bluuebunny/crossref_metadata_2025_split huggingface dataset:
0535 Evaluation of Insomnia Symptoms in a Double-Blind, Randomized, Placebo-Controlled Phase 3 Trial of Sage-217 in Postpartum Depression
Authors: Mittal A , Deligiannidis K , Huang M , Suthoff E , Acaster S , Fridman M , Li S , Gunduz-Bruce H , Lasser R , Campbell A D , Bonthapally V , Hodgkins P , Kanes S J , Werneburg B 
Published: May 2020

Abstract

Introduction
Postpartum depression (PPD) is a specifier of major depressive disorder (MDD) with peripartum onset. SAGE-217, an investigational, oral neuroactive steroid GABAA receptor positive allosteric modulator, demonstrated improvements in depressive and anxiety symptoms versus placebo in a Phase 3 trial in PPD (NCT02978326; ROBIN) and a pivotal trial in MDD (NCT03000530). In PPD and MDD, insomnia symptoms are key diagnostic features, comorbid sleep disorders are frequent, and insomnia is a common residual symptom. Here we conducted post-hoc analyses to assess insomnia symptoms in the ROBIN trial.

Methods
Women (n=151) ages 18-45, ≤6 months postpartum, with PPD (major depressive episode beginning in 3rd trimester or ≤4 weeks postpartum) and a Hamilton Rating Scale for Depression (HAM-D) total score ≥26, were randomized 1:1 to receive outpatient SAGE-217 30mg or placebo for two weeks, with 4 weeks follow-up. Change from baseline (CFB) in HAM-D score at Day 15 was the primary endpoint. Secondary endpoints included CFB in HAM-D at other time points and the Montgomery-Åsberg Depression Rating Scale (MADRS). Post-hoc analyses assessed HAM-D insomnia subscale (HAM-D-Ins) and MADRS individual insomnia item (MADRS-Ins) scores. HAM-D and MADRS measures were evaluated using a mixed-effects model for repeated measures. Safety and tolerability were assessed by adverse event (AE) reporting.

Results
SAGE-217 demonstrated statistically significant Day 15 CFB versus placebo in HAM-D (primary endpoint: -17.8 vs. -13.6, p=0.0028), MADRS (-22.1 vs. -17.6, p=0.0180), and associated insomnia sub-scales/items (difference SAGE-217 vs. placebo; HAM-D-Ins: -1.003, p=0.0038; MADRS-Ins: -0.773, p=0.0116). Significant CFB in insomnia sub-scales/items favoring SAGE-217 were observed by Day 3 (HAM-D-Ins: -0.841, p=0.0142; MADRS-Ins: -0.710, p=0.017) and at Day 45 (HAM-D-Ins: -0.730, p=0.0207; MADRS-Ins: -0.636, p=0.0221). Most common (≥5%) AEs were somnolence, headache, dizziness, upper respiratory tract infection, diarrhea, and sedation.

Conclusion
SAGE-217 demonstrated improvements in depression symptoms, including insomnia symptoms, and was generally well tolerated.

Support
This study was sponsored by Sage Therapeutics, Inc.
0536 Motivation at Pretreatment and its Correlates in a Trial of Digital CBT For Insomnia: Preliminary Findings
Authors: Ji X , Cheung J M , Ivers H , Morin C M 
Published: May 2020

Abstract

Introduction
Pretreatment motivation is a critical variable in any intervention seeking to modify behaviors. Lack of motivation may hamper the effects of cognitive-behavioral therapy for insomnia (CBT-I), especially when delivered online. This study aims to investigate baseline correlates of pretreatment motivation and its influence on treatment outcomes in the context of digitalized CBT-I.

Methods
This is a secondary analysis of an ongoing pragmatic trial conducted in primary care clinics of Québec City, Canada. The trial was designed to assess the efficacy of a stepped-care intervention for chronic insomnia in which participants received a digital CBT-I (SHUTi), alone or in addition to sleep medication they were already using. Pre-treatment motivation was measured using two items based on the perceived importance of improving sleep and readiness to change behaviors to improve sleep (Score range: 0 to 20; cronbach’s alpha 0.79). Baseline questionnaires included an extended version of Insomnia Severity Index (ISI), Fatigue Severity Scale (FFS), Generalized Anxiety Disorder (GAD-7) and Patient Health Questionnaire (PHQ-9). Treatment outcome was measured by a change in ISI scores (i.e. ISI post - ISI pre).

