Sleep Stages

Study Objectives: Polysomnographic respiratory events in children should be scored using pediatric respiratory rules. However, due to a lack of data on adolescents, recently revised rules allow children aged 13-18 years to be scored by adult or pediatric criteria. To clarify which criteria to use, we describe the evolution of respiratory events with Tanner stage, and we compare events in children aged 13-18 years with the new American Academy of Sleep Medicine adult and pediatric respiratory rules. Design: Cross-sectional Setting: Academic hospital Participants: Healthy subjects aged 8-18 years recruited for research purposes Interventions: Physical examination to determine Tanner stage, overnight polysomnogram, and determination of sex hormones. Results: Sixty-eight subjects (Tanner 1-5) were studied, mean age [SD] = 13 ± 3 years, median apnea hypopnea index (AHI) = 0.1 (range: 0-1.2)/h. The median percentages of total sleep time (TST) with SpO 2 < 92% were 0.1 (0-4.2)%, and with end-tidal CO 2 > 50 torr was 0.1 (0-88.6)%. Thirty-two subjects were aged 13-18 years, (Tanner 3-5). The difference between AHI scored by pediatric (median = 0 [0-0.9]/h) and adult (median = 0 [0 -0.5]/h) criteria was statistically significant (P = 0.043), but not clinically relevant. conclusions: Respiratory events in normal children aged 8-18 years are rare and unrelated to Tanner stage. Adult or pediatric respiratory rules can be used for scoring polysomnograms in asymptomatic subjects approaching adulthood. Further studies are needed in symptomatic children within this age group.

The early literature suggests that hypoventilation in infants with congenital central hypoventilation syndrome (CHS) is less severe during rapid eye movement (REM) than during non-REM (NREM) sleep. However, this supposition has not been rigorously tested, and subjects older than infancy have not been studied. Given the differences in anatomy, physiology, and REM sleep distribution between infants and older children, and the reduced number of limb movements during REM sleep, we hypothesized that older subjects with CHS would have more severe hypoventilation during REM than NREM sleep. Nine subjects with CHS, aged (mean ± SD) 13 ± 7 yr, were studied. Spontaneous ventilation was evaluated by briefly disconnecting the ventilator under controlled circumstances. Arousal was common, occurring in 46% of REM vs. 38% of NREM trials [not significant (NS)]. Central apnea occurred during 31% of REM and 54% of NREM trials (NS). Although minute ventilation declined precipitously during both REM an...

Magneto-elastic bilayers (BLs), consisting of a magnetostrictive layer and a non-magnetic counter layer, show highest sensitivity with respect to bending. This paper describes a biomedical application in the field of sleep apnea screening. A multi-parametric detector fixed at the thorax contains two BLs. One BL yields a skin curvature sensor adjusting itself to curvature variations given by physiological activities. The second BL exhibits a free end thus working as a motion sensor. The two signals are fed into artificial neural networks for the detection of events like normal respiration and apneas, as well as body movements and position.

Accuracy and limitations of automatic scoring of sleep stages and electroencephalogram arousals from a single derivation (F p1 -F p2 ) were studied in 29 healthy adults using a portable wireless polysomnographic recorder. All recordings were scored five times: twice by a referent scorer who viewed the standard polysomnographic montage and observed the American Academy of Sleep Medicine rules (referent scoring and blind rescoring); and once by the same scorer who viewed only the F p1 -F p2 signal (alternative scoring), by another expert from the same institution, and by the algorithm. Automatic, alternative and independent expert scoring were compared with the referent scoring on an epoch-by-epoch basis. The algorithm's agreement with the reference (81.0%, Cohen's κ = 0.75) was comparable to the inter-rater agreement (83.3%, Cohen's κ = 0.78) or agreement between the referent scoring and manual scoring of the frontopolar derivation (80.7%, Cohen's κ = 0.75). Most misclassifications by the algorithm occurred during uneventful wake/sleep transitions, whereas cortical arousals, rapid eye movement and stable non-rapid eye movement sleep were detected accurately. The algorithm yielded accurate estimates of total sleep time, sleep efficiency, sleep latency, arousal indices and times spent in different stages. The findings affirm the utility of automatic scoring of stages and arousals from a single frontopolar derivation as a method for assessment of sleep architecture in healthy adults.

The forced oscillation technique (FOT) has been demonstrated to be a very sensitive tool for the assessment of upper airway obstruction during nasal continuous positive airway pressure (CPAP) therapy for obstructive sleep apnoea (OSA). The present study was designed to evaluate the therapeutic efficacy of a novel auto-CPAP device based exclusively on the FOT. Following manual CPAP titration, 18 patients with OSA (mean apnoea/hypopnoea index (AHI) 48.028.1) were allocated to conventional CPAP and auto-CPAP treatment under polysomnographic control in randomized order. The patients were asked to assess their subjective daytime sleepiness using the Epworth Sleepiness Scale (ESS). The mean AHI during auto-CPAP treatment was 3.43.4 and was comparable with that obtained during conventional CPAP treatment (4.23.6). The analysis of sleep architecture, the arousal index (6.62.1 versus 7.34.4) or the ESS (5.61.8 versus 7.34.4) did not reveal any significant differences. However, the mean CPAP pressure during auto-CPAP treatment (0.840.26 kPa) and in particular the pressure applied in the lateral body position (0.740.35 kPa), was significantly lower than that employed in conventional CPAP treatment (0.930.16 kPa, both comparisons: p<0.05). The auto-continuous positive airway pressure device proved equally as effective as conventional continuous positive airway pressure. However, the mean treatment pressure was significantly reduced, especially when patients were sleeping in the lateral position.

Studying the biology of sleep requires the accurate assessment of the state of experimental subjects, and manual analysis of relevant data is a major bottleneck. Recently, deep learning applied to electroencephalogram and electromyogram data has shown great promise as a sleep scoring method, approaching the limits of inter-rater reliability. As with any machine learning algorithm, the inputs to a sleep scoring classifier are typically standardized in order to remove distributional shift caused by variability in the signal collection process. However, in scientific data, experimental manipulations introduce variability that should not be removed. For example, in sleep scoring, the fraction of time spent in each arousal state can vary between control and experimental subjects. We introduce a standardization method, mixture z-scoring, that preserves this crucial form of distributional shift. Using both a simulated experiment and mouse in vivo data, we demonstrate that a common standardization method used by state-of-the-art sleep scoring algorithms introduces systematic bias, but that mixture z-scoring does not. We present a free, open-source user interface that uses a compact neural network and mixture z-scoring to allow for rapid sleep scoring with accuracy that compares well to contemporary methods. This work provides a set of computational tools for the robust automation of sleep scoring.

