bluuebunny/crossref_metadata_2025_split huggingface dataset:
0750 Nocturnal Sleep Stability and Cerebrospinal Fluid Orexin-A Levels: Sleep and Wake Bouts
Authors: Barateau L , Lopez R , Chenini S , Rassu A , Scholz S , Lotierzo M , Cristol J , Jaussent I , Dauvilliers Y 
Published: May 2020

Abstract

Introduction
The orexin (ORX)/hypocretin system stabilizes sleep-wake regulation by sustaining long periods of wakefulness in humans and animals. We aimed to evaluate the relationships between cerebrospinal fluid (CSF) ORX levels and markers of nocturnal sleep stability assessed by polysomnography (PSG) in humans.

Methods
Nocturnal PSG data and CSF ORX levels of 300 drug-free subjects (55% men, 29.9±15.5 years old, mean ORX levels 155.1±153.7 pg/mL) with a complaint of hypersomnolence were collected in the National Reference Center for Narcolepsy, France. Several markers of nocturnal sleep stability were analyzed: wake (WB), sleep bouts (SB), and sleep/wake transitions. Groups were categorized according to ORX levels: two categories (≤110, &gt;110 pg/mL, the current established threshold of ORX-deficiency), and tertiles (≤26,]26;254], &gt;254 pg/mL); and were compared using logistic regression models. Results were adjusted for age, gender and body mass index.

Results
ORX-deficient subjects had more WB, SB, and sleep-wake transitions than the others. The WB duration was longer and the SB duration shorter in ORX-deficient category. The proportion of the shortest WB (30 sec) was lower in the ORX-deficient category whereas the proportion of WB above 1 min 30 sec was higher. The proportion of SB ≤ 14min was higher among ORX-deficient patients, with opposite results for longer SB. Subsequent analyses performed in the population categorized according to tertiles of CSF ORX-A confirmed all these findings, with a strong dose-response effect of ORX levels in post-hoc comparisons. All results remained highly significant in adjusted statistical models.

Conclusion
This study provides a strong evidence of the direct effect of ORX on nocturnal sleep stabilization in humans. WB and SB are reliable markers of nighttime sleep stability, strongly correlated to CSF ORX-A levels in a dose dependent way. These PSG biomarkers are promising to be applied in clinical and research settings.

Support
none
0762 Efficacy Of Pitolisant In Patients With High Burden Of Narcolepsy Symptoms
Authors: Davis C W , Kallweit U , Krahn L E , Vaughn B , Thorpy M J 
Published: May 2020

Abstract

Introduction
Recent literature suggests that histamine may play an important role in narcolepsy. This post hoc analysis evaluates the efficacy of pitolisant, a histamine 3 (H3)-receptor antagonist/inverse agonist, in patients with high burden of the main narcolepsy symptoms.

Methods
Data were pooled from 2 randomized, placebo-controlled, 7- and 8-week studies of pitolisant (individually titrated; maximum dose, 35.6 mg/day) in adults with narcolepsy. Analyses included 3 independent patient subgroups: baseline score of &gt;16 on the Epworth Sleepiness Scale (ESS), sleep latency of ≤8 minutes on the Maintenance of Wakefulness Test (MWT), and ≥15 cataplexy attacks per week.

Results
The analysis populations included 108 patients for the ESS (pitolisant, n=54; placebo, n=54), 105 for the MWT (pitolisant, n=59; placebo, n=46), and 31 for cataplexy (pitolisant, n=20; placebo, n=11). Mean change in ESS from baseline was significantly greater for pitolisant (-6.1) compared with placebo (-2.6; P=0.0002). A significantly greater percentage of pitolisant-treated patients were classified as treatment responders: for ESS score reduction ≥3, 68.5% in the pitolisant group versus 35.2% in the placebo group (P=0.0006); for final ESS score ≤10, 35.2% versus 9.3%, respectively (P=0.0026). Mean increase in sleep latency on the MWT was significantly greater for pitolisant (7.0 minutes) compared with placebo (3.4 minutes; P=0.0089). Decrease in mean weekly rate of cataplexy was significantly greater for pitolisant (baseline, 21.8; final, 3.9) compared with placebo (baseline, 20.9; final, 18.2); the rate ratio was 0.35 (95% CI, 0.26‒0.47; P&lt;0.001). The adverse event profile in the analysis populations was consistent with the known safety profile for pitolisant; headache was the most common adverse event in pitolisant-treated patients (10.0%-20.4%).

