bluuebunny/crossref_metadata_2025_split huggingface dataset:
0760 SUVN-G3031, A Potent And Selective Histamine H3 Receptor Inverse Agonist: Safety, Tolerability And Pharmacokinetics Following Single And Multiple Ascending Doses In Healthy Adult Subjects
Authors: Bhyrapuneni G , Goyal V , Pandey S , Muddana N , Palacharla R , Ajjala D , Ravula J , Jetta S , Badange R , Benade V , Nirogi R 
Published: May 2020

Abstract

Introduction
SUVN-G3031 is a potent and selective histamine H3 receptor inverse agonist currently being developed for the treatment of narcolepsy. SUVN-G3031 produced robust wake promoting and anticataplectic effects in animal model relevant to the disease. This supports its therapeutic utility in the treatment of sleep related disorders like narcolepsy with and without cataplexy.

Methods
Two Phase 1 studies were conducted to assess safety, tolerability and pharmacokinetics (PK) of SUVN-G3031. In the first study, single ascending doses of 0.1 mg to 20 mg SUVN-G3031 were administered to healthy subjects. For multiple ascending dose cohorts, doses of 1 mg to 6 mg were administered for 14 days. In the second Phase 1 study, effects of food, gender and age on the PK of SUVN-G3031 were assessed.

Results
SUVN-G3031 absorbed rapidly following single oral administration and the exposures (Cmax and AUC) were dose proportional at the tested doses between 0.1 mg to 20 mg. SUVN-G3031 attained steady state on day six and achieved projected efficacy concentrations following repeated administrations. Food, gender and age had no effect on pharmacokinetics of SUVN-G3031. SUVN-G3031 was well tolerated up to 20 mg/ day single dose and 6 mg repeated dose in healthy adult subjects. There were no serious adverse events reported by any subject during Phase 1 studies.

Conclusion
SUVN-G3031 was well tolerated in humans with adequate plasma exposures for efficacy and has favorable pharmacokinetics suitable for once a day oral administration. SUVN-G3031 is currently being evaluated in a Phase 2 study as monotherapy for the treatment of narcolepsy with and without cataplexy (ClinicalTrials.gov Identifier: NCT04072380).

Support
None
0774 Factors Associated With The Continuous Use Of Psychotropic Treatments For Narcolepsy
Authors: Ohayon M M , Krystal A D , Black J , Shapiro C M , Sullivan S , Swick T J , Wells C C 
Published: May 2020

Abstract

Introduction
Narcolepsy is a debilitating disorder characterized by excessive sleepiness and cataplexy episodes. There is no cure for this disease. Current treatments focus on controlling the symptoms with CNS stimulants for sleepiness and antidepressants and/or CNS depressants for cataplexy. This study examines the factors that can contribute to the cessation of narcolepsy treatment.

Methods
The study includes 291 narcoleptic individuals who were interviewed twice, approximately five to seven years apart, in Wave 1 (W1) and Wave 2 (W2). Telephone interviews were conducted with the help of the Sleep-EVAL system; narcolepsy individuals were initially evaluated and diagnosed by a Sleep Specialist.

Results
At W1, 49.2% of narcoleptic individuals were taking a CNS stimulant; at W2, 37% of narcoleptic individuals were taking a CNS stimulant. The use was chronic (i.e., present at W2 and W1) for 52.7% of the W2 subjects. CNS depressants were used by 19.1% at W1 and 17% at W2. Of the W1 subjects, 67.6% still reported using CNS depressants at W2. In terms of antidepressants, 38.6% and 29.6% of subjects reported using these medications at W1 and W2 respectively. Of those taking antidepressants at W2, 58.9% reported chronic use (ie, were also on antidepressants at W1). At least one of the aforementioned medication classes was used by 72% of participants at W1 and 56.1% at W2. Chronicity of nocturnal awakenings (RR: 2.7), the frequency of cataplexy episodes (RR: 2.3) and the chronicity of hypnopompic hallucinations (RR: 2.8) were associated with long-term use of narcolepsy treatment.

Conclusion
Narcolepsy treatments are mostly taken to long term. Some narcoleptics individuals were able to reduce or stop treatment either because the intensity of symptoms decreased or because they developed coping mechanisms to deal with the symptoms.