Inter-patient comparisons of cardiovascular metrics indicative of patient health have been shown to be successful in differentiating patients on a group rather than an individual level. This is in part due to the range of mental (as well as physical) activity-based variations for each patient and the difficulty assessing physical and mental activity during conscious states. In order to provide an objective scale for measuring central nervous system activity during sleep, the heart rate (RR) interval time series is divided into coarse sleep stage segments in which the LF HF -ratio (the relative balance between low and high frequency power) is estimated for age and sex-matched populations of apnoeic and healthy subjects. Activity-based noise is therefore reduced and a more useful comparison of heart rate variability can be made. Additionally, the spectral estimation performances of the FFT and the Lomb-Scargle periodogram (LSP), a Fourier-based technique for unevenly sampled time series are compared. Separation of patients according to condition is shown to be more pronounced when using the LSP than the FFT. Furthermore, separation is found to be most marked in slow wave sleep.

By monitoring the Q wave/T wave (QT) interval computed from electrocardiography (ECG) signals during sleep, it is possible to create a link between the ventricular repolarization and sleep stages. In this study, we aimed to find a robust and simple approach to automatically determine the fiducials on each 30-s sleep epoch, such as the Q, R, and T-end points, on long sleep ECG recordings in order to statistically analyze the effect of obstructive sleep apnea (OSA) and sleep stages on QT intervals. This is a retrospective study in which the ECG data extracted from the polysomnography recordings of 7 healthy women and 5 women with OSA, acquired in a sleep laboratory, were used. Experts annotated the sleep stage and OSA presence information for each 30-s epoch. Later, we visually selected epochs with clean signals from a total of 8324 epochs. On the selected epochs, we determined R peaks on each heartbeat, and by aligning each ECG portion corresponding to a heartbeat using those R points, we computed an average ECG signal for each epoch. On the average ECG signals, we developed a novel approach to find the Q and T-end points. With the help of Bazzet's formula, we computed the corrected QT interval (QTc) values for each epoch using the QT and the median RR interval. Finally, we analyzed the QTc values for the different sleep stages and healthy or OSA groups. We employed statistical approaches such as the Mann-Whitney U test, Freidman's test, and the Wilcoxon signed-rank test. As a result of this study, we found that OSA has a prolongation effect on the total duration of the ventricular depolarization and repolarization. We also observed that the QTc values computed in each sleep stage were significantly different between the healthy and OSA groups. Additionally, we discovered that within the healthy group, the QTc values were distinctive in the different sleep stages.

This research aimed at investigating the time course of the EEG background activity level before spontaneous awakening out of rapid eye movement (REM) sleep, and non-rapid eye movement sleep with and without slow wave sleep (NREMSWS þ , NREMSWS 2 ) in the second semester of life. Twelve infants from 25 to 54 weeks of life were continuously monitored by polygraphic recording and behavioural observation during the night, and the EEG activity was analyzed by a method of automatic analysis. The EEG activation level increased before the awakening out of NREMSWS þ sleep, and was always high both in REM sleep and in NREMSWS 2 .

This research aimed at investigating the time course of the EEG background activity level before spontaneous awakening out of rapid eye movement (REM) sleep, and non-rapid eye movement sleep with and without slow wave sleep (NREMSWS þ , NREMSWS 2 ) in the second semester of life. Twelve infants from 25 to 54 weeks of life were continuously monitored by polygraphic recording and behavioural observation during the night, and the EEG activity was analyzed by a method of automatic analysis. The EEG activation level increased before the awakening out of NREMSWS þ sleep, and was always high both in REM sleep and in NREMSWS 2 .

Electroencephalographic sleep stage transitions and altered first REM sleep period transitions have been identified as biomarkers of type 1 narcolepsy in adults, but not in children. Studies on memory complaints in narcolepsy have not yet investigated sleep-dependent memory consolidation. We aimed to explore stage transitions; more specifically altered REM sleep transition and its relationship with sleep-dependent memory consolidation in children with narcolepsy. Twenty-one children with narcolepsy-cataplexy and twenty-three healthy control children completed overnight polysomnography and sleep-dependent memory consolidation tests. Overnight transition rates (number of transitions per hour), global relative transition frequencies (number of transitions between a stage and all other stages/total number of transitions × 100), overnight transitions to REM sleep (transition from a given stage to REM/total REM transitions × 100), and altered first REM sleep period transitions (transitions from wake or N1 to the first REM period) were computed. Narcoleptic children had a significantly higher overnight transition rate with a higher global relative transition frequencies to wake. A lower sleep-dependent memory consolidation score found in children with narcolepsy was associated with a higher overnight transition frequency. As observed in narcoleptic adults, 90.48% of narcoleptic children exhibited an altered first REM sleep transition. As in adults, the altered sleep stage transition is also present in children with narcolepsy-cataplexy, and a higher transition rate could have an impact on sleep-dependent memory consolidation. These potential biomarkers could help diagnose type 1 narcolepsy in children more quickly; however, further studies with larger cohorts, including of those with type 2 narcolepsy and hypersomnia, are needed.

