bluuebunny/crossref_metadata_2025_split huggingface dataset:
357 Daridorexant Does Not Impair Respiratory Function in Patients with Mild/Moderate Obstructive Sleep Apnea Irrespective of Severity
Authors: Boof Marie-Laure , Fietze Ingo , Lederer Katharina , Guern Anne-Sophie , Lemoine Vincent , Dingemanse Jasper , Ufer Mike 
Published: May 2021

Abstract

Introduction
Daridorexant is a dual orexin receptor antagonist developed for the treatment of insomnia. The effect of the highest phase-3 dose of 50 mg daridorexant on nighttime respiratory function was evaluated in patients with mild/moderate obstructive sleep apnea (OSA). This study showed that repeated doses of daridorexant had no clinically meaningful effect on nighttime respiration (i.e., apnea-hypopnea index [AHI] and peripheral oxygen saturation [SpO2]). In the same study, other relevant respiratory endpoints were evaluated.

Methods
In this randomized, double-blind, placebo-controlled, two-period, crossover study, daridorexant or placebo was administered in each period once daily for 5 consecutive nights to 28 patients. Treatment differences (daridorexant – placebo) for total number and mean/longest duration of apneas and hypopneas as well as mean and lowest SpO2 during apnea/hypopnea events in Night 5 were explored using linear mixed-effects modeling. Treatment differences for the above-mentioned endpoints versus AHI during TST at baseline (i.e., OSA severity) was analyzed by linear regression using least square approach.

Results
Of 28 patients enrolled, 25 completed the study and were included in the analysis (n=15/10 with mild/moderate OSA; mean [standard deviation, SD] AHI: 16.3 events/h [8.2]). Compared to placebo, daridorexant increased mean duration of TST and accordingly to a not statistically significant extent the mean number of apneas + hypopneas by 16.4 events (n=103 versus 86.2; 90% confidence interval [CI]: -0.4–33.2]) without difference in mean [SD] AHI between daridorexant (15.1 events/h [7.9] and placebo (14.2 [7.7]). No treatment difference was detected for mean (0.0 sec [-2.6–2.7]) or longest (0.8 sec [-8.9–10.5]) duration of apneas nor for mean (0.2 sec [-2.2–2.5]) or longest (8.3 sec [6.4–23.1]) duration of hypopneas. No treatment difference was observed for mean (0.3% [-0.2–2.1]) and lowest (0.9% [0.3–2.1]) SpO2 during apnea/hypopnea events. Treatment differences for any of the evaluated endpoints did not significantly correlate with AHI at baseline as a marker of OSA severity (r2 ≤ 0.09).

Conclusion
Daridorexant can safely be administered to patients with mild/moderate OSA as treatment differences for respiratory-related endpoints were not of statistical significance and independent of disease severity in the studied population.

Support (if any)
Funded by Idorsia Pharmaceuticals Ltd.
361 Relative Effectiveness of Cognitive Behavioral Therapy and its Components in Improving Insomnia Symptoms in Older Adults
Authors: O’Hora Kathleen , Hernandez Beatriz , Lazzeroni Laura , Zeitzer Jamie , Friedman Leah , Posner Donn , Kushida Clete , Yesavage Jerome , Goldstein-Piekarski Andrea 
Published: May 2021

Abstract

Introduction
The prevalence of insomnia complaints in older adults is 30–48%, compared to 10–15% in the general population. Cognitive Behavioral Therapy for Insomnia (CBT-I) is a first-line, non-pharmacological sleep treatment for Insomnia. However, the relative impact of Behavioral (BT) and Cognitive (CT) components compared to that of CBT-I in older adults is unknown.

Methods
128 older adults with insomnia were randomized to receive CBT-I, BT, or CT. Sleep diaries and the Insomnia Severity Index (ISI) were collected pre- and post-treatment and at a 6-month follow-up. We conducted split-plot linear mixed models with age and sex as covariates to assess within and between subject changes to test effects of group, time, and their interaction on ISI, sleep onset latency (SOL), wake after sleep onset (WASO), total sleep time (TST), time in bed (TIB), sleep efficiency (SE), and percent of treatment responders (ISI decrease&gt;7) and remitters (ISI&lt;8). Effect size (d) was calculated by dividing the difference between means by the root-mean-squared error of the mixed effects model.

