bluuebunny/crossref_metadata_2025_split huggingface dataset:
0729 Sleep Apnea Diagnosis And Severity And Their Impact On Cognition After TBI: A VA TBI Model Systems Study
Authors: Silva M A , Brennan E M , Noyes E , Royer A , Nakase-Richardson R 
Published: May 2020

Abstract

Introduction
For persons with moderate-to-severe traumatic brain injury (TBI), chronic cognitive impairment contributes to long term disability. Health comorbidities may contribute to the neurologic burden in TBI. Indeed, obstructive sleep apnea (OSA) is associated with neuropathological and cognitive changes. The objective of this study was to examine the relationship between OSA and cognition after TBI.

Methods
Participants were prior inpatient rehabilitation patients drawn from the Tampa VA TBI Model Systems longitudinal study. Post-discharge interviews occurred 2 to 6 years post-TBI. Participants reported whether they were diagnosed with OSA and completed the Brief Test of Adult Cognition by Telephone (BTACT) which measures recall, working memory, processing speed, fluency, and reasoning. Participants with polysomnography (PSG) were separately analyzed to examine the impact of sleep apnea severity (i.e., Apnea-Hypopnea Index [AHI]) on cognition.

Results
Participants (N=104) were mostly male (95.2%), age M=37.7 (SD=12.5), Education M=13.6 years (SD=2.1), and 45.2% were diagnosed with OSA. Participants with and without OSA did not differ by age, education, gender, or time since injury at time of BTACT (ps &gt; .05). ANCOVAs were conducted examining OSA diagnosis on BTACT subscale scores, covarying TBI severity level, but results did not reach statistical significance (ps &gt; .05). A subset of participants with OSA had PSG (n=27), AHI score quartiles = 6.7/10.4/21.6. Higher AHI was associated with poorer reasoning (Spearman ρ = -0.45, p = .019). Nonsignificant results were found for word recall (Spearman ρ = -0.35, p = .074) and processing speed (Spearman ρ = -0.36, p = .069).

Conclusion
Severity of sleep apnea may influence aspects of cognition among persons with TBI, although these results are preliminary and need replication with a larger and more representative sample.

Support
This work was supported by the Veterans Health Administration Central Office VA TBI Model Systems Program of Research and subcontract from General Dynamics Information Technology [W91YTZ-13-C-0015, HT0014-19-C-0004] from the Defense and Veterans Brain Injury Center (DVBIC); and from the United States Department of Veterans Affairs [W81XWH-13-2-0095]; and from the United States Department of Defense Congressionally Directed Medical Research Programs; and from the Patient Centered Outcomes Research Institute (PCORI) [CER-1511-33005].
0734 Does Noise Masking Improve Sleep Consolidation In Patients Weaning From Prolonged Mechanical Ventilation?
Authors: Shaikh H , Chung P , Jubran A , Tobin M , Laghi F 
Published: May 2020

Abstract

Introduction
Sound masking is a noise reduction strategy that adds a mixed-frequency blend of ambient sound to the environment and may improve sleep. Critically ill patients often cite noise as one of the main factors preventing sleep while they are cared for in an intensive care unit (ICU). The effect of sound masking on sleep in patients weaning from prolonged mechanical ventilation is unknown.

Methods
12-hour overnight polysomnography was obtained in eight patients undergoing weaning from prolonged mechanical ventilation. None had hearing impairment, delirium, sedation or agitation. In random order, patients were exposed to sound masking half of the recording time. Noise events were defined a 10dB increase from baseline or any sound peak over 75dB. Arousals or awakenings were attributed to noise if they occurred within 5 seconds of the noise event.

Results
Environmental sound was 61.7± 0.9 dB (mean±SE) during sound masking and 55.9±1.4 dB during no sound masking. During sound masking, there were fewer sound events per hour of sleep when compared to no sound masking (4.1/hr vs 9.3/hr p=0.03). The percentage of sound events leading to a subsequent arousal or awakening with sound masking was less than during no sound masking:11% vs 22% (p=0.04). Arousal index and fragmentation index (arousal and awakenings/hr of sleep) were similar between the two conditions. In a post-study survey, five patients reported improved sleep quality with sound masking while the remaining three reported no difference.

