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Obstructive sleep apnea is a prevalent sleep-disordered breathing condition characterized by repetitive reduction in breathing during sleep. The current care standard for obstructive sleep apnea is continuous positive air pressure devices, often suffering from low tolerance due to limited adherence. Capitalizing on the unique neurocircuitry of olfactory perception and its retained function during sleep, we conducted a pilot study to test transient, respiration-based olfactory stimulation as a treatment for obstructive sleep apnea markers. Thirty-two patients with obstructive sleep apnea (apnea-hypopnea index ≥ 15 events per hr) underwent two polysomnography sessions, "Odour" and "Control", in random order. In "Odour" nights, patients were presented with transient respiratory-based olfactory stimulation delivered via a computer-controlled commercial olfactometer (Scentific). The olfactometer, equipped with a wireless monitoring, analysed respiratory patterns and presented odour upon detection of respiratory events. No odours were presented in "Control" nights. Following exclusions, 17 patients entered the analysis (four women, 47.4 (10.5) years, body mass index: 29.4 (6.3) kg m -2 ). We observed that olfactory stimulation during sleep reduced the apnea-hypopnea index ("Odour": 17.2 (20.9), "Control": 28.2 (18.6), z = -3.337, p = 0.000846, BF 10 [Bayesian Factor 10]= 57.9), reflecting an average decrease of 31.3% in the number of events. Relatedly, stimulation reduced the oxygen desaturation index by 26.9% ("Odour": 12.5 (15.8), "Control": 25.7 (25.9), z = -3.337, p = 0.000846, BF 10 = 9.522). This effect was not linked to the severity of baseline obstructive sleep apnea markers (ρ = -0.042, p = 0.87). Olfactory stimulation did not arouse from sleep or affect sleep structure, measured as time per sleep stage (F 1,16  = 0.088, p = 0.77). In conclusion, olfactory stimulation during sleep was effective in reducing the severity of obstructive sleep apnea markers without inducing arousals, and may provide a novel treatment for obstructive sleep apnea, prompting continued research., (© 2024 Appscent medical Ltd. and The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

The main study aim was to compare the validity of children sleep apnea data obtained from standard polysomnography (PSG) to a home sleep apnea test (HSAT) accompanied by an attending online video technician. Our study population was comprised of 100 children, 54 boys and 46 girls, ages 3-11 (average age 5.2, SD 1.2) assigned randomly either to in-lab full PSG or to a HSAT with real-time, online technical support to rule out obstructive sleep apnea (OSA). A t test comparison did not yield significant differences between data obtained from the in-lab PSG and HSAT with real-time, online, technical support for any of the following measures: Apnea-Hypopnea Index, Oxygen desaturation Index, baseline O2, or minimum O2 parameters. However, a significant difference was found for time in bed and total sleep time, which was significantly longer in the HAST. Online HSAT can provide a safe, convenient and a reliable way to perform sleep studies in young children for diagnosing OSA in their familiar home environment., Competing Interests: Conflict of interestAll authors declare no conflicts of interests and/or competing interest., (© The Author(s), under exclusive licence to Japanese Society of Sleep Research 2022.)

Purpose: Excessive daytime sleepiness (EDS) is a main symptom in patients with obstructive sleep apnea (OSA); however, patients with OSA have significant variability in their reported EDS which cannot be fully explained by the apnea-hypopnea index (AHI). The purpose of this study was to investigate gender differences regarding the sleep test variables contributing to excessive daytime sleepiness., Methods: Retrospective study of 578 men and 270 women with suspected OSA who underwent home overnight sleep test. We assessed the correlation between sleep test variables and EDS, using the Epworth Sleepiness Scale (ESS)., Results: Among the group of men, correlation was found between ESS to BMI (r = .107, p = .010), AHI (r = .158, p < .001), number of apneas (r = .129, p = .002), number of hypopneas (r = .115, p = .006), number of blood oxygen desaturations (r = .145, p  < .001), and percent of time the blood oxygen saturation was under 90% (r = .130, p = .002). However, among the group of women, no significant correlation was found between any of the sleep test parameters or BMI to ESS. Among the group of women, a negative correlation was found between age and EDS (r = - .208, p < .001)., Conclusion: Men showed correlations between sleep test variables and EDS, while women did not show such correlations. The results suggest that men's sleepiness is more influenced by OSA and sleep variables compared to women. To our knowledge, this is the first study which shows difference between genders in the influence of sleep variables and OSA on EDS., (© 2021. The Author(s).)