Conclusion
In patients with severe symptom burden, pitolisant produced significantly greater improvements in excessive daytime sleepiness and cataplexy compared with placebo, highlighting the important role of histamine in narcolepsy.

Support
Bioprojet Pharma and Harmony Biosciences, LLC.
0776 Differences in Well-Being in Dayworkers Compared to Shift Workers: A Study of United States Navy Sailors
Authors: Shattuck N L , Matsangas P 
Published: May 2020

Abstract

Introduction
On United States Navy (USN) ships, most sailors are shift workers, required to support 24/7 operations. However, ~15% of the ship’s company are solely dayworkers who do not work in shifts. It is often assumed that the quality of life for dayworkers is better than that of shift workers. This study compared the well-being of dayworkers with that of shift workers.

Methods
Longitudinal, naturalistic observations were made of sailors (N=926; 18-59 years of age, ~80% males, ~84% enlisted personnel) on seven US Navy ships while performing their normal underway duties. Sleep-related attributes (actigraphy, Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, Insomnia Severity Index), mood (Profile of Mood States), and work/rest patterns were assessed.

Results
Dayworkers (DW; n=98) were on average older (p=0.001) and more senior (p=0.001) than shift workers (SW). Of the dayworkers, 31% reported elevated daytime sleepiness (SW:45.5%; p=0.008), 64.2% were poor sleepers (SW:82.6%; p&lt;0.001), and 26.3% had ISI score≥15 (SW:24.8%; p=0.782). Also, 13.8% of the dayworkers had ESS&gt;10 and ISI≥15 (SW:16.8%; p=0.626).Dayworkers had better mood (Total Mood Disturbance, anger/hostility, vigor, fatigue; all p&lt;0.050), slept more (7.03±0.74hrs sleep/day; SW:6.52±1.03hrs; p&lt;0.001) and had more consolidated sleep (1.1±0.3 sleep episodes/day; SW:1.4±0.6; p&lt;0.001). Yet, split sleep was commonplace for both groups (DW:~62%; SW:~92%).The two groups do not differ (all p&gt;0.300) in their use of caffeinated beverages (82%-86%), use of nicotine products (30%-36%), or having a regular exercise routine (69%-75%). In both groups, ~9% of sailors drank caffeinated beverages, used nicotine products and did not have an exercise routine (p=0.999). Dayworkers worked 10.1 hours/day, i.e., 1.7 hours/day less than watchstanders (p&lt;0.001).

Conclusion
Quality of life of dayworkers is a bit better when compared to shift workers, but sleep-related issues are evident in almost all US Navy sailors. Living and working on a naval vessel takes a toll on almost everyone aboard. A culture change is required!

Support
Supported by the Naval Medical Research Center’s Advanced Medical Development Program, the US Navy 21st Century Sailor Office, and the US Navy OPNAV N1.
0779 Circadian Entrainment in 12h Night Shift Workers: The Environmental Lights Matter?
Authors: Choi S , Park H , Joo E 
Published: May 2020

Abstract

Introduction
Shift workers frequently suffer sleep disturbance in relation with the atypical work schedules. In particular, night shift workers are exposed to inevitable sunlight or bright indoor lights during the morning hours that may disturb their daytime sleep. We aimed to find out the optimal environmental lights to facilitate circadian entrainment of 12h-shift workers by assessing melatonin profiles in the morning and daytime sleep quality.

Methods
We enrolled 12h-shift female nurses working at one hospital (n=10, mean age 29.4±3.5 years). The schedules of participants are identical such as day-day-night-night shifts and four consecutive off days. Participants admitted to the laboratory at 9:00 following 2nd night shift schedule. Saliva melatonin was taken six times every 30 minute from 10:00 to 12:30 under two different lighting conditions with organic light emitting diodes (OLED) or light emitting diodes (LED) with 150 lux of light intensity. Dim light condition (10 lux) was conducted as controls. Three sessions were randomly ordered with 8-10 days intervals. Participants were allowed to sleep after 12:30 with light off and woke up ad libitum.

