bluuebunny/crossref_metadata_2025_split 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

Abstract

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

Abstract

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&lt;0.0001), component I scores (LS mean difference [95% CI], −3.9 [−4.9, −2.9]; nominal P&lt;0.0001), and component II scores (LS mean difference [95% CI], −7.8 [−9.6, −5.9]; nominal P&lt;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

Abstract

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 &lt;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

Abstract

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 &lt; 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

Abstract

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

Abstract

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&lt;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&lt;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&lt;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.
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513 Young patients with hypersomnia at Tufts Medical Center
Authors: Oster Joel , Jost-Price Emma , Tucker Matthew , Grover Aarti 
Published: May 2021

Abstract

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

Abstract

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 &lt;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

Abstract

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 &lt;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.
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522 Reduced sympatho-vagal responses to orthostatic stress in drug-naïve idiopathic restless legs syndrome
Authors: Shin Jung-won 
Published: May 2021

Abstract

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):