The well-known Two-Process Model of Sleep Regulation describes the integration of the circadian rhythm of arousal and sleep - Process C, and the homeostatic pressure to sleep - Process S. Presently, the known biological markers for Process C are melatonin and core body temperature; whereas, for Process S, there is no biological marker except that of aspects of the electroencephalogram (EEG). Endozepines are a class of endogenous compounds that act like benzodiazepines (BZ), i.e., serving as ligands for the BZ binding sites on GABA A receptors. Not much is known about the role of endozepines, in particular non-peptide endozepines, in the sleep field except very few reports about high concentrations observed in endozepine stupor, a rare phenomenon of idiopathic recurring stupor. We focused on hypoxanthine and thromboxane A2, which are considered to have endozepine function. This study aimed to examine the effect of 24 h of acute sleep deprivation on blood levels of hypoxanthine and thromboxane A2 of healthy subjects without sleep problems or disorders. The results showed a significant decrease of both compounds in the morning after sleep deprivation in comparison to the unrestricted normal sleep condition, thereby suggesting that these endozepines are secreted regularly while asleep, and, thus, are necessary for the sleep process. This study is the first to suggest a connection between specific biological markers - endozepines and Process S - in the Two-Process Model of Sleep Regulation and, furthermore, it sheds light on the possible role of endozepines in sleepiness and fatigue.

Current hypertension guidelines fail to provide a recommendation on when-to-treat, thus disregarding relevant circadian rhythms that regulate blood pressure (BP) level and 24 h patterning and medication pharmacokinetics and pharmacodynamics. The ideal purpose of ingestion-time (chronopharmacology, i.e. biological rhythm-dependent effects on the kinetics and dynamics of medications, and chronotherapy, i.e. the timing of pharmaceutical and other treatments to optimize efficacy and safety) trials should be to explore the potential impact of endogenous circadian rhythms on the effects of medications. Such investigations and outcome trials mandate adherence to the basic standards of human chronobiology research. In-depth review of the more than 150 human hypertension pharmacology and therapeutic trials published since 1974 that address the differential impact of upon-waking/morning versus at-bedtime/evening schedule of treatment reveals diverse protocols of sometimes suboptimal or defective design and conduct. Many have been "time-of-day," i.e. morning versus evening, rather than circadian-time-based, and some relied on wake-time office BP rather than around-the-clock ambulatory BP measurements (ABPM). Additionally, most past studies have been of too small sample size and thus statistically underpowered. As of yet, there has been no consensual agreement on the proper design, methods and conduct of such trials. This Position Statement recommends ingestion-time hypertension trials to follow minimum guidelines: (i) Recruitment of participants should be restricted to hypertensive individuals diagnosed according to ABPM diagnostic thresholds and of a comparable activity/sleep routine. (ii) Tested treatment-times should be selected according to internal biological time, expressed by the awakening and bed times of the sleep/wake cycle. (iii) ABPM should be the primary or sole method of BP assessment. (iv) The minimum-required features for analysis of the ABPM-determined 24 h BP pattern ought to be the asleep (not "nighttime") BP mean and sleep-time relative BP decline , calculated in reference to the activity/rest cycle per individual. (v) ABPM-obtained BP means should be derived by the so-called adjusted calculation procedure, not by inaccurate arithmetic averages. (vi) ABPM should be performed with validated and calibrated devices at least hourly throughout two or more consecutive 24 h periods (48 h in total) to achieve the highest reproducibility of mean wake-time, sleep-time and 48 h BP values plus the reliable classification of dipping status. (vii) Calculation of minimum required sample size in adherence with proper statistical methods must be provided. (viii) Hypertension chronopharmacology and chronotherapy trials should preferably be randomized double-blind, randomized open-label with blinded-endpoint, or crossover in design, the latter with sufficient washout period between tested treatment-time regimens.

Background: Studies on the prevalence of sleep disorders have found great variability due to different data collection methods and case definitions. We aimed at assessing the prevalence of sleep disorders in a large, unselected population using validated clinical patient records. To the best of our knowledge, this is the first large clinically based study on sleep disorders., Methods: This retrospective study used the computerized data of 2.3 million members of Maccabi Healthcare Services (MHS) public mandated health provider. Among enrolled MHS members alive in June 2018, electronic medical records were searched from January 2010 for sleep disorders using diagnosis codes, sleep medications, and recorded sleep studies., Results: A total of 195,201 patients (9% of the total MHS population) were identified. Patients were 48.3% men and the average age at diagnosis was 50.4 years (SD = 20.9). Prevalence increased with age; 3.2% in children under 10 years, 5.2% in young adults, and 22.3% among seniors aged 75 or older. The two most prevalent disorders were insomnia (7.4%), and sleep-related breathing disorders (2%). Less prevalent disorders included central disorders of hypersomnolence (100 per 100,000), circadian rhythm sleep-wake disorders (49 per 100,000), parasomnias (140 per 100,000), and sleep-related movement disorders (20 per 100,000)., Conclusions: The overall prevalence of sleep disorders including insomnia and sleep related breathing disorders in Israel were similar to other western countries despite stressful life events of ongoing war and terrorism. The large sample size allowed us to calculate the prevalence of more rare sleep disorders, which have been generally less known., (Copyright © 2019. Published by Elsevier B.V.)

