bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of Dimdazenil in adults with insomnia disorder: results from a multicenter, randomized, double-blind, placebo-controlled phase III trials
Authors: Huang Zhaoyang , Zhan Shuqin , Chen Chunyan , Zhang Ruoxi , Zhou Yanling , He Jingjing , Lin Zhaocun , Bao Cungang , Zhu Shuangpeng , Zhao Jianjun , Zhang Shengan , Jiang Yu , Wang Yuping 
Published: October 2023

Abstract

Study Objectives
To evaluate the efficacy and safety of Dimdazenil, a novel partial positive allosteric modulator for GABAA receptor in adults with insomnia disorder.

Methods
This was a 2-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group phase III study of Dimdazenil. The primary efficacy outcome was total sleep time (TST) analyzed by polysomnography (PSG) on day 13/14. Latency to persistent sleep (LPS), sleep efficiency (SE), and wake after sleep onset (WASO) were analyzed in the same way by polysomnography (PSG). The other secondary outcomes including the average subjective sleep latency (sSL), subjective TST (sTST), subjective SE (sSE), subjective WASO (sWASO), and subjective number of awakenings (sNAW) were analyzed from sleep diary data, and the insomnia severity index (ISI) was also assessed. Treatment-emergent adverse events (TEAEs) were monitored throughout the study.

Results
A total of 546 participants with insomnia (age ≥18 years) were randomized (2:1), received treatment with an oral dose of Dimdazenil (2.5 mg) or placebo, and analyzed. Compared to baseline and placebo, Dimdazenil demonstrated significant improvements in PSG measures, increased TST (71.09, 31.68 minutes, respectively; both p &lt; 0.001), increased SE (13.26%, 5.55%, respectively; both &lt; 0.001), reduced WASO (49.67, 20.16 minutes, respectively; both p &lt; 0.001), and reduced LPS (21.65 minutes, p &lt; 0.001; 6.46 minutes, p = 0.023). Compared to placebo, Dimdazenil also improved key self-reported measures of sTST (18.33 minutes, p &lt; 0.001), sWASO (14.60 minutes, p &lt; 0.001), sSL (4.23 minutes, p &lt; 0.001), sSE (2.97%, p &lt; 0.001), and sNAW (0.29, p &lt; 0.001). Participants treated with Dimdazenil reported a significant improvement in ISI. Dimdazenil was well tolerated. The majority of TEAEs were mild or moderate. There were no clinically relevant treatment-related serious AEs and no deaths.

Conclusions
Dimdazenil of 2.5 mg provided significant benefit on sleep maintenance and sleep onset in individuals with insomnia disorder versus placebo, with a favorable safety profile and was well tolerated.

Clinical Trial Information
A multicenter, randomized, double-blind phase III clinical study evaluating the efficacy and safety of EVT201 capsules compared to placebo in patients with insomnia disorders (http://www.chinadrugtrials.org), with the number of CTR20201068.
O002 High strain evening exercise disrupts sleep: Insights from a real-world examination of ~7-million nights
Authors: Leota J , Presby D , Czeisler M , Mascaro L , Capodilupo E , Drummond S , Rajaratnam S , Facer-Childs E 
Published: October 2023

Abstract

Introduction
Exercise is among the most effective daytime behaviors for promoting and maintaining sleep. However, late-night bouts of strenuous exercise that require high physiological demand (i.e., high strain) induce persistent increases in sympathetic arousal, which may disrupt sleep. We examined whether exercise strain moderates the relationship between evening exercise and objective sleep in free-living conditions.

Methods
A total of 19,977 individuals (26% female, M-age=37.9 years) wore a validated sleep and exercise biometric wearable device for 365 days between Sep 1, 2021 and Aug 31, 2022 (n=6,943,372 nights). Summated-heart-rate-zone-scores were used to categorize exercise strain into four groups: light, moderate, high, and all-out. Exercise timing was normalized to each individual’s habitual bedtime to account for individual differences in sleep/wake timing. Generalized additive mixed model analyses were used to model the non-linear relationship between exercise timing and sleep at different levels of exercise strain.

Results
Later exercise timing was associated with delayed sleep onset, reduced sleep quantity and quality, and increased sympathetic activity compared to no-exercise rest days (ps&lt;.001). Importantly, a dose-response relationship was observed such that higher levels of exercise strain predicted worse sleep (ps&lt;.001). Regardless of strain, exercise bouts ending at least 4 hours before habitual bedtime were not associated with changes in sleep.