Sleep stage scoring is a first, crucial step in analysing a sleep electroencephalogram (EEG) recording, whether in research settings or clinical practice. As it is partly subject to expert interpretation, it can carry substantial inter-expert variability. Although the algorithm for automated scoring methods is becoming increasingly available, time-consuming human expert sleep stage scoring remains the reference method. Previous studies on inter-expert agreement have reported average kappa values showing almost perfect agreement (κ ~ 0.82) after prior

Brain recovery after prolonged wakefulness is characterized by increased density, amplitude and slope of slow waves (SW, ,4 Hz) during non-rapid eye movement (NREM) sleep. These SW comprise a negative phase, during which cortical neurons are mostly silent, and a positive phase, in which most neurons fire intensively. Previous work showed, using EEG spectral analysis as an index of cortical synchrony, that Morning-types (M-types) present faster dynamics of sleep pressure than Evening-types (E-types). We thus hypothesized that single SW properties will also show larger changes in M-types than in Etypes in response to increased sleep pressure. SW density (number per minute) and characteristics (amplitude, slope between negative and positive peaks, frequency and duration of negative and positive phases) were compared between chronotypes for a baseline sleep episode (BL) and for recovery sleep (REC) after two nights of sleep fragmentation. While SW density did not differ between chronotypes, M-types showed higher SW amplitude and steeper slope than E-types, especially during REC. SW properties were also averaged for 3 NREM sleep periods selected for their decreasing level of sleep pressure (first cycle of REC [REC1], first cycle of BL [BL1] and fourth cycle of BL [BL4]). Slope was significantly steeper in M-types than in E-types in REC1 and BL1. SW frequency was consistently higher and duration of positive and negative phases constantly shorter in M-types than in E-types. Our data reveal that specific properties of cortical synchrony during sleep differ between M-types and E-types, although chronotypes show a similar capacity to generate SW. These differences may involve 1) stable trait characteristics independent of sleep pressure (i.e., frequency and durations) likely linked to the length of silent and burst-firing phases of individual neurons, and 2) specific responses to increased sleep pressure (i.e., slope and amplitude) expected to depend on the synchrony between neurons.

Sleep is an essential phase in human circadian rhythm with importance in restoring human vigour and vitality. Conventional sleep examination is done using Polysomnography with many sensors connected to various parts of human body. Recently, research in sleep is geared toward alternative feasibility of using only ECG signal. In this research, sleep stages classification using only features derived from single-lead ECG is conducted. The capability of Generalized Learning Vector Quantization (GLVQ) in discriminating sleep stages is tested. We showed that GLVQ which is configured with multi codebooks shows promising result in discriminating complex sleep stages data.

Background and Aims: Few large studies have evaluated the adverse events associated with therapeutic colonoscopy for colorectal neoplasia, including bleeding and bowel perforation. Our aim was to investigate factors associated with these events, using a Japanese national inpatient database. : We extracted data from the nationwide Japan Diagnosis Procedure Combination database for patients who underwent therapeutic colonoscopy for colorectal neoplasia between 2013 and 2014. Therapeutic colonoscopy included endoscopic submucosal dissection (ESD), endoscopic mucosal resection (EMR) and polypectomy. Outcomes included bleeding, perforation, cerebro-cardiovascular events, and in-hospital death. A multivariable logistic regression model was used to evaluate factors associated with bleeding and bowel perforation. We analyzed 345,546 patients, including 16,812 (4.9%) who underwent ESD, 219,848 (63.6%) who underwent EMR and 108,886 (31.5%) who underwent polypectomy. The rates of bleeding, bowel perforation, cardiovascular events, cerebrovascular events, and death were 32.5, 0.47, 0.05, 0.88, and 1.32 per 1,000 patients, respectively. In the multivariate analysis, a higher bleeding rate was associated with male, comorbid diseases, ESD, tumor size ≥2 cm, and use of drugs including low-dose aspirin, thienopyridines, non-aspirin antiplatelet drugs, novel oral anticoagulants, warfarin, non-steroidal anti-inflammatory drugs (NSAIDs), and steroids. A higher bowel perforation rate was associated with male, renal disease, ESD, tumor size ≥2 cm, and drugs including warfarin, NSAIDs, and steroids.

Spontaneous rhythmic masticatory muscle activity (RMMA) during sleep occurs in relation to transient activation in the cerebral and autonomic nervous systems of normal subjects and in patients with sleep bruxism (SB). In this study, we made a quantitative assessment of the sequential changes in cortical electroencephalographic (EEG) and autonomic-cardiac activities associated with micro-arousals preceding RMMA episodes. We matched 10 SB patients with 10 normal subjects. The onset of RMMA episodes was defined in terms of the onset of activation in the suprahyoid muscles. In SB patients, an increase in cortical EEG activity was observed 4 seconds before the onset of suprahyoid activity in 79% of episodes. A significant acceleration in heart rate was initiated one cardiac cycle before RMMA onset. A clear sequence of cortical to autonomic-cardiac activation precedes jaw motor activity in SB patients. This suggests that SB is a powerful oromotor manifestation secondary to micro-arousal.

The psychomotor vigilance test (PVT) is a widely-used, minimally invasive, inexpensive, portable, and easy to administer behavioral measure of vigilance that is sensitive to sleep loss. We conducted analyses to determine the relative sensitivity of the PVT vs. the multiple sleep latency test (MSLT) and the maintenance of wakefulness test (MWT) during acute total sleep deprivation (TSD) and multiple days of sleep restriction (SR) in studies of healthy adults. Twenty-four studies met the criteria for inclusion. Since sleepiness countermeasures were administered in some of these studies, the relative sensitivity of the three measures to these interventions was also assessed. The difference in weighted effect size (eta-squared) was computed for each pair of sleepiness measures based on available raw test data (such as average PVT reaction time). Analyses revealed that the sleep measures were differentially sensitive to various types of sleep loss over time, with MSLT and MWT more sensit...

The effects of radiotherapy on subsequent growth hormone (GH) secretion and sleep organization was studied by simultaneous evaluation of spontaneous sleep-related GH secretion (SSRGHS), arginine-insulin tolerance test (AITT) and polygraphic sleep recording in a follow up of 19 children who underwent surgical removal of an intracranial tumour and cranial radiotherapy 1-7 years previously. Electrophysiological patterns of sleep phases, the amount and distribution of sleep stages were normal, suggesting that the procedure utilized should not entail modifications of SSRGHS per se. Long-term after radiotherapy SSRGHS and AITT GH responses were lower than those of the medium-term group. The lack of correlation between SSRGHS and AITT GH secretion suggests that SSRGHS and AITT measure different aspects of GH secretion. The highest value of GH plasma level (peak) corresponded to slow wave sleep, mainly during the first non-rapid eye movement-rapid eye movement (NREM-REM) cycle, in practically all the patients. Although the SSRGHS synchronization with SWS of the first NREM-REM cycle was preserved, no sleep measure was correlated with the SSRGHS. The usefulness of polygraphic monitoring of sleep patterns was confirmed.