The last several decades have been characterized by the widespread usage of digital devices, especially smartphones. At the same time, there have been reports of both decline in sleep duration and quality and male fertility decline. The aim of this study was to assess the relationship between evening exposure to the light-emitting screens of digital media devices and measures of both sleep and sperm quality. Semen samples were obtained from 116 men undergoing fertility evaluation for the following sperm variables: volume (mL), pH, sperm concentration (million/mL), motility percentage (progressive% + non-progressive motility%), and total sperm count. Exposure to the screens of electronic devices and sleep habits was obtained by means of a questionnaire. Smartphone and tablet usage in the evening and after bedtime was negatively correlated with sperm motility (-0.392; -0.369; p < .05), sperm progressive motility (-0.322; -0.299; p < .05), and sperm concentration (-0.169; p < .05), and positively correlated with the percentage of immotile sperm (0.382; 0.344; p < .05). In addition, sleep duration was positively correlated with sperm total and progressive motility (0.249; 0.233; p < .05) and negatively correlated with semen pH (-0.349; p < .05). A significant negative correlation was observed between subjective sleepiness and total and progressive motility (-0.264; p < .05) as well as total motile sperm number (-0.173; p < .05). The results of this study support a link between evening and post-bedtime exposure to light-emitting digital media screens and sperm quality. Further research is required to establish the proposed causative link and may lead to the future development of relevant therapeutic and lifestyle interventions.

Sleep deprivation (SD) is suggested to be associated with reduced thermo-regulatory functions. This study aimed to quantify the effect of partial (PSD) and total (TSD) 24 h SD using a standard heat tolerance test (HTT). Eleven participants underwent HTT after well-rested state, PSD and TSD. No significant physiological differences were found between the exposures but subjective discomfort was higher after TSD. Evening chronotypes' temperature during HTT was higher after TSD compared with PSD (p = 0.017). After TSD, evening chronotypes compared to intermediate chronotypes' temperature was higher during the first hour of the HTT (p < 0.05), suggesting that thermo-regulatory function during exercise in the heat is influenced by chronotype.

Background and Purpose: Obstructive sleep apnea (OSA) disorder has a deleterious impact on health. Using the continuous positive airway pressure (CPAP) device effectively lessens OSA. The purpose of this study was to examine the factors affecting patients' intention and actual decision to get treatment., Methods: Questionnaires were distributed at three sleep laboratories in Israel among 633 participants suspected of having OSA. Six months later, 194 OSA patients were contacted to verify whether they had purchased a CPAP device., Results: Factors affecting intention to use the device included Health Belief Model variables, income level, and sleep laboratory location. The decision to get treatment was positively affected by the intention to use CPAP, the number of CPAP trial days, age, and number of years in the country., Conclusions: Patients' attitudes and health beliefs prior to diagnosis may predict their intention to be treated for OSA, and in turn, affect their actual decision to get treatment. Awareness of behavioral intention can enable decision makers developing targeted interventions to promote treatment.

To assess the feasibility of using odors as a potential mechanism for treating sleep apnea, we set out to test the hypothesis that odorants delivered during sleep would modify respiratory patterns without inducing arousal or wake in healthy sleepers. We used 2 mildly trigeminal odorants: the pleasant lavender and unpleasant vetiver oil and 2 pure olfactory odorants: the pleasant vanillin and unpleasant ammonium sulfide. During sleep, an olfactometer delivered a transient odorant every 9, 12, or 15 min (randomized), providing 21-37 odorant presentations per night. Each of 36 participants was studied for 1 night and with 1 of the 4 different odorants tested. In addition to standard overnight polysomnography, we employed highly accurate measurements of nasal and oral respiration. Odorants did not increase the frequency of arousals or wake but did influence respiration. Specifically, all 4 odorants transiently decreased inhalation and increased exhalation for up to 6 breaths following odor onset. This effect persisted regardless of odorant valence or stage of sleep. These results suggest that the olfactory system may provide a path to manipulate respiration in sleep.

Arousals are considered one of the main causes of daytime sleepiness. They impede the proper flow of sleep cycles and cause weariness. Manual scoring of arousals is time-consuming, requires expert knowledge, and has high inter-scorer variability. A major difficulty in detecting arousals automatically is the existing variance across patients. Based on data mining techniques, we present a different approach to the automatic detection of arousals that overcomes the hurdle of differences in signal characteristics across patients. Offline we used a training-set of adult patients to define a set of general rules to detect arousals (termed meta-rules). This was done by analyzing the correlations between occurrences of arousals and the EEG, EMG, pulse and SaO2 signals as follows: (1) each signal was mathematically projected into several spaces (termed projected-signals); (2) from each such projected-signal, the algorithm extracted time points that indicated meaningful changes (termed critical-points); (3) data mining techniques were applied to all the critical-points to discover patterns of repeating behavior; (4) classes of patterns which were highly correlated with manually scored arousals were formalized as meta-rules. Online we used a test-set of adult patients from two other different sleep laboratories. Using the meta-rules, the algorithm extracted individual rules for each patient (termed actual-rules), and used them to automatically detect the patients' arousals. These arousals were significantly correlated (R=0.88, p<0.0001; sensitivity=75.2%, positive predictive value=76.5%) with those detected manually by experts. Since the total number of arousals is a measure of sleep quality, this algorithm constitutes a novel approach to automatically estimate sleep quality.