Discussion
Evening exercise—particularly involving high exercise strain—can disrupt subsequent sleep (both duration and quality). It is recommended individuals stop exercising at least 4 hours before their habitual bedtime. However, when evening exercise is unavoidable, individuals could select lighter strain exercises to mitigate sleep disruption.
O007 Validation of an under-mattress sleep tracker to estimate sleep and wake during day and night sleep opportunities
Authors: Manners J , Kemps E , Lechat B , Stuart N , Guyett A , Proctor S , Eckert D , Catcheside P , Scott H 
Published: October 2023

Abstract

Introduction
Consumer sleep trackers are useful for tracking daily sleep, particularly in shift-workers, yet large, multi-night validations against direct sleep measures are lacking. Conducted as one of the largest sleep tracker validation studies to date, this study evaluated performance of an under-mattress sensor (Withings Sleep Analyzer [WSA]) to classify sleep and wake versus polysomnography (PSG) in a multi-night laboratory protocol with both day and night sleep opportunities.

Methods
27 healthy sleepers attended the laboratory twice, for 8 consecutive days (48% male, mean[SD] age=27[9]years). Participants underwent simultaneous PSG and WSA recordings for the initial night-time sleep (22:00-07:00) and 6 subsequent daytime sleeps (10:00-19:00) during simulated night-shift work. Epoch-by-epoch analysis of the 252 nights tested accuracy, sensitivity, and specificity for the first night-time sleep opportunity versus subsequent daytime sleeps. Sleep duration estimates were compared between WSA and PSG.

Results
Across all recordings, the WSA showed 83% sleep-wake classification accuracy, 87% sensitivity to sleep and 25% specificity to wake. The WSA significantly overestimated sleep duration versus PSG (25[65]minutes, p&lt;0.05). Accuracy and specificity were higher for night versus day sleeps (88% and 38% versus 81% and 18% respectively, all p&lt;0.05), while sensitivity (90% versus 88%) did not significantly differ.

Discussion
The WSA was moderately accurate compared to PSG, and comparable to other movement-based sleep trackers. The WSA was more accurate at classifying sleep and wake during night sleep opportunities compared to daytime sleeps. This differential performance is likely due to poorer sleep quality commonly observed during daytime sleep that is harder to accurately classify.
O008 Refining the Hypoxic Burden Algorithm by Investigating different Methods for Calculating the SpO2 Baseline
Authors: He S , Bin Y , Cistulli P , de Chazal P 
Published: October 2023

Abstract

Introduction
Intermittent hypoxia is a key mechanism linking Obstructive Sleep Apnoea (OSA) to cardiovascular disease (CVD). Oximetry analysis could enhance understanding of which OSA phenotypes are associated with CVD risk. The hypoxic burden (HB) is a measure calculated from the oximetry signal that shows promise for predicting CVD mortality, but its calculation is complex. With a view to simplifying its calculation, we investigated three different baseline calculation methods and its impact on predicting CVD mortality for the HB algorithm.

Methods
Data from Sleep Heart Health Study (SHHS) with CVD mortality outcome and complete covariate information was used. We implemented the HB method of Azarbarzin et al 2018 ERJ. The three baseline methods included an event-based baseline (same as Azarbarzin et al 2018 ERJ), a record-based baseline, and a fixed baseline. The performance of each parameter in predicting CVD mortality was assessed using an adjusted Cox proportional hazard ratio (HR) analysis.

Results
The best performing method was the record-based baseline method which returned a fully adjusted model hazard ratio of 1.83 (95% CI: 1.03-3.27, p&lt;0.05). The results for the event-based and record-based baseline methods were 1.60 (95% CI: 0.86-3.00, p=0.14) and 1.73 (95% CI: 0.93-3.22, p=0.08) respectively.

Discussion
HB with the record-based baseline was easier to calculate than the original event-based baseline method by Azarbarzin at al. and resulted in improved CVD mortality prediction performance. We believe that this method provides a step towards providing a novel parameter with easy calculation providing early risk stratification in cardiovascular patients.
O011 Exploring Nocturnal Blood Pressure Surges Relationships with Brain Health and Cognitive Function.
Authors: Bull C , Zhang T , Burke P , Butlin M , Botansky C , Srirengan A , Cysique L , Lancaster K , Brown E , Bilston L , Jugé L 
Published: October 2023

Abstract

Introduction
Cerebral small vessel disease is a possible mechanism to explain the link between long-term incompletely treated obstructive sleep apnoea (OSA) and dementia. Recent evidence suggests nocturnal blood pressure (BP) surges triggered by OSA-related sympathetic hyperactivity could play a critical role. However, this remains to be determined as they often occur concurrently with desaturation events.