Results
Melatonin concentration had decreased gradually from 10.6±11.4 to 5.0±8.2 pg/ml. Among three different lighting conditions, there were no statistical differences in salivary melatonin and sleep parameters recorded by polysomnography. Circadian entrainment in night shift workers was defined as that salivary melatonin concentration had maintained above 5 pg/ml at the time to bed. 20% of sessions (6/30) were classified as circadian entrainment (CE) and 80% (24/30) were as non-entrainment (NE). Mean melatonin concentration was 22.1±11.2 in CE and 3.9±4.1 pg/ml in NE (p&lt;.001). CE showed significantly shorter sleep latency (0.5±0.3 vs. 1.5±1.4 min, p=.025) and wakefulness after sleep onset (13.6±6.3 vs. 27.9±16.8%, p=.015), and higher sleep efficiency (94.6±2.6 vs. 88.7±6.3%, p=.011) than NE. The number of each lighting condition was not different between CE and NE (p=.847).

Conclusion
This is a preliminary study with small number of participants. We found that environmental lights including dim light did not affect daytime sleep of 12h shift workers. Instead, daytime sleep quality was influenced by circadian entrainment with higher melatonin concentration in the morning.

Support
0780 Effect Of A Sleep/Circadian Friendly Protocol On The Outcomes Of Patients Admitted To The Medical Intensive Care Unit: A Randomized Control Trial
Authors: Wakefield C , Morrow J , Hamati F , Sanzo G , Peterson S , Balk R A , Burgess H , Swanson G , Keshavarzian A 
Published: May 2020

Abstract

Introduction
Critically ill patients often suffer from fragmented sleep due to light and noise in the intensive care unit (ICU). We investigated whether placing patients in a sleep/circadian friendly protocol improved patient-reported sleep quality and ICU outcomes.

Methods
Patients were included if they were expected to have a &gt;24-hour stay. Exclusion criteria included age &lt;18 years, pregnancy, frequent overnight assessments, poor prognosis, pre-existing cognitive impairment, and severe psychological disorders. Patients were randomized to a sleep/circadian protocol or control protocol. Demographic, treatment, sound (dB), light (lux), patient-reported sleep, and medical outcomes were collected. Those who were not maintained in the sleep/circadian protocol were combined with the controls for statistical analysis. Univariate analysis was performed with Chi-Square test and Wilcoxon rank-sum test.

Results
Sixty-one patients were enrolled: 28 randomized to sleep/circadian protocol, 33 to control protocol. 14 subjects were excluded from analysis due to developing criteria for exclusion. Nine patients (median age 50 years, 6 females) maintained in the sleep/circadian protocol, 13 patients were not maintained in sleep/circadian protocol and 25 patients in control protocol (median age 64 years, 20 females). There was no difference in age, gender, or race between groups (p&gt; 0.05). Median ICU first overnight dB level (10:00pm-6:00am) was 44.2 (±2.7) for sleep/circadian protocol and 50.5 (±4.9) for combined group (p= 0.008). Median ICU first overnight lux (10:00pm-4:00am) was 2.28 (±61.3) in sleep/circadian protocol and 18.42 (±90.9) in combined group (p=0.0374). A continued stay in the sleep/circadian protocol resulted in decreased total decibel level (p= 0.0018) decreased total overnight lux exposure (p= 0.0025) and decreased reported awakenings in first night (p= 0.0175). There were no differences in ICU length of stay, inpatient mortality, or readmission rates between groups (p&gt;0.05). Three patients developed delirium, all originally randomized to control group.

Conclusion
We report on the successful outcomes associated with a sleep/circadian friendly protocol within a large tertiary center medical ICU which resulted in significant decreases in objectively assessed noise and light, and subjectively reported nocturnal awakenings. We continue to collect data to determine if the sleep/circadian friendly protocol should be permanently implemented in the ICU.

Support
None.
0796 Dipyridamole for the Treatment of RLS: Preliminary Results of a Cross-Over, Placebo-Controlled, Double-Blind Trial
Authors: Garcia-Borreguero D , Granizo J , Ferre S 
Published: May 2020

Abstract

Introduction
Recent animal models of restless legs syndrome (RLS) suggest that brain iron deficiency is associated with a hypoadenosinergic state, with downregulation of adenosine A1 receptors (A1R) in the striatum. Dipyridamole is a non-selective inhibitor of ENT1/ENT2 (the main reuptake mechanism of adenosine) and increases thereby extracellular adenosine. We hypothesized that treatment with dipyridamole would improve RLS symptoms more than placebo.