Results
All treatments lead to a significant improvement across outcome measures at post-treatment (p’s&lt;0.001) and 6-months (p’s&lt;0.01), with the exception of TIB, response, and remission. For TIB, there was a significant Group x Time interaction (p&lt;0.001): while all treatments significantly reduced TIB post-treatment relative to baseline, CBT-I (p&lt;0.001,d=-2.26) and BT (p&lt;0.001,d=-1.59) performed significantly better than CT (p=0.003, d=-0.68). In contrast, at 6-months CBT-I (p&lt;0.001,d=-1.16) performed significantly better at reducing TIB than CT (p=0.195,d=-0.24) or BT (p=0.023,d=-0.61) relative to baseline. There was also a non-significant trend for a Group x Time interaction for remission status (p=0.062). Whereas, the percentage of remitters within all groups post-treatment did not differ from chance (p&gt;0.234), at 6 months, the percentage of remitters was significantly higher than chance in CBT-I (73.63%,p=0.026) and BT (78.08%,p=0.012), but not CT (47.85%,p=0.826). There were no other significant time or interaction effects (all p&gt;0.05).

Conclusion
CBT-I and its components are effective in improving subjective insomnia symptoms in older adults. Evidence suggests CBT-I may be superior to either CT or BT alone in improving TIB in older adults.

Support (if any)
NIMHR01MH101468; MIRECC at VAPAHCS
364 Use of Blinded Hypnotic Tapering for Hypnotic Discontinuation: Final Report
Authors: Edinger Jack , Wamboldt Frederick , Holm Kristen , Johnson Rachel , Simmons Bryan , Tsai Sheila , Morin Charles 
Published: May 2021

Abstract

Introduction
Many patients have difficulties achieving hypnotic discontinuation due to anxiety that arises when they knowingly reduce their hypnotic dose or withhold it entirely. This study tested a blinded tapering approach to reduce patients’ anxiety and help them discontinue their hypnotics.

Methods
The study sample included 78 (M age = 55.2 ± 12.8 yrs.; 65.4% women) users of benzodiazepine and benzodiazepine receptor agonists. Following baseline assessments, enrollees first completed 4 sessions of cognitive behavioral insomnia therapy (CBTI). Subsequently they were randomized to one of three 20-week, double-blinded tapering protocols wherein their medication dosage either remained unchanged (CTRL) or was reduced by 25% or 10% every two weeks. At the end of the 20-week period the study blind was eliminated and those who completed one of the two blinded tapering protocols entered a 3-month follow-up period, whereas CTRL participants were offered an open label taper before completing the follow-up.

Results
Among those who completed one of the blinded tapering protocols, 92.9% totally discontinued their medication use by the end of the 20-week tapering phase, whereas 77.3% in the CTRL group discontinued hypnotic use by the end of their open label tapering. At follow-up 72.1% of those who completed blinded tapering remained medication free whereas only 52% of those who underwent open-label tapering remained medication free. Comparisons at follow-up showed those who received the open-label taper continued to use hypnotics on average 2.06 nights/week compared to .051 times per week for the blinded taper group (p = .042). The average weekly diazepam equivalent dose of medication used by the open label tapering group was 11.29 mg whereas the weekly dose for the blinded tapering group was 3.22 (p = .069).

Conclusion
CBTI combined with blinded hypnotic tapering is a promising treatment approach for helping hypnotic users overcome their medication dependence.

Support (if any)
National Institute of Drug Abuse, Grant # R34 DA042329-01
365 Cognitive Behavioral Therapy and Light Dark Therapy for Postpartum Insomnia Symptoms: Findings from a Randomized Controlled Trial
Authors: Verma Sumedha , Quin Nina , Astbury Laura , Wellecke Cornelia , Wiley Joshua , Davey Margot , Rajaratnam Shantha , Bei Bei 
Published: May 2021

Abstract

Introduction
Symptoms of insomnia are common in the postpartum period and are associated with a range of negative outcomes. Despite this, interventions to improve maternal postpartum sleep remain scarce. Cognitive Behavioral Therapy (CBT) and Light Dark Therapy (LDT) target two different mechanisms to reduce sleep disturbance. This randomized controlled trial examined the efficacy of CBT and LDT against a treatment-as-usual (TAU) condition in reducing maternal postpartum insomnia symptoms.

Methods
Nulliparous women 4–12 months postpartum with self-reported symptoms of insomnia (Insomnia Severity Index scores [ISI] &gt;7) were included; excluded were those with: current severe health/psychiatric conditions, unsettled infant behaviors, sleep-affecting medication use and photosensitivity. Eligible women were randomized 1:1:1 to 6 weeks of CBT (CBT for insomnia and fatigue), LDT (morning bright light therapy, evening light hygiene), or TAU. Interventions were therapist-assisted and personalized through two telephone calls and included automated self-help intervention materials (i.e., emails) delivered over six weeks. Symptoms of insomnia (ISI; primary outcome), fatigue, sleepiness, depression, and anxiety were assessed at baseline, mid-intervention, post-intervention, and 1-month post-intervention. Analyses were intention-to-treat latent growth models.

