cut-off score ≥57.5 provided a sensitivity/specificity of 0.77/0.65, while a cut-off score ≥61.5 provided a sensitivity/specificity of 0.71/0.70 to identify CDH vs. ESS<10 (AUC=0.76).

Conclusion

The SIQ shows satisfactory indices of reliability and construct validity in a clinically-diverse sleep disorders sample. Its criterion validity is supported by its divergent association with hypersomnia vs. insomnia disorders, as well as its adequate sensitivity/specificity to identify patients with CDH. The SIQ can help clinicians easily assess the complex dimensionality of sleep inertia and target behavioral sleep treatments. Future studies should confirm the best SIQ cut-off score by including good sleeping controls, while clinical studies should determine its minimal clinically important difference after pharmacological or behavioral treatments.

Support (if any):
513 Young patients with hypersomnia at Tufts Medical Center
Authors: Oster Joel , Jost-Price Emma , Tucker Matthew , Grover Aarti
Published: May 2021

Introduction

Young people with hypersomnia (up to 30 years old) represent unique clinical patients that are relatively unstudied. This population has complex presentations, may have increased utilization of medical resources, and have additional and or untreated comorbid conditions such as mild OSA (Obstructive Sleep Apnea). This project looks to characterize and inventory clinical variables of this subset of sleep medicine patients at Tufts Medical Center. In addition, we seek to tabulate management of these patients in order to specifically delineate whether or not treating mild OSA in this group resulted in clinical improvement.

Methods

After IRB approval, a retrospective database was used to search for patients up to age 30 with comorbid hypersomnia diagnoses from 5/1/2015 to 12/2020. De-indentified datasets, including multiple clinical variables and demographics were analyzed and compared to an age-matched control group of patients who also included an OSA diagnosis.

Results

Various clinical and demographic data sets were collected in the hypersomnia patient population to characterize the quality and nature of their sleep and hospital utilization. Our preliminary results for this sub-population of 96 patients have found that on average these patients had 2.16 visits to our medical center with some outliers with as many as 6–10 visits in a two-year period from the initial contact. This group had a mean WASO (Wake After Sleep Onset) of 48.95 minutes, a mean sleep latency of 8.56 minutes, and a mean amount of stage N1 sleep of 25.6 minutes (6.4%). Further research will be done to compare these values and more to a similar population with OSA.

Conclusion

Our retrospective review identifies clinically important data relevant to the sleep quality, patient management, and resource utilization of young patients with hypersomnia. Further research with a comparison to a control group with OSA may identify important differences or nuances between these groups.

Support (if any)

None
515 Excessive daytime sleepiness: beyond the Epworth Sleepiness Scale results from a population-based study
Authors: Treptow Erika , Ohayon Maurice , Piovesan Ronaldo , Oliveira Luciana , Drager Luciano , Andersen Monica , Tufik Sergio , Poyares Dalva
Published: May 2021

Introduction

Excessive daytime sleepiness (EDS) is a common symptom present in several clinical, mental and sleep disorders. However, its subjective metrics have been criticized in the literature due to lack of association with disorder severity, or disagreement with objective measures. Epworth Sleepiness Scale (ESS) is a widely used questionnaire to evaluate EDS, however it may not be sufficient as a sole measure to identify cases of somnolence in the general population. Study objectives: To investigate the association between EDS with socio-demographic, body composition and PSG measures in the general population of São Paulo, Brazil.

Methods

1,042 participants from a population-based epidemiological study underwent full in-lab PSG, questionnaires (ESS, fatigue, quality of life, depression and anxiety scales), bio impedance, socio-demographic and anthropometric measures at baseline and in the follow-up 9 years later. A univariate linear regression analysis including the whole sample (baseline and follow-up) was performed to analyze predictors of EDS and ESS score in the follow-up was the dependent variable. All variables with a p-value <0.15 were included in an exploratory factor analysis (principal component analysis with Varimax rotation) to assess the factorial structure of EDS.

Results

The results supported a five-factorial structure associated with EDS as follows: Factor 1 - Quality of life (Physical and Psychological domains of WHOQOL), Factor 2 – Fatigue (questions from Chalder Fatigue Scale concerning weakness, tiredness, lack of energy and less strength in the muscles), Factor 3 – PSG – sleep duration (wake after sleep onset, sleep efficiency, total time spent awake), Factor 4 – PSG – sleep structure (arousal index, N1 and N3 duration), Factor 5 – Body composition (body mass index). PSG variables related to sleep disordered breathing and movement disorders were not associated with EDS.

