Abstract Introduction Alcohol and opioids disturb sleep, but the impact of substance use on recovery sleep after sleep deprivation is largely unknown. Here we piloted a study protocol to assess the combined impact of total sleep deprivation (TSD) and substance administration on recovery sleep. Methods N=6 healthy normal sleepers (ages 28.2±5.6y; 4 males) completed two 24h laboratory study sessions. During each session, which began at 15:00, participants were kept awake for 15h until 06:00 the next day. They were then given an 8h recovery sleep opportunity (06:00–14:00) and went home. During the second study session, participants were randomly assigned to receive alcohol (n=3; peak BAC of 0.043±0.008% at 00:55, decayed to zero by 06:00) or an opioid (n=3; 10mg oxycodone administered at 22:30). Recovery sleep was recorded polysomnographically and scored using AASM criteria; analyses focused on total sleep time (TST), sleep efficiency, sleep latency, sleep stages N1–N3 and REM, and latency to each of the sleep stages. Results Session 1 (pre-substance) TST was considerably shorter in the opioid group (282±28min) than the alcohol group (403±24min). Therefore, we analyzed sleep variables for the two groups separately, using mixed-effects ANOVA with a fixed effect for study session (TSD vs. TSD+drug) and a random effect over subjects on the intercept. For the opioid group, latency to N3 sleep was significantly longer by 10±2min after opioid administration compared to TSD alone (F=33.8, p=0.028). There were no significant effects of TSD+alcohol compared to TSD alone. Conclusion Opioid administration during TSD delayed N3 onset, but no other effects of opioid or alcohol administration were seen during recovery sleep. Our sample was small, but the within-subjects study design provided considerable statistical power – substance effects on neurobehavioral performance during TSD (reported elsewhere) were readily detectable. However, BAC at the onset of recovery sleep had decayed to zero, and elevated homeostatic sleep pressure from TSD may have negated any residual substance effects other than the opioid-induced delay in N3. Investigating the impact of substances on recovery sleep after TSD, as well as post-recovery neurobehavioral functioning, is important for safety and health in today’s sleep-deprived society. Support (if any) National Safety Council

Study Objectives: This study evaluated the utility and ecological validity of the 3-minute psychomotor vigilance test (PVT) completed by safety-critical personnel in an air medical transport operation as part of a fatigue risk management program. Methods: Crewmembers in an air medical transport operation self-administered an alertness assessment incorporating a 3-minute PVT at different time points during their duty schedule. The prevalence of alertness deficits was evaluated based on a failure threshold of 12 errors considering both lapses and false starts. To evaluate the ecological validity of the PVT, the relative frequency of failed assessments was evaluated relative to crewmember position, timing of the assessment within the duty schedule, time of day, and sleep quantity in the last 24 h. Results: 2.1% of assessments were associated with a failing PVT score. Crewmember position, timing of assessment within the duty shift, time of day, and sleep quantity in the last 24 h were found to affect the relative frequency of failed assessments. Obtaining less than 7-9 h of sleep was associated with systematic increases in the failure rate (F[1, 54 612] = 168.1, p < .001). Obtaining less than 4 h of sleep was associated with a frequency of a failed assessment 2.99 times higher than the frequency of a failed assessment when obtaining 7-9 h of sleep. Conclusions: Results provide evidence for the utility and ecological validity of the PVT as well as the suitability of the PVT failure threshold to support fatigue risk management in safety-critical operations.

Astronauts are required to maintain optimal neurobehavioral functioning despite chronic exposure to the stressors and challenges of spaceflight. Sleep of adequate quality and duration is fundamental to neurobehavioral functioning, however astronauts commonly experience short sleep durations in spaceflight (<6 h). As humans embark on long-duration space exploration missions, there is an outstanding need to identify the consequences of sleep deficiency in spaceflight on neurobehavioral functions. Therefore, we conducted a longitudinal study that examined the sleep-wake behaviors, neurobehavioral functions, and ratings of stress and workload of N = 24 astronauts before, during, and after 6-month missions aboard the International Space Station (ISS). The computerized, Reaction SelfTest (RST), gathered astronaut report of sleep-wake behaviors, stress, workload, and somatic behavioral states; the RST also objectively assessed vigilant attention (i.e. Psychomotor Vigilance Test-Brief). Data collection began 180 days before launch, continued every 4 days in-flight aboard the ISS, and up to 90 days post-landing, which produced N = 2,856 RSTs. Consistent with previous ISS studies, astronauts reported sleeping ~6.5 h in-flight. The adverse consequences of short sleep were observed across neurobehavioral functions, where sleep durations <6 h were associated with significant reductions in psychomotor response speed, elevated stress, and higher workload. Sleep durations <5 h were associated with elevated negative somatic behavioral states. Furthermore, longer sleep durations had beneficial effects on astronaut neurobehavioral functions. Taken together, our findings highlight the importance of sleep for the maintenance of neurobehavioral functioning and as with humans on Earth, astronauts would likely benefit from interventions that promote sleep duration and quality.