The prevalence of chronic insomnia in the adult population in Israel is 29.8%, which is comparable to other Western countries. The consequences of insomnia include fatigue, accidents, low level of well-being, and a high need for medical services. One of the well-known treatments for insomnia is sleeping pills. Physicians are educated that hypnotics are an appropriate treatment for transient insomnia but not for chronic use. It is believed that transient users are at high risk of becoming addicted to sleep medications although research has not proven this theory. NonetheLess, physicians often try to convince insomnia patients not to use these medications. In the U.S.A., only 3% of chronic insomniacs use sleep medications. There are no data on the use of sleep medications in Israel. The present study was performed using a large database comprised of 1.1 million adult patients of Maccabi Health Services. It is the first study examining sleep medication usage habits of the adult population in IsraeL. The main findings are: 2.8% of Maccabi patients use sleep medications, however only 4.5% of this group are chronic users; most chronic users started sleep medications at the age of 65 or older and they suffer more than the transient users from medical conditions such as ischemic heart disease, hypertension, and diabetes mellitus, have higher usage of antidepressant and anxiolytic medication, receive greater national financial support and are more likely to be new immigrants. The results of this study should evoke physicians to reassess their position against prescribing sleep medications to patients for whom it may help in relieving their insomnia.

Objectives: We assessed the value of an ultrasound (US) examination in the diagnostic workup of patients with sleep-related breathing disorders by correlating US measurements with known parameters for the presence and severity of obstructive sleep apnea., Methods: Forty-one male patients who complained of snoring and/or daytime somnolence participated. The diagnostic protocol included history-taking, physical examination, polysomnography, and transcervical US examination of the tongue. The US results were compared with all of the other parameters., Results: The US imaging was reliable for demonstrating anatomic structures of the tongue base, discriminating between muscle, mucosa, and blood vessels. The lingual arteries were clearly visualized entering the tongue base at its lower lateral borders. There was a significant relationship between the severity of sleep-related breathing disorders (measured by polysomnography) and the width of the lower tongue base (measured as the distance between the lingual arteries). The distance between the lingual arteries also correlated with physical examination findings and patient complaints of daytime somnolence and the sensation of choking during the night., Conclusions: Tongue base width, measured by US, may influence the severity of obstructive sleep apnea. This is the first demonstration of the possible role of US examination, an inexpensive, noninvasive, and non-irradiating office procedure, in the diagnostic workup for sleep-related breathing disorders.

Context: Medical school admissions traditionally rely heavily on cognitive variables, with non-cognitive measures assessed through interviews only. In recognition of the unsatisfactory reliability and validity of traditional interviews, medical schools are increasingly exploring alternative approaches that can provide improved measures of candidates' personal and interpersonal qualities., Methods: An innovative assessment centre (MOR [Hebrew acronym for 'selection for medicine']) was designed to measure candidates' personal and interpersonal attributes. Three assessment tools were developed: behavioural stations, including encounters with simulated patients and group tasks; an autobiographical questionnaire, and a judgement and decision-making questionnaire. Candidates were evaluated by trained raters on four qualities: interpersonal communication; ability to handle stress; initiative and responsibility, and self-awareness., Results: In the years 2004-05, the 588 medical school candidates with the highest cognitive scores were tested; this resulted in a change of approximately 20% in the cohort of accepted students compared with previous admission criteria. Internal consistency ranged from 0.80 to 0.88; inter-rater reliability ranged from 0.62 to 0.77 for the behavioural stations and from 0.72 to 0.95 for the questionnaires; test-retest score correlation was 0.7. The correlation between candidates' MOR scores and cognitive scores approached zero, reflecting the value of MOR in the screening process. Feedback from participants indicated that MOR was perceived as fair and appropriate for medical school screening., Discussion: MOR is a reliable tool for measuring non-cognitive attributes in medical school candidates. It has high content and face validity. Furthermore, its implementation conveys the importance of maintaining humanist characteristics in the medical profession to students and faculty staff.

Normal circadian rhythms are synchronized to a regular 24 h environmental light-dark cycle, and the suprachiasmatic nucleus and the hormone melatonin have important roles in this process. Desynchronization of circadian rhythms, as occurs in chronobiological disorders, can produce severe disturbances in sleep patterns. According to the International Classification of Sleep Disorders, circadian rhythm sleep disorders (CRSDs) include delayed sleep phase syndrome, advanced sleep phase syndrome, non-24 h sleep-wake disorder, jet lag and shift-work sleep disorder. Disturbances in the circadian phase position of plasma melatonin levels have been documented in all of these disorders. There is compelling evidence to implicate endogenous melatonin as an important mediator in CRSD pathophysiology, although further research involving large numbers of patients will be required to clarify whether the disruption of melatonin secretion is a causal factor in CRSDs. In this Review, we focus on the use of exogenous melatonin and light therapy to treat the disturbed sleep-wake rhythms seen in CRSDs.