Conclusion

EDS measured by ESS was associated with domains other than sleep disorders in the general population. ESS metrics was significantly associated with fatigue and sleep duration.

Support (if any)

Associação Fundo Incentivo à Pesquisa (AFIP), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES – Processo 88887.468428/2019-00).
517 Factorial Structure of Hypersomnolence as Measured by the Epworth Sleepiness Scale
Authors: Ohayon Maurice , Poyares Dalva , Cote Marie-Lise
Published: May 2021

Introduction

Hypersomnolence, or excessive sleepiness, is highly prevalent in the general population. It can be a cause or a consequence of several sleep, psychiatric disorders or physical diseases. However, self-report tools to assess hypersomnolence are relatively limited; apart the Epworth Sleepiness Scale (ESS), there is little choice to measure hypersomnolence. Our aim is to examine the association between hypersomnolence with health, psychiatric disorders and sleep in the general population

Methods

The initial study was carried with 15,929 individuals from 15 US States. The longitudinal study was carried on in eight of these states. A total of 12,218 subjects were interviewed by phone during the first wave (W1) and 10,930 at the second wave (W2) three years apart. The analyses were carried on the subjects who participated in both interviews (N=10,930). A univariate linear regression analysis including the whole sample (baseline and follow-up) was performed to analyze predictors of hypersomnolence and ESS score in the follow-up was the dependent variable. All variables with a p-value <0.15 were included in an exploratory factor analysis (principal component analysis with Varimax rotation) to assess the factorial structure of hypersomnolence.

Results

Our results support a three-factor structure associated with hypersomnolence. The first factor explained 24.9% of the variance and grouped together presence of medical conditions, psychiatric disorders, body mass index and sleep-disordered breathing. The second factor explained 12.9% of the variance and grouped together napping, fatigue (as measured the Fatigue Severity Scale) and poor quality of life. Finally, the third factor grouped together disrupted sleep and sleep duration and explained 11.7% of the variance.

Conclusion

Hypersomnolence as measured by the ESS is associated with pathologies unrelated to sleep disorders in the general population. The first factor is mostly related to health factors while the second factor might be related to hypersomnia and the third factor to insomnia.

Support (if any):
522 Reduced sympatho-vagal responses to orthostatic stress in drug-naïve idiopathic restless legs syndrome
Authors: Shin Jung-won
Published: May 2021

Introduction

Restless legs syndrome (RLS) is a risk factor for cardiovascular disease (CVD). However, there are no electrophysiological biomarkers to assess this risk. This study aimed to evaluate the heart rate variability (HRV) and autonomic control of cardiovascular reflexes in the supine and standing positions in patients with RLS during wakefulness.

Methods

Fourteen drug-naïve RLS patients (12 women, 2 men; mean age: 42.14 ± 7.81 years) and 10 healthy controls underwent tests for blood pressure, heart rate when in the supine-rest and standing positions, deep breathing, and handgrip in controlled laboratory conditions. Five-minute R-R intervals in each position were collected and analyzed for HRV.

Results

Cardiovascular changes during deep breathing and isometric handgrip maneuvers were normal and similar between the two groups. The normalized unit of the low frequency component and low frequency/high frequency (LH/HF) ratio during standing were lower in the RLS patients than in the controls. LF/HF ratio responses during positional change from supine-rest to standing were significantly reduced in the RLS patients (RLS patients: mean ± SD, 2.94 ± 3.11; controls: 7.51 ± 5.58; P = 0.042). In Spearman’s rank correlation, ISI and PSQI were associated with HRV parameters.

Conclusion

The RLS patients showed reduced sympatho-vagal responses during positional change from supine-rest to standing during wakefulness, and RLS-related sleep disturbance was an important contributing factor for autonomic nervous system dysfunction. Reduced HRV responses during wakefulness might be a good predictor for CVD risk.