Conclusion
Sound masking decreases sound-induced arousal from sleep in patients being weaned from prolonged mechanical ventilation.

Support
Veterans Administration Research Service
0739 Efficacy and Safety of AXS-12 in the Treatment of Narcolepsy: Results from a Phase 2, Double-Blind, Placebo-Controlled, Crossover Trial
Authors: O’Gorman C , Jones A , Thorpy M J , Tabuteau H 
Published: May 2020

Abstract

Introduction
Narcolepsy is a chronic, debilitating, neurological disease characterized by excessive daytime sleepiness (EDS), cataplexy, and sleep-wake dysregulation. Existing treatments are limited, provide variable efficacy, and have significant tolerability issues. AXS-12 (reboxetine) is a potent, and highly selective norepinephrine reuptake inhibitor with potential for therapeutic differentiation in narcolepsy.

Methods
The CONCERT study was a Phase 2, double-blind, randomized, placebo-controlled, crossover trial of AXS-12 in narcolepsy subjects exhibiting moderate and severe symptoms of cataplexy and EDS. Subjects were randomized (1:1) to treatment with AXS-12 followed by placebo, or placebo followed by AXS-12. AXS-12 dosing was 8mg/day for week 1, escalated to 10mg/day for week 2. Crossover occurred after a one-week down-titration/washout. The primary endpoint was the change in weekly cataplexy attacks from baseline, averaged over the 2-week treatment period for overall treatment effect. Secondary endpoints included improvements in EDS, cognitive function, sleep quality and sleep-related symptoms.

Results
Twenty-one subjects were randomized. The baseline mean weekly number of cataplexy attacks was 30.0 and mean ESS score was 18.1, reflecting moderate and severe illness on both core symptoms. AXS-12 met the prespecified primary endpoint, demonstrating a statistically significantly greater reduction in the mean number of weekly cataplexy attacks (-13.0 with AXS-12 vs -0.3 with placebo; p&lt;0.001) over 2 weeks of treatment. Statistically significant reductions in EDS were observed for AXS-12 compared to placebo, assessed by changes in the Epworth Sleepiness Scale (-6.0 vs -3.1; p=0.003), number of weekly inadvertent naps (-5.88 vs -0.98; p&lt;0.001). AXS-12 was associated with improved cognitive function (p&lt;0.002) and sleep quality (p&lt;0.007), and reduced night awakenings (p&lt;0.05). Rapidity of effect was observed with significant symptomatic improvements occurring as early as week 1 starting at the lower 8mg dose. AXS-12 was safe and well-tolerated with no serious adverse events or discontinuations due to adverse events.

Conclusion
AXS-12 is a novel approach for the treatment of narcolepsy with the potential for comprehensive clinical symptom management compared to current treatments. In this Phase 2 study, AXS-12 resulted in statistically significant improvements in cataplexy, excessive sleepiness, cognitive function and night awakenings in patients with narcolepsy with a favorable safety profile.

Support
Axsome Therapeutics.
0744 Cardiac Safety Profile of Pitolisant in Patients with Narcolepsy
Authors: Winter W , Wanaski S P , Patroneva A , Dayno J M 
Published: May 2020

Abstract

Introduction
Cardiovascular diseases are comorbid in patients with narcolepsy. Cardiovascular adverse effects are of concern with narcolepsy medications because of this comorbidity and most patients require lifelong pharmacotherapy. Pitolisant, a selective histamine 3 (H3)-receptor antagonist/inverse agonist, increases histamine transmission in the brain. In a QT study of healthy volunteers, pitolisant (35.6 mg/day) led to a mean increase of 4.2 msec in QTc interval. This analysis further characterized the cardiac safety of pitolisant (maximum dose, 35.6 mg/day) in adults with narcolepsy.