Two behavioral phenomena characterize human motor memory consolidation: diminishing susceptibility to interference by a subsequent experience and the emergence of delayed, offline gains in performance. A recent model proposes that the sleep-independent reduction in interference is followed by the sleep-dependent expression of offline gains. Here, using the finger-opposition sequence-learning task, we show that an interference experienced at 2 h, but not 8 h, following the initial training prevented the expression of delayed gains at 24 h post-training. However, a 90-min nap, immediately post-training, markedly reduced the susceptibility to interference, with robust delayed gains expressed overnight, despite interference at 2 h post-training. With no interference, a nap resulted in much earlier expression of delayed gains, within 8 h post-training. These results suggest that the evolution of robustness to interference and the evolution of delayed gains can coincide immediately post-training and that both effects reflect sleep-sensitive processes.

Data Mining, or knowledge discovery, is the computer-assisted process of digging through and analyzing large quantity of data in order to extract meaningful knowledge. Data mining methods are used in many studies to identify phenomena quicker and better than human experts. One class of these methods was designed for dealing with time series data. However, when several channels of data are collected simultaneously, data mining algorithms encounter numerous difficulties since channels may be measured in different units, may be recorded at different sampling-rates, or may have completely different characteristics. Furthermore, as the size of these data increases, the amount of irrelevant data usually increases as well and the process becomes impractical. Hence, in such cases, the analyst must be capable of focusing on the informational parts while ignoring the noise data. These kinds of difficulties complicate the analysis of multichannel data as compared to the analysis of single-channel data. This paper presents a useful technique for preprocessing multi channel data. Our technique supplies tools for coping with all the above-mentioned difficulties, and prepares the data for further analysis (using common algorithms, especially from the data mining field). The paper is divided as follows. After the introduction (Section I) we describe the state of the art (Section II), follows by the main section-methodology (Section III) which is divided to four steps (3.2-3.5). The results are described in a separate section (Section IV). Then, a discussion and conclusions of the proposed methodology are given in (Sections V and VI). Acknowledgements and the references follow.

Autonomic function during sleep and wakefulness has been extensively investigated, however information concerning autonomic changes during the wake to sleep transition is scarce. The objective of the present study was to non-invasively characterize autonomic function and additional physiologic changes during sleep onset in normal and abnormal sleep. The estimation of autonomic function was based on time-frequency analysis of the RR interval series, using the power components in the very-low-frequency range (0.005-0.04 Hz), low-frequency (0.04-0.15 Hz), and high-frequency range (0.15-0.5 Hz). The ratio of low to high frequency power represented the sympathovagal balance. Thirty-four subjects who underwent whole night polysomnography were divided into 3 groups according to their complaints and study results: normal subjects, apneic patients (OSAS), and subjects with various sleep disorders (VSD). The results indicated a significant increase in RR interval during sleep onset, although its variability decreased; respiratory rate did not change, yet respiration became more stable; EMG amplitude and its variability decreased with sleep onset. Very-low-frequency power started to decrease significantly 2 min before sleep onset in all groups; low-frequency power decreased and high-frequency power did not change significantly in all groups, accordingly their ratio decreased and reflected a shift towards parasympathetic predominance. Although autonomic function displayed similar behavior in all subjects, OSAS and VSD patients presented a higher sympathovagal balance reflecting enhanced sympathetic predominance in those groups compared to normal subjects, both before and after sleep onset. All parameters reached a nadir at a defined time point during the process of falling asleep. We conclude that the wake-sleep transition period represents a transitional process between two physiologically different states; this transition starts with a decrease in the very slow oscillations in heart rate that anticipates a step-change resetting of autonomic function, followed by a decrease in sympathovagal balance towards the end of the process.

This retrospective study describes the effects of long-term treatment with melatonin in 33 adolescents (age range, 10-18 years) with delayed sleep phase syndrome (DSPS). Patients were treated with oral melatonin, 3 to 5 mg/day for an average period of 6 months. During the treatment, sleep onset was advanced and sleep duration was longer. Treatment was also associated with a decrease in the proportion of patients reporting school difficulties. No adverse effects of melatonin were noted. This study indicates that long-term treatment with melatonin can be beneficial for adolescents with DSPS in terms of sleep-wake schedule and school performance.