Decreased levels of physical and social activity associated with aging can be particularly pronounced in residents of assisted living facilities. Reduced exposure to important behavioral and time-giving cues may contribute to the age-related changes in circadian rhythmicity and sleep. The present study was conducted to test the hypothesis that an enforced schedule of structured social and physical activity (0:900 to 10:30 and 19:00 to 20:30 daily for two weeks) can have beneficial effects on circadian rhythmicity, nocturnal sleep, daytime functioning, mood, and vigor. The subjects were 14 elderly residents of continued-care retirement facilities while a similar group of 9 elderly residents served as controls. The group exposed to structured activities had increased amounts of slow-wave sleep and demonstrated improvement in memory-oriented tasks following the intervention. Conversely, no significant changes were noted in the amplitude and phase of the body temperature rhythm or in subjective measures of vigor and mood. These results indicate that short-term exposure to structured social intervention and light physical activity can significantly improve memory performance and enhance slow-wave sleep in older adults without alterations to the circadian phase or amplitude of body temperature. This is the first report to demonstrate that low intensity activity in an elderly population can increase deep sleep and improve memory functioning. The high degree of interest in these activities paired with the simple nature of the tasks makes this a potentially practical intervention which can be adapted for both community dwelling and assisted-living elders.

The purpose of this study is to develop a stimulation, which has an active physiological influence to prevent severe driver drowsiness while driving. This paper presents a heartbeat-synchronized vibration, which is the rhythmic pulsation of a motor with each beat of the heart, as an effective means to ease drivers&#39; slight deprivation of oxygen with the appearance of cardiorespiratory coordination. The effects of this stimulation were confirmed by the results of an experiment done in cooperation with 15 subjects. The results showed that cardiorespiratory coordination appeared under the stimulation and it played an active influence on the oxygen supply to the body. We conclude that the vibratory stimulation has an active influence to prevent drowsiness. It might be effective to prevent severe drowsiness while driving.

Introduction: Interactions between circadian and homeostatic systems modulate our sleep-wake cycle but also variations in cognitive performance. Additionally, individuals exhibit differences in their preferred schedules for sleep and activity patterns. Here we investigated the cerebral bases of these differences in the context of an interference task. Methods: Thirty extreme chronotypes (16 early (ET), 14 late types (LT)) underwent 2 fMRI sessions, 1.5 and 10.5 h after preferred waking up controlled throughout actimetry the week prior testing. Order of the sessions was counter-balanced over subjects. The day before each fMRI session, subjects stayed in dim-light, circadian phase was asserted by detecting melatonin secretion onset (saliva samples). Polysomnography was recorded the nights preceding test sessions. During fMRI scanning, subjects performed a Stroop conflict paradigm where subjects must name the printed colour of a colour name, with congruent (C), incongruent (I) and neutral (N) trials. Results: ET and LT significantly differed in their sleep timing and mid range crossings of melatonin expression. Circadian phase angles were similar in both LT and ET indicating a stable relationship between the adopted sleep timing and circadian phase. At the behavioral level, RTs were lower for I than N trials, but no significant time of day or chronotype effects were observed. In the morning, the interference-related activation effect (I versus N events) was significantly higher in LT than ET in the inferior and medial frontal gyrus as well as a parietal and a parahippocampal region. Conversely, in the evening, orbital, inferior and medial frontal gyri, superior temporal and occipital regions were more activated in ET than LT. Discussion: Inferior frontal areas are known to be involved in a conflict resolution network. Interestingly, activation in this area was higher for LT than ET in the morning, whereas it was higher for ET than LT in the evening. This cannot be accounted for by differences in time awake or in circadian phase per se. Previously reported chronotypical differences in the dynamics of the sleep pressure, mainly differences in its built up and dissipation are however potential candidates to explain our data.

Background and objective The profession of anaesthesiologist is demanding and potentially hazardous. Extended work shifts combined with intensive work load may adversely affect physicians' performance. The aim of this study was to explore the impact of a single in-hospital 24 h shift on the cognitive and psychomotor performance of anaesthesiologists in a surgical emergency department. Methods Following ethical and institutional approval, 11 staff anaesthesiologists [six men, five women, age 48 (35-50), years of experience 17 (7-20), median (range)] successfully completed the study protocol. Four computergenerated psychological tests (CRD, Complex Reactionmeter Drenovac, Croatia) consisting of light signal position discrimination (CRD 311), simple visual orientation (CRD 21), simple arithmetic operations (CRD 11), and complex psychomotor coordination (CRD 411) were used to measure objective parameters of cognitive and psychomotor performance at four time points (D1 U 8:00 a.m., D2 U 3:00 p.m., D3 U 11:00 p.m.; and D4 U 7:00-8:00 a.m. next day) during the 24 h working day. The control testing on an ordinary working day was performed at two time points (C1 U 8:00 a.m., C2 U 3:00 p.m.). Three parameters were recorded: total test solving time (TTST), total variability, and total number of errors for all four tests. Results TTST was significantly impaired during the 24 h shift in all tests, and TTST was prolonged in CRD 21 test at different time points from 1.6 W 1.4 to 5.5 W 1.6 s compared with the control (F U 6.39, P U 0.001). The reaction times were prolonged from 1.3 W 1.8 to 5.4 W 1.2 s (F U 3.49, P U 0.009) in CRD 311, from 3.8 W 9.0 to 34.3 W 5.8 s (F U 5.05, P U 0.002) in CRD 11 TTST, and from 0.8 W 3.0 to 16.3 W 8.6 s (F U 2.67, P U 0.034) in CRD 411. Total variability was significantly altered during the 24 h shift only in CRD 411 (F U 2.63, P U 0.036). There was no difference in the total number of errors between the 24 h shift and the ordinary working day. Conclusion Anaesthesiologists' 24 h working day in the emergency department altered cognitive and psychomotor function in comparison with ordinary working days. Speed, reliability and mental endurance (measured by TTST) were significantly impaired in all four tests. Stability and reaction time (measured by total variability) were only slightly impaired. Paradoxically, attention and alertness (measured by total number of errors) were not adversely affected. In conclusion, anaesthesiologists' psychomotor performance was impaired during the single 24 h shift. Eur J Anaesthesiol 26:825-832 Q 2009 European Society of Anaesthesiology.