Results
A total of 28 participants were included in the analysis. All participants preferentially selected ISI either as monotherapy (n=13)or in combination with their usual sleep medication (n=15). Participants’ motivation before treatment was high (Mean: 18.04; SD: 1.93). We did not find any associations between motivation and ISI score change or incidence of dropout. However, baseline fatigue was positively correlated with pretreatment motivation (r = 0.51, p = 0.005) and more severe insomnia symptoms were also associated with higher motivation (r=0.43, p=0.03). Specifically, perceived importance was associated with both nighttime and daytime insomnia symptoms while readiness for behavioral change was only associated with daytime impairments on energy, mood and social activities (all p = 0.01). Baseline anxiety and depressive symptoms were not correlated with motivation.

Conclusion
Insomnia-related daytime impairments and elevated fatigue levels appear to be linked to pretreatment motivation, especially for behavioral changes. Further study with greater statistic power is warranted to understand the relationship between participants’ motivation and treatment adherence or outcomes.

Support
CIHR0083000212
0541 Exploratory Study of Closed-Loop, Artificial Intelligence Driven Neurotechnology Improves Self-Reported Symptoms of Insomnia, Stress, and Anxiety in First Responders
Authors: Tegeler C L , Howard L J , Brown K L , Kellar D C , Shaltout H A , Gerdes L , Tegeler C H 
Published: May 2020

Abstract

Introduction
First responders (FR) have decreased life expectancy, attributed to work-related exposure to traumatic stress and circadian disruption. In prior studies, High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM®) reduced symptoms and improved heart rate variability (HRV) in law enforcement personnel. HIRREM is operator dependent, difficult to scale, and many medications were excluded for prior studies. Cereset Research™ (CR) uses HIRREM core technology, echoing tones linked to brainwaves, with updated components, artificial intelligence (AI) driven protocols, and software management of designs to improve scalability. We report symptom changes in a series of first responders enrolled in an exploratory study evaluating CR for self-reported symptoms of insomnia, stress, or anxiety, including subjects taking previously excluded medications.

Methods
11 adults (4 females) meeting criteria for insomnia (ISI, of ≥8 points for ≥1 month), stress (PSS of ≥14), or anxiety (GAD-7 of ≥5), who are also FR, enrolled in this ongoing exploratory trial. Subjects receive six to twelve 60 minute sessions of CR, plus continued current care. Data collection is at baseline (V1), 0-21 days post-intervention (V2), 4-7 weeks later (V3), and 4-7 weeks thereafter (V4). Primary outcome is change in autonomic cardiovascular regulation at V3, with change in ISI, PSS, GAD-7, CES-D, and PCL-C as secondary outcomes. We report interim results for symptom outcomes at V3. HRV and baroreflex sensitivity results are pending.

Results
2 dropped out during follow-up. For n=9, median change from V1 to V3 ISI score: -6; PSS score: -4; GAD-7: -4; CES-D: -3; and PCL-C: -8. The cohort moved to no anxiety and low stress categories from V1 to V3.

Conclusion
Results suggest relevant symptom reductions among FR following use of CR, as seen previously with HIRREM for law enforcement, even with additional medications. This informs future randomized clinical trials using this scalable, non-drug intervention. Updated results will be presented.

Support: Support
Research grant received from, The Susanne Marcus Collins Foundation, Inc.
0553 Hallucinogen Use Among College and University Students: Associations with Insufficient Sleep and Insomnia
Authors: Holbert C , Bastien C , c S , Killgore W D , Wills C C , Grandner M A 
Published: May 2020

Abstract

Introduction
Previous studies have shown that poor sleep is associated with alcohol use, smoking, and other substance use, especially among young adults. Yet, very little is known about hallucinogen use.

Methods
Data from the 2011-2014 National College Health Assessment were used (N=113,749), representing a wide range of students across the US. Hallucinogen use was reported as “never,” “past,” and “present” (reflecting use in the past 30 days). Students also self-reported nights/week they did not get enough sleep to feel rested (insufficient sleep), as well as nights/week they had difficulty falling asleep (initial insomnia). Responses for both were categorized as 0, 1-2, 3-4, 5-6, or 7 nights/week. Multinomial logistic regressions examined hallucinogen use as outcome (past or present vs never) and sleep as predictor, with adjustment for covariates (age, sex, race/ethnicity, and survey year) and mental health (past 30 days depression/anxiety).