Alzheimer's dementia (AD) is a neurodegenerative disease that is often accompanied by severe sleep disturbances. The manifestation of the sleep disturbances is twofold: nighttime hyperarousal sometimes accompanied by irritability and agitation, and daytime excessive sleepiness. Thus, although treatment with sedatives or hypnotics may offer some relief to the nighttime hyperarousal, the daytime excessive sleepiness remains mostly unresolved. Recently, however, more promising results in relief of excessive daytime sleepiness, as well as nighttime hyperarousal, are offered by the chronobiological approach. This approach attributes the sleep problems of AD patients to a dysfunction in a broader neuronal mechanism, namely the biological clock, that paces various physiological functions, among which is the sleep-wake cycle. The biological clock, situated in the suprachiasmatic nuclei (SCN) of the hypothalamus, receives environmental light input via neuronal signals from the retina. The SCN, in turn, innervates the pineal gland, that is responsible for the production and release of melatonin. Light stimulus causes the attenuation of melatonin secretion from the pineal gland; whereas the cessation of light increases melatonin secretion. In diurnal mammals, the dim light melatonin onset (DLMO) is in accordance with sleep onset. The chronobiological approach offers two main treatments to the sleep problems in AD patients: morning exposure to bright light and evening administration of melatonin, both of which show at least moderate success in restoring the sleep-wake cycle in AD patients, that is more marked in the early stages of the disease.

Objectives: Obstructive sleep apnea (OSA) is the main predisposing factor of excessive daytime sleepiness (EDS), and, therefore, increases the risk of road crashes. However, it is difficult to rely on medical intake for OSA or fatigue since drivers' symptoms reports are not reliable. On the other hand, direct measurement of EDS among large numbers of drivers carries serious practical drawbacks. Obstructive sleep apnea, in turn, is strongly related to obesity, and elevated body mass index (BMI) is considered one of the major risk factors for OSA. Thus, it could be postulated that BMI may carry predictive value for EDS proneness., Methods: The present study examined the interrelation between BMI, degree of OSA, as measured with Respiratory Distress Index (RDI), and the degree of EDS, as measured with the mean sleep onset latency in the Multiple Sleep Latency Test (MSLT) among obese (BMI = 32) professional drivers. The drivers went through polysomnography followed by the five sessions of MSLT in the next day., Results: In accordance with prior studies, we have found strong correlation between BMI and the degree of OSA on the one hand, and between the degree of OSA and EDS on the other hand. OSA was detected among 77.7% of the drivers, 47.1% were sleepy, 19% had severe sleepiness [mean sleep latency [MSL < or = 5 min.], 28.1% had moderate sleepiness [MSL < or = 10 min.]. None of the drivers complained about any sleep problem, including snoring, and all reported that they do not experience excessive daytime sleepiness. Thus, there was no correlation between their subjective report and objective findings., Conclusions: Obese drivers with BMI above 32 are highly prone to be sleepy during the day. Their subjective reports of OSA or fatigue symptoms are not reliable. Therefore it is highly recommended to screen them easily by weight and height measure for further sleep study and decision about their driving abilities.

Cognitive performance at night exhibits a substantial drop, typically before dawn. One of the means of dealing with this phenomenon, as well as with the accompanying sleepiness during sustained wakefulness, is the administration of stimulants. The most widely used and well-documented stimulants are caffeine, amphetamines, and modafinil. Of these, amphetamines are the least recommended, as they may severely affect behavior. Caffeine and modafinil seem to produce relatively milder side effects and usually only at high doses. Previous comparison studies have revealed equal efficacy of both the stimulants in maintaining alertness and performance during sustained wakefulness. However, these studies used relatively high, and thus not completely safe, doses of these drugs (600 mg caffeine and 400 mg modafinil). Therefore, the aim of the present study was to assess the efficacy of a low and medically safe dose of caffeine (200 mg) and modafinil (200 mg) in maintaining cognitive performance during sustained wakefulness. A flight simulation task was chosen for the assessment of the stimulants in a counter-balanced, within-subject design under four different conditions: baseline (no drugs), placebo, caffeine (200 mg), and modafinil (200 mg). The equal effectiveness of both drugs in abolishing the nocturnal drop in cognitive performance, as well as of oral temperature and blood pressure, supported the use of low doses of caffeine and modafinil for the maintenance of alertness in healthy subjects during sustained wakefulness.

This case study describes a 14-year-old male suffering from significant academic and personal difficulties, who has been diagnosed with depression, schizotypal personality disorder, and learning disabilities. Because of excessive sleepiness, assessment for a potential sleep disorder was performed. An overnight polysomnographic study revealed no primary sleep disorders. Wrist actigraphy revealed a non-24-hour sleep-wake pattern. Delay in temperature rhythm and dissociation with melatonin rhythms were also noted. Treatment with oral melatonin restored normal sleep-wake schedule. In a follow-up psychiatric evaluation, none of the above diagnoses were present. Greater awareness of sleep disorders may prevent psychiatric misdiagnosis of treatable sleep-wake schedule disorders.

