Effects of sleep fragmentation and partial sleep restriction on heart rate variability during night.

We developed a cross-over study design with two interventions in randomized order to compare the effects of sleep fragmentation and partial sleep restriction on cardiac autonomic tone. Twenty male subjects (40.6 ± 7.5 years old) underwent overnight polysomnography during 2 weeks, each week containing one undisturbed baseline night, one intervention night (either sleep restriction with 5 h of sleep or sleep fragmentation with awakening every hour) and two undisturbed recovery nights. Parameters of heart rate variability (HRV) were used to assess cardiac autonomic modulation during the nights. Sleep restriction showed significant higher heart rate (p = 0.018) and lower HRV-pNN50 (p = 0.012) during sleep stage N1 and lower HRV-SDNN (p = 0.009) during wakefulness compared to the respective baseline. For HR and SDNN there were recovery effects. There was no significant difference comparing fragmentation night and its baseline. Comparing both intervention nights, sleep restriction had lower HRV high frequency (HF) components in stage N1 (p = 0.018) and stage N2 (p = 0.012), lower HRV low frequency (LF) (p = 0.007) regarding the entire night and lower SDNN (p = 0.033) during WASO during sleep. Sleep restriction increases sympathetic tone and decreases vagal tone during night causing increased autonomic stress, while fragmented sleep does not affect cardiac autonomic parameters in our sample.

Initiation of therapy for obstructive sleep apnea syndrome: a randomized comparison of outcomes of telemetry-supported home-based vs. sleep lab-based therapy initiation.

PURPOSE: Diagnosis and treatment of obstructive sleep apnea are traditionally performed in sleep laboratories with polysomnography (PSG) and are associated with significant waiting times for patients and high cost. We investigated if initiation of auto-titrating CPAP (APAP) treatment at home in patients with obstructive sleep apnea (OSA) and subsequent telemonitoring by a homecare provider would be non-inferior to in-lab management with diagnostic PSG, subsequent in-lab APAP initiation, and standard follow-up regarding compliance and disease-specific quality of life. METHODS: This randomized, open-label, single-center study was conducted in Germany. Screening occurred between December 2013 and November 2015. Eligible patients with moderate-to-severe OSA documented by polygraphy (PG) were randomized to home management or standard care. All patients were managed by certified sleep physicians. The home management group received APAP therapy at home, followed by telemonitoring. The control group received a diagnostic PSG, followed by therapy initiation in the sleep laboratory. The primary endpoint was therapy compliance, measured as average APAP usage after 6 months. RESULTS: The intention-to-treat population (ITT) included 224 patients (110 home therapy, 114 controls); the per-protocol population (PP) included 182 patients with 6-month device usage data (89 home therapy, 93 controls). In the PP analysis, mean APAP usage at 6 months was not different in the home therapy and control groups (4.38 ± 2.04 vs. 4.32 ± 2.28, p = 0.845). The pre-specified non-inferiority margin (NIM) of 0.3 h/day was not achieved (p = 0.130); statistical significance was achieved in a post hoc analysis when NIM was set at 0.5 h/day (p < 0.05). Time to APAP initiation was significantly shorter in the home therapy group (7.6 ± 7.2 vs. 46.1 ± 23.8 days; p < 0.0001). CONCLUSION: Use of a home-based telemonitoring strategy for initiation of APAP in selected patients with OSA managed by sleep physicians is feasible, appears to be non-inferior to standard sleep laboratory procedures, and facilitates faster access to therapy.

Effect of the novel dual orexin receptor antagonist daridorexant on night-time respiratory function and sleep in patients with moderate chronic obstructive pulmonary disease.