Results
Hallucinogen use was infrequently reported, with 4.8% (N=5,493) reporting past use and 0.98% (N=1,119) reporting present use. In adjusted analyses, increase likelihood of past use was associated with insufficient sleep on 1-2 (RRR=1.28, p=0.001), 3-4 (RRR=1.37, p&lt;0.0005), 5-6 (RRR=1.30, p&lt;0.0005), and 7 (RRR=1.34, p&lt;0.0005) nights per week, as well as 1-2 (RRR=1.30, p&lt;0.0005), 3-4 (RRR=1.52, p&lt;0.0005), 5-6 (RRR=1.58, p&lt;0.0005), and 7 (RRR=1.49, p&lt;0.0005) nights per week of initial insomnia. Present use was associated with 1-2 (RRR=1.44, p&lt;0.0005), 3-4 (RRR=1.76, p&lt;0.0005), 5-6 (RRR=2.05, p&lt;0.0005), and 7 (RRR=1.83, p&lt;0.0005) nights per week of initial insomnia. When mental health was entered into the model, results were maintained.

Conclusion
Past use of hallucinogens was associated with insufficient sleep as well as insomnia. Present use was also associated with insomnia. When mental health was included in models, all results were maintained. It is not clear whether hallucinogen use leads to, or is predicted by, sleep difficulties.

Support
Dr. Grandner is supported by R01MD011600
0579 Non Intrusive and Unattended Sleep Analyzer Effectively Screens Patients Suspected of Sleep Apnea: A Comparison With Polysomnography
Authors: Edouard P , Campo D , Bartet P , Marais L , Petitjean M , Roisman G , Bruyneel M , Escourrou P 
Published: May 2020

Abstract

Introduction
Sleep Apnea Syndrome (SAS) is largely underdiagnosed due to the cost and availability of Polysomnography (PSG). We aimed at evaluating the diagnosis of SAS with the WITHINGS Sleep Apnea Detector (SAD), a non-intrusive pressure and sound sensor placed under the mattress.

Methods
118 patients (67 F, 49 years, BMI 33kg/m²) suspected of SAS had an in-laboratory PSG together with Sleep Apnea Detector. From the pressure signal, Sleep Apnea Detector derives respiratory and cardiac signals and movements. From the microphone, snoring and snorting are detected. These features are used to detect sleep periods with a Random Forest classifier and apnea and hypopnea events with a Convolutional Neural Network. The Total Sleep Time (TST) and Apnea Hypopnea Index (AHI) deduced (TSTsad, AHIsad) are compared with the PSG results scored according to AASM rules (TSTpsg, AHIpsg). AHI and TST were compared using bias and Mean Absolute Error (MAE). Sensitivity, specificity, likelihood ratios (LR) and AUROC were calculated for AHI thresholds of 15 and 30/hr.

Results
The average (SD) TSTpsg was 367 (61) minutes. Sleep Apnea Detector overestimated TST by 25 minutes, 7.0% of the average duration in the sample. The precision is acceptable, with a MAE=53 minutes. Average AHIpsg was 32.5 (30.1) and AHIsad 32.8 (29.9). The bias was 0.3 (95% CI [-2.7, 3.3]), MAE=10.3. The sensitivity (Se15) and specificity (Sp15) and their 95% confidence intervals were Se15=88.0% [79.0, 94.1] and Sp15=88.6% [73.3, 96.8]. Positive and negative LR were respectively LR+15=7.70 and LR-15=0.136. AUROC15=0.926. At the 30 threshold, Se30=86.0% [73.3, 94.2] and Sp30=91.2% [81.8, 96.7]. Positive and negative LR were LR+30=9.75 and LR-30=0.153. AUROC30=0.954.

Conclusion
Sleep Apnea Detector has excellent sensitivity and specificity, low bias and good precision. Thus it can be used as an unattended SAS screening device in patients likely to suffer from SAS.

Support
WITHINGS
0595 Obstructive Sleep Apnea Characteristics in Younger Versus Older Women
Authors: Budhiraja R , Limbekar N , Quan S 
Published: May 2020

Abstract

Introduction
There are few large studies of obstructive sleep apnea (OSA) comparing the clinical and polysomnographic characteristics between men and women, and between younger and older women.

Methods
The current study involves retrospective analyses of data from the Apnea Positive Pressure Long-term Efficacy Study (APPLES), a prospective multicenter randomized controlled trial in persons with OSA. The mean age of the 1105 participants was 51.6 ± 12 years (range 18-83 years). The participants included 723 men (65.4%) and 382 women (34.6%). Of all women, 25% were &lt;=45 years of age (likely pre-menopausal) and 50% were above &gt;=53 years of age (likely post-menopausal). We used these 2 groups to define younger women and older women, respectively.

