Inter-sleep stage variations in corrected QT interval differ between obstructive sleep apnea patients with and without stroke history

Obstructive sleep apnea (OSA) is related to the progression of cardiovascular diseases (CVD); it is an independent risk factor for stroke and is also prevalent post-stroke. Furthermore, heart rate corrected QT (QTc) is an important predictor of the risk of arrhythmia and CVD. Thus, we aimed to investigate QTc interval variations in different sleep stages in OSA patients and whether nocturnal QTc intervals differ between OSA patients with and without stroke history. 18 OSA patients (apnea-hypopnea index (AHI)≥15) with previously diagnosed stroke and 18 OSA patients (AHI≥15) without stroke history were studied. Subjects underwent full polysomnography including an electrocardiogram measured by modified lead II configuration. RR, QT, and QTc intervals were calculated in all sleep stages. Regression analysis was utilized to investigate possible confounding effects of sleep stages and stroke history on QTc intervals. Compared to patients without previous stroke history, QTc intervals were significantly higher (β = 34, p<0.01) in patients with stroke history independent of age, sex, body mass index, and OSA severity. N3 sleep (β = 5.8, p<0.01) and REM sleep (β = 2.8, p<0.01) increased QTc intervals in both patient groups. In addition, QTc intervals increased progressively (p<0.05) towards deeper sleep in both groups; however, the magnitude of changes compared to the wake stage was significantly higher (p<0.05) in patients with stroke history. The findings of this study indicate that especially in deeper sleep, OSA patients with a previous stroke have an elevated risk for QTc prolongation further increasing the risk for ventricular arrhythmogenicity and sudden cardiac death.publishedVersionPeer reviewe

Deep Learning Enables Accurate Automatic Sleep Staging Based on Ambulatory Forehead EEG

We have previously developed an ambulatory electrode set (AES) for the measurement of electroencephalography (EEG), electrooculography (EOG), and electromyography (EMG). The AES has been proven to be suitable for manual sleep staging and self-application in in-home polysomnography (PSG). To further facilitate the diagnostics of various sleep disorders, this study aimed to utilize a deep learning-based automated sleep staging approach for EEG signals acquired with the AES. The present neural network architecture comprises a combination of convolutional and recurrent neural networks previously shown to achieve excellent sleep scoring accuracy with a single standard EEG channel (F4-M1). In this study, the model was re-trained and tested with 135 EEG signals recorded with AES. The recordings were conducted for subjects suspected of sleep apnea or sleep bruxism. The performance of the deep learning model was evaluated with 10-fold cross-validation using manual scoring of the AES signals as a reference. The accuracy of the neural network sleep staging was 79.7% (kappa = 0.729) for five sleep stages (W, N1, N2, N3, and R), 84.1% (kappa = 0.773) for four sleep stages (W, light sleep, deep sleep, R), and 89.1% (kappa = 0.801) for three sleep stages (W, NREM, R). The utilized neural network was able to accurately determine sleep stages based on EEG channels measured with the AES. The accuracy is comparable to the inter-scorer agreement of standard EEG scorings between international sleep centers. The automatic AES-based sleep staging could potentially improve the availability of PSG studies by facilitating the arrangement of self-administrated in-home PSGs.Peer reviewe

