To assess drug induced driving impairment, initial screening is needed. However, no consensus has been reached about which initial screening tools have to be used. The present study aims to determine ...the ability of a battery of psychometric tests to detect performance impairing effects of clinically relevant levels of drowsiness as induced by one night of sleep deprivation.
Twenty four healthy volunteers participated in a 2-period crossover study in which the highway driving test was conducted twice: once after normal sleep and once after one night of sleep deprivation. The psychometric tests were conducted on 4 occasions: once after normal sleep (at 11 am) and three times during a single night of sleep deprivation (at 1 am, 5 am, and 11 am).
On-the-road driving performance was significantly impaired after sleep deprivation, as measured by an increase in Standard Deviation of Lateral Position (SDLP) of 3.1 cm compared to performance after a normal night of sleep. At 5 am, performance in most psychometric tests showed significant impairment. As expected, largest effect sizes were found on performance in the Psychomotor Vigilance Test (PVT). Large effects sizes were also found in the Divided Attention Test (DAT), the Attention Network Test (ANT), and the test for Useful Field of View (UFOV) at 5 and 11 am during sleep deprivation. Effects of sleep deprivation on SDLP correlated significantly with performance changes in the PVT and the DAT, but not with performance changes in the UFOV.
From the psychometric tests used in this study, the PVT and DAT seem most promising for initial evaluation of drug impairment based on sensitivity and correlations with driving impairment. Further studies are needed to assess the sensitivity and validity of these psychometric tests after benchmark sedative drug use.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Study Objectives
To assess potential effects of lemborexant on next-morning driving performance in adult and elderly healthy volunteers.
Methods
Randomized, double-blind, double-dummy, ...placebo and active-controlled, four period incomplete crossover study in 48 healthy volunteers (22 females), 23–78 years old. Participants were treated at bedtime for eight consecutive nights with two of three dose levels of lemborexant (2.5, 5, or 10 mg), zopiclone 7.5 mg (on the first and last night with placebo on intervening nights), or placebo. Driving performance was assessed in the morning on days 2 and 9 using a standardized highway driving test in normal traffic, measuring standard deviation of lateral position (SDLP). Drug–placebo differences in SDLP >2.4 cm were considered to reflect clinically meaningful driving impairment.
Results
Mean drug–placebo differences in SDLP following lemborexant 2.5, 5, and 10 mg on days 2 and 9 were 0.74 cm or less. The upper bound of the 95% confidence intervals (CIs) for lemborexant treatment groups were all below 2.4 cm and the 95% CIs included zero, indicating that the effects were neither clinically meaningful nor statistically significant. Symmetry analysis further supported the lack of clinically meaningful impairment with lemborexant.
Conclusions
When assessed starting ~9 h after lemborexant administration at bedtime the previous night, there was no statistically significant or clinically meaningful effect on driving performance in healthy adults and elderly, as assessed by either mean differences in SDLP relative to placebo or symmetry analysis. In this study, lemborexant at doses up to 10 mg was well-tolerated.
Clinical Trial Registration
clinicaltrials.gov, NCT02583451. https://clinicaltrials.gov/ct2/show/NCT02583451.
Rationale
The mechanisms underlying impaired sleep quality in insomnia are not fully known, but an important role for sleep fragmentation has been proposed.
Objectives
The aim of this study is to ...explore potential mechanisms of sleep fragmentation influencing alterations of perceived sleep quality.
Methods
We analyzed polysomnography (PSG) recordings from a double-blind crossover study with zopiclone 7.5 mg and placebo, in elderly participants with insomnia complaints and age-matched healthy controls. We compared survival dynamics of sleep and wake across group and treatment. Subsequently, we used a previously proposed model to estimate the amount of sleep onset latency (SOL) misperception from PSG-defined sleep fragmentation. Self-reported and model-estimated amount of SOL misperception were compared across group and treatment, as well as model prediction errors.