Methods
We performed a randomized, double-blind, placebo-controlled clinical trial on 15 previously untreated idiopathic RLS patients that underwent a two week treatment with either 300 mg dipyridamol or placebo (randomized for the order of treatments), following a cross-over design. Treatment started with a dose of 100 mg/day, followed by a forced up-titration to 200 mg on day 4, and to 300 mg on day 7. Severity was assessed at baseline, day 7 and day 14 of each treatment condition by means of the IRLS and CGI scales. The primary endpoint was therapeutic response (50% improvement in IRLS total score).

Results
Fifteen patients (nine women), never before treated with dopaminergic agents, completed both arms of the study. Mean age was 60,2 (±7,1), and the mean duration of illness was 6,03 (±3,1) yrs. IRLS score improved during treatment with dipyridamole from a mean (±S.D.) of 24,36 (±3,3) to 9,78 (±3,4), in contrast to a change from 23,9 (±3,8) to 16,6 (±3,7) under placebo (p&lt; 0.05). Corresponding improvements on the CGI were 61,3% and 11,8% for dipyridamole and placebo, respectively. 7/ 15 patients improved by more than 50% during treatment with dipyridamole vs. 4/15 under placebo. Main side effects were abdominal cramps, diarrhea, dizziness, and flushing.

Conclusion
These preliminary results suggest that dipyridamole is an effective agent on RLS symptoms. It also provides evidence of hypoadenosinergic mechanisms playing a central role in RLS.

Support
No funding was provided for this investigation.
0811 Periodic Limb Movements In Patients With Dysautonomia
Authors: Tallavajhula S 
Published: May 2020

Abstract

Introduction
Periodic Limb Movements in Sleep (PLM) have been thought to result in increase in sympathetic tone in sleep, tachycardia, elevated systolic blood pressure and therefore elevation in risk of cardiovascular disease. However, evidence of a direct causative relationship has been elusive. We discuss the presence of PLM in patients with dysautonomia, proposing that autonomic dysfunction may be either a causative factor for PLM or share common pathogenesis with PLM.

Methods
Three patients with dysautonomia, referred to the TIRR Memorial Hermann Hospital neurological sleep disorders center with varying sleep-related symptoms were studied with polysomnography, recorded under AASM guidelines. PLM were scored using standard criteria described in the AASM scoring manual.

Results
The three patients described all carried a diagnosis of dysautonomia, diagnosed by tilt table testing. The first patient was an 18 year old woman with complaints of palpitations during sleep and frequent arousals. Her PLM index was 49.8. Serum ferritin level was pending. The second patient was a 35-year-old woman who complained of nonrestorative sleep. Polysomnogram demonstrated a PLM index of 17.6. Ferritin level was 36 ng/mL. The third patient was a 34-year-old woman with insomnia who was also found to have a PLM index of 15.1. Her serum ferritin level was 24. She underwent therapeutic iron infusions and experienced substantial improvement in subjective sleep quality. None of the patient described symptoms of restless legs syndrome or had any bleeding disorders to explain low ferritin levels.

Conclusion
The patients described above all were relatively healthy young women with symptoms of dysautonomia and disturbed sleep. It would be unusual for young individuals to present with PLM which are commonly associated with advancing age. In at least one patient, iron infusions improved sleep quality dramatically. Work needs to be done to establish relationship between autonomic imbalance and PLM, suggesting that the previously thought unidirectional relationship, [i.e. PLM causing change in sympathetic tone] may actually be bidirectional.

Support
None
0817 Abnormal REM Sleep Atonia Control In Patients With Chronic Post-traumatic Stress Disorder
Authors: Feemster J , Steele T , Tao Y , Rivera S , Gossard T , Teigen L , Timm P , McCarter S , St. Louis E 
Published: May 2020

Abstract

Introduction
Post-traumatic stress disorder (PTSD) is characterized by persistent mental and emotional stress following one or more significant physical or psychological traumatic incidents earlier in life. Vivid recall of the events, including traumatic nightmares, and prominent sleep disturbance are usual in PTSD. Previous studies have suggested that PTSD may share some clinical features with idiopathic REM sleep behavior disorder (iRBD) including altered REM sleep without atonia (RSWA) levels. Our group has previously found evidence for altered RSWA control in patients with psychiatric disease, including a pilot sample of PTSD patients with iRBD. We aimed to comparatively analyze RSWA levels between patients with PTSD, PTSD and RBD (PTSD+RBD), iRBD, and controls.