Background Medical interns are at risk for sleep deprivation from long and often rotating work schedules. However, the effects of specific rotations on sleep are less clear. Objective To examine differences in sleep duration and alertness among internal medicine interns during inpatient intensive care unit (ICU) compared to general medicine (GM) rotations. Methods This secondary analysis compared interns during a GM or ICU rotation from a randomized trial (2015-2016) of 12 internal medicine residency programs assigned to different work hour limit policies (standard 16-hour shifts or no shift-length limits). The primary outcome was sleep duration/24-hour using continuous wrist actigraphy over a 13-day period. Secondary outcomes assessed each morning during the concomitant actigraphy period were sleepiness (Karolinska Sleepiness Scale [KSS]), alertness (number of Brief Psychomotor Vigilance Test [PVT-B] lapses), and self-report of excessive sleepiness over past 24 hours. Linear mixed-effect models with random program intercept determined associations between each outcome by rotation, controlling for age, sex, and work hour policy followed. Results Of 398 interns, 386 were included (n = 261 GM, n = 125 ICU). Average sleep duration was 7.00±0.08h and 6.84±0.10h, and number of PVT lapses were 5.5±0.5 and 5.7±0.7 for GM and ICU, respectively (all P > .05). KSS was 4.8±0.1 for both rotations. Compared to GM, ICU interns reported more days of excessive sleepiness from 12am-6am (2.6 vs 1.7, P < .001) and 6am-12pm (2.6 vs 1.9, P = .013) and had higher percent of days with sleep duration < 6 hours (27.6% vs 23.4%, P < .001). GM interns reported more days with no excessive sleepiness (5.3 vs 3.7, P < .001). Conclusions Despite ICU interns reporting more excessive sleepiness in morning hours and more days of insufficient sleep (<6 hours), overall sleep duration and alertness did not significantly differ between rotations.

Abstract Introduction Little is known about the impact of specific rotations on medical residents’ sleep. The purpose of this analysis was to examine the difference in sleep duration and alertness among internal-medicine resident interns during intensive care unit (ICU) compared to general medicine (GM) rotations. Methods This is a secondary report of a randomized non-inferiority trial of 63 United States internal-medicine residency programs. Programs were assigned to either standard duty-hour (80h workweek/16h shifts) or flexible (80h workweek/no shift-length limit) policies. Interns were followed for 2 weeks during either a GM or ICU rotation. The primary outcome was sleep duration/24h (actigraphy). Secondary outcomes were sleepiness (Karolinska Sleepiness Scale [KSS]) and alertness (number of Brief Psychomotor Vigilance Test [PVT-B] lapses). Data were averaged across days (thirteen 24-hour periods). Linear mixed-effect models with random program intercept were used to determine the association between each outcome by rotation, controlling for age, sex, and policy followed. Results N=386 interns were included (mean age 27.9±2.1y, 194 (50.3%) males), with n=261 (67.6%) in GM, and n=125 (32.4%) in ICU. Average sleep duration was 7.00±0.08h and 6.84±0.10h for GM and ICU respectively (p=.09; 95%CI -0.02;0.33h). Percent of days with self-reports of excessive sleepiness were significantly more likely for ICU vs GM from 12am-6am (ICU: 20.2%; GM: 12.5%) and 6am-12pm (ICU: 20.5%; GM: 14.3%). GM had significantly more days with no excessive sleepiness (GM: 40.5%; ICU: 28.1%). Average KSS was 4.8±0.1 for both GM and ICU (p=.60; 95%CI -0.18;0.32). Average number of PVT-B lapses were 5.5±0.5 and 5.7±0.7 for GM and ICU respectively (p=.83; 95%CI -1.48;1.18 lapses). There were no significant differences in PVT-B response speed or false starts between rotations. Conclusion Interns in ICU may experience more excessive sleepiness compared to GM interns, especially in early morning hours. However, sleep duration and alertness were not significantly different between rotations. Support Funded by the National Heart, Lung, and Blood Institute and American Council for Graduate Medical Education