Sleep problems are one of the main health issues raised by families. Therefore, we aimed to evaluate the sleep problems of pre-school children in Iran. Five hundred and seventy-nine children aged 3-6 years were randomly recruited from 15 kindergartens in the city of Qazvin in Iran. The Iranian version of BEARS (Bedtime problems, Excessive daytime sleepiness, Awakenings during the night, Regularity and duration of sleep and Snoring) and the Children&#39;s Sleep Habits questionnaire (CSHQ) were completed by interviewers. Data analysis was performed using SPSS version 19. The data were analysed with a Student&#39;s t-test, chi-square and Fisher&#39;s exact tests. A P value &lt; 0.05 was considered significant. The study population consisted of 299 boys (51.6%) and 280 (48.3%) girls with a mean age of 4.1 years (SD 0.8). The mean body mass index (BMI) of the children was 15 (SD 2.1). The average sleep duration among the children was 10:54 h/day (SD 00:48). They went to bed late (23:18 h...

SummaryObstructive sleep apnea (OSA) syndrome is the most common sleep‐related breathing disorder, characterized by excessive snoring and repetitive apneas and arousals, which leads to fragmented sleep and, most importantly, to intermittent nocturnal hypoxaemia during apneas. Considering previous studies about morphovolumetric alterations in sleep apnea, in this study we aimed to investigate for the first time the functional connectivity profile of OSA patients and age–gender–matched healthy controls, using resting‐state functional magnetic resonance imaging (fMRI). Twenty severe OSA patients (mean age 43.2 ± 8 years; mean apnea–hypopnea index, 36.3 h−1) and 20 non‐apneic age–gender–body mass index (BMI)‐matched controls underwent fMRI and polysomnographic (PSG) registration, as well as mood and sleepiness evaluation. Cerebro‐cerebellar regional homogeneity (ReHo) values were calculated from fMRI acquisition, in order to identify pathology‐related alterations in the local coherence ...

Background: Cough is one of the most frequent symptoms in children and is the most common symptom for which children visit a health care provider. Methods: This is an observational study on acute cough associated with upper respiratory tract infection (URTI) in children. The study evaluates the epidemiology and impact of cough on quality of sleep and children's activities, and the outcome of cough with antitussive treatments in pediatric routine clinical practice. Study assessments were performed through a pediatric cough questionnaire (PCQ), developed by the Italian Society of Cough Study. A total of 433 children visited by family care pediatricians for acute cough due to a URTI were enrolled in this study, with mean age of 6.1 years (SD 3.6). Cough type, duration, severity and frequency, cough impact on sleep disturbances of children and parents and on school and sport activities were assessed at baseline. In a subset of 241 children who were either treated with antitussive drugs (levodropropizine n = 101, central antitussives n = 60) or received no treatment (n = 80), the outcome of cough after 6 days was analyzed in terms of resolution, improvement, no change, or worsening. Descriptive analysis, χ 2 test, and multivariate analysis with stepwise logistic regression were performed. Results: Cough disturbed sleep in 88% of children and 72% of parents. In children treated with cough suppressants, the duration, type, intensity, and frequency cough were similar at baseline in the two groups respectively treated with levodropropizine and central antitussives (cloperastine and codeine). Both levodropropizine and central drugs reduced cough intensity and frequency. However, percentage of cough resolution was higher with levodropropizine than with central antitussives (47% vs. 28% respectively, p = 0.0012). Conclusions: Acute cough disturbs sleep in most children and their parents. Both levodropropizine and central antitussives reduced cough intensity, with levodropropizine producing a higher cough resolution rate.

Study Objectives: This study aimed to analyze the association between habitual meal timing and sleep parameters, as well as habitual meal timing and apnea severity in individuals with obstructive sleep apnea (OSA). Methods: Patients in whom mild to severe OSA was diagnosed were included in the study (n = 296). Sleep parameters were analyzed by polysomnography. Dietary pattern was obtained by a food frequency questionnaire and meal timing of the participants. Individuals with OSA were categorized by meal timing (early, late, and skippers). Results: Dinner timing was associated with sleep latency (β = 0.130, P = .022), apnea-hypopnea index (AHI) (β = 1.284, P = .033) and poor sleep quality (β = 1.140, P = .015). Breakfast timing was associated with wake after sleep onset (WASO) (β = 3.567, P = .003), stage N1 sleep (β = 0.130, P < .001), and stage R sleep (β = -1.189, P = .001). Lunch timing also was associated with stage N1 sleep (β = 0.095, P = .025), sleep latency (β = 0.293, P = .001), and daytime sleepiness (β = 1.267, P = .009). Compared to early eaters, late eaters presented lower duration of stage R sleep and greater values of sleep latency, WASO, stage N1 sleep, and AHI, in addition to increased risk of poor sleep quality and daytime sleepiness (P < .005). Conclusions: Late meal timing was associated with worse sleep pattern and quality and apnea severity than early meal timing. Despite some of these results having limited clinical significance, they can lead to a better understanding about how meal timing affects OSA and sleep parameters.

Health-related Quality of Life (HRQoL) has become an important construct in contemporary medicine and health care, permitting assessment of disorder burden and evaluation of interventions on various aspects of functioning, in a standardized manner. Here we review literature on the measurement of HRQoL in insomnia populations, and the extent to which insomnia treatment improves domains of HRQoL. It is concluded from the relatively small literature that insomnia impacts on diverse areas of HRQoL, and that both pharmacological and non-pharmacological interventions can produce, to varying degrees, improvements in domains spanning physical, social and emotional functioning. Limitations of the current literature are identified; with particular emphasis on measurement and conceptual shortcomings. Suggestions are made in relation to improving the quality of future research, and how to further shed light on the impact of insomnia -and treatment thereof -on both HRQoL and global quality of life.