Results
The overall mean body mass index (BMI) and apnea hypopnea index (AHI) were 32.2 ± 7.1 Kg/m2 and 40.1 ± 25.2 (range 6-156/hour), respectively. Women had a higher BMI and Epworth Sleepiness Scale (ESS) than men but a lower AHI and lower arousal index (AI). The Hamilton Rating Scale for Depression (HAMD) score was also significantly higher in women. Younger men and women had no other PSG differences including total sleep time (TST), Sleep Efficiency (SE), Sleep Onset Latency (SOL). Older women had lower AHI, higher TST and higher SE than older men. Morningness-Eveningness Questionnaire (MEQ) scores were lower in women than in men in all age groups (suggestive of eveningness). Compared to the older women, younger women had higher BMI, HAMD score and ESS, but lower MEQ score. On PSG, younger women had higher TST and SE but similar SOL, AHI and AI.

Conclusion
In this cohort with OSA, the prevalence of sleepiness and depression is higher in women than in men despite a lower AHI and lower AI. Sleepiness and depression are more common in younger compared to older women with OSA despite similar AHI and AI and a higher SE. Women with OSA demonstrate more ‘eveningness’ compared to men with OSA, as do younger women compared to older women.

Support
Contract 5UO1-HL-068060 from the National Heart, Lung and Blood Institute
0625 The Effects of Topical Nasal Steroids on Continuous Positive Airway Pressure Compliance in Patients with Obstructive Sleep Apnea
Authors: Segsarnviriya C , Mahakit P 
Published: May 2020

Abstract

Introduction
Continuous positive airway pressure (CPAP) for treatment of moderate to severe obstructive sleep apnea can produce troublesome nasal symptoms (i.e. congestion, rhinorrhea, sneezing, itching) that may affect the continuity and decrease the compliance of CPAP. Topical nasal steroids are often prescribed to reduce these side effects, although recent studies are scarce supporting any benefit of this treatment for CPAP-induced nasal side effects.

Methods
80 patients who were previously diagnosed with OSA and pretreatment nasal symptoms were enrolled. All of them were selected for CPAP treatment and divided randomly into two groups. The study group was prescribed Fluticasone furoate nasal spray 55 ug daily before bedtime. The patients’ compliance to CPAP was recorded by the memory card in CPAP device. Total nasal symptom score was assessed using a questionnaire by direct interview. The follow-up was performed in 30 and 90 days after treatment.

Results
The compliance to CPAP (Percent days with usage, Average time usage and Percent of days with usage ≥ 4 hours) increased in both groups with higher significance in topical nasal steroid group (P-value=0.002, 0.001, 0.002) after 90 days of treatment. There was no difference in nasal symptom between both groups after 30 days of treatment. However, addition of topical nasal steroid resulted in decreased rhinorrhea and congestion symptom (P-value &lt;0.001, &lt;0.001) after 90 days of treatment.

Conclusion
The addition of topical nasal steroid decreased the frequency of nasal symptoms (esp. rhinorrhea and congestion) in OSA patients initiating CPAP therapy and increased the compliance to CPAP after 90 days of treatment.

Support
Keywords: Obstructive sleep apnea, Continuous positive airway pressure, CPAP, Topical nasal steroid
0630 Comparison Between the Use of APAP and Manual Titration During Split Night Polysomnography for Diagnosis and Treatment of OSA
Authors: Gharraf H S , Shaarawy H m 
Published: May 2020

Abstract

Introduction
CPAP remains the gold standard treatment for OSA, CPAP titration can be done using manual titration or using APAP devices, CPAP titration can be done using full night or split night protocol. The aim of the study Is to compare between the use of APAP and manual titration to determine the needed CPAP pressure during split night polysomnography for diagnosis and treatment of OSA.

Methods
100 patients with severe OSA were enrolled after exclusion of patients with heart failure or respiratory failure. After diagnostic polysomnography, patients were divided into 2 groups: group1 offered manual CPAP titration and Group2 offered APAP titration, the time for CPAP titration was at least 4 hours in both groups.

Results
both groups were matched as regard age, gender, BMI, sleep parameters and AHI (44.52 ± 7.81/hour in group1 and 42.66 ± 9.68/hour in group2 with no statistical significance, after CPAP titration AHI was significantly improved in both groups, the time needed to reach the therapeutic pressure was significantly lower in group2 than in group1, attended technician was needed only in group1.

Conclusion
Use of APAP was equal to manual titration in this group of patients with severe OSA, with decreased cost and lesser time to reach the therapeutic pressure, large multicenter trials are needed to modify the guidelines in view of using APAP in split night protocol for diagnosis and treatment of OSA.