Support
NIH (R01NS044199), the Arrillaga Foundation and Jazz Pharmaceuticals Inc.
0787 Autonomic Dysfunction and Phenoconversion in Idiopathic/Isolated REM Sleep Behavior Disorder
Authors: McCarter S , Gehrking T , St. Louis E , Suarez M , Boeve B , Silber M , Low P , Singer W 
Published: May 2020

Abstract

Introduction
REM-sleep behavior disorder (RBD) is a common finding among patients with synucleinopathies. We aimed to determine the degree of autonomic dysfunction in patients presenting with idiopathic RBD (iRBD), and the predictive value of autonomic dysfunction for phenoconversion to a defined neurodegenerative disease.

Methods
We searched our electronic medical record for patients diagnosed with iRBD who also underwent standardized autonomic function testing within 6 months of iRBD diagnosis, and who had clinical follow-up of at least 3 years following iRBD diagnosis. Patients who received a diagnosis of phenoconversion within 3 months of autonomic testing were excluded. The composite autonomic severity score (CASS) was derived and compared between phenoconverters and non-converters using chi-square and Wilcoxon rank-sum tests.

Results
We identified 18 patients who fulfilled in- and exclusion criteria. Average age at autonomic testing was 67 ± 6.6 years. Twelve (67%) patients phenoconverted during the follow-up period; 6 developed PD, the other 6 DLB. Fifteen (83%) patients had at least mild autonomic dysfunction. There were no significant differences between overall converters and non-converters in total CASS or CASS subscores. However, iRBD patients who developed DLB had significantly higher total and cardiovagal CASS scores compared with those who developed PD (p &lt;0.05), and a trend for higher adrenergic CASS scores compared to those who developed PD and those who did not phenoconvert (p=0.08 for each).

Conclusion
Autonomic dysfunction was seen in 83% of iRBD patients, and more severe baseline cardiovagal and adrenergic autonomic dysfunction in iRBD was associated with phenoconversion to DLB but not PD. Prospective studies are needed to confirm the value of autonomic testing for predicting phenoconversion and disease phenotype in iRBD.

Support
0794 Reduction in Restless Legs Syndrome Symptoms with Non-Invasive Peripheral Nerve Stimulation
Authors: Charlesworth J D , Baker F C , Kolotovska V , Adlou B , de Zambotti M , Ismail M , Raghunathan S , Singh H , Buchfuhrer M J 
Published: May 2020

Abstract

Introduction
Restless Legs Syndrome (RLS) is a sensorimotor neurological condition characterized by an uncontrollable urge to move the legs that interferes with falling and staying asleep. For the over 5 million Americans with clinically significant RLS, these symptoms occur multiple nights per week, significantly impair quality of life, increase the prevalence of depression and anxiety, and increase suicide risk. FDA-approved medications for RLS are associated with progressively worsening RLS symptoms and numerous adverse events, whereas existing medical device treatments have limited efficacy.

Methods
We evaluated a novel neurostimulation intervention for RLS developed by Noctrix Health; electrical stimulation was applied non-invasively and bilaterally to the peroneal nerve of patients with moderate-to-severe primary RLS. Stimulation parameters were engineered to maximize therapeutic efficacy while minimizing interference with sleep. To assess the therapeutic efficacy of this technique, we conducted a multi-site randomized patient-blinded crossover trial comparing active neurostimulation treatment to a sham device. Following a lab visit for calibration, optimization, and training, each patient was instructed to self-administer each treatment - active and sham - for 14 consecutive nights at home.

Results
Active neurostimulation treatment resulted in a clinically significant reduction in RLS severity of 4.2 points on the International RLS Rating Scale (IRLS) relative to sham (P&lt;0.01), comparable to FDA-approved medications. Moreover, 79% of patients demonstrated a clinically significant improvement on the Clinical Global Impressions-Improvement scale (CGI-I) compared to 7% for sham (P&lt;0.01).

Conclusion
To our knowledge, this is the first sham-controlled study demonstrating a clinically significant reduction in RLS severity resulting from a non-pharmacological intervention. This therapeutic effect was sustained over 2-weeks of in-home patient-administered usage, indicating consistent efficacy. A medical device based on this technology could be a promising alternative or complement to medications.