Circadian rhythm sleep disorders (CRSDs) arise when an individual's sleep-wake rhythm mismatches the environmental 24-h schedule. Physiological data and genetic studies in patients with CRSDs suggest that these disorders result from abnormal functioning of the circadian timing system. Diagnosis involves recognition of the characteristics of CRSDs, which can be achieved by clinical interview and actigraphic monitoring of rest-activity patterns. Bright-light therapy and melatonin administration have proved to be the most effective treatment modalities of CRSDs. In psychiatric practice, CRSDs can be encountered on various occasions. Some evidence indicates that a deviant sleep-wake schedule might be a predisposing factor to personality disorders. CRSDs can emerge as an iatrogenic effect of certain psychoactive drugs, such as haloperidol and fluvoxamine. It is not uncommon that the daytime functional difficulties that accompany CRSDs are misinterpreted as symptoms of psychopathology. Recognition and awareness of these disorders should prevent years of erroneous diagnosis and treatment in these patients.

A patient who developed an irregular sleep-wake pattern following prolactin-secreting pituitary microadenoma is described. The patient reported difficulties in sleep onset and awakening at the desired time, which caused major dysfunction in his daily life activities. Despite these difficulties, the sleep-related complaints of the patient remained unrecognized for as long as three yrs. Statistical analyses of the patient's rest-activity patterns revealed that the disruption of the sleep-wake circadian rhythm originated from a disharmony between ultradian (semicircadian) and circadian components. The circadian component displayed shorter than 24 h periodicity most of the time, but the semicircadian component fluctuated between longer and shorter than 12 h periods. Additionally, desynchrony in terms of period length was found in the tentative analyses of the rest-activity pattern, salivary melatonin, and oral temperature. While the salivary melatonin time series data could be characterized by a best-fit cosine curve of 24 h, the time series data of oral temperature was more compatible with 28 h best-fit curve. The rest-activity cycle during the simultaneous measurements, however, was best approximated by a best-fit curve of 21 h. The dysregulation of circadian rhythms occurred concomitantly, but not beforehand, with the onset of pituitary disease, thus suggesting an association between the two phenomena. This association may have interesting implications to the modeling of the circadian time-keeping system. This case also highlights the need to raise the awareness to circadian rhythm sleep disorders and to consider disruptions of sleep-wake cycle in patients with pituitary adenoma.

Obstructive sleep apnea syndrome (OSAS) is associated with mild to severe cardiovascular risks. The most common standard treatment for OSAS, continuous positive airway pressure, was found to have beneficial effects on cardiovascular sequelae of OSAS. Additionally, commercial companies promote nonprescription treatments for OSAS. These products frequently lack scientific support for their efficacy and need further research. We report an objective test of magnetic therapy, one such product, in a patient with OSAS and cardiovascular comorbidities. Two nights of polysomnographic recording using the split-night protocol did not reveal any consistent differences in OSAS symptoms whether the patient slept with or without the magnetic equipment. It was concluded that magnetic treatment was unsuccessful in reducing OSAS symptoms in our patient and may even increase possible cardiovascular and stroke risks by preventing the patient from pursuing an adequate medical treatment, such as continuous positive airway pressure.

Purpose of Review: High blood pressure and obstructive sleep apnea are closely related, and the latter is considered to induce hypertension. The primary underlying mechanism is sympathetic activation triggered by apneic episodes. This type of hypertension is difficult to treat. The purpose of this review is (1) to evaluate the epidemiological data in view of the current focus on preclinical sleep apnea and prehypertension, (2) to examine additional factors that might contribute to high blood pressure, and (3) to indicate the best therapeutic strategy for treatment of hypertension in these patients., Recent Findings: Cardiovascular effects of sleep apnea can be detected early in the course of the disease, and young subjects are particularly susceptible to its deleterious effect. Blood pressure profiles in these patients show higher diastolic blood pressure and no nocturnal dipping. The renin-angiotensin axis in conjunction with other vasoactive hormones add to the sympathetic activation in elevating blood pressure in sleep apnea. Pro-inflammatory cytokines further contribute to the atherosclerotic consequences that primarily affect the heart and brain, and spare the kidneys. Mounting evidence indicates that treatment of sleep apnea using positive airway pressure, palato-nasal surgery and weight reduction correct the associated hypertension. Conversely, antihypertensive therapy is less effective., Summary: Even the early stages of sleep apnea are associated with high blood pressure and cardiovascular consequences. Despite our knowledge of the role of the sympathetic activation and vasoactive hormones, no specific antihypertensive therapy is superior, and the optimal way of controlling hypertension is to treat sleep apnea and associated obesity.

Background: Obstructive sleep apnea syndrome (OSAS) is associated with long-term cardiovascular morbidity. Little is known about these relations at early stages. We conducted a case-control study in which we analyzed the clinical characteristics of young adults who underwent a periodic health examination and were screened for, and eventually found to experience, OSAS., Methods: We identified 121 subjects newly diagnosed in a sleep study as having OSAS, and 229 matched control subjects in which screening for OSAS was negative. All had a medical interview, physical examination, and routine laboratory tests., Results: Subjects who had OSAS had a higher, body mass index (3-kg/m(2) difference) and a higher diastolic blood pressure (4-mm Hg difference) value, without elevation in systolic blood pressure. There was no metabolic difference (lipids profile and fasting glucose levels) between groups., Conclusions: Diastolic blood pressure is higher early in the course of OSAS. Long term follow-up may determine effects of prevention and early intervention in OSAS and associated hypertension.