Support (if any):
524 NAPS
Authors: Elliott Jonathan , Lim Miranda , Keil Allison , Avidan Alon , Bliwise Donald , Gagnon Jean-Francois , Howell Michael , Huddleston Daniel , McCleland Jennifer , St. Louis Erik , Postuma Ronald , Videnovic Aleksandar , Boeve Bradley , Ju Yo-El
Published: May 2021

Introduction

Rapid Eye Movement (REM) Sleep Behavior Disorder (RBD) is characterized by a lack of muscle atonia during REM sleep with dream enactment. RBD is regarded as a prodromal synucleinopathy as a high proportion of patients eventually phenoconvert to Parkinson’s Disease and related synucleinopathies, suggesting RBD may be an early non-motor symptom of disease. Accordingly, patients with RBD are ideally situated to test potential therapeutic interventions to prevent phenoconversion to synucleinopathy. However, RBD itself, and associated patient registries, are rare. The North American Prodromal Synucleinopathy Consortium (formed in 2018) establishes a multisite registry of RBD patients with standardized neurological, neuropsychiatric, and neuropsychological assessments and biomarker collection. The present work reports baseline characteristics of this RBD patient database at its current state.

Methods

Seven participating sites have contributed n=170 polysomnographically-confirmed RBD patients. Data includes past medical and family history, self-report questionnaires, and neuropsychological, motor, sensory, and autonomic function testing. Additionally, all subjects have contributed blood, and a subset of subjects have contributed cerebrospinal fluid samples to the National Centralized Repository for Alzheimer’s Disease and Related Dementias for future analysis. A final diagnosis for each subject was determined through an adjudication process by NAPS Consortium PIs; subjects were categorized as ether: 1) isolated RBD, 2) RBD+, 3) Early Symptomatic, or 4) Phenoconverted.

Results

Of the n=170 subjects, there were n=39 isolated RBD, n=81 RBD+, n=45 Early Symptomatic, and n=4 Phenoconverted. Isolated RBD subjects have no other early neurodegeneration signs/symptoms, those with RBD+ have at least one other identifiable early/mild symptom. The early symptomatic group includes those with mild or subjective cognitive impairment, pure autonomic failure, or possible multiple systems atrophy. The Phenoconverted group consists of those with Dementia with Lew Bodies, Dementia NOS, Parkinson’s Disease, or Parkinson’s NOS. The distribution of impairment across the 5 major domains (motor, cognitive, autonomic, sensory, and psychiatric) for each of the 4 groups will be described.

Conclusion

This interim analysis presents data on n=170 subjects. The target enrollment is n=360 across the 7 original sites plus 3 new sites. Future work will follow these subjects longitudinally to assess rates and predictors of phenoconversion.

Support (if any)

NIH NIA R34 AG056639 (YJ, BB)
525 A population-based study of phenoconversion to parkinsonism from REM sleep behavior: a Population-based Study in the CLSA
Authors: Yao Chun , Zolfaghari Sheida , Chaudhuri Paramita Saha , Pelletier Amelie , Wolfson Christina , Postuma Ronald
Published: May 2021

Introduction

To date, studies have estimated the phenoconversion rate from sleep clinics, using polysomnography proven RBD. However, no population-based estimates have been reported, testing to what degree possible RBD, screened by questionnaire is associated with increased risk of neurodegeneration.

Methods

We included those aged 45–85 years, living in one of 10 Canadian provinces in between 2012–2015 (at the baseline), recruited via three population-based sampling methods. Dream enactment behavior/possible RBD was screened using the RBD1Q single question-questionnaire. De-novo parkinsonism was defined as free of pre-existing diagnosis at the baseline with a ‘new’ diagnosis at the follow-up (205–2019). Relative risk (log-binomial regression), hazard ratio (Cox regression), incidence rate (Poisson regression) between the affected group and the symptom naïve group were assessed, adjusting for age and sex (and total years of education and language).

Results

Overall, 58 participants phenoconverted into parkinsonism and 53 into dementia at the follow-up (mean intervals=3.06±0.37 years). Participants with dream enactment behavior had 2.75 times higher risk to phenoconvert into parkinsonism than the symptom-free. Similarly, those with dream enactment behavior at the baseline possessed higher risk to screening positive of parkinsonism. No difference in time to phenoconversion was found between groups, The results remained robust after excluding non-RBD related symptoms, such as apnea and non-REM sleep parasomnia.

Conclusion

Compared to symptom-free, those with pRBD had higher risk to developing parkinsonism in near future.