Methods
During an in-lab polysomnography study of 7 controls [AHI≤5] and 20 untreated OSA patients [AHI&gt;5] aged 45-65 years the frequency of blood pressure surges (&gt;10% systolic ↑BP) in the presence or not of desaturation events (↓SpO2&gt;3%) were quantified with a SOMNOtouch™ NIBP device. Cerebral perfusion was assessed with pCASL MRI and brain lesions with anatomical MRI scans. The global deficit score was determined for cognitive function assessment. Inflammation was quantified with blood hs-CRP.

Results
After controlling for age, BMI, gender, blood glucose and cholesterol, higher AHI was associated with more frequent BP surges (r=0.52, P=0.03), BP surges occurring with desaturation events (r=0.87, P&lt;0.001), but not with BP surges without oxygen desaturation (P = 0.11). Concurrent BP surges and oxygen desaturation was associated with increased hs-CRP (r=0.55, P=0.02). Frequency of BP surges was not related to cerebral perfusion, brain lesions or the global deficit score.

Conclusions
Recording nocturnal blood pressure surges during polysomnography may provide insight into the cardiovascular burden associated with OSA. Interestingly, an inflammatory response is associated with BP surges only during desaturations, i.e. during respiratory events. Further work is needed to assess the utility of BP surges in predicting longer-term cognitive deficits.
O015 Measuring Body Movements during Sleep. Sonomat Vs Video Polysomnography
Authors: Lu M , Fitzgerald D , Sullivan C , Waters K 
Published: October 2023

Abstract

Background
Restless sleep is common in children, and video polysomnography (vPSG) has been used to score body movements during sleep. The Sonomat provides a contactless, portable alternative for home sleep studies over several nights. This study aimed to compare body movements measured by the Sonomat with those scored using vPSG.

Methods
Twenty-nine children (13 females, 16 males) with a median age of 5.4 years underwent concurrent Sonomat and vPSG studies. Movement indices per hour of sleep period and movement duration (%) were blindly scored on separate days. Statistical analysis included the Wilcoxon rank test and Pearson's correlations.

Results
Movement indices were higher on the Sonomat than vPSG (median 38.6/hr vs. 22.7/hr, p &lt; 0.001), but movement duration did not differ (median 10.8% vs. 10.5%, p = 0.092). Comparing movements above 5 seconds, the indices became more comparable (15.9/hr vs. 19.2/hr, p = 0.05). The correlation between devices was weak for movement indices (r = 0.37, p = 0.051) but strong for movement duration (r = 0.81, p &lt; 0.001). The Sonomat identified 82.5% of movements seen on vPSG, while vPSG identified only 43.6% of those on the Sonomat.

Conclusion
The Sonomat offers a contactless and portable alternative to vPSG for assessing body movements during sleep in children. It exhibited higher sensitivity in detecting shorter movements and was comparable to vPSG in movement duration. These findings suggest that the Sonomat holds promise for evaluating restless sleep in children.
O016 Caregivers’ Perspectives on the Sonomat as a Polysomnography Alternative in Children with Down syndrome
Authors: Sclip K , Collaro A , Chawla J 
Published: October 2023

Abstract

Introduction
Children with Down syndrome (DS) frequently require repeated polysomnography (PSG) to diagnose and monitor sleep disordered breathing (SDB). PSG set-up can be distressing for this population, who may struggle with sensor and lead application. The Sonomat, a non-invasive mattress overlay, has now been shown to accurately detect and profile SDB in this population. The aim of this study was to evaluate caregiver experiences of undertaking home Sonomat monitoring in their child with DS, compared to conventional lab PSG.

Method
Children with DS aged 2-17yrs undergoing a diagnostic PSG at the Queensland Children’s Hospital completed a PSG questionnaire about their child’s experience of this test. Those that also undertook home Sonomat monitoring completed a questionnaire about their experience of using the Sonomat in the home.

Results
Caregivers of fifty-one children with DS (median age 7yrs, 52% male) completed the PSG questionnaire and twenty-five completed the Sonomat questionnaire. 45% (n=51) of caregivers reported that in-lab PSG was ‘hard’ or ‘very hard’ for their child. 100% (n=25) of the caregivers rated their experience of using the Sonomat at home as good, very good or excellent. 88% (n=25) of caregivers felt that the Sonomat was their preferred option for monitoring in children with DS, as opposed to a traditional in-lab PSG.