Duty hour regulations affect resident sleep, education, and patient care in complex ways. We performed a national cluster-randomized trial (iCOMPARE) in 63 internal medicine residency programs comparing the effects of the 2011 duty-hour standards to a more flexible set of duty hour rules characterized by maintaining an 80-hour workweek but without limits on shift length or mandatory time off between shifts, relative to patient mortality, intern educational outcomes, and intern sleep and alertness. In the sleep and alertness sub-study, sleep duration and morning sleepiness and alertness were assessed with actigraphy, the Karolinska Sleepiness Scale, and a 3-minute Psychomotor Vigilance Test (PVT-B) for 14 days in 193 interns from 6 standard programs and 205 interns from 6 flexible programs. During the 14-day study periods, interns in standard and flexible programs averaged 7.03h sleep/24h (95% confidence interval [CI] 6.78h, 7.27h) and 6.85h sleep/24h (95% CI 6.61h, 7.10h), respectively. Sleep duration (difference between arms of -0.17h/24h; 1-sided lower 95% confidence limit -0.45h; NIM -0.5h; P=0.02 for noninferiority) and KSS sleepiness (difference 0.12 points; 1-sided upper 95% confidence limit 0.31 points; NIM 1 point; P<0.001) were noninferior in flexible versus standard programs. We could not establish noninferiority for PVT-B alertness (difference -0.3 lapses; 1-sided upper 95% confidence limit 1.6 lapses; NIM 1 lapse; P=0.10). Based on analyses by shift type, sleep duration was 1.77h shorter on days when interns in flexible programs finished an overnight shift relative to a regular day shift (p<.001), with significant decreases in subjective and objective alertness, and frequent reports of excessive sleepiness, especially between 12am and 6am. There were no signs of relevant chronic sleep loss across shifts in interns in flexible programs relative to their standard program counterparts. Interns were able to compensate for the sleep lost during extended overnight shifts by increasing sleep duration on nights prior to day shifts, night shifts, and days off. Increased sleepiness and reduced alertness of interns following extended overnight shifts need to be mitigated and suggest a role for fatigue-risk management programs. Supported by NHLBI grants U01HL125388 and U01HL126088 and grants from the ACGME.

An observational study of CMV drivers was undertaken to assess the operational, safety, health, and fatigue impacts of the restart provisions in Sections 395.3(c) and 395.3(d) of Title 49, Code of Federal Regulations. N=235 drivers (224 males, 20-69y) participated in an observational study for up to 5 months duration. All drivers held a valid CMV driver's license, worked >60 hours/week, completed drives during the day and night, and made use of the restart provisions. They were recruited to reflect diverse types of vehicles and operational distances. They reported either driving mostly during the day (10.2%), mostly during the night (14.9%), or a combination of day and night (74.9%). They were monitored via electronic devices to track driving (including safety critical events) and work hours. Smartphone apps were used to track their behavioral alertness on the Brief Psychomotor Vigilance Test (PVT-B), and their ratings of fatigue, sleepiness, stress, and sleep quality. Statistical comparisons were performed using linear and non-linear mixed-effects modeling. A total of 26,964 days of data were acquired, including >79,000 PVT-B tests. During on-duty days, drivers slept an average of 6.6h/day, compared to 8.7h/day during restart (off-duty) days (p<0.0001). During restart periods drivers rated their sleepiness higher (p<0.0001), their sleep quality higher (p<0.0001), and their stress lower (p<0.0001), compared to on-duty days. Drivers' fatigue ratings were higher, and sleep quality ratings were lower, during 1-night vs. 2-night restarts. They had more PVT-B lapses during restart periods than during on-duty periods (p<0.0001), and more lapses when restarts occurred after 168 hours than prior to 168 hours (p<0.0087). Although there were no safety critical events in the study, there was evidence that CMV drivers were in need of more sleep when they undertook a restart as they slept an average of 2h longer during restarts than when they were working. DTMC75-14-D-00011, Task Order #9

Fatigue causes decrements in vigilant attention and reaction time and is a major safety hazard in the trucking industry. There is a need to quantify the relationship between driver fatigue and safety in terms of operationally relevant measures. Hard-braking events are a suitable measure for this purpose as they are relatively easily observed and are correlated with collisions and near-crashes. We developed an analytic approach that predicts driver fatigue based on a biomathematical model and then estimates hard-braking events as a function of predicted fatigue, controlling for time of day to account for systematic variations in exposure (traffic density). The analysis used de-identified data from a previously published, naturalistic field study of 106 U.S. commercial motor vehicle (CMV) drivers. Data analyzed included drivers' official duty logs, sleep patterns measured around the clock using wrist actigraphy, and continuous recording of vehicle data to capture hard-braking events. The curve relating predicted fatigue to hard-braking events showed that the frequency of hard-braking events increased as predicted fatigue levels worsened. For each increment on the fatigue scale, the frequency of hard-braking events increased by 7.8%. The results provide proof of concept for a novel approach that predicts fatigue based on drivers' sleep patterns and estimates driving performance in terms of an operational metric related to safety. The approach can be translated to practice by CMV operators to achieve a fatigue risk profile specific to their own settings, in order to support data-driven decisions about fatigue countermeasures that cost-effectively deliver quantifiable operational benefits.