Results
In the zopiclone night, the average segment length of NREM sleep was increased (group F = 1.16,
p
= 0.32; treatment F = 8.89,
p
< 0.01
; group x treatment F = 0.44,
p
= 0.65), while the segment length of wake was decreased (group F = 1.48,
p
= 0.23; treatment F = 11.49,
p
< 0.01
; group x treatment F = 0.36,
p
= 0.70). The self-reported and model-estimated amount of SOL misperception were lower during the zopiclone night (self-reported group F = 6.08,
p
< 0.01
, treatment F = 10.8,
p
< 0.01
, group x treatment F = 2.49,
p
= 0.09; model-estimated F = 1.70,
p
= 0.19, treatment F = 16.1,
p
< 0.001
, group x treatment F = 0.60,
p
= 0.55). The prediction error was not altered (group F = 1.62,
p
= 0.20; treatment F = 0.20,
p
= 0.65; group x treatment F = 1.01,
p
= 0.37).
Conclusions
Impaired subjective sleep quality is associated with decreased NREM stability, together with increased stability of wake. Furthermore, we conclude that zopiclone-induced changes in SOL misperception can be largely attributed to predictable changes of sleep architecture.
The number of patients with Alzheimer's disease (AD) is increasing and so is the number of patients driving a car. To enable patients to retain their mobility while at the same time not endangering ...public safety, each patient should be assessed for fitness to drive. The aim of this study is to develop a method to assess fitness to drive in a clinical setting, using three types of assessments, i.e. clinical interviews, neuropsychological assessment and driving simulator rides. The goals are (1) to determine for each type of assessment which combination of measures is most predictive for on-road driving performance, (2) to compare the predictive value of clinical interviews, neuropsychological assessment and driving simulator evaluation and (3) to determine which combination of these assessments provides the best prediction of fitness to drive. Eighty-one patients with AD and 45 healthy individuals participated. All participated in a clinical interview, and were administered a neuropsychological test battery and a driving simulator ride (predictors). The criterion fitness to drive was determined in an on-road driving assessment by experts of the CBR Dutch driving test organisation according to their official protocol. The validity of the predictors to determine fitness to drive was explored by means of logistic regression analyses, discriminant function analyses, as well as receiver operating curve analyses. We found that all three types of assessments are predictive of on-road driving performance. Neuropsychological assessment had the highest classification accuracy followed by driving simulator rides and clinical interviews. However, combining all three types of assessments yielded the best prediction for fitness to drive in patients with AD with an overall accuracy of 92.7%, which makes this method highly valid for assessing fitness to drive in AD. This method may be used to advise patients with AD and their family members about fitness to drive.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Sleep and physical activity are both modifiable behavioural factors that are associated with better health and are potentially related. Following traumatic brain injury, damage to the brain caused by ...an external force, sleep disturbances are common. Exploring bidirectional relationships between sleep and physical activity might provide insight into whether increasing physical activity could decrease these sleep disturbances. The current study, therefore, examined inter‐ and intra‐individual temporal associations between sleep and daytime physical activity in 64 people with traumatic brain injury reporting sleep problems or fatigue (47 males; mean age, 40 years). Sleep and physical activity were measured using actigraphy with corroborating sleep diaries over 14 consecutive days. Multilevel models were used to examine inter‐ and intra‐individual associations between physical activity and sleep. Inter‐individual variations showed that earlier bedtimes, earlier wake‐up times and lower sleep efficiency were associated with more physical activity. Intra‐individual temporal variations showed no significant association of daytime physical activity with sleep duration or continuity. However, shorter sleep time and less wake after sleep onset than usual were associated with more time spent in light‐intensity activity the next day. Therefore, sleep may have more of an influence on physical activity than physical activity has on sleep in people with traumatic brain injury. In conclusion, the results do not confirm a potential beneficial effect of physical activity on sleep but suggest that improving sleep quality might be relevant to support of a physically active lifestyle in people with traumatic brain injury. Further research is necessary to confirm these results.
To evaluate next-morning driving performance in adults younger than 65 years, after single and repeated doses of suvorexant 20 and 40 mg.
Double-blind, placebo-controlled, 4-period crossover study.
...Maastricht University, The Netherlands.
28 healthy volunteers (15 females), aged 23 to 64 years.
Suvorexant (20 and 40 mg) for 8 consecutive nights; zopiclone 7.5 mg nightly on day 1 and 8; placebo.