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533 Characteristics of patients with REM sleep without atonia (RSWA)/persistent periodic limb movements of sleep (PLMS) in REM sleep
Authors: Barker Lina , Tippmann-Peikert Maja
Published: May 2021

Introduction

While RSWA in REM sleep behavior disorder (RBD) is associated with male sex, age > 50 years, alpha-synucleinopathies, and narcolepsy, the characteristics of patients with RSWA/PLMS in REM sleep (RSWA/PLMS-REM) without dream enactment behaviors are unexplored. The aim of this study was to compare the demographics, comorbidities and concomitant medication use between RSWA/PLMS-REM patients and non-RSWA/non-PLMS-REM controls. Based on anecdotal clinical observations we hypothesized that these patients are more commonly young, women, have psychiatric or neurological diseases, and use antidepressants.

Methods

We conducted a retrospective review of the Mayo Clinic electronic medical record to identify all patients with RSWA/ PLMS-REM between November 2018 and November 2020. After excluding all patients with RBD, restless legs syndrome, narcolepsy and RSWA/non-PLMS-REM we identified 27 patients. All PSGs were reviewed to calculate the periodic limb movement index per hour of REM sleep (REM-PLMI). We also identified a covenience sample of 15 non-RSWA controls, reviewed their PSGs and calculated REM-PLMI.

Results

The mean REM-PLMI of patients with RSWA was 64+/-8.3 (SEM)/hour versus 1+/-0.6 (SEM)/hours in non-RSWA controls (p< 0.001). Patients with RSWA/PLMS-REM and non-RSWA controls had similar age and gender, 62 +/- 3 (SEM) versus 58 +/-3 (SEM) years and 81% versus 87% men, respectively. However psychiatric diagnosis, neurological disorders and antidepressants use was more common among RSWA/PLMS-REM patients compared to non-RSWA controls, p=0.0002, p=0.0035 and p=0.0074, respectively. (Fisher’s Exact Test)

Conclusion

Psychiatric diagnosis, neurological disorders and antidepressant use are more common among RSWA/PLM-REM patients compared to non-RSWA controls. Further research to determine the implications of a diagnosis of RSWA/PLMS-REM for the future development of alpha-synucleinopathies are needed and currently ongoing.

Support (if any):
540 Age Trends in Sleep Across the Lifespan: Findings from the Pittsburgh Lifespan Sleep Databank
Authors: Wallace Meredith , Kissel Nicholas , Hall Martica , Germain Anne , Matthews Karen , Troxel Wendy , Franzen Peter , Buysse Daniel , Roecklein Kathryn , Gunn Heather , Hasler Brant , Goldstein Tina , McMakin Dana , Szigethy Eva , Soehner Adriane
Published: May 2021

Introduction

Sleep continuously changes over the human lifespan and it does so across multiple dimensions, including duration, timing, efficiency, and variability. Although studies focused on specific developmental periods have shown age-related changes in sleep, methodological differences make it difficult to synthesize information across studies to fully understand precisely when these sleep changes occur. Our goal was to use individual-level actigraphy and self-report sleep data from a single site to characterize age trends and sex differences in actigraphy and self-report sleep dimensions across the healthy human lifespan. To accomplish this goal, we developed the Pittsburgh Lifespan Sleep Databank (PLSD), a large aggregate databank of participants from sleep research studies conducted at the University of Pittsburgh.

Methods

In the present analysis, we included N=1,070 PLSD participants from 21 studies without a major psychiatric, sleep, or medical condition. We used Generalized Additive Models to examine flexible, potentially non-linear relationships between age and sleep dimensions (actigraphy and self-report duration, efficiency, and timing; actigraphy variability) from ages 10 to 87. We also examined whether these sleep characteristics differed by sex across the lifespan.

Results

The most dramatic age-related trends were observed in sleep timing. Actigraphy and self-report sleep onset time shifted later between ages 10–18 and then shifted earlier again during the 20s. Actigraphy and self-report wake-up time also shifted earlier during the mid-20s through late 30s. Self-report duration became shorter from approximately ages 10–20. Self-report sleep efficiency and actigraphy variability both decreased over the entire lifespan. Relative to males, females tended to have earlier self-report sleep onset, higher actigraphy sleep efficiency, and longer actigraphy duration.

Conclusion

By focusing on lifespan sleep rather than specific age segments of the samples, we can provide a unified assessment of age-related changes and sex differences from childhood through older adulthood. An understanding of age trends and sex differences in sleep in healthy individuals – and explicating the timing and nature of these difference – can be used to identify periods of sleep-related risk or resilience and guide intervention efforts.