Methods
Data were obtained from a pooled analysis of 2 randomized, placebo-controlled, 7- or 8-week studies and from a 12-month, open-label study.

Results
Pooled analysis included 166 patients (pitolisant, n=85; placebo, n=81). Mean change in heart rate from baseline to end-of-treatment was -0.5 beats/min with pitolisant and -0.2 beats/min with placebo (LS mean difference, -0.4; P=0.744). Mean change was also similar for pitolisant versus placebo in systolic (LS mean difference, 0.0; P=0.983) and diastolic (LS mean difference, -0.6; P=0.552) blood pressure, as was mean change in QTc interval (LS mean difference, 0.4; P=0.911). Cardiac adverse events with pitolisant included heart rate increase (n=4), right bundle branch block (n=1), sinus tachycardia (n=1), and palpitations (n=1), and with placebo included blood pressure increase (n=1). In the long-term study, mean change from baseline in QTc interval was 3.1 msec at Month 6 (n=70) and 6.1 msec at Month 12 (n=67); 3 patients had a postbaseline increase &gt;60 msec but none had QTc &gt;500 msec.

Conclusion
In this analysis, no cardiac safety signals were observed during treatment with pitolisant administered up to the maximum recommended dose. Because concomitant use of pitolisant with other drugs known to increase the QT interval may add to the QT effects of pitolisant, avoid use of pitolisant in combination with these medications.

Support
Bioprojet Pharma and Harmony Biosciences, LLC.
0757 Increasing Number of Cases Who Had Both Hypersomnolence Disorders and Developmental Disorders With Orexin Measurements
Authors: Imanishi A , Yoshizawa K , Tsutsui K , Omori Y , Ono T , Ito Uemura S , Mishima K , Kondo H , Kanbayashi T 
Published: May 2020

Abstract

Introduction
Recently, attention has been paid to the relationship between developmental disorders such as attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), and sleep disorders. We meet many developmental disorder patients who complaint hypersomnolence. Among these patients, cases with coexistence of central hypersomnia and developmental disorders, or developmental disorder alone were increased. Therefore, we first investigated patients with the complaint of hypersomnolence, who were also suspected developmental disorders. Furthermore, we have been measuring CSF orexin in 17 cases suspected of both disorders to investigate orexin levels of these patients.

Methods
86patients who complained of EDS with suspicion of developmental disorders had been examined. In order to diagnose hypersomnolence disorders, PSG and MSLT were performed. Psychological examinations were performed for diagnosing developmental disorders.We have been measuring for CSF orexin in 17 cases suspected both hypersomnolence and developmental disorders. We examined the onset of hypersomnolence and the clinical history of these ADHD or ASD cases for more details.

Results
In 86 examined cases, developmental disorders coexisted in 30 cases. Among 30 cases, ADHD were 18, ASD were 6 and both diagnosed were 6 cases. Among them, 20 cases diagnosed as having coexistence of hypersomnia (8: narcolepsy, 12: IHS) and developmental disorders (ADHD:12, ASD:4, ADHD/ASD:4). In 17 cases with orexin measurements, 10 cases coexisted ADHD and 4 cases coexisted ASD. Two cases diagnosed as both ADHD and ASD. In 10 ADHD cases, 3 cases had low orexin levels, and 7 cases had normal orexin levels. Other 7 ASD cases had normal orexin levels.

Conclusion
ADHD has a higher rate of central hypersomnia (12/18) compared with ASD and the rate of narcolepsy was also high (5/12). While patients in ASD was diagnosed as IHS (3/6), narcolepsy cases were not observed. It became clear that the majority of patients had developmental disorder or had a tendency for developmental disorder before the onset of hypersomnolence.Although it is possible that ADHD/ASD symptoms may be exacerbated by orexin dysfunctions, ADHD/ASD may not newly occur. There were cases with low orexin levels, but it seems that narcolepsy happened to coexist with developmental disorders.