In patients with chronic obstructive pulmonary disease (COPD), sleep is often fragmented while, conversely, the use of sleep medications is of concern in these patients due to potential impairment of nocturnal breathing. This randomised, double-blind, placebo-controlled, two-period crossover study was conducted to evaluate the effect of the new dual orexin receptor antagonist daridorexant on night-time respiratory function and sleep in patients with moderate COPD. In each period, the highest Phase-III dose of 50 mg daridorexant or placebo was administered once daily in the evening for 5 consecutive days. The primary endpoint was peripheral oxygen saturation (SpO2 ) during total sleep time (TST) after last dosing. Night-time respiratory function and sleep were further evaluated based on the apnea-hypopnea index (AHI), sleep duration, and objective sleep parameters. Pharmacokinetics, safety, and tolerability were also assessed. Primary endpoint analysis revealed no significant mean treatment difference (i.e. daridorexant - placebo) for SpO2 during TST as it was 0.18% (90% confidence interval: -0.21 to 0.57). There was also no difference from placebo for SpO2 during non-rapid eye movement (REM) and REM sleep at Night 5 and after first dosing. The AHI was slightly increased compared to placebo, but not to a clinically meaningful extent. In addition, daridorexant improved objective sleep parameters (i.e. prolonged TST, increased sleep efficiency, and decreased wake after sleep onset), reached expected plasma concentrations, and was safe and well tolerated. In conclusion, single and multiple doses of 50 mg daridorexant do not impair night-time respiratory function and improves sleep in patients with moderate COPD.

Effect of the new dual orexin receptor antagonist daridorexant on nighttime respiratory function and sleep in patients with mild and moderate obstructive sleep apnea.

In this randomized, double-blind, placebo-controlled, two-period crossover study, the effect of the dual orexin receptor antagonist daridorexant was evaluated on nighttime respiratory function and sleep in 28 patients with mild and moderate obstructive sleep apnea (OSA). In each period, 50 mg daridorexant or placebo was administered every evening for 5 days. The primary endpoint was apnea/hypopnea index (AHI) during total sleep time (TST) after the last dosing. Other endpoints included peripheral oxygen saturation (SpO2), sleep duration, latency to persistent sleep (LPS), wake after sleep onset (WASO), and sleep efficiency index (SEI). Pharmacokinetics, safety, and tolerability were also assessed. The mean treatment difference for AHI during TST (i.e. daridorexant - placebo) after the last dosing was 0.74 events/hour (90% confidence interval [CI]: -1.43, 2.92). The corresponding treatment difference for SpO2 during TST was 0.16% [90% CI: -0.21, 0.53]. Overall, there was no clinically relevant effect of daridorexant on AHI or SpO2-related data after single and repeated dosing irrespective of sleep phase (i.e. rapid eye movement [REM] vs non-REM). Moreover, after single and repeated dosing, daridorexant prolonged TST by 39.6 minutes (90% CI: 16.9, 62.3) and 38.8 minutes (19.7, 57.9), respectively, compared with placebo and favorably modulated other sleep-related endpoints (i.e. increased SEI, decreased WASO, and shortened LPS). It attained expected plasma concentrations and was well tolerated in patients with mild and moderate OSA. These results indicate that single and repeated doses of 50 mg daridorexant do not impair nighttime respiratory function and improve sleep in patients with mild and moderate OSA. Clinical Trial Registration: ClinicalTrials.gov NCT03765294. A study to investigate the effects of ACT-541468 on nighttime respiratory function in patients with mild to moderate obstructive sleep apnea. https://clinicaltrials.gov/ct2/show/ NCT03765294.

Screening for obstructive sleep apnea with novel hybrid acoustic smartphone app technology.