Support (if any)

University of Pittsburgh Clinical and Translational Science Institute (UL1TR001857).
541 Cognitive Hyperarousal, Sleep Problems and Temperament Linked to Impaired Maternal-Infant Bonding
Authors: Arnett Lily , Kalmbach David , O’Brien Louise , Pitts D’Angela , Harb Nicholas , Drake Christopher
Published: May 2021

Introduction

Emerging evidence links maternal and infant sleep problems to impairments in the mother-to-infant bond, but the independence and directionality of these associations remain unclear. The present study characterized concurrent and prospective effects of maternal sleep disturbances and poor infant sleep on the mother-infant relationship. As common sequalae of problematic sleep, nocturnal cognitive hyperarousal and daytime sleepiness were investigated as facilitating mechanisms.

Methods

Sociodemographic information and clinical symptoms were measured prenatally then weekly across the first two postpartum months in 67 women. Participants reported insomnia symptoms, sleep duration, snoring, daytime sleepiness, nocturnal cognitive arousal (broadly focused and perinatal-specific), perseverative thinking, depression, infant colic, infant sleep quality, and mother-infant relationship quality. Mixed effects models were conducted to test hypotheses.

Results

Prenatal snoring and weak maternal-fetal attachment augured poorer postpartum bonding. Poor infant sleep was associated with increased odds for maternal insomnia and short sleep. Impairments in the mother-to-infant bond were linked to maternal insomnia, nocturnal perinatal-focused rumination, daytime sleepiness, depression, and poor infant sleep. Postnatal insomnia predicted future decreases in mother-infant relationship quality, and nocturnal cognitive hyperarousal partially mediated this association.

Conclusion

Both maternal and infant sleep problems were associated with impairments in mother-to-infant bonding, independent of the effects of maternal depression and difficult infant temperament. Perseverative thinking at night, particularly on infant-related concerns, was linked to impaired bonding, rejection and anger, and infant-focused anxiety. Improving maternal and infant sleep, as well as maternal cognitive-emotional regulation, may improve the maternal-to-infant bond.

Support (if any)

This work was funded by the American Academy of Sleep Medicine (198-FP-18, PI: Kalmbach). Dr. Cheng’s effort was supported by the National Heart, Lung, and Blood Institute (K23 HL138166, PI: Cheng).
548 Predicting Perceived Functional Limitation in Midlife and Older Adulthood: The Role of Sleep and Perceived Control
Authors: Williams Claire , Ghose Sarah , Reid Morgan , Sabet Sahar , MacPherson Ashley , Dautovich Natalie , Dzierzewski Joseph
Published: May 2021

Introduction

Functional limitations become increasingly common and debilitating as individuals age, potentially impacting several facets of well-being. As such, it is important to understand malleable factors that may potentially impact functional limitation outcomes. Both sleep and perceived control have been linked to the development of functional limitation. The current study sought to clarify the unique contributions of both sleep quality and perceived control to functional limitation status in middle-aged and older adults.

Methods

Data from the second wave of the Midlife in the United States study were used for the current study. Participants included 527 participants (59.9% female, Mage=59.83 years, SD=9.75 years) who completed measures of functional limitation levels (Functional Status Questionnaire), subjective sleep quality (Pittsburg Sleep Quality Index), and perceived control (MIDI Sense of Control Scales). A hierarchical regression analysis was conducted to examine sleep quality and perceived control as predictors in a unique model for predicting functional limitation. Demographic variables of age, gender, and race were used as covariates in study analyses.

Results

The overall model predicted 19.0% of the variance in functional limitation levels. Sleep quality was significantly associated with self-reported functional limitation (β=-.27, p<.001) over and above perceived control (β=.20, p<.001). Specifically, findings indicate that worse sleep quality is associated with increased functional limitation, while higher levels of perceived control are associated with lower levels of functional limitation.

Conclusion

Though perceived control is known to be associated with functional limitation status, the present study suggests a unique effect of sleep quality on functional limitation even after accounting for perceived control. Due to the potential for negative effects of functional limitation in middle-aged to older adults, it is important to identify and target constructs for research and intervention related to the development of these limitations. Care models for individuals who report experiencing functional limitations may benefit from targeting sleep health and control beliefs in intervention and assessment.