Support
a
0767 Analysis Of The Effect On Blood Pressure And Heart Rate When Adding Solriamfetol (Sunosi) To Stimulant Therapy
Authors: Meskill G J , Meskill S D 
Published: May 2020

Abstract

Introduction
Solriamfetol is a non-stimulant wakefulness-promoting agent (WPA) indicated for the treatment of excessive daytime sleepiness in adult patients with obstructive sleep apnea or narcolepsy. It acts by inhibiting reuptake of dopamine and norepinephrine. Since many patients with excessive daytime sleepiness take stimulants, clinicians commonly ponder the safety of adding solriamfetol in this population due to concern of increased blood pressure and/or heart rate (HR).

Methods
We conducted a retrospective chart review and identified 18 patients who had solriamfetol added to their stimulant therapy. Of those, 7 to date have had a follow-up appointment after the addition of solriamfetol (6 on 150mg, 1 on 75mg). We collected the blood pressure and HR readings at the appointment immediately prior to and following the addition of solriamfetol and conducted a paired t-test.

Results
The systolic blood pressure (SBP) had a mean difference of -0.57 (95% CI -9.6 to 8.5, p=0.88), diastolic blood pressure (DBP) 1.7 (95% CI -4.4 to 7.9, p=0.52), mean arterial pressure (MAP) 0.95 (95% CI -5.6 to 7.5, p=0.73), and HR 6.6 (95% CI -0.07 to 13.2, p=0.052).

Conclusion
The addition of solriamfetol to stimulant therapy did not lead to a significant increase in SBP, DBP, MAP, or HR.

Support
none
0771 Explaining Self-reported Hypersomnolence In Seasonal Depression
Authors: Wescott D L , Hasler B P , Franzen P L , Roecklein K A 
Published: May 2020

Abstract

Introduction
Hypersomnolence is commonly reported in Major Depressive Disorder with Seasonal Pattern (Seasonal Affective Disorder; SAD). However, self-reported hypersomnolence may conflate long sleep duration, daytime sleepiness, fatigue, increased time in bed, or maladaptive sleep cognitions, undermining treatment efforts.

Methods
Eighty-eight participants ages 18-65 years old were recruited during the winter (SAD = 43, Control = 45). Depression severity was assessed by a clinician rated interview, and self-reported hypersomnolence was determined by assessing self-reported sleep duration. Participants wore an Actiwatch for 4-14 days and completed self-report measures of daytime sleepiness and fatigue. We performed a hierarchical linear regression to determine which factors best explain self-reported winter hypersomnolence: actigraphic total sleep time (TST), time in bed (TIB), depression severity, sleepiness, or fatigue. Due to collinearity of TST and TIB, we separated those variables into two models predicting hypersomnolence.

Results
SAD participants endorsed greater hypersomnolence than controls during the winter (B = .714; p &lt; .001). In model 1, TST (OR(1,14) = .024, p &lt;.001) and daytime sleepiness (OR(1,14) = .208, p = .03) significantly predicted the presence of self-reported winter hypersomnolence above and beyond age, gender, depression, and fatigue. In model 2, only TIB (OR(1, 14) = .021, p = .001) was a significant predictor. Post-hoc analyses indicated that fatigue and depression severity significantly predicted self-reported hypersomnolence when entered separately into the model. Sleepiness accounted for the largest change in pseudo-R2 in bth models.

Conclusion
We found evidence for the multifaceted etiology of self-reported hypersomnolence. Daytime sleepiness, sleep duration, time in bed, and the shared variance between fatigue and depression severity all explained self-reported hypersomnolence. Treatment of hypersomnolence should include actigraphy, and should be individually tailored based on presentation.

