Respiration-triggered olfactory stimulation reduces obstructive sleep apnea severity: A prospective pilot study.

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, BF10 [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, BF10 = 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 (F1,16 = 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.

Comparing in-lab full polysomnography for diagnosing sleep apnea in children to home sleep apnea tests (HSAT) with an online video attending technician.

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.

Gender differences in the sleep variables contributing to excessive daytime sleepiness among patients with obstructive sleep apnea.

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.

Guidelines for the design and conduct of human clinical trials on ingestion-time differences - chronopharmacology and chronotherapy - of hypertension medications.

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.

The Possible Role of Endozepines in Sleep Regulation and Biomarker of Process S of the Borbély Sleep Model.

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 GABAA 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.

Exposure by males to light emitted from media devices at night is linked with decline of sperm quality and correlated with sleep quality measures.

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.

The epidemiology of sleep disorders in Israel: results from a population-wide study.

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.

Heat tolerance after total and partial acute sleep deprivation.

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.

Factors affecting the intention and decision to be treated for obstructive sleep apnea disorder.

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.

The influence of odorants on respiratory patterns in sleep.

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.

[Chronic use of sleep medications--how serious is it in Israel?].

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.

Data mining techniques for detection of sleep arousals.

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.

Tongue base ultrasound: a diagnostic tool for predicting obstructive sleep apnea.

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.

MOR: a simulation-based assessment centre for evaluating the personal and interpersonal qualities of medical school candidates.

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.

The roles of melatonin and light in the pathophysiology and treatment of circadian rhythm sleep disorders.

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.

[Diseases don't sleep at night].

Although humans spend as much as a third of their life sleeping, many schools of medicine around the world do not provide sufficient knowledge about the physiology and pathology of sleep to their students, as if diseases fall asleep at night. People suffering from impaired sleep are often unaware of the problem. Along with poor knowledge of sleep pathologies on the part of medical staff, this leads to underdiagnosis and misdiagnosis of sleep disorders. One of the symptoms indicating sleep abnormality is complaint of fatigue, which can represent: physical weakness, mental fatigue, or sleepiness. The latter type is associated with several sleep disorders, among which are: obstructive sleep apnea, periodic limb movement in sleep, narcolepsy, idiopathic hypersomnia and circadian rhythm sleep disorders. To provide accurate diagnosis and appropriate treatment, medical education programs should offer the students a deeper knowledge of sleep medicine.

Daytime sleep condenses the time course of motor memory consolidation.

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.

Processing of multichannel recordings for data-mining algorithms.

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.

Melatonin treatment in adolescents with delayed sleep phase syndrome.

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.

Cognitive performance during sustained wakefulness: A low dose of caffeine is equally effective as modafinil in alleviating the nocturnal decline.

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.