Support (if any):
550 Laryngomalacia and obstructive sleep apnea in infants with PWS
Authors: Powell Weston , Wrede Joanna , Salehi Parisa
Published: May 2021

Introduction

Growth hormone (GH) improves tone, body composition, development, and growth in infants with Prader-Willi Syndrome (PWS). Concerns about sudden death following GH initiation and worsening obstructive sleep apnea (OSA) in children with PWS resulted in guidelines for polysomnography (PSG) evaluation before and after starting GH. We review novel evidence of laryngomalacia as a mechanism for this worsening of OSA and describe the incidence of laryngomalacia in this patient population.

Methods

A retrospective review of infants and children seen at the Seattle Children’s PWS clinic between October 2014 and May 2020 who had undergone polysomnography (PSG) before and after growth hormone initiation was performed. Findings on otolaryngology evaluation via flexible fiberoptic laryngoscopy (FFL) or drug-induced sleep endoscopy were reviewed to characterize obstruction, diagnosis of laryngomalacia, and response to surgical intervention.

Results

A total of 28 cases were identified. 12 (41%) were evaluated with FFL between ages 4 and 21 months old (median 5) for noisy breathing, worsening or persistent OSA, or dysphagia. Out of these, 9 (75% of FFL, 31% of total) were diagnosed with laryngomalacia. Children with laryngomalacia were more likely to have worsening of OSA after GH initiation. Surgical interventions including supraglottoplasty or adenotonsillectomy led to improvement in OSA in 86% of children who had worsening after GH initiation.

Conclusion

Worsening OSA after GH initiation is seen in 38% of patients with PWS. Laryngomalacia is a common comorbid condition and more frequent in those with worsening OSA after GH initiation that is amenable to targeted surgical intervention.

Support (if any):
552 Impact of Adenotonsillectomy on Growth Trajectories in Preschool Children with Mild Obstructive Sleep Apnea
Authors: Kevat Ajay , Chawla Jasneek , Bernard Anne , Harris Margaret-Anne , Heussler Helen , Black Robert , Waters Karen
Published: May 2021

Introduction

Adenotonsillectomy forms part of first-line management for pediatric obstructive sleep apnea (OSA). In nonrandomized studies of preschool-aged children, it is associated with postoperative weight gain. Being overweight or obese in childhood is a predictor of cardiovascular and metabolic disease in later life. Using longitudinal data from a multicenter randomised controlled trial, we assessed the impact of adenotonsillectomy on growth trajectory in preschool-aged children with mild-moderate OSA. Secondary aims were to assess the influence of social factors and baseline polysomnography parameters on growth trajectory.

Methods

A total of 190 children (aged 3–5 years) with obstructive apnea hypopnea index ≤10 were randomly assigned to early (within 2 months) or routine (12-month wait) adenotonsillectomy. Anthropometry and polysomnography were performed at baseline, 12-month and 24-month timepoints for 126 children. Social risk factors were recorded using a questionnaire. Baseline characteristics were compared using a Mann-Whitney or t-test for continuous variables, and Fisher’s exact test for categorical variables. Data were analyzed using linear mixed modelling.

Results

Demographic and polysomnographic parameters were similar between groups at baseline. Baseline body mass index (BMI) z-score was 0.52 for both groups. For BMI z-score, there was a significant increase in the early surgery group between 0 and 12 months (0.4, 95%CI 0.1–0.8) but not from 12–24 months. For the routine surgery group, there was a significant BMI z-score increase following surgery between 12 and 24 months (0.45, 95%CI 0.1–0.8), but not from 0–12 months. Final BMI z-score was similar between the two groups. Findings for weight-for-age z-score were similar to the abovementioned findings for BMI z-score. Height-for-age z-score was not significantly different between different timepoints or intervention groups. Children with an unemployed primary income earner had a higher BMI z-score than those with a full-time employed income earner. No other social risk or polysomnography parameters were statistically significant.

Conclusion

This study provides randomized controlled trial evidence of notable weight increase in preschool children with milder spectrum OSA that occurs in the months immediately following adenotonsillectomy. For children undergoing adenotonsillectomy, counselling regarding nutritional intake and exercise alongside weight monitoring should be considered, especially for those already at risk of becoming overweight or obese.