Results
114 women were randomized (mean age = 32.20 ± 4.62 years) and 108 women completed the intervention. Compared to TAU, symptoms of insomnia significantly reduced from baseline to post-intervention in both CBT and LDT groups (p-values &lt;.001), with very large effect sizes (d &gt; 1.5) at post-intervention; gains were maintained at follow-up. Fatigue symptoms significantly reduced in the CBT group (p&lt;.0001; d = 0.85) but not LDT (p = 0.11) compared to TAU at post-intervention; gains were maintained for CBT at follow-up. Group differences in sleepiness, depression, and anxiety were nonsignificant (all p &gt; 0.08).

Conclusion
Therapist-assisted self-help CBT and LDT with different therapeutic mechanisms are both efficacious for reducing maternal insomnia symptoms during the postpartum period. Findings were mixed for fatigue, sleepiness and mood. Future research on predictors of treatment responses is needed.

Support (if any)
Australian National Health and Medical Research Council, Department of Education RTP Scholarship. Lucimed SA supplied light therapy glasses. Funders had no role in design/implementation of the trial. ANZCTR: ACTRN12618000842268.
366 Predictors of Dropout in University Students Participating in an 8-week E-mail Based Cognitive Behavioral Therapy for Insomnia
Authors: Nam Hyojin , Chang Jinyoung , Manber Rachel , Trockel Mickey , Okajima Isa , Yang Chien-Ming , Li Shirley , Suh Sooyeon 
Published: May 2021

Abstract

Introduction
As dropout from treatment potentially diminishes its therapeutic effect and poses clinical concern, it is important to find out which characteristics of participants are suitable for online-based treatment. Therefore, we aimed to identify factors that predicted a dropout in the e-mail based cognitive behavioral therapy (REFRESH) developed by Stanford University for the purpose of psychological intervention for insomnia.

Methods
Participants who participated in the REFRESH program consisted of 158 university and graduate students aged 18 to 30 in Hong Kong and Korea who scored higher than 10 on the Insomnia Severity Index (ISI), and the intervention was delivered in 8 weekly sessions sent via weekly e-mails. Among them, 110 were women (70%) and the average age was 22 (±2.71) years old. All participants were asked to answer the following self-reporting questionnaires before and after the intervention: Insomnia Severity Index; ISI, Depression Anxiety Stress Scale 21; DASS-21, Sleep Hygiene Practice Scale; SHPS, Dysfunctional Beliefs and Attitude about Sleep 16; DBAS-16. Descriptive statistics and ROC decision tree analysis were conducted to address our aim.

Results
Of the 158 participants, 68 completed the program, and 90 participants (57%) dropped out. The best predictor of dropout was DASS score with an optimal cup-point of &lt;34. Of the 107 participants who reported DASS &lt;30, 70(65.4%) dropped out. In contrast, of the 50 participants who reported DASS ≥34, 12(38%) dropped out. The second-level predictor was expectations for sleep score with a cut-point of &lt;18. Among participants with DASS &lt;34 and expectations for sleep score &lt;18, 57(73.1%) dropped out. Of the 29 participants who reported DASS &lt;34 and expectations for sleep score ≥18, 13(44.8%) dropped out.

Conclusion
Mild levels of depression, anxiety and stress and expectations for sleep appear to be predictive of dropout in an e-mail based intervention. People with mild symptoms may experience less distress and impairment, which may result in lower motivation to receive treatment. This may lead to inability to complete treatment and higher rates of dropout.
Support (if any):
367 A sleep hygiene and relaxation training program after the Great East Japan Earthquake: What aspects of sleep could be improved?
Authors: Sato Toshihiko , Ambo Hideo 
Published: May 2021

Abstract

Introduction
After a natural disaster, the incidence of sleep difficulties tends to increase. Specifically, the prevalence of suspected insomnia was reported to have increased among disaster victims after the Great East Japan Earthquake of March 11, 2011. In a previous study, we have reported that education on sleep hygiene and relaxation training was effective in improving nighttime sleep in students of universities in Sendai city after the earthquake of March 2011. According to analyses of subscale scores of the Pittsburgh Sleep Quality Index (PSQI), the present study aimed to determine what aspects of sleep difficulties were successfully improved.