Support
Funding was provided by Noctrix Health, Inc.
0798 “Uncovering My Feet Alleviates My Restless Legs”: Impact of Different Activities and Conditions on Restless Legs Symptoms
Authors: Karroum E G , Leu-Semenescu S , Amdur R , Arnulf I 
Published: May 2020

Abstract

Introduction
The restless legs syndrome (RLS) is a resting wake state disorder with inactivity/decreased movement as an aggravating factor and activity/increased movement as an alleviating factor. Other activities and conditions may impact RLS symptoms but have not been systematically studied.

Methods
Fifty-six patients with primary severe RLS (age: 64.1±11.3; 66% women) responded about the effect of 20 activities/conditions on their RLS symptoms. Responses were assigned a numerical value: Aggravation (-1), No effect/Don’t know (0), Alleviation (+1), with calculating a mean effect score for each activity/condition and using a sign test to determine if that score was significantly above or below zero (no effect). Responses were further analyzed based on age, age at RLS onset, duration of RLS, RLS severity, gender, Familial/Non-familial RLS, and Painful/Non-Painful RLS. Association of continuous variables and categorical variables with each activity/condition was examined using Spearman correlation test and Fisher exact test, respectively. Bonferroni p threshold was set at p=0.00036.

Results
Activities/conditions with significant (p&lt;0.0001) positive mean effect scores were: Feet uncovering (0.70); Leg massaging (0.63); Cold showers (0.54); and Manual activities (0.46). Activities with significant negative mean effect scores were: Vehicle passenger (-0.80); Show attendance (-0.70); Bedsheets weight on legs (-0.57); Watching TV (-0.54); High ambient temperature (-0.45); During meals (-0.39) (all p&lt;0.0001); and Bedsheets rubbing on legs (-0.34; p=0.0002). Activities/conditions with no significant (all p&gt;0.00036) mean effect scores were: Driving (0.00); Gambling (0.02); Professional activities (0.13); Hot showers (0.13); Using computer (0.14); Low ambient temperature (0.21); Sexual activities (0.27); Mental activities (0.29); and Sports activities (0.34). There was no significant association between each activity/condition and age, age at RLS onset, duration of RLS, RLS severity, gender, Familial/Non-familial RLS, or Painful/Non-Painful RLS.

Conclusion
There is a wide range of impact of different activities/conditions on RLS symptoms. These could be further considered in the non-pharmacological treatment or prevention of RLS symptoms.

Support
This study was not funded.
0807 NREM Parasomnias: Retrospective Analysis Of Treatment And Outcomes
Authors: Limbekar N , Pham J , Yusuf H , Budhiraja R , Javaheri S , Epstein L J , Pavlova M 
Published: May 2020

Abstract

Introduction
NREM parasomnias are relatively common among children and sometimes persist in adulthood. These behaviors may result in injury or have negative impacts on functioning and quality of life thus necessitating treatment. The treatment is challenging given the lack of evidence for frequently used medications such as benzodiazepines (BDZ) or tricyclic antidepressants (TCA). The aim of this retrospective analysis is to determine the most frequently prescribed medications for treatment of NREM parasomnias and evaluate reported outcomes.

Methods
We performed a retrospective chart review of all patients with NREM parasomnia diagnosed within BWH clinics examining the date of diagnosis, date of starting therapy, comorbidities, type of medication prescribed, and the reported change in symptoms or side effects at the individual’s follow-up visits.

Results
From 2012 to 2019, 123 patients (64 females, 59 male) at BWH clinics received the diagnosis of NREM parasomnia, including sleepwalking and night terrors. Mean age was 44. Comorbidities included depression=16, anxiety=32, seizures=6, RLS=9, epilepsy=5, insomnia=29, and OSA=57. Initial treatment included safety counseling (72), BDZ (7), TCA (4), and treatment of comorbidity (23). Treatment of OSA only (n=15) was effective in 66% (n=10) and 33% were lost to follow up. Of those with OSA treatment plus BDZ (n=6), treatment was effective in 50% (n=3). Of those receiving BDZ only (n=7), treatment was effective in 43%. Of those receiving Melatonin (8),treatment was effective among 62.5% (n=5). TCAS (n=4) were effective in 3 patients (75%). Treatment of comorbid conditions without pharmacotherapy (23) was effective in 35% (n=8) while the remaining 65% (n=15) were lost to follow up.