Support (if any):
556 Lost to Follow-Up: Post-Operative Polysomnography in High-Risk, Pediatric OSAs
Authors: Long Benjamin , Arora Subodh , McKinlay Alex , Foster Shannon , Hansen Shana
Published: May 2021

Introduction

Post-operative polysomnography (PSG) is recommended in certain pediatric populations at risk for residual sleep disordered breathing: moderate to severe obstructive sleep apnea syndrome (OSAS), obesity, craniofacial abnormalities, and neurologic disorders. In light of multiple stakeholders involved in follow-up management, variability in completion of a post-operative PSG may exist. We hypothesize that patients with isolated severe OSAS or severe plus a co-morbidity will have greater incidence of a post-operative PSG.

Methods

A chart review of 373 pediatric patients revealed 67 patients who met inclusion criteria for our high-risk cohort. Chart review included the presence of an ENT, Primary Care, or Sleep Medicine encounter, time to follow-up, the presence of a post-operative PSG, time to post-operative PSG, and the presence of an annual follow-up with any provider.

Results

Although 83% of our cohort followed-up with any provider, only 31% completed a post-operative PSG. Patients consistently followed-up with ENT 6–8 weeks postoperatively (76%) and haphazardly followed-up with primary care (38%). All patients with a Sleep Medicine follow-up (19%, n=13) completed a post-operative PSG, with 11 of the 13 occurring within 1 year from surgery. There was no significant difference across isolated moderate, isolated severe, or moderate/severe with a comorbidity for incidence of follow-up by specialty, annual follow-up, or post-operative PSG completion. However, patients with isolated severe (AHI >10) completed a PSG on average 13.5 weeks post-operatively which was significantly sooner than 36.2 weeks for isolated moderate OSA (p=0.04).

Conclusion

Although Sleep Medicine providers may consistently follow AASM practice parameters, variability exists for which patients return to complete a post-operative PSG. Severity of OSAS or presence of a concerning co-morbidity does not seem to correlate with acquiring a postoperative PSG. An inconsistent standard across disciplines may contribute to this discrepancy. These findings will inform future quality improvement discussions with key stakeholders. In light of this baseline assessment, we plan to recommend a standardized, multi-disciplinary care pathway for the management of high-risk, pediatric OSAS.

Support (if any)

None
557 Nasal cavity narrowing in pediatric obstructive sleep apnea
Authors: Cielo Christopher , Vasisht Shubha , Stefanovski Darko , Whelan Rachel , McDonough Joseph , Tapia Ignacio
Published: May 2021

Introduction

The contribution of nasal cavity narrowing to obstructive sleep apnea (OSA) in children has not been well-defined. Acoustic rhinometry is a non-invasive technique that uses acoustic pulses to measure nasal cavity cross-sectional area (CSA) at defined distances from the tip of the naris. This study evaluated the relationship between nasal cavity CSA and OSA in children. We hypothesized that OSA severity would correlate with reduced nasal CSA.

Methods

Children 5–12 years of age with OSA underwent polysomnography and acoustic rhinometry at baseline and after 3 months and 12 months of growth as part of a randomized controlled trial. Statistical analysis of the nasal cavity CSA up to 6 cm from the tip of the naris was performed using mixed-effects linear regression model with visit month, age at visit, trial number, OSA severity, and side (left or right naris), and statistical interaction between OAHI category and distance from the tip of the nose as a fixed effect and the random effects set on the level of individual subject. Least significant differences were used to account for multiple comparisons. An unbiased approach using latent class analysis was used to determine OSA severity categories based on obstructive apnea hypopnea index (OAHI). Post-hoc analysis was used assess the model adjusted (marginal) means and pairwise effects.

Results

112 participants completed testing (50% male, aged 7.9±2.1 years). Median (IQR) OAHI for subjects with mild OSA (n=69) was 4.4/hr (3.2), moderate OSA (n=35) was 9.7/hr (7.1), and severe OSA (n=8) was 21.3/hr (17.2). There was a significant difference in linear trend for nasal cavity narrowing of the CSA between patients with mild vs. moderate OSA, p=0.023. There was no difference in nasal cavity narrowing between the severe group and other groups, likely due to the small sample size of this group.

Conclusion

There is a difference in the anterior nasal cavity narrowing between children with mild OSA and moderate OSA. In addition to structural narrowing from adenotonsillar hypertrophy, this may be another contributor to pediatric OSA.

Support (if any)

R01 HL120909 K23 HL135346 K01 HL130719