Increased nocturnal arterial pulsation frequencies of obstructive sleep apnoea patients is associated with an increased number of lapses in a psychomotor vigilance task.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadObjectives: Besides hypoxaemia severity, heart rate variability has been linked to cognitive decline in obstructive sleep apnoea (OSA) patients. Thus, our aim was to examine whether the frequency domain features of a nocturnal photoplethysmogram (PPG) can be linked to poor performance in the psychomotor vigilance task (PVT). Methods: PPG signals from 567 suspected OSA patients, extracted from Type 1 diagnostic polysomnography, and corresponding results of PVT were retrospectively examined. The frequency content of complete PPGs was determined, and analyses were conducted separately for men (n=327) and women (n=240). Patients were grouped into PVT performance quartiles based on the number of lapses (reaction times ≥500 ms) and within-test variation in reaction times. The best-performing (Q1) and worst-performing (Q4) quartiles were compared due the lack of clinical thresholds in PVT. Results: We found that the increase in arterial pulsation frequency (APF) in both men and women was associated with a higher number of lapses. Higher APF was also associated with higher within-test variation in men, but not in women. Median APF (β=0.27, p=0.01), time spent under 90% saturation (β=0.05, p<0.01), female sex (β=1.29, p<0.01), older age (β=0.03, p<0.01) and subjective sleepiness (β=0.07, p<0.01) were significant predictors of belonging to Q4 based on lapses. Only female sex (β=0.75, p<0.01) and depression (β=0.91, p<0.02) were significant predictors of belonging to Q4 based on the within-test variation. Conclusions: In conclusion, increased APF in PPG provides a possible polysomnography indicator for deteriorated vigilance especially in male OSA patients. This finding highlights the connection between cardiorespiratory regulation, vigilance and OSA. However, our results indicate substantial sex-dependent differences that warrant further prospective studies.Research Committee of the Kuopio University Hospital Catchment Area for the State Research Funding Academy of Finland Seinajoki Central Hospital Competitive State Research Financing of Expert Responsibility Area of Tampere University Hospital VTR3242 Business Finland Paulo Foundation Paivikki & Sakari Sohlberg Foundation Research Foundation of the Pulmonary Diseases Finnish Cultural Foundation Alfred Kordelin Foundation Tampere Tuberculosis Foundation Respiratory Foundation of Kuopio Regio

Oral Treatment with Cu[superscript II](atsm) Increases Mutant SOD1 In Vivo but Protects Motor Neurons and Improves the Phenotype of a Transgenic Mouse Model of Amyotrophic Lateral Sclerosis

Mutations in the metallo-protein Cu/Zn-superoxide dismutase (SOD1) cause amyotrophic lateral sclerosis (ALS) in humans and an expression level-dependent phenotype in transgenic rodents. We show that oral treatment with the therapeutic agent diacetyl-bis(4-methylthiosemicarbazonato)copper[superscript II] [Cu[superscript II](atsm)] increased the concentration of mutant SOD1 (SOD1G37R) in ALS model mice, but paradoxically improved locomotor function and survival of the mice. To determine why the mice with increased levels of mutant SOD1 had an improved phenotype, we analyzed tissues by mass spectrometry. These analyses revealed most SOD1 in the spinal cord tissue of the SOD1G37R mice was Cu deficient. Treating with Cu[superscript II](atsm) decreased the pool of Cu-deficient SOD1 and increased the pool of fully metallated (holo) SOD1. Tracking isotopically enriched ⁶⁵Cu[superscript II](atsm) confirmed the increase in holo-SOD1 involved transfer of Cu from Cu[superscript II](atsm) to SOD1, suggesting the improved locomotor function and survival of the Cu[superscript II](atsm)-treated SOD1G37R mice involved, at least in part, the ability of the compound to improve the Cu content of the mutant SOD1. This was supported by improved survival of SOD1G37R mice that expressed the human gene for the Cu uptake protein CTR1. Improving the metal content of mutant SOD1 in vivo with Cu[superscript II](atsm) did not decrease levels of misfolded SOD1. These outcomes indicate the metal content of SOD1 may be a greater determinant of the toxicity of the protein in mutant SOD1-associated forms of ALS than the mutations themselves. Improving the metal content of SOD1 therefore represents a valid therapeutic strategy for treating ALS caused by SOD1.This is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by the Society for Neuroscience. The published article can be found at: http://www.jneurosci.org/