Support
NIMH K.A.R. MH103303
0772 Effects Of Solriamfetol On 24-hour Blood Pressure Patterns In Participants With Excessive Daytime Sleepiness Associated With Narcolepsy
Authors: Strollo P J , Malhotra A , Strohl K , Pepin J , Schweitzer P , Lammers G , Hedner J , Baladi M , Carter L , Bujanover S , Menno D , Dauvilliers Y 
Published: May 2020

Abstract

Introduction
Solriamfetol is a dopamine and norepinephrine reuptake inhibitor indicated to improve wakefulness in adult patients with excessive daytime sleepiness associated with narcolepsy (75-150 mg/d) or obstructive sleep apnea (37.5-150 mg/d). Previous studies reported small mean increases in blood pressure (BP); however, the time course of these effects has not been evaluated. In addition, effects on BP dipping, which has been shown to be a risk factor for adverse cardiovascular outcomes, have not been evaluated. These analyses evaluated the effects of solriamfetol treatment on BP using 24-hour ambulatory blood pressure monitoring (ABPM) and on the percentage of narcolepsy patients with a non-dipping BP profile.

Methods
Twenty-four-hour ABPM was conducted at baseline and week 8 in a 12-week randomized controlled trial in participants with narcolepsy (n=236).

Results
At week 8, increases in BP were apparent in the 150 and 300 mg dose groups from 8 AM until 4 PM and 6 PM, respectively. At baseline, 52% (placebo) and 48% (combined solriamfetol) of participants were non-dippers (defined as &lt;10% decrease in mean arterial pressure [MAP] during sleep). There was no increase in the percentage of non-dippers at week 8 relative to baseline (placebo, 44%; combined solriamfetol, 39%). Results were similar when dipping was defined by changes in systolic BP and diastolic BP.

Conclusion
The effects of solriamfetol on BP at the highest approved dose of 150 mg/d are transient across the day. Solriamfetol was not observed to have an increase in non-dipping classification in participants with narcolepsy at any dose studied.

Support
Jazz Pharmaceuticals
0791 Effects of Low Frequency Electrical Stimulators as Nonpharmacological Treatment in Restless Legs Syndrome
Authors: Cho Y , Lee Y , Ku J , Kim K 
Published: May 2020

Abstract

Introduction
Non-pharmacological treatments for restless legs syndrome (RLS) is a treatment option for patients who have not yet started medical treatment, who do not respond to their prescribed medication, or who suffer from adverse effects of medication. This study aims to investigate the clinical effectiveness of low frequency electronic stimulators (LFES) as a non-pharmacological treatment.

Methods
This is a randomized, single-blind study. After screening 64 patients according to the inclusion/exclusion criteria, a total of 46 patients participated in the study. The participants were separated into an active group and a sham group with 22 and 24 members, respectively. The stimulation was administered using the tapping mode (3Hz) present on the machines used, and symptom changes were measured in both groups. The effects of the stimuli were analyzed with repeated measures ANOVA.

Results
Symptom severity was significantly reduced in the active group, and showed significant interaction effects in the time multiple group. Although both the active and sham groups reported improved symptoms upon receiving longer periods of treatment, the effect of the LFES was greater in the active group.

Conclusion
Analyzing the effects of LFES by dividing the active and sham groups revealed that LFES treatment resulted in symptom improvement when using effective stimulation intensity. LFES can be a non-pharmacological treatment option for RLS.

Support
None
0793 Nearly 25% of Restless Legs Syndrome (RLS) Patients Nationally Treated with Dopamine Agonists are Taking Higher Doses than the Maximum Recommended by FDA and Expert Guidelines
Authors: Winkelman J W 
Published: May 2020

Abstract

Introduction
Dopamine agonists (DAs) have been first-line therapy for restless legs syndrome (RLS) for 30 years. Long-term DA use is associated with augmentation, a dose-related iatrogenic worsening of RLS, which results in a vicious cycle of escalating DA dosing to manage worsening symptoms. The objective of this study was to investigate rates of high-dose DA prescribing in patients with RLS nationally.