Methods
University undergraduates and graduates who reported having sleep difficulties were asked to respond to a questionnaire including the PSQI thrice, before attending a 90-min lecture on sleep hygiene and relaxation training, and a month and three months after attending the program. All participants who reported the total PSQI score of the cutoff point (6) or more were divided into two groups based on their PSQI scores before the program, that attending the course and that not attending it, that is, the “waiting list” group.

Results
The “attending” group exhibited a decrease in the total PSQI score in the first month after attending the program, and the score in this group reduced further three months later; Nine of twenty (45.0%) attending participants reported the score of less than 6 after a month, while only three of seventeen (17.6%) wait-list participants did. The PSQI subscale scores reported by the nine successful attending participants indicated a significant decrease in the subscale scores on subjective sleep quality, sleep latency, sleep duration, and sleep disturbance from before the program to one month later.

Conclusion
These results suggest that the short course on sleep hygiene and relaxation training intended for university students was effective, and about a half of the attended participants reported the PSQI score of less than the PSQI cutoff score one month later. This substantial effect would be mainly based on the improvement of their subjective sleep quality, latency, duration, and disturbance.

Support (if any)
This study was supported by a research grant from the Japanese Psychological Association, Tokyo, Japan.
369 Insomnia with objective short sleep duration is associated with increased cortisol in patients with Mild Cognitive Impairment
Authors: Vgontzas Alexandros , Basta Maria , Li Yun , Fernandez-Mendoza Julio , Zaganas Ioannis , Panagiotakis Symeon , Simos Panagiotis 
Published: May 2021

Abstract

Introduction
Mild cognitive impairment (MCI) is frequent in the elderly and is in a continuum with dementia in a significant amount of people. Both insomnia and increased cortisol levels have been suggested as risk factors for MCI. The goal of this study was to examine whether activation of the hypothalamic-pituitary-adrenal (HPA) axis, as measured by plasma cortisol levels, is associated with the insomnia with short sleep duration (ISS) phenotype, as measured by actigraphy, in elderly with MCI.

Methods
A sub-sample of 109 subjects with MCI and 92 cognitively non-impaired controls 60 years or older (75.37±6.54y) was recruited from a population-based cohort residing on Crete, Greece. Subjects underwent medical history, physical examination, neuropsychiatric evaluation, neuropsychological testing, 3-day 24-h actigraphy, assessment of subjective insomnia symptoms (i.e., difficulties initiating and/or maintaining sleep), and a morning blood draw to assay for plasma cortisol levels. The ISS phenotype was defined by the presence of at least one insomnia symptom and an actigraphy-measured sleep efficiency below the median of the entire sample (i.e., ≤81%). Group differences in plasma cortisol levels between MCI subjects with and without the ISS phenotype were tested using ANCOVA adjusting for age, gender, BMI and depression.

Results
Subjects with MCI had higher cortisol levels compared to controls (105.34±9.34 vs. 70.3±10.02 nmol/L, p&lt;0.05). Subjects with MCI and the ISS phenotype (138.38±16.57 nmol/L) had significantly higher cortisol levels compared to those without insomnia (97.74±19.68 nmol/L) or those with insomnia and normal sleep duration (INS; 79.97±16.02 nmol/L, p=0.044). The association between the ISS phenotype and cortisol levels was modified by amnestic symptoms (p-interaction=0.079); commensurate, the ISS phenotype was associated with higher cortisol levels among the amnestic MCI subgroup (INS: 79.12±21.93 vs. ISS: 155.55±20.40 nmol/L, p=0.040), but not among the non-amnestic MCI subgroup (INS: 64.06±23.62 vs. ISS: 89.33±29.00 nmol/L, p=0.559).

Conclusion
The ISS phenotype is associated with increased cortisol levels in elderly with MCI, particularly those with amnestic type. Improving sleep quality, decreasing cortisol levels and lengthening sleep duration may slow down the progression of these individuals into dementia.

Support (if any)
National Strategic Reference Framework(NSRF), Program: THALES entitled “UOC-Multidisciplinary network for the study of Alzheimer’s Disease” Grant Cod:MIS 377299
373 Historical Use of Substances for Insomnia Impacts Current Beliefs about Hypnotic Medications
Authors: Dietch Jessica , Simpson Norah , Tutek Joshua , Tully Isabelle , Rangel Elizabeth , Manber Rachel 
Published: May 2021

Abstract

Introduction
The purpose of the current study was to examine the relationship between current beliefs about hypnotic medications and historical use of prescription hypnotic medications or non-prescription substances for sleep (i.e., over the counter [OTC] medications, alcohol, and cannabis).