Methods
We selected 18 PTSD, 18 PTSD+RBD, 15 iRBD, and 51 healthy control patients matched for age and sex from the Mayo Clinic Center for Sleep Medicine’s polysomnography database for RSWA quantification. RSWA amounts in the submentalis (SM) and anterior tibialis (AT) were quantitatively analyzed as a percentage of REM sleep duration, in accordance with previously published methods. Non-parametric analyses were performed to compare RSWA, patient demographics, and PSG data across groups. Significance was set at p &lt; 0.016.

Results
Patients with PTSD had significantly higher RSWA than controls in all RSWA density measures (p &lt; 0.016 for all). All measures of RSWA, excluding average SM duration, were significantly greater in PTSD+RBD patients compared with controls (p &lt; 0.016 for all). Within the PTSD group, patients on antidepressants did not have significantly higher RSWA in any of the measures. PTSD+RBD patients had significantly higher SM Phasic, AT Any, SM+AT Any, and Tonic RSWA measures than PTSD patients (p &lt; 0.016 for all).

Conclusion
PTSD patients have significantly higher RSWA than controls, with PTSD+RBD patients having higher RSWA levels than PTSD patients. These data provide the first evidence for abnormal RSWA control in patients with chronic PTSD. This provides evidence of a unique biology in PTSD that could imply a future risk for neurodegenerative disease in PTSD similar to RBD patients. Further prospective studying will need to be performed on patients with PTSD to understand the unique biology.

Support
0824 Improving Subjective Sleep Quality Measures Through Mindfulness Training in the Elderly: Preliminary Data from the Mindfulness Sleep Therapy (MIST) Study
Authors: Perini F , Foong Wong K , Teng J , Hassirim Z , Lin J , Leow Z , Lee Henderson S , Fan Q , Lo J C , Ong J C , Doshi K , Lim J 
Published: May 2020

Abstract

Introduction
Poor sleep is a modifiable risk factor for multiple chronic disorders. Mindfulness-based therapies potentially improve sleep by enhancing awareness and acceptance of internal and external experiences, thus reducing pre-sleep hyper-arousal. In this pre-registered, randomized controlled trial, we tested the effect of mindfulness-based treatment for insomnia (MBTI) on subjective sleep quality measures (Pittsburgh Sleep Quality Questionnaire, PSQI) in the elderly.

Methods
Participants above 50 years old with sleep difficulties (PSQI ≥ 5) (mean (sd) age = 62.0 (6.35), 44 female) attended either an 8-week MBTI (N = 34) or sleep hygiene education and exercise program (SHEEP; N = 35). Before and after the interventions, we collected PSQI, insomnia symptoms and features measures (Pre-Sleep Arousal Scale, PSAS; Insomnia Severity Index, ISI; Dysfunctional Beliefs and Attitudes about Sleep, DBAS-30), mindfulness (Five-Facets Mindfulness Questionnaire, FFMQ), and mood and anxiety (Back Depression Inventory, BDI; State-Trait Anxiety Inventory, STAI). PSQI and PSAS (N = 26 to date) were collected at 6-month follow-up. Data were analysed with repeated-measures ANCOVA with group as a between-subject variable for the first 69 participants who completed the study.

Results
We observed significant improvement across both groups for sleep measures (PSQI: F1,67=36.442, p&lt;.01; PSAS-Cognitive: F1,67=12.664, p&lt;.01; ISI: F1,67=36.442, p&lt;.0; DBAS: F1,67=28.749, p&lt;.01) and mood (BDI: F1,67=26.393, p&lt;.01; STAI-State: F1,67=4.608, p=.04; STAI-Trait: F1,67=7.687, p&lt;.01), but not for Mindfulness (F1,67=2.256, p=.14) nor PSAS-somatic. No significant group by time interactions were found. We observed a correlation between PSQI decreases and FFMQ increases in MBTI (r=-.53, p&lt;.01), but not in SHEEP (r=-.07, p=.70) participants. ANCOVA of 6-month PSQI data revealed a significant group by time interaction (F1,24=19.525, p=.03), with reduction from baseline in MBTI (t12=4.769, p&lt;.01), but not in SHEEP group (t12=3.813, p=.08).

Conclusion
Preliminary results support MBTI as an accessible but effective behavioural intervention with potential long-term benefits for improving sleep and mood, and reducing cognitive-emotional arousal in the elderly.

Support
This study was supported by an award from the 7th grant call of the Singapore Millennium Foundation Research Grant Programme