Methods
Patients with a diagnosis of RLS (ICD-10 G255.81), and no diagnosis of Parkinson’s disease, treated with rotigotine, pramipexole, and ropinirole, alone or in combination for &gt;180 days, were identified from National Prescription Audit database from October 2017-September 2018. Daily total dosage was grouped into low (FDA-approved) and high (above FDA-approved) dose ranges, respectively (rotigotine: &gt;0-≤3mg/&gt;3mg; pramipexole: &gt;0-≤0.75mg/&gt;0.75mg; ropinirole: &gt;0-≤4mg/&gt;4mg). When DAs were used in combination with each other, dose-equivalent algorithms were used (rotigotine/ropinirole/pramipexole, 1:1:4).

Results
Prescriptions for 244,423 patients meeting inclusion criteria were sampled, constituting 71,181,466 therapy days. For all patients on DA therapy for RLS, 23.5% (57,552/244,423) were prescribed higher than FDA-recommended doses. For patients on DA monotherapy, high-dose prescriptions were provided to 42.7% (819/1919) on rotigotine, 40.7% (38,342/94,275) on pramipexole, and 11.5% (16,900/146,355) on ropinirole. Nearly one-quarter (23.2%) of all pramipexole monotherapy prescriptions were for very high dosages (&gt;1.25 mg). For patients on DA combination therapy, high-dose prescriptions were provided to 79.6% (1,491/1,874).

Conclusion
Roughly 25% of RLS patients treated with DAs were prescribed doses above FDA and expert guideline-recommended maximum doses. Patients on DA combination therapy had substantially higher rates of cumulative high-dose prescriptions. High-dosage DA use is likely due to dose escalation in response to augmentation, risking further augmentation and adverse events such as impulse control disorders. Prescriber education on risks of high-dose DA prescribing for RLS is important.

Support
Arbor Pharmaceuticals, LLC
0799 A Population-based Study of Adult Patients With Recurrent, Clinician Diagnosed Sleepwalking and/or Sleep Related Eating Disorder
Authors: Krahn L E , Tashman Y S , Lyng P J , Lloyd R M , Silber M H 
Published: May 2020

Abstract

Introduction
The ICSD-3 describes NREM-related parasomnias as abnormal sleep related complex movements where motor behavior occurs in the setting of absent or very minimal higher cognitive function. A population-based twin study reported that 3.9% of men and 3.1 % of women sleepwalk (SW) with 30% reported experiencing injury (Hublin 1997). Sleep related eating disorder (SRED) may be a variant of SW with a reported prevalence of 0.5-5 % (Michalska 2016). This study examined SW and SRED in a population-based sample permitting review of associated features, risk factors and outcomes.

Methods
The records-linkage system of the Rochester Epidemiology Project that includes all adults residing in Olmsted County MN was searched for documentation of patients seeking care for at least two episodes of sleepwalking and/or sleep eating. Records from 2007-2016 were included.

Results
56 cases were identified with 50 (89 %) having SW and 16 (29%) SRED. The gender breakdown was 50% male and 50% female with the mean age at diagnosis of 40 (SD 13). Childhood parasomnia events were reported by 23/36 (62%) and a family history in 21/35 (64%). Data were unavailable for the others. The number of parasomnia incidents was ≥ 10 for 21 (37%). A variety of experiences were documented, including leaving the bedroom (39%), injury (25%), and exiting through a window/balcony (5%). Associated factors were sleep deprivation (52%), untreated obstructive sleep apnea (34%), antidepressant use (41%), zolpidem use (18%), circadian disruption (14%) and alcohol use (9%). Polysomnography was conducted for 41 (74%). Documented interventions were medication discontinuation (18%) and starting a benzodiazepine (16%). In 21%, no treatment was given.

Conclusion
This population-based study of adults with clinician diagnosed recurrent SW and SRED revealed equal rates in men and women. The majority of patients with SRED also had SW. 25% of cases were associated with injuries.

Support
Rochester Epidemiology Project supported by NIH R01 AG034676 and AG052425 and the Mayo Foundation.