Objective: The objective of the pilot program was to evaluate the utility of the psychomotor vigilance test (PVT) in aiding clinicians in making fitness for work determinations. Methods: A 10-minute PVT was incorporated into fitness for work examinations by occupational health staff at two integrated refining/petrochemical plants. Based on all evidence from the clinical examination, including PVT results, clinicians made their fitness for work determination. Results: Employees who were determined to be fit for work had significantly fewer PVT errors than did employees determined to be unfit for work or fit for work with limitations, with t(98) = - 14.71, P < 0.001. Conclusions: The pilot assessed a new application of the PVT as an adjunct to occupational health evaluations focused on determining fitness for work. Results demonstrated that the PVT can be a valuable tool for this purpose.

Commercial motor vehicle (CMV) drivers in the US may start a new duty cycle after taking a 34-h restart break. A restart break provides an opportunity for sleep recuperation to help prevent the build-up of fatigue across duty cycles. However, the effectiveness of a restart break may depend on its timing, and on how many nighttime opportunities for sleep it contains. For daytime drivers, a 34-h restart break automatically includes two nighttime periods. For nighttime drivers, who are arguably at increased risk of fatigue, a 34-h restart break contains only one nighttime period. To what extent this is relevant for fatigue depends in part on whether nighttime drivers revert back to a nighttime-oriented sleep schedule during the restart break. We conducted a naturalistic field study with 106 CMV drivers working their normal schedules and performing their normal duties. These drivers were studied during two duty cycles and during the intervening restart break. They provided a total of 1260days of data and drove a total of 414,937 miles during the study. Their duty logs were used to identify the periods when they were on duty and when they were driving and to determine their duty cycles and restart breaks. Sleep/wake patterns were measured continuously by means of wrist actigraphy. Fatigue was assessed three times per day by means of a brief psychomotor vigilance test (PVT-B) and a subjective sleepiness scale. Data from a truck-based lane tracking and data acquisition system were used to compute lane deviation (variability in lateral lane position). Statistical analyses focused on 24-h patterns of duty, driving, sleep, PVT-B performance, subjective sleepiness, and lane deviation. Duty cycles preceded by a restart break containing only one nighttime period (defined as 01:00-05:00) were compared with duty cycles preceded by a restart break containing more than one nighttime period. During duty cycles preceded by a restart break with only one nighttime period, drivers showed more nighttime-oriented duty and driving patterns and more daytime-oriented sleep patterns than during duty cycles preceded by a restart break with more than one nighttime period. During duty cycles preceded by a restart break with only one nighttime period, drivers also experienced more lapses of attention on the PVT-B and increased lane deviation at night, and they reported greater subjective sleepiness. Importantly, drivers exhibited a predominantly nighttime-oriented sleep schedule during the restart break, regardless of whether the restart break contained only one or more than one nighttime period. Consistent with findings in laboratory-based studies of the restart break, the results of this naturalistic field study indicate that having at least two nighttime periods in the restart break provides greater opportunity for sleep recuperation and helps to mitigate fatigue.