Methods
Participants were 142 middle age and older adults with insomnia (M age = 62.9 [SD = 8.1]; 71.1% female) enrolled in the RCT of the Effectiveness of Stepped-Care Sleep Therapy In General Practice (RESTING) study. Participants reported on history of substances they have tried for insomnia and completed the Beliefs about Medications Questionnaire-Specific with two subscales assessing beliefs about 1) the necessity for hypnotics, and 2) concerns about potential adverse consequences of hypnotics. Participants were grouped based on whether they had used no substances for sleep (No Subs, 11.6%), only prescription medications (Rx Only, 9.5%), only non-prescription substances (NonRx Only, 26.6%), or both prescription and non-prescription substances (Both, 52.3%).

Results
Sixty-one percent of the sample had used prescription medication for sleep and 79% had used non-prescription substances (74% OTC medication, 23% alcohol, 34% cannabis). The greater number of historical substances endorsed, the stronger the beliefs about necessity of hypnotics, F(1,140)=23.3, p&lt;.001, but not about concerns. Substance groups differed significantly on necessity beliefs, F(3,1)=10.68, p&lt;.001; post-hocs revealed the Both group had stronger beliefs than the No and NonRx Only groups. Substance groups also differed significantly on the concerns subscale, F(3,1)=6.68, p&lt;.001; post-hocs revealed the NonRx Only group had stronger harm beliefs than the other three groups.

Conclusion
The majority of the sample had used both prescription and non-prescription substances to treat insomnia. Historical use of substances for treating insomnia was associated with current beliefs about hypnotics. Individuals who had used both prescription and non-prescription substances for sleep in the past had stronger beliefs about needing hypnotics to sleep at present, which may reflect a pattern of multiple treatment failures. Individuals who had only tried non-prescription substances for sleep may have specifically sought alternative substances due to concerns about using hypnotics. Future research should seek to understand the impact of treatment history on engagement in and benefit from non-medication-based treatment for insomnia.

Support (if any)
1R01AG057500; 2T32MH019938-26A1
376 dCBT-I with Chatbot and Artificial Intelligence: a feasibility study in Brazil
Authors: Castro Laura , Baraças Lucas , Hashioka Guilherme , Carvalho Adriana 
Published: May 2021

Abstract

Introduction
Digital cognitive-behavioral therapies for insomnia (dCBT-I) provide low-cost, evidence-based technology, effective in improving mental health and reducing healthcare costs. However, dropout rates still challenge dCBT-I scalability. Moreover, few solutions are available in middle-and-low-income economies where they are most needed. Our goal was to investigate feasibility, describing real-world data and preliminary findings of a novel, fully automated program, developed by Vigilantes do Sono (Sleep Watchers) using Chatbot and Artificial Intelligence (AI).

Methods
A digital coach interacts with users daily for 5–10 minutes, asking them to complete tailored diaries and delivering CBT-I knowledge pills in ~50 sessions, during ~7 weeks. The Insomnia Severity Index (ISI) is used before and after sleep restriction cycles, weekly revised by an algorithm. Participants (18+ years) were recruited (Jan-Oct/2020) through advertisements on social media, organic search, or were referred by health-care professionals, without face-to-face evaluation. All electronically signed an informed consent. We estimated engagement dividing number of complete diaries by number of days in the program. Generalized Estimating Equations (GEE) evaluated changes in sleep parameters, adjusting for baseline characteristics.

Results
Of 3,887 individuals who completed initial assessment, 3,139 (81%) had insomnia (ISI ≥11) and 1,489 (42±11 years, 91% women) fulfilled 7+ diaries, commenced sleep restriction, and were included in analysis. Of them, 604 (41%) completed a second ISI and 326 (22%) finished the program. GEE analyzing 42,802 diaries showed sleep duration increased 16.8 (11.9–21.6) minutes from first to second week and 67.3 (52.8–81.8) after week seven; parallel to a relative increase of 34% in sleep efficiency among women and 26% among men. Of 296 participants who reached therapeutic response (ISI reduction ≥8), 66% completed all sessions and 34% crossed half-way. Insomnia remission (ISI≤7) was seen for 55% and 33% of those with subthreshold (n=171) or clinical (n=419) baseline insomnia, respectively. Median (interquartile) engagement was 86% (65–98) and 90% of users recommend the program.

Conclusion
Chatbot and AI provide a framework to customize dCBT-I and personalize insomnia therapy, potentially favoring engagement and effectiveness. Our findings demonstrate feasibility of the program and support moving forward to continued development and testing the effects in clinical trials.
Support (if any):