Conclusion
In this study, the Sonomat was viewed favourably by caregivers of children with DS, and in the majority of instances was preferred to in-hospital PSG.
O017 Real-World Utility of Overnight Oximetry for the Screening of Obstructive Sleep Apnoea in Children
Authors: Hartnett C , Wilson A , Kilner D , Davies K , Slee N , Chawla J , Iyer K , Kevat A 
Published: October 2023

Abstract
Obstructive sleep apnoea (OSA) is a common problem in children, and can result in developmental and cognitive complications if untreated. The gold-standard tool for diagnosis is polysomnography (PSG); however, it is an expensive and time-consuming test to undertake. Overnight oximetry has been suggested as a faster and cheaper alternative to PSG as it can be performed at home using limited, reusable equipment. This study aims to evaluate the effectiveness of a home oximetry service (implemented in response to extended waiting times for routine PSG) in reducing the time between patient referral and treatment. All patients who utilised the Queensland Children’s Hospital home oximetry service since its inception in 2021 (n=165) were compared to a historic group of patients who underwent PSG in 2018 (n=313). The time from request of the sleep-related study to definitive treatment (ENT surgery or continuous positive airway pressure trial) was significantly reduced (161 days for the HITH oximetry group vs 348 days for the comparable PSG group; p-value &lt;0.02), and time from sleep study request to the report of results was significantly lower for patients in the oximetry group compared to those in the PSG group (12 days vs 86 days p-value &lt;0.01). These results suggest that a home oximetry service can be effective in reducing the waiting time for patients diagnosed with OSA to receive treatment. Further research should examine larger sample sizes to confirm the study findings, investigate the health economic impacts of the service and explore patient/family perspectives.
O025 Sleep outcomes in paediatric patients pre- and post-pharyngoplasty
Authors: Jarvis S , Chatwal G , Jia M , Waters K 
Published: October 2023

Abstract

Background
Pharyngoplasty surgery is undertaken to correct velopharyngeal insufficiency (VPI). The resultant narrowing of the pharyngeal airway can cause obstructive sleep apnoea (OSA), but limited data is available regarding the incidence or severity of this problem. This study will evaluate the effect of pharyngoplasty on the development of OSA in children.

Methods
We are undertaking a retrospective audit of medical records for children who underwent both polysomnography (PSG) and pharyngoplasty at a tertiary paediatric centre between January 2013 and December 2022. Data from children who underwent PSG and pharyngoplasty will be evaluated and separated according to the timing pre- or post-pharyngoplasty. Analyses will determine the effect of pharyngoplasty on the development and or progression of sleep disordered breathing.

Results
176 paediatric patients underwent pharyngoplasty procedures from January 2013-December 2022, including 73 (41%) who also underwent PSG. Full PSG data are available for analysis including sleep staging, arousal, respiratory and gas exchange. Primary outcome will be the obstructive apnoea-hypopnoea index (OAHI), but additional impacts on total apnoea-hypopnea index (AHI), oxygen saturation, CO2, and arousals will also be evaluated. Not all children had studies before and after their surgery so statistical comparison will be made between parameters measured before and after pharyngoplasty, using both paired (where available) and unpaired (for the entire group) testing as appropriate.
Intended outcome/impact: This study will evaluate the impact of pharyngoplasty on children’s breathing during sleep. The results will assist in determining the indications for, and appropriate timing for PSG in children undergoing pharyngoplasty procedures for VPI.
O030 GABAA Receptor Expression in the Suprachiasmatic Nucleus under Different Light Conditions
Authors: Chong J , Cheeseman J , Pawley M , Kwakowsky A , Warman G 
Published: October 2023