that might differentiate individuals with and without insomnia among those with a high vulnerability to stress-related insomnia. Materials and Methods: Participants were 847 adults (mean age = 47.3 years; 73.3% women) selected from a larger population-based sample enrolled in a longitudinal study of insomnia. They were selected for the present analysis on the basis of their high vulnerability to stress-related insomnia as assessed with the Ford Insomnia Response to Stress Test (score higher than 21). Among those, two groups were formed based on their sleep status: Good Sleepers (n = 509) and Insomnia Syndrome (n = 338). Dependent variables were trait anxiety, arousal predisposition, stress perception and coping strategies, and beliefs and attitudes about sleep. Results: A MANCOVA controlling for age and a past episode of insomnia revealed that Good Sleepers with high vulnerability to stress-related insomnia were significantly less anxious (eta2 = 0.22), less predisposed to activation (eta2 = 0.07), appraised life's events as less stressful (eta2 = 0.18), and endorsed fewer dysfunctional beliefs about sleep (eta2 = 0.15) compared to individuals with an Insomnia Syndrome and a high vulnerability to stress-related insomnia. The Good Sleepers group also relied less on emotion-focused strategies (eta2 = 0.06), but more on task-(eta2 = 0.04) and avoidance-oriented strategies (eta2 = 0.02). Conclusion: Lower levels of anxiety, perception of stress, and arousal predisposition, and less dysfunctional beliefs about sleep might be protective against chronic insomnia among individuals otherwise vulnerable to stressrelated insomnia. A longitudinal design is needed to test more rigorously this hypothesis.

Background: The growing interest in the utility of electronic healthcare records (EHR) databases for drug safety surveillance has spurred development of new methodologies for signal detection. There is, however, no definitive list of known adverse drug reactions and which drugs can cause them. [1] As there is no true gold standard, most of the methods used in drug safety signal detection have not been prospectively evaluated. Methods: There are two human papillomavirus vaccines, Gardasil and Cervarix, available in Italy since 2008. The HPV vaccine is offered free of charge by Local Health Units (LHU) and an active programme is aimed at immunizing all female adolescents in the twelfth year of life. Some Regions have extended the HPV vaccine offer to other cohorts, either free of charge or with a limited co-payment. The study population is represented by all the women who received the HPV in a LHU and gave their consent to participation. Common adverse events occurring in two weeks following each dose administration were collected by vaccinated woman using a structured diary. An ad hoc web platform was available to enter data at regional level. Results: The surveillance involves 33 LHUs in 9 Italian Regions. From July 2009 to June 2011, 10 785 immunised women (8332 receiving Cervarix and 2453 Gardasil), were included in the surveillance for a total of 23 740 administered doses. 38% of women concluded the vaccination cycle, 66% with Gardasil and 30% with Cervarix. Out of 14 732 doses 9061 adverse events were reported. The vast majority consisted of swelling at the injection site, headache, nausea, fainting and pain. The vaccination cycle was interrupted by 33 women (0.1%): 16 for refusing, 3 for changing residence, and 11 for adverse reactions (3 of whom required the hospitalization). Conclusions: The surveillance is still ongoing and final results will be available by the end of 2011. The high proportion of adverse events reported is mainly due to the design of the study; however the majority of the events were mild and transient. [1] The low number of vaccinated women included in the study could be partly explained by the voluntary participation of the Regions. As for all vaccines, and in particular for newly marketed ones, the surveillance of adverse events represents an essential step in the evaluation of a vaccination programme. [2] References

Sleep architecture is characterized by classifying polysomnographic epochs into mutually exclusive stages. Notwithstanding the clinical importance of staging, it has the drawback of representing sleep as a discrete process. Metrics based on the electroencephalogram (EEG) are needed to supplement conventional sleep staging by allowing a description of sleep in terms of unitary, continuous markers. Traditional linear and nonlinear techniques for achieving this goal have not proved sufficient. Employing recurrence analysis, we developed a method for capturing and quantifying the dynamical states of the brain during sleep. The method yields markers for continuously determining sleep depth, for detecting sleep-specific phasic events, and for objectively defining potentially useful sleep markers and indices. Recurrence markers captured the coarse-and fine-grained temporal activity of the sleep EEG, thereby permitting continuous quantitation of brain electrical activity on any desired time scale. The markers were validated with respect to the tonic behavior (time scale of seconds) of the sleep EEG by establishing that they disambiguated the stages of sleep that are defined solely on the basis of EEG activity. Validation of the markers over time scales of milliseconds was achieved by showing that common types of sleep-EEG phasic events could be detected by recurrence analysis. The method was also used to define a generalized EEG arousal index that quantified previously unrecognized sleep-stage-dependent deterministic properties of brain electrical activity. Using nonlinear analysis that quantified the recurrence properties of the EEG, we described a novel method for producing dynamic markers of brain states during sleep.

Background: Sleep disturbance is a common subjective complaint of minor traumatic brain-injured (mTBI) patients, but little is known about the characteristics of sleep disturbance in adults years after the injury. Methods: Polysomnographic (PSG) and multiple sleep latency test (MSLT) records of 26 mTBI adult patients with normal brain computerized tomography and negative encephalographic studies, no past history of CNS pathology, no premorbid or present major psychiatric diagnosis, and no sleep apnea syndrome were compared to a matched group of apparently healthy individuals (controls). Results: Sleep patterns were disturbed in the mTBI patients. Their sleep architecture was altered, with significantly higher light-sleep non-rapid eye movement (NREM) stage 2 scores compared to controls (54.5 ± 13.4% vs. 46.6 ± 10.4%, respectively, p = 0.03) and significantly lower REM sleep scores (21.2 ± 8.4% vs. 25.4 ± 4.5%, respectively, p = 0.05). The MSLT findings documented significant excessive daytime episodes of falling asleep. Conclusions: Sleep disturbances of adult patients with chronic mTBI may manifest characteristic alterations in both timing and architecture of their sleep patterns. Sleep lab evaluations may help identify subgroups of mTBI patients who would probably benefit from treatment.

Six adult male research volunteers, in two groups of 3 subjects each, lived in a residential laboratory for 15 days. All contact with the experimenters was through a networked computer system, and subjects&#39; behavior was monitored continuously and recorded. During the first part of each day, subjects remained in private rooms doing planned work activities, and during the remainder of each day, they were allowed to socialize. Two cigarettes containing active marijuana (2.7% Δ9‐THC) or placebo were smoked during the private work period and the period of access to social activities. Three‐day contingency conditions requiring subjects to engage in a low‐probability work activity (instrumental activity) in order to earn time that could be spent engaging in a high‐probability work activity (contingent activity) were programmed during periods of placebo and active‐marijuana smoking. During placebo administration, the contingency requirement reliably increased the amount of time that sub...