Support
no conflict of interest
0654 Obstructive Sleep Apnea in Older Adults: Geographic Variation in CPAP Treatment
Authors: Yu Y , Levine R S , Braley T J , Burke J F , Chervin R D , Dunietz G L 
Published: May 2020

Abstract

Introduction
Obstructive sleep apnea (OSA) is prevalent and consequential among older adults. Positive airway pressure (PAP) is likely to reduce associated morbidity, but adherence is inconsistent. Regional treatment variations that may reflect addressable differences in care are not sufficiently studied. We examined geographic variations in PAP treatment among older US adults.

Methods
A representative 5% sample of all Medicare beneficiaries, age 65+, enrolled in fee-for-service program in 2013 was analyzed. OSA diagnosis was defined by ICD-9 codes. PAP treatment was identified by HCPCS codes. Treatment adherence was defined as ≥2 HCPCS claims for PAP supplies on separate months. We examined state-specific proportions of Medicare beneficiaries with OSA who obtained PAP and showed adherence. Maps were created to represent state-specific proportions of beneficiaries who were treated and adherent, by quantiles. To examine more granular regional variations, we created maps representing hospital referral region (HRR)-specific proportions of treated among diagnosed, and adherent among treated. Scatterplots were used to identify the relationship between proportions of PAP treatment and adherence, by state.

Results
For the state-level data, PAP treatment and adherence rates were between 54%-87% and 59%-81%, respectively. Midwest states had higher CPAP treatment proportions (&gt;80%), while Northeast, Southwest and Southern states had CPAP treatment rates &lt;73%. State-level CPAP adherence showed similar patterns, with lowest rates in southern states and California (&lt;70%). Within-state variability of treatment patterns were observed, especially along the east and the west coasts. A scatterplot revealed that state-level CPAP treatment and adherence rates were linearly correlated, with Washington D.C., NY and NJ ranked lowest. In contrast, MT, ND and VT had the highest treatment and adherence rates.

Conclusion
These data show substantial state-level and regional variability of CPAP treatment and adherence among Medicare beneficiaries. Some geographic areas may merit prioritization in efforts to improve OSA treatment and adherence.

Support
This study was supported by The American Sleep Medicine Foundation Strategic Research Award 115-SR-15
0665 Bilateral Hypoglossal Nerve Stimulation for Treatment of Obstructive Sleep Apnea
Authors: Eastwood P R , Barnes M , MacKay S G , Wheatley J R , Lewis R , Campbell M C , Jones A C , Palme C E , Petelle B , Meslier N , Bertolus C , Denoncin K , Attali V , Gagnadoux F , Launois S H 
Published: May 2020

Abstract

Introduction
Hypoglossal Nerve Stimulation (HGNS) decreases obstructive sleep apnea (OSA) severity by contracting the tongue and decreasing upper airway collapsibility. This study assessed the safety and effectiveness of a new implantable device that delivers bilateral HGNS: the Genio™ system.

Methods
The BLAST OSA study (BiLAteral Hypoglossal Nerve Stimulation for Treatment of Obstructive Sleep Apnea), was a prospective, open-label, non-randomized, single arm treatment study conducted at eight centres in three countries (Australia, France, UK). Primary outcomes were the incidence of device-related Serious Adverse Events (SAEs) and change in the Apnea-Hypopnea Index (AHI). The secondary outcome was change in the 4% Oxygen Desaturation Index (ODI). Additional outcomes included measures of sleepiness, quality of life, snoring, and device use. Participants were eligible if: 21-75 years old; BMI ≤ 32 kg/m2; obstructive AHI 20-60 events/hr and combined central and mixed AHI &lt; 10 events/hr; no positional OSA; no Complete Concentric Collapse of the soft palate during Drug Induced Sleep Endoscopy; and failed to tolerate or accept Positive Airway Pressure treatments.

Results
27 participants were implanted (63% male, aged 55.9±12.0 years, BMI 27.4±3.0 kg/m2). 22 completed the protocol. At 6 months, AHI decreased from 23.7±12.2 to 12.9±10.1 events/hr [p&lt;0.001]; and ODI decreased from 19.1±11.2 to 9.8±6.9 events/hr [p&lt;0.001]. Daytime sleepiness (ESS, p=0.011) and sleep-related quality of life (FOSQ-10, p=0.016) both significantly improved. 91% of participants reported using their device &gt;5 days per week, and 77% used it &gt;5 hours per night. The number of bed partners reporting disruptive snoring decreased from 96% to 35%. No device-related SAE occurred.

Conclusion
In a targeted population of individuals with moderate-to-severe OSA, the Genio system reduced OSA severity and sleepiness, improved quality of life, and was associated with high adherence and an acceptable safety profile.

Support
This study trial was funded by Nyxoah S.A. This trial was registered with ClinicalTrials.gov, number NCT03048604.