Conclusion
Treating comorbid conditions such as OSA, insomnia, RLS, depression, and anxiety is a frequent treatment strategy. Additional pharmacologic treatment most commonly includes melatonin, BDZs, and TCAs.

Support
None
0808 High Density EEG Correlates Of NREM Sleep Parasomnia Episodes
Authors: Valomon A , Nakamura K P , De Cuntis I , Kummerow E , Bazalakova M , Plante D T , Riedner B A , Jones S G , Tononi G , Boly M 
Published: May 2020

Abstract

Introduction
Parasomnia episodes (PE) consist of abnormal behaviors during sleep. Using high-density EEG (HDEEG), we sought to quantify topographical differences in spectral power during PE in comparison to wake and sleep.

Methods
17 adult subjects with a history of NREM sleep parasomnia underwent 256-electrode HDEEG recordings during recovery sleep after 25h of sleep deprivation. PE occurred either spontaneously or when triggered by a sound. Data preprocessing of PE, sleep and wake data included filtering at 1-25 Hz, careful epoch and channel selection, and adaptive mixture independent component analysis (AMICA). We compared topographies of delta (slow wave activity, or SWA) and theta power, alpha power, and beta/delta ratio (a marker of cortical arousal) between states using paired t-tests. All results were thresholded at p&lt;0.05 corrected for multiple comparison using statistical non parametric mapping (SNPM).

Results
Clean data were obtained in 26 PE arising out of N2/N3 sleep in 11 subjects. During PE, delta and theta power were significantly higher than during wake but lower than during sleep in central regions (at uncorrected p&lt;0.05 for sleep vs. PE delta power). Occipital alpha was lower during PE compared to wake, but higher during PE compared to sleep. Finally, beta/delta ratio values during PE were globally higher than in wake, but globally lower than during sleep.

Conclusion
The present results confirm and extend our previous findings of decreased SWA in central areas during baseline sleep in patients with NREM sleep PE. They suggest that higher cortical arousal in central regions may precipitate motor behaviors during PE. Alpha power and beta-delta ratio during PE were intermediate between sleep and wake, suggesting that PE are transitional states with an admixture of cortical arousal and cortical sleep. Future analyses will use source reconstruction to identify the cortical generators of observed scalp differences.

Support
This work was funded by the Swiss National Science Foundation and the Tiny Blue Dot foundation.
0828 Descriptive Model of Sleep Quality in the Older Adults
Authors: Morelhao P K , Fernandes G L , Dokkedal-Silva V , Pires G N , Tufik S , Andersen M L 
Published: May 2020

Abstract

Introduction
Poor sleep quality is a health condition that impacts the quality of life of the older population. In the literature, there are questions about which objective sleep parameters should be considered to describe precisely the definition of sleep quality. There is ongoing debate with this term usually being used in relation to subjective sleep perception. This study aimed to investigate which objective and subjective sleep parameters contribute to a measurement of sleep quality in older adults.

Methods
A cross-sectional study using a representative sample of adults from the city of São Paulo, Brazil was performed. We used a dataset from the 2015 Epidemiological Study of Sleep from the City of São Paulo (EPISONO), including only individuals aged 60 years or more. We used exploratory factor analysis and structural equation modelling to identify relevant variables to a descriptive model of sleep quality.

Results
A total of 152 older adults were included. The final model consists of two factors, objective sleep quality which comprises sleep efficiency, total sleep time and sleep latency, and poor sleep perception, constituted by scores in the Pittsburgh Sleep Quality Index and Insomnia Severity Index.

Conclusion
The results suggested that sleep quality had both an objective (sleep efficiency, total sleep time, latency of sleep onset) and subjective dimensions (subjective questionnaires). These results may be useful in the clinical scenario, serving as leads for a better understanding of the sleep quality in aging patients. Future studies may also benefit from this descriptive model to further researches other associations, such as sleep and pain in this population.

Support
The study was supported by Associação Fundo de Incentivo à Pesquisa (AFIP) and Coordenação de Aperfeiçoamento de Nível Superior (CAPES). ST and MLA received support from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).
0836 Self-Reported Difficulty Initiating Sleep and Early Morning Awakenings are Associated With Nocturnal Diastolic Non-Dipping in Older Men
Authors: Tan X , Benedict C 
Published: May 2020

Abstract

Introduction
Aging increases the risk of insomnia and elevated blood pressure (BP). Here, we examined in older men whether reports of difficulty falling asleep (DIS) and early morning awakenings (EMA) are associated with 24-h BP and heart rate.