We sought to clarify the effect of short-acting benzodiazepine hypnotic on the relationship of arterial blood pressure and arterial partial pressure of carbon dioxide (Paco2) to regional cerebral blood flow (rCBF) during human non-rapid-eye-movement (non-REM) sleep. Nine young normal volunteers were treated in a randomized, crossover design with triazolam or placebo and underwent positron emission tomography at night. During wakefulness and stage 2 and slow wave (stages 3 and 4) sleep, we measured mean arterial blood pressure (MAP), Paco2, and absolute CBF. With triazolam compared to placebo, MAP reduced gradually. During stage 2 sleep, Paco2increased and whole-brain mean CBF decreased. With triazolam, relative rCBF of the left orbital basal forebrain decreased more during stage 2 than slow wave sleep, whereas absolute CBF of the occipital cortex and cerebral white matter remained constant. During triazolam-induced stage 2 sleep, absolute CBF of the cerebral white matter correlated ...

This study aimed to identify brain regions with the least decreased cerebral blood flow (CBF) and their relationship to physiological parameters during human non-rapid eye movement (NREM) sleep. Using [15O]H2O positron emission tomography, CBF was measured for nine normal young adults during nighttime. As NREM sleep progressed, mean arterial blood pressure and whole brain mean CBF decreased significantly; arterial partial pressure of CO2 and, selectively, relative CBF of the cerebral white matter increased significantly. Absolute CBF remained constant in the cerebral white matter, registering 25.9 ± 3.8 during wakefulness, 25.8 ± 3.3 during light NREM sleep, and 26.9 ± 3.0 (ml·100 g−1·min−1) during deep NREM sleep ( P = 0.592), and in the occipital cortex ( P = 0.611). The regression slope of the absolute CBF significantly differed with respect to arterial partial pressure of CO2 between the cerebral white matter (slope 0.054, R = − 0.04) and frontoparietal association cortex (slope...

Following a 30-day baseline, 60 days of sodium pentobarbital treatment (5 mg/kg) were given to squirrel monkeys 2 h prior to the start of a 12-h recording of EEG and EOG. Following the drugtreatment phase, an additional 30-day period was used to determine the rate of recovery. Repeated pentobarbital treatment significantly reduced awake time and slow wave sleep while it elevated the time spent in drowsy and light sleep, The recovery phase indicated a brief recovery of rapid eye movement sleep while the other stages failed to return to baseline levels. The cyclical nature of the changes observed with chronic pentobarbital suggest the importance of circadian fluctuations in the study of chronic drug treatment and the sleep-wakefulness process.

1. Heightened sympathetic activity plays a role in the cardiovascular sequelae of obstructive sleep apnoea (OSA). Cardiac autonomic function may be assessed non-invasively by studying heart rate variability (HRV). The aim of the present study was to compare overnight HRV between a control group and a group of subjects with severe OSA. The potential confounding effects of age, sex, baseline autonomic status and sleep stage distribution were taken into account. 2. Our prospective Holter study compared overnight (0030 -0530 hours) HRV in 23 controls (apnoea hypopnoea index (AHI) = 5 ± 3 /h) and 23 subjects with severe OSA (AHI = 65 ± 23 /h), matched for age and sex and with a similar percentage of rapid eye movement sleep. 3. The mean normal-to-normal RR interval (NN) was shorter in the OSA compared with control group (903 vs 1039 ms, respectively), whereas the other time-domain indices of HRV, as well as the classic frequency-domain indices, were similar. Essentially similar results were obtained hourly and when only subjects with high mean values of the standard deviation of all NN ( 90 ms) were evaluated. In the 0.01-0.06 Hz range corresponding to the typical OSA pattern of bradycardia-tachycardia termed cyclic variation of heart rate (CVHR), higher power was documented hourly in OSA, with a significant correlation between overnight power and both AHI and mean oxyhaemoglobin saturation. The percentage of NN > x ms different from the previous one (pNNx family) had no diagnostic value. 4. The results of the present study suggest that NN may be the best index to quantify the overnight sympathovagal balance in OSA and that a spectral band overlapping the apnoea-related pattern of CVHR slightly improved the characterization of the apnoea-related HRV patterns.

To investigate whether seizure lateralization affects sleep macrostructure in patients with left and right temporal lobe epilepsy (TLE), as rapid eye movement (REM) sleep is shorter in patients with right hemispheric cerebral infarction than with left. We retrospectively analyzed data from 16 patients with TLE (6 men and 10 women aged 34.9 ± 11.4 years) who underwent polysomnography as well as long-term video electroencephalography. Ten patients were diagnosed with left TLE and six patients with right TLE. Sleep stages and respiratory events were scored based on the American Academy of Sleep Medicine criteria. Sleep and respiratory parameters were compared between the patient groups. Percentage of REM stage sleep was significantly (p &lt; 0.05) lower in patients with left TLE (median 8.8 %, interquartile range 5.5-13.8 %) than in patients with right TLE (median 17.0 %, interquartile range 14.1-18.3 %). The other parameters showed no significant differences. Shorter REM sleep in pati...