BACKGROUND: Obstructive sleep apnea (OSA) has a high prevalence, with an estimated 425 million adults with apnea hypopnea index (AHI) of ≥15 events/hour, and is significantly underdiagnosed. This presents a significant pain point for both the sufferers, and for healthcare systems, particularly in a post COVID-19 pandemic world. As such, it presents an opportunity for new technologies that can enable screening in both developing and developed countries. In this work, the performance of a non-contact OSA screener App that can run on both Apple and Android smartphones is presented. METHODS: The subtle breathing patterns of a person in bed can be measured via a smartphone using the "Firefly" app technology platform [and underpinning software development kit (SDK)], which utilizes advanced digital signal processing (DSP) technology and artificial intelligence (AI) algorithms to identify detailed sleep stages, respiration rate, snoring, and OSA patterns. The smartphone is simply placed adjacent to the subject, such as on a bedside table, night stand or shelf, during the sleep session. The system was trained on a set of 128 overnights recorded at a sleep laboratory, where volunteers underwent simultaneous full polysomnography (PSG), and "Firefly" smartphone app analysis. A separate independent test set of 120 recordings was collected across a range of Apple iOS and Android smartphones, and withheld for performance evaluation by a different team. An operating point tuned for mid-sensitivity (i.e., balancing sensitivity and specificity) was chosen for the screener. RESULTS: The performance on the test set is comparable to ambulatory OSA screeners, and other smartphone screening apps, with a sensitivity of 88.3% and specificity of 80.0% [with receiver operating characteristic (ROC) area under the curve (AUC) of 0.92], for a clinical threshold for the AHI of ≥15 events/hour of detected sleep time. CONCLUSIONS: The "Firefly" app based sensing technology offers the potential to significantly lower the barrier of entry to OSA screening, as no hardware (other than the user's personal smartphone) is required. Additionally, multi-night analysis is possible in the home environment, without requiring the wearing of a portable PSG or other home sleep test (HST).

Overnight pulse wave analysis to assess autonomic changes during sleep in insomnia patients and healthy sleepers.

Insomnia has been associated with increased cardiovascular (CV) risk, which may be linked to sympathetic activation. Non-invasive overnight pulse wave analysis may be a useful tool to detect early signs of autonomic changes during sleep in insomniacs. Fifty-two participants (26 men, 37±13 years, BMI: 24±5 kg/m2, 26 insomniacs/ 26 controls) underwent overnight polysomnography with pulse oximetry and pulse wave analysis including pulse rate, vascular stiffness (pulse propagation time, PPT), and a composite cardiac risk index based on autonomic function and overnight hypoxia. We identified two subgroups of insomniacs, with and without objectively disturbed sleep (sleep efficiency SE≤80%, n = 14 vs. SE>80%, n = 12), and observed increased pulse rate and vascular stiffness in insomnia cases when diagnosis was based on both, subjective and objective criteria. Both insomnia groups were associated with higher overnight pulse rate than controls (median/ IQR: low-SE (low sleep efficiency): 67/ 58-70bpm; high-SE: 66/ 63-69bpm; controls: 58/ 52-63bpm; p = 0.01). Vascular stiffness was higher (reduction of PPT) in low-SE insomniacs compared with high-SE insomniacs and controls (169/ 147-232ms; 237/ 215-254ms; 244/ 180-284ms; p = 0.01). The cardiac risk index was increased in low-SE insomniacs (0.2/ 0.0-0.7; 0.0/ 0.0-0.4; 0.0/ 0.0-0.3; p = 0.05). Our results suggest a hyperarousal state in young and otherwise healthy insomniacs during sleep. The increased pulse rate and vascular stiffness in insomniacs with low SE suggest early signs of rigid vessels and potentially, an elevated CV risk. Overnight pulse wave analysis may be feasible for CV risk assessment in insomniacs and may provide a useful tool for phenotyping insomnia in order to provide individualized therapy.

Effects of sleep on a high-heat capacity mattress on sleep stages, EEG power spectra, cardiac interbeat intervals and body temperatures in healthy middle-aged men‡.

STUDY OBJECTIVES: This study deals with the question whether a slow (non-disturbing) reduction of core body temperature (CBT) during sleep increases sleep stage N3 and EEG slow wave energy (SWE) and leads to a slowing of heart rate in humans. PARTICIPANTS: Thirty-two healthy male subjects with a mean ± SD age 46 ± 4 years and body mass index 25.2 ± 1.8 kg/m2. METHODS: A high-heat capacity mattress (HM) was used to lower body temperatures in sleep and was compared to a conventional low-heat capacity mattress (LM) in a double-blinded fashion. Polysomnography was performed accompanied by measurements of skin-, core body- and mattress surface-temperatures, and heart rate. EEG power spectral analyses were carried out using Fast Fourier Transform. Interbeat intervals were derived from the electrocardiogram. RESULTS: The HM led to a larger decline in CBT, mediated through higher heat conduction from the core via the proximal back skin onto the mattress together with reduced heart rate. These effects occurred together with a significant increase in sleep stage N3 and standardized slow wave energy (sSWE, 0.791-4.297 Hz) accumulated in NREM sleep. In the 2nd half of the night sSWE increase was significantly correlated with body temperature changes, for example with CBT decline in the same phase. CONCLUSIONS: A HM subtly decreases CBT, leading to an increased amount of sleep stage N3 and of sSWE, as well as a slowing of heart rate.