Asset life span in a government funded CPAP device program

Study Objectives: To determine the life span of devices in a government long-term continuous positive airway pressure (CPAP) device loan program. Methods: Retrospective review of CPAP devices provided under theQueensland Health Sleep Disorders programin Queensland, Australia, fromdata recorded in an in-house database that has collected data since 1995. Primary outcomes were hours of use and age of device at end-of-life. Device survival analysis was performed collectively for all devices and for different models. Reasons for device end-of-life were compared between models. Results: There were 9,222 CPAP devices provided on long-term loan over this period, with asset end-of-life date available in 90%. Median life span was 15,178 hours (interquartile range 8,167-20,296 hours) and 12.4 (interquartile range 7.6-18.8) years. Five percent of devices were condemned in the first 3 years, and 13% of devices were condemned in the first 5 years. There were significant differences in survival patterns between different models, but after correction for run hours, only one model differed (related to manufacturer policy to replace not repair equipment). Reasons for end-of-life differed between models (P < .001) with manufacturer recall, excessive noise and faulty buttons the most common reasons. Conclusions: GovernmentCPAP loan programs can develop assetmanagement planswith an anticipated average asset life span of 15,178 hours or 12.4 years; however, they should also plan for the need to replace equipmentwhere earlier failure occurs. Early equipment failures are seen with variability between models, and appropriate warranty periods to cover these early failures should be negotiated with manufacturers.</p

Usefulness of self-administered questionnaires in screening for direct referral for polysomnography without sleep physician review

Study objectives: To evaluate self-administered screening questionnaires (Epworth Sleepiness Scale [ESS], Berlin, OSA50, and STOP-Bang questionnaires) in patients considered for polysomnography for probable obstructive sleep apnea suitable for direct polysomnography without sleep specialist review and to evaluate the usefulness of combining questionnaires in this population.Methods: This was a retrospective review of tertiary sleep center referrals (November 2017 to April 2020) where ≥ 3 screening questionnaires were completed and type 1 polysomnography was performed. Sensitivity, specificity, positive and negative predictive values, and likelihood ratios to detect an apnea-hypopnea index (AHI) ≥ 15 or ≥ 30 events/h were calculated for each questionnaire (with or without ESS ≥ 8) or any positive questionnaire with ESS ≥ 8.Results: We included 2,152 patients. The questionnaires were completed in the majority (ESS 96%, Berlin 77%, OSA50 84%, and STOP-Bang 90%) of referrals. Berlin was most sensitive (82.5% and 85% to detect AHI ≥ 15 and ≥ 30 events/h, respectively) but least specific (23% both thresholds). STOP-Bang was least sensitive (66% and 42%, respectively) but most specific (68% and 60%, respectively). Sensitivity declined for the Berlin, OSA50 and STOP-Bang questionnaires when combined with ESS ≥ 8. Combining any questionnaire with ESS ≥ 8 returned an intermediate sensitivity of 61% and 73% and a specificity of 49% and 47% for AHI ≥ 15 and ≥ 30 events/h, respectively. STOP-Bang alone was predictive of obstructive sleep apnea on multivariate analysis but was only associated with a clinically nonsignificant positive likelihood ratio. However, STOP-Bang is associated with unacceptable false-positive and -negative rates, which did not support its use.Conclusions: Self-administered questionnaires are inadequate in patients under consideration for polysomnography and should not be used as clinical support for suitability of direct polysomnography without sleep specialist review. Combining questionnaires causes deteriorated performance

The 2012 AASM respiratory event criteria increase the incidence of hypopneas in an adult Sleep center population