Meditation training has been shown to improve attention and emotion regulation. However, the mechanisms responsible for these effects are largely unknown. In order to make further progress, a rigorous interdisciplinary approach that combines both empirical and theoretical experiments is required. This dissertation uses such an approach to analyze electroencephalogram (EEG) data collected during two three-month long intensive meditation retreats in four steps. First, novel tools were developed for preprocessing the EEG data. These tools helped remove ocular artifacts, muscular artifacts, and interference from power lines in a semi-automatic fashion. Second, in order to identify the cortical correlates of meditation, longitudinal changes in the cortical activity were measured using spectral analysis. Three main longitudinal changes were observed in the retreat participants: (1) reduced individual alpha frequency after training, similar reduction has been consistently found in experienced meditators; (2) reduced alpha-band power in the midline frontal region, which correlated with improved vigilance performance; and (3) reduced beta-band power in the parietal-occipital regions, vii which correlated with daily time spent in meditation and enhanced self-reported psychological well-being. Third, a formal computational model was developed to provide a concrete and testable theory about the underlying mechanisms. Four theoretical experiments were run, which showed, (1) reduced intrathalamic gain after training, suggesting enhanced alertness; (2) increased cortico-thalamic delay, which strongly correlated with the reduction in individual alpha frequency (found during spectral analysis); (3) reduction in intrathalamic gain provided increased stability to the brain; and (4) anterior-posterior division in the modeled reticular nucleus of the thalamus (TRN) layer and increased connectivity in the posterior region of TRN after training. Fourth, correlation analysis was performed to ground the changes in cortical activity and model parameters into changes in behavior and self-reported psychological functions. Through these four steps, a concrete theory of the mechanisms underlying focusedattention meditation was constructed. This theory provides both mechanistic and teleological reasoning behind the changes observed during meditation training. The theory further leads to several predictions, including the possibility that customized meditation techniques can be used to treat patients suffering from neurodevelopmental disorders and epilepsy. Lastly, the dissertation attempts to link the theory to the long-held views that meditation improves awareness, attention, stability, and psychological well-being. viii

Unfolding the overnight dynamics in human sleep features plays a pivotal role in understanding sleep regulation. Studies revealed the complex reorganization of the frequency composition of sleep electroencephalogram (EEG) during the course of sleep, however the scale-free and the oscillatory measures remained undistinguished and improperly characterized before. By focusing on the first four non-rapid eye movement (NREM) periods of night sleep records of 251 healthy human subjects (4–69 years), here we reveal the flattening of spectral slopes and decrease in several measures of the spectral intercepts during consecutive sleep cycles. Slopes and intercepts are significant predictors of slow wave activity (SWA), the gold standard measure of sleep intensity. The overnight increase in spectral peak sizes (amplitudes relative to scale-free spectra) in the broad sigma range is paralleled by a U-shaped time course of peak frequencies in frontopolar regions. Although, the set of spectral ind...

Objectives. To evaluate sleep quality, sleep-related symptoms, and degree of excessive daytime sleepiness (EDS) in severe obesity, independently of obstructive sleep apnoea syndrome (OSAS). Design. A cross-sectional study. Setting. Primary-care setting. Subjects, main outcome measures. Anthropometric parameters, respiratory function data and sleep related symptoms were evaluated in 78 severely obese patients (aged 16-75 years) without OSAS and in 40 healthy sex-and age-matched normal weight subjects, who underwent a full-night polysomnography. Results. Obese patients and control subjects had similar sleep latency and rapid eye movement (REM) latency, but they showed lower percentage of REM (P < 0.01) and sleep efficiency (P < 0.05) than controls. All sleep-related symptoms (observed or reported apnoea, awakenings, choking and unrefreshing sleep) were significantly more frequent in obese patients than in control subjects. Loud snoring was present in 46.7% of the obese patients and in 8.1% of the control individuals (P < 0.01). Excess daytime sleepiness was reported by 34.7% of the obese patients and by 2.7% of the normal weight subjects (P < 0.01). The Epworth Sleepiness Scale (ESS) was higher in the obese group than in the control group (P < 0.01), whereas arousals were not different between the two groups. Conclusions. This study clearly shows that severe obesity, even in the absence of OSAS, is associated with sleep-related disorders and EDS. All these alterations may be partly responsible for a lower quality of life, a higher prevalence of medical complications, an increased risk of occupational injury, and both social and family problems characterizing obese patients, independently of the presence of OSAS.

Although a growing body of research indicates that frequent nightmares are related to impaired sleep regulation, the pathophysiology of nightmare disorder is far from being fully understood. We examined the relative spectral power values for NREM and REM sleep separately in 19 individuals with nightmare disorder and 21 healthy controls, based on polysomnographic recordings of the second nights' laboratory sleep. Nightmare subjects compared to controls exhibited increased relative high alpha (10-14.5 Hz) and fronto-central increases in high delta (3-4 Hz) power during REM sleep, and a trend of increased fronto-central low alpha (7.75-9 Hz) power in NREM sleep. These differences were independent of the confounding effects of waking emotional distress. High REM alpha and low NREM alpha powers were strongly related in nightmare but not in control subjects. The topographical distribution and spectral components of REM alpha activity suggest that nightmare disordered subjects are characterized by wakelike electroencephalographic features during REM sleep.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • ‘Bepotastine besilate’ is a novel second‐generation antihistamine developed in Japan and its antiallergic effects have already been demonstrated by various studies.• However, only a few clinical studies regarding its sedative property are available.• In addition, histamine H1 receptor occupancy (H1RO) of this new antihistamine has never been measured by positron emission tomography (PET). WHAT THIS STUDY ADDS • This paper provides the first measurement result of cerebral H1RO of bepotastine besilate (approximately 15%) as determined by PET.• This result is in accordance with the clinical classification of bepotastine as a second‐generation antihistamine.• In addition, the relationship between subjective sleepiness and cerebral H1RO of this second‐generation antihistamine is demonstrated for the first time using a placebo‐controlled crossover study design.AIMSAntihistamines are frequently used for treating various allergic diseases, but ofte...

Our aim was to investigate the effects of the negative pressure reflex on mechanically opposing pharyngeal muscles during wakefulness, slow-wave sleep (SWS), and rapid eye movement (REM) sleep. In four goats with isolated upper airways, we measured tracheal airflow and electrical activity of the thyropharyngeus (TP; constricting), the stylopharyngeus (SP; dilating), and the diaphragm (Dia). In the wakefulness state in response to negative pressure tests, TP decreased (65%), SP increased (198%), and tidal volume (Vt) (66%) and rate of rise of Dia (Diaslope, 69%) decreased ( P &lt; 0.02). Similarly, during SWS, the negative pressure response of TP (31%), Vt (61%), and Diaslope (60%) decreased, whereas SP (113%) increased, relative to SWS control ( P &lt; 0.02). In REM sleep, the negative pressure response by TP and SP were small, whereas both Vt (38%) and Diaslope (24%) were greatly decreased ( P &lt; 0.02) compared with REM control. Inspiratory duration remained unchanged in response...