A sleep intervention study comparing effects of sleep restriction and fragmentation on sleep and vigilance and the need for recovery.

PURPOSE: Sleep deprivation is present not only in sleep disorders but also in numerous high demanding jobs and negatively affects cognition, performance and health. We developed a study design to distinguish the effects and need for recovery of two short-term disturbances - intermittent sleep fragmentation and partial sleep restriction. METHODS: The randomized within-subjects design contained two weeks each with a baseline night, an intervention night of either sleep deprivation (5 h) or sleep fragmentation (light on every hour) and two undisturbed recovery nights. Twenty healthy male participants (mean age: 39.9 ± 7.4 years, mean BMI: 25.5 ± 2.2 kg/m²) underwent polysomnography, a psychomotor vigilance task (PVT), and subjective questions on well-being and sleep efficiency. RESULTS: Percentage-wise, the restriction night had significant less wake times, less light sleep (stage 1), less REM sleep, but more deep sleep (stage 3) than the fragmentation night. The restriction week displayed a significant recovery effect regarding these sleep stages. The sleep fragmentation week presented a significant recovery effect regarding sleep onset times. PVT performance showed only a slight recovery effect after sleep restriction. Subjective sleep quality was reduced after both interventions with a significant recovery effect during restriction week only. CONCLUSIONS: Short-term sleep restriction presented as a stronger sleep disturbance than short-term intermittent sleep fragmentation, including a stronger need for recovery. Already a one night sleep deprivation had an effect beyond two recovery days. The PVT was not sensitive enough to reveal significant changes. Next, autonomic parameters as possible biomarkers will be investigated.

Sleep Staging Monitoring Based on Sonar Smartphone Technology.

This paper presents the validation results of a new non-contact ultrasonic technology, which employs inaudible Sonar to monitor the movements and respiration of a subject in bed. Sleep monitoring can be achieved by placing a smartphone onto the bedside table and starting a custom app. The app employs sophisticated and novel proprietary algorithms to identify sleep stages: Wake (W), Light Sleep (N1, N2 sleep), Deep Sleep (N3 sleep), Rapid Eye Movement (REM) Sleep or Absence.The sleep staging performance of the app were assessed by testing it against expert manually scored polysomnography (PSG) of 38 subjects gathered in a sleep laboratory. As a secondary assessment, on the same dataset, the performance of the app is compared to that of a reference non-contact device, the S+ by ResMed.Performance across different sleep stage detections was balanced, exceeding the agreement typically reported for actigraphy based devices [1], [2] thanks to a significantly higher sensitivity for all sleep stages. Furthermore, the performance of the app was found to be comparable to the S+ by ResMed product [3], [4].The combination of unobtrusive non-contact sensing and accurate sleep quality assessment, coupled with removal of the requirement to purchase a custom device to enable monitoring of sleep, enables consumers to measure their sleep in the home environment in a zero-cost and accessible manner, while providing sleep staging information not otherwise available with actigraphy based devices.

Detection of Sleep Apnea Using Sonar Smartphone Technology.