Abstract
Our research group has made inroads investigating the phase shifting effects of general anaesthesia (GA) on the circadian clock. Most clinical anaesthetics function by potentiating the effect of GABA on the GABA type A receptor (GABAARs). While the precise role of GABA in the suprachiasmatic nucleus (SCN) is still not fully understood, it has been implicated in circadian functions including photic entrainment and clock coupling. However, we have discovered that the expression of GABAARs in the central circadian clock remains poorly understood. To address this gap in knowledge, we examined the expression of GABAAR subunits α1, α5, β3, and γ2 in male (n = 80) and female (n = 82) C57Bl/6 mice under light-dark (LD) and constant darkness (DD) conditions (male, n = 95). Analysis of GABAAR subunit expression in the SCN was quantified by immunohistochemical analysis. Additionally, we investigated the time-dependent effects of isoflurane GA and light on GABAAR subunit expression in the SCN (male, n = 60). Our findings revealed rhythmic expression of GABAAR subunits in the mouse SCN under LD conditions which differed by sex, suggesting environmental light conditions may regulate GABAAR expression in the circadian clock in a sex-specific manner. In the SCN, γ2 subunit expression was increased following light and GA treatment compared to light-alone, while α1 subunit expression was increased at times of large behavioural phase delays. We conclude that the expression of GABAAR’s in the SCN is phase-dependent and may contribute to the time-dependent relationship between light and GA on the clock.
O034 Insomnia Management in Australia: An Overview of Patient, Clinician and Health System Factors
Authors: Haycock J , Lack L , Hoon E , Sweetman A , Lovato N 
Published: October 2023

Abstract

Introduction
Insomnia is the most prevalent sleep disorder in Australia. The recommended treatment is Cognitive Behavioural Therapy for insomnia (CBTi), however most people with insomnia do not access this treatment. Understanding reasons for the discrepancy between clinical guidelines and clinical practice is essential to identify opportunities to increase access to CBTi. This research explores the perspectives of people with insomnia, clinicians, and the health system to provide a comprehensive picture of insomnia management in Australia.

Methods
A mixed-methods program was undertaken to comprehensively identify facilitators and barriers to CBTi access in Australia. This included two large quantitative surveys of the Australian community and people with insomnia, and semi-structured qualitative interviews with GPs and psychologists.

Results
Most people with chronic insomnia symptoms reported they did not receive a diagnosis of insomnia, only 37% had discussed sleep with their GP, 9% discussed sleep with a psychologist, and &lt;1% received CBTi. Barriers to effective management of insomnia include low priority of sleep from all perspectives, impaired knowledge and awareness, and inadequate access to care. GPs are under substantial time pressure, other health conditions are often prioritised over insomnia, existing funding mechanisms are not clear, and few psychologists trained to deliver CBTi.

Discussion
To improve the management of insomnia in Australia efforts are needed to improve clinician and patient recognition of the importance of identifying and managing insomnia. More psychologists and primary care clinicians need to be trained in CBTi delivery, to increase awareness, understanding and access to CBTi in the community.
O035 Digital CBT-i versus digital sleep education control in an Australian community-based cohort: A randomised controlled trail.
Authors: Sweetman A , Reynolds C , Richardson C 
Published: October 2023

Abstract

Background
Insomnia is a prevalent and debilitating condition in Australia. Cognitive behavioural therapy for insomnia (CBT-i) is the recommended first-line treatment, but is accessed by very few people with insomnia. We aimed to develop and test an interactive self-guided digital CBT-i program in an Australian community-based sample.

Methods
A randomised controlled trial was used to investigate the effect of digital CBT-i, versus digital sleep education control, on changes in insomnia (ISI), depression (PHQ-9) and anxiety symptoms (GAD-7) by 8-week follow-up in people with insomnia symptoms (ISI≥15). Intention-to-treat linear mixed models and complete-case chi-square analyses were used.

Results
Participants included 62 adults with insomnia symptoms (82% female, Age M [sd] = 52.5 [16.3]). There were no between-group differences in baseline characteristics, or rates of missing data at 8-weeks. CBT-i was associated with significantly greater improvements in the ISI (M [95%CI] reduction = 9.7 [7.8-11.6], d = 3.5) and PHQ-9 (M reduction = 4.8 [3.1-6.6], d = 1.0), but not GAD-7, compared to control (M ISI reduction = 1.6 [-0.2-3.4]; M PHQ-9 reduction = 1.0 [-0.7-2.6]; both interaction p &lt; 0.001). Compared to control, CBT-i resulted in greater rates of insomnia improvement (ISI reduction ≥6; 7%, vs 75%), insomnia remission (ISI&lt;8; 0%, vs 42%), and lower rates of clinically significant insomnia by 8-weeks (ISI≥15; 61%, vs 12%, all p &lt; 0.001).

Conclusion
This digital CBT-i program leads to large improvements in insomnia and depression symptoms adults with insomnia. Implementation programs are required to increase access to digital CBT-i in Australia.