Exploration-type missions will require humans to live in isolated, confined, and extreme environments for prolonged periods of time. NASA’s Mars Design Reference Mission 5.0 has a duration of 910 days, which is well beyond the duration astronauts and cosmonauts have remained confined in a spacecraft. NASA’s recent evidence-based review of the behavioral health risks to crew and mission success during exploration spaceflight concluded they were among the most serious unmitigated risks to such missions. Due to their complex logistical operations, harsh threatening environmental conditions such as extreme cold, altered photoperiod, low humidity, isolation, and confinement, as well as the analogous population of researchers with multicultural backgrounds, but similar educational background compared to astronauts, Antarctic research stations are considered a high-fidelity analog for long-duration space missions. While NASA and NSBRI have begun collecting some neuroimaging data before and after missions, our knowledge on the effects of prolonged periods in space or space analog environments on neurostructural and neurobehavioral changes is still limited. To address this knowledge gap, we are investigating neurostructural, cognitive, behavioral, physiologic, and psychosocial changes in a total of N=25 crewmembers during two 1-year Antarctic winter-over seasons (2015/2016) in the French/Italian Concordia station. We will assess subjects using quantitative structural and functional magnetic resonance imaging (MRI) before, immediately after (via collaborations with neuroimaging centers in Christchurch, NZ and Hobart, AUS), and 6-months after the winter-over. We will assess Concordia crew members during the mission using sensitive but unobtrusive methods to measure cognitive performance (Cognition test battery [1], monthly), sleep-wake behavior and sleep continuity (actigraphy, continuously [2]), heart rate and heart rate variability (24-h electrocardiography, monthly), relative proximity (actigraphy, continuously), psychomotor vigilance (PVT-B, weekly [3]) and subjective assessments of stress, mood, fatigue, health, workload, monotony, boredom, loneliness, and crewmember conflicts (questionnaires, weekly). A control group with individuals matched to each crewmember according to age and gender will be investigated with similar methodology at the German Aerospace Center (DLR, Cologne). Neuroimaging and Cognition data will also be compared to N=9 crewmembers over-wintering in the German Neumayer-III station in 2015. Furthermore, Cognition data will be compared to 13 crewmembers over-wintering in the British Halley station in 2015. Baseline data collection for both winter-over seasons was finalized in October 2015. Human phantom scans at envihab Cologne, Christchurch, and Hobart were also completed in October 2015. Data acquisition in the first winter-over crew is ongoing with overall good compliance.

BACKGROUND: Sustained high-level cognitive performance is of paramount importance for the success of space missions, which involve environmental, physiological, and psychological stressors that may affect brain functions. Despite subjective symptom reports of cognitive fluctuations in spaceflight, the nature of neurobehavioral functioning in space has not been clarified.METHODS: We developed a computerized cognitive test battery (Cognition) that has sensitivity to multiple cognitive domains and was specifically designed for the high-performing astronaut population. Cognition consists of 15 unique forms of 10 neuropsychological tests that cover a range of cognitive domains, including emotion processing, spatial orientation, and risk decision making. Cognition is based on tests known to engage specific brain regions as evidenced by functional neuroimaging. Here we describe the first normative and acute total sleep deprivation data on the Cognition test battery as well as several efforts underway to establish the validity, sensitivity, feasibility, and acceptability of Cognition.RESULTS: Practice effects and test-retest variability differed substantially between the 10 Cognition tests, illustrating the importance of normative data that both reflect practice effects and differences in stimulus set difficulty in the population of interest. After one night without sleep, medium to large effect sizes were observed for 3 of the 10 tests addressing vigilant attention (Cohen's d = 1.00), cognitive throughput (d = 0.68), and abstract reasoning (d = 0.65).CONCLUSIONS: In addition to providing neuroimaging-based novel information on the effects of spaceflight on a range of cognitive functions, Cognition will facilitate comparing the effects of ground-based analogues to spaceflight, increase consistency across projects, and thus enable meta-analyses.

PURPOSE:Protected sleep periods for internal medicine interns have previously resulted in increased amount slept and improved cognitive alertness but required supplemental personnel. The authors evaluated intern and patient outcomes associated with protected nocturnal nap periods of three hours that are personnel neutral.METHOD:Randomized trial at Philadelphia Veterans Affairs Medical Center (PVAMC) Medical Service and Hospital of the University of Pennsylvania (HUP) Oncology Unit. During 2010-2011, four-week blocks were randomly assigned to a standard intern schedule (extended duty overnight shifts of up to 30 hours), or sequential protected sleep periods (phone sign-out midnight to 3:00 AM [early shift] intern 1; 3:00 to 6:00 AM [late shift] intern 2). Participants wore wrist Actiwatches, completed sleep diaries, and performed daily assessments of behavioral alertness. Between-group comparisons of means and proportions controlled for within-person correlations.RESULTS:HUP interns had significantly longer sleep durations during both early (2.40 hours) and late (2.44 hours) protected periods compared with controls (1.55 hours, P < .0001). At PVAMC sleep duration was longer only for the late shift group (2.40 versus 1.90 hours, P < .036). Interns assigned to either protected period were significantly less likely to have call nights with no sleep and had fewer attentional lapses on the Psychomotor Vigilance Test. Differences in patient outcomes between standard schedule months versus intervention months were not observed.CONCLUSIONS:Protected sleep periods of three hours resulted in more sleep during call and reductions in periods of prolonged wakefulness, providing a plausible alternative to 16-hour shifts.