This paper assesses the performance of a new noncontact sensing system based on Sonar technology as a Sleep Disordered Breathing (SDB) screener. The respiration and movements of a subject in bed can be measured via a smartphone placed onto a bedside table equipped with a custom app. The app employs novel proprietary algorithms to identify sleep stages and detect SDB patterns.The SDB screener was trained on a set of 94 overnights recorded at a sleep laboratory, where volunteers underwent simultaneous monitoring via a full polysomnography (PSG) system and a smartphone equipped with the app. An additional fully independent set of 68 recordings, uniformly distributed across SDB severity classes, were held out for independent testing. The performance on the test set is excellent and comparable to other existing ambulatory SDB screeners, with a sensitivity of 94% and specificity of 97%, for a clinical threshold for the Apnea Hypopnea Index (AHI) of 15 events/hour.The technology can easily be adopted to scale, as no purchase of dedicated sensors is needed, providing a much needed low- cost alternative for monitoring and potentially screening of large population segments. Furthermore, the non-invasive, contactless sensing does not interfere with the sleeping habits of the user, facilitating longitudinal assessment. This, in combination with the simultaneous measurement of the user's sleep quality, could provide invaluable insights in the subject's response to SDB therapy and lead to increased patient adherence.

White matter microstructure and impulsivity in methamphetamine dependence with and without a history of psychosis.

BACKGROUND: Methamphetamine (MA) use may lead to white matter injury and to a range of behavioral problems and psychiatric disorders, including psychosis. The present study sought to assess white matter microstructural impairment as well as impulsive behavior in MA dependence and MA-associated psychosis (MAP). METHODS: Thirty patients with a history of MAP, 39 participants with MA dependence and 40 healthy controls underwent diffusion tensor imaging (DTI). Participants also completed the UPPS-P impulsive behavior questionnaire. We applied tract-based spatial statistics (TBSS) to investigate group differences in mean diffusivity (MD), fractional anisotropy (FA), axial (λ‖ ) and radial diffusivity (λ⊥ ), and their association with impulsivity scores and psychotic symptoms. RESULTS: The MAP group displayed widespread higher MD, λ‖ and λ⊥ levels compared to both controls and the MA group, and lower FA in extensive white matter areas relative to controls. MD levels correlated positively with negative psychotic symptoms in MAP. No significant DTI group differences were found between the MA group and controls. Both clinical groups showed high levels of impulsivity, and this dysfunction was associated with DTI measures in frontal white matter tracts. CONCLUSIONS: MAP patients show distinct patterns of impaired white matter integrity of global nature relative to controls and the MA group. Future work to investigate the precise nature and timing of alterations in MAP is needed. The results are further suggestive of frontal white matter pathology playing a role in impulsivity in MA dependence and MAP. Hum Brain Mapp 37:2055-2067, 2016. © 2016 Wiley Periodicals, Inc.

Frontal white matter changes and aggression in methamphetamine dependence.

Chronic methamphetamine (MA) use can lead to white matter (WM) changes and increased levels of aggression. While previous studies have examined WM abnormalities relating to cognitive impairment, associations between WM integrity and aggression in MA dependence remain unclear. Diffusion Tensor Imaging (DTI) was used to investigate WM changes in 40 individuals with MA dependence and 40 matched healthy controls. A region of interest (ROI) approach using tract based spatial statistics (TBSS) in FSL was performed. We compared fractional anisotropy (FA), mean diffusivity (MD), parallel diffusivity (λ║) and perpendicular diffusivity (λ┴) in WM tracts of the frontal brain. A relationship of WM with aggression scores from the Buss & Perry Questionnaire was investigated. Mean scores for anger (p < 0.001), physical aggression (p = 0.032) and total aggression (p = 0.021) were significantly higher in the MA group relative to controls. ROI analysis showed increased MD (U = 439.5, p = 0.001) and λ┴ (U = 561.5, p = 0.021) values in the genu of the corpus callosum, and increased MD (U = 541.5, p = 0.012) values in the right cingulum in MA dependence. None of the WM changes were significantly associated with aggression scores. This study provides evidence of frontal WM changes and increased levels of aggression in individuals with MA dependence. The lack of significant associations between WM and aggressive behaviour may reflect methodological issues in measuring such behaviour, or may indicate that the neurobiology of aggression is not simply correlated with WM damage but is more complex.