A patient with Gilles de la Tourette syndrome treated with haloperidol, ingested once daily after awakening from sleep, exhibited an irregular sleep-wake pattern with a free-running component of approximately 48 h. Transfer to risperidone, ingested once daily after awakening from sleep, was beneficial resulting in a sleep-wake cycle more synchronized at the appropriate phase to the external zeitgebers, and fewer nocturnal disturbances. The circadian sleep-wake schedule was fully synchronized when the patient had been subsequently treated with melatonin at 21:00h, before intended nocturnal sleep, in addition to risperidone in the morning. Restoration of the sleep-wake circadian pattern was accompanied by the patient's subjective report of significant improvement in his quality of life, social interactions, and occupational status. This observation suggests that circadian rhythm sleep disorders can be related to the typical neuroleptic haloperidol and restored by the atypical neuroleptic risperidone. Similar findings reported in patients suffering from other disorders support the hypothesis that the described disruption of the sleep-wake schedule is medication rather than illness-related. Therefore, it is very important to realize that circadian rhythm sleep disorders may be a side effect of neuroleptics.

We evaluated 32 nonmedicated male adolescents diagnosed with attention-deficit/hyperactivity disorder (ADHD) in childhood, 35 male adolescents similarly diagnosed who were receiving methylphenidate (MPH), and 77 control boys. Both ADHD groups completed self-report questionnaires assessing sleep disturbances; weekday and holiday sleep duration; and symptoms of ADHD, anxiety, and depression. Parents and teachers rated the severity of the participants' ADHD. The control group completed self-report questionnaires assessing sleep disturbances. We found that nonmedicated participants and controls did not differ in the severity of sleep disturbance. In contrast, the medicated participants demonstrated a significantly greater severity of sleep disturbance compared with the nonmedicated participants and reported elevated levels of symptoms of ADHD, anxiety, and depression. Specific analyses showed that depressive symptoms contributed significantly to the degree of sleep disturbance when controlling for ADHD diagnosis and MPH treatment. These findings suggest that among adolescents with ADHD symptoms, the severity of symptoms of depression may contribute to the degree of sleep disturbance in addition to the effect of their primary disorder and MPH treatment.

Background: In this study we examined the effects of caffeine on sleep quality and melatonin secretion. Melatonin is the principal hormone responsible for synchronization of sleep. Melatonin secretion is controlled by neurotransmitters that can be affected by caffeine., Methods: In the first part of the study, six volunteers drank either decaffeinated or regular coffee in a double-blind fashion on one day, and the alternate beverage 7 days later. Sleep parameters were assessed by actigraphy. In the second part of the study, the subjects again drank either decaffeinated or regular coffee, and they then collected urine every 3h for quantitation of 6-sulphoxymelatonin (6-SMT), the main metabolite of melatonin in the urine., Results: We found that drinking regular caffeinated coffee, compared to decaffeinated coffee, caused a decrease in the total amount of sleep and quality of sleep, and an increase in the length of time of sleep induction. Caffeinated coffee caused a decrease in 6-SMT excretion throughout the following night., Conclusions: The results of our study confirm the widely held belief that coffee consumption interferes with sleep quantity and quality. In addition, we found that the consumption of caffeine decreases 6-SMT excretion. Individuals who suffer from sleep abnormalities should avoid caffeinated coffee during the evening hours.

Circadian Rhythm Sleep Disorders (CRSD) are a group of sleep disorders characterized by a malsynchronization between a person's biological clock and the environmental 24-h schedule. These disorders can lead to harmful psychological and functional difficulties and are often misdiagnosed and incorrectly treated due to the fact that doctors are unaware of their existence. In the following review we describe the characteristics of CRSD, diagnosis, treatment as well as their relationship to psychopathology, psychotropic drugs and head trauma.

Circadian Rhythm Sleep Disorders (CRSD) are a group of sleep disorders characterized by a de-synchronization between a person's biological clock and the environmental 24-hour schedule. There are four main types of CRSD, namely, Delayed Sleep Phase Syndrome (DSPS) (the most common), Advanced Sleep Phase Syndrome (ASWD), Non-24-hour Sleep-Wake Syndrome (Free-Running Pattern) and Irregular (or Disorganized) Sleep Wake Pattern. These disorders lead to harmful psychological and functional difficulties and certain personality disorders may also be related to them. It has been found that psychotropic drugs, SSRI and haloperidol can cause CRSD, and this is also true for some cases of minor head trauma. They are often misdiagnosed and incorrectly treated due to the fact that many doctors are unfamiliar with them. This review describes the disorders, their consequences and available treatment.