Methods
We utilized variables from 995 men (mean age: 71 years) who participated in the Uppsala Longitudinal Study of Adult Men (ULSAM). BP and heart rate were measured over 24 hours.

Results
Non-dippers (night-to-day BP ratio &gt; 0.90) had a higher risk of hypertension than dippers (systolic non-dippers vs. systolic dippers, OR [95%CI]: 1.64 [1.21, 2.21], P=0.001; diastolic non-dippers vs. diastolic dippers, 1.50 [1.10, 2.04], P=0.01). Compared to men without DIS, men who reported DIS (10% of the cohort) had a higher risk of diastolic non-dipping (1.85 [1.19, 2.87], P=0.006). Similarly, men who reported EMA (19% of the cohort) had a higher risk of diastolic non-dipping than those without EMA (1.59 [1.12, 2.24], P=0.009). Despite a slightly higher nocturnal diastolic BP among men with EMA vs. those without EMA (+1.4 mmHg, P=0.035), no other differences in BP and heart rate were found between men with and those without insomnia complaints.

Conclusion
Our findings uncover a link between disruption in nocturnal dipping of diastolic BP and insomnia symptoms related to difficulty initiating sleep and early morning awakening in older men.

Support
Authors’ work is funded by the Novo Nordisk Foundation (C.B., NNF19OC0056777), Swedish Brain Research Foundation (C.B., FO2019-0028), Swedish Research Council (C.B., 2015-03100), Åke Wiberg Foundation (X.T., M18-0169, M19-0266), Fredrik and Ingrid Thuring Foundation (X.T., 2018-00365), and the Swedish Medical Research Society (X.T., P18-0084).
0852 Geriatric Health Conditions And The Combined Outcome Of Poor Sleep Quality With Objective Short Sleep Duration
Authors: Miner B , Vaz Fragoso C A , Han L , Yaggi H K , Redeker N S , Stone K L 
Published: May 2020

Abstract

Introduction
Poor sleep quality with objective short sleep duration (≤6 hours) is a high-risk phenotype. The associations of geriatric health conditions with this sleep phenotype have not been described.

Methods
Using data on 3,127 older women from the Study of Osteoporotic Fractures (SOF), mean age 84 years, and 3,058 older men from the Osteoporotic Fractures in Men Sleep Study (MrOS), mean age 76 years, we evaluated cross-sectional associations between geriatric health conditions and the combined outcome of poor sleep quality with actigraphic short sleep duration. Geriatric health conditions included cognitive impairment (modified MMSE score 1.5SD below the cohort mean value), physical impairment (inability to do a chair stand), falls (≥2 in past year), and vision impairment (acuity ≤20/40). Poor sleep quality was defined by Pittsburgh Sleep Quality Index (PSQI) score &gt;5 and short sleep duration by average total sleep time ≤6 hours from wrist actigraphy (averaged over ~5 days). Women (SOF) and men (MrOS) were evaluated separately and multivariate logistic regression models also included age, race, education, comorbidities (medical, psychiatric, and primary sleep disorders), and medication use.

Results
Poor sleep quality with actigraphic short sleep duration was present in 475 (15.6%) men and 400 (13.1%) women. In men, the unadjusted odds of having combined poor sleep quality with actigraphic short sleep duration were statistically higher with cognitive impairment (OR=1.45 [CI 1.05, 1.98]), physical impairment (2.90 [1.87, 4.51]), and falls (1.97 [1.48, 2.62]). In women, the unadjusted odds of having combined poor sleep quality with actigraphic short sleep duration were statistically higher with physical impairment (1.54 [1.16, 2.04]) and falls (1.63 [1.21, 2.20]). However, these associations were no longer statistically significant in adjusted models (men and women).

Conclusion
Older persons with geriatric health conditions are more likely to have the combined phenotype of poor sleep quality with actigraphic short sleep duration, but this association is likely explained by comorbidity and medication use.

Support
Dr. Miner is supported by the Yale Claude D. Pepper Older Americans Independence Center (P30AG021342), the American Academy of Sleep Medicine Foundation, a foundation of the American Academy of Sleep Medicine, and the National Institute on Aging T32AG019134.