Study Objectives To investigate the effect of the 2012 American Academy of Sleep Medicine (AASM) respiratory event criteria on severity and prevalence of obstructive sleep apnea (OSA) relative to previous respiratory event criteria. Methods A retrospective, randomized comparison was conducted in an Australian clinical sleep laboratory in a tertiary hospital. The polysomnograms (PSG) of 112 consecutive patients undertaking polysomnography (PSG) for suspected OSA were re-scored for respiratory events using either 2007 AASM recommended (AASM2007Rec), 2007 AASM alternate (AASM2007Alt), Chicago criteria (AASM1999), or 2012 AASM recommended (AASM2012) respiratory event criteria. Results The median AHI using AASM2012 was approximately 90% greater than the AASM2007Rec AHI, approximately 25% greater than the AASM2007Alt AHI, and approximately 15% lower than the AASM1999 AHI. These changes increased OSA diagnoses by approximately 20% and 5% for AASM2007Rec and AASM2007Alt, respectively. Minimal changes in OSA diagnoses were observed between AASM1999 and AASM2012 criteria. To achieve the same OSA prevalence as AASM2012, the threshold for previous criteria would have to shift to 2.6/h, 3.6/h, and 7.3/h for AASM2007Rec, AASM2007Alt, and AASM1999, respectively. Differences between the AASM2007Rec and AASM2012 hypopnea indices (HI) were predominantly due to the change in desaturation levels required. Alterations to respiratory event duration rules had no effect on the HI. Conclusions This study demonstrates that implementation of the 2012 AASM respiratory event criteria will increase the AHI in patients undergoing PSG, and more patients are likely to be diagnosed with OSA

A randomized crossover trial comparing autotitrating and continuous positive airway pressure in subjects with symptoms of aerophagia: Effects on compliance and subjective symptoms

Study Objective: To assess the benefit and tolerance of auto-titrating positive airways pressure (APAP) versus continuous positive airways pressure (CPAP) in subjects who experience aerophagia. Design: Prospective, two-week, double-blinded, randomised crossover trial. Setting: Australian clinical sleep laboratory in a tertiary hospital. Subjects or Participants: Fifty-six subjects who reported symptoms of aerophagia that they attributed to CPAP were recruited. Full-face masks were used by 39 of the 56 subjects recruited. Interventions: Subjects were randomly and blindly allocated to either CPAP at their treatment recommended pressure or APAP 6-20 cm H2O, in random order. Subjects spent two weeks on each therapy mode. Measurements and Results: Therapy usage hours, 95th centile pressure, maximum pressure, 95th centile leak and residual Apnea Hypopnea Index (AHI) were reported at the end of each two week treatment period. Functional Outcome of Sleepiness Questionnaire (FOSQ), Epworth Sleepiness Scale (ESS), Visual Analogue Scale (VAS) to measure symptoms of aerophagia were also completed at the end of each two-week treatment arm. The median pressure (p<0.001) and 95th centile pressure (p<0.001) were reduced with APAP but no differences in compliance (p=0.12) and residual AHI were observed. APAP reduced the symptoms of bloating (p=0.011), worst episode of bloating (p=0.040), flatulence (p=0.010) and belching (p=0.001) compared to CPAP. There were no differences in ESS or FOSQ outcomes between CPAP and APAP. Conclusions: APAP therapy reduces the symptoms of aerophagia while not affecting compliance when compared to CPAP therapy

A new measure to quantify sleepiness using higher order statistical analysis of EEG

Chronic sleepiness is a common symptom in the sleep disorders, such as, Obstructive Sleep Apnea, Periodic leg movement syndrome, narcolepsy etc. It affects 5% of the adult population and is associated with significant morbidity and increased risk to individual and society. MSLT and MWT are the existing tests for measuring sleepiness. Sleep Latency (SL) is the main measures of sleepiness computed in these tests. Existing method of SL computation relies on the visual extraction of specific features in multi-channel electrophysiological data (EEG, EOG, and EMG) using the R&K criteria (1968). This process is cumbersome, time consuming, and prone to inter and intra-scorer variability. In this paper we propose a fully automated, objective sleepiness analysis technique based on the single channel of EEG. The method uses a one-dimensional slice of the EEG Bisprectrum representing a nonlinear transformation of the underlying EEG generator to compute a novel index called Sleepiness Index. The SL is then computed from the SI. A strong correlation (r=0.93, ρ=0.0001) was found between technician scored SL and that computed via SI. The proposed Sleepiness Index can provide an elegant solution to the problems surrounding manual scoring and objective sleepiness