Performance on day 2 and 9 (9 h after dosing) using a one-hour standardized highway driving test in normal traffic, measuring standard deviation of lateral position (SDLP). Drug-placebo changes in SDLP > 2.4 cm were considered to reflect meaningful driving impairment.
Mean drug-placebo changes in SDLP following suvorexant 20 and 40 mg were 1.01 and 1.66 cm on day 2, and 0.48 and 1.31 cm on Day 9, respectively. The 90% CIs of these changes were all below 2.4 cm. Symmetry analysis showed that more subjects had SDLP changes > 2.4 cm than < -2.4 cm following suvorexant 20 and 40 mg on day 2, and following suvorexant 40 mg on day 9. Four female subjects requested that a total of 5 driving tests--all following suvorexant--stop prematurely due to self-reported somnolence.
As assessed by mean changes in standard deviation of lateral position (SDLP), there was no clinically meaningful residual effect of suvorexant in doses of 20 and 40 mg on next-morning driving (9 h after bedtime dosing) in healthy subjects < 65 years old. There may be some individuals who experience next-day effects, as suggested by individual changes in SDLP and prematurely stopped tests.
clinicaltrials.gov NCT01311882.
Summary
Gaboxadol is a selective extrasynaptic GABAA receptor agonist previously in development for the treatment of insomnia. Due to its short half‐life (1.5–2 h) it is expected to be free from ...residual effects the next morning. The present study assessed the residual effects of evening and middle‐of‐the‐night administration of 15 mg of gaboxadol on cognitive, psychomotor and driving performance. Twenty‐eight healthy volunteers entered the study with 25 (12 women; mean age 31.4 years) completing a double‐blind, placebo‐controlled, active‐referenced five‐way cross‐over study. Each treatment night subjects ingested one capsule at 23:00 hours and one at 04:00 hours. Treatments were placebo at both times, 15 mg gaboxadol or 7.5 mg zopiclone followed by placebo, and placebo followed by 15 mg gaboxadol or 10 mg zolpidem. Effects on cognition and psychomotor performance were assessed between 07:30 and 08:30 hours and on driving between 09:00 and 10:00 hours. Driving, as measured by standard deviation of lateral position in an on‐the‐road driving test, was almost significantly (P < 0.07) impaired after evening administration of gaboxadol for the all‐subjects‐completed set (n = 25) but significantly (P < 0.05) in the full analysis set (n = 28). Effects of all other active treatments on driving were significant. Evening administration of gaboxadol had minor effects on divided attention only, whereas middle‐of‐the‐night administration impaired performance significantly in all tests except memory. Zolpidem and zopiclone impaired performance significantly in every test except tracking after zopiclone; 15 mg of gaboxadol can produce minor residual effects on driving after evening administration. Administration later at night is associated with moderately impairing residual effects on driving and psychomotor performance but not on memory.
Acute benzodiazepine intoxication produces severe impairment of neurocognitive skills related to driving. It is less clear whether such impairments also occur in patients who use benzodiazepines ...chronically. The current review evaluated neurocognitive skills of long-term benzodiazepine users and addressed 2 major questions: do long-term users develop tolerance for the impairing effects of benzodiazepines on neurocognitive performance, and if so, does tolerance warrant a change in driver fitness classification systems that currently deem users of benzodiazepines unfit to drive? Neurocognitive impairments were reported in patients who on average used benzodiazepines for 5-15 years. In addition, sensitivity to acute benzodiazepine impairment decreased in long-term users, suggesting (partial) tolerance. Definitions of clinical relevance of neurocognitive impairments in long-term users and how these were affected by duration of benzodiazepine use were generally lacking. Also, sensitivity of neurocognitive tasks to drug effects and their validity to predict fitness to drive were generally unknown. Because of these limitations, no firm conclusion can be drawn regarding a re-classification of long-term benzodiazepine effects on driver fitness.
To evaluate the construct validity of Psychomotor Vigilance Test performance for measuring fatigue in people with acquired brain injury.
Observational cross-sectional study.
Fifty-four people with ...acquired brain injury and 61 healthy controls.
Participants performed the Psychomotor Vigilance Test and reported momentary fatigue before and after this test and general fatigue. Associations between performance and fatigue in patients were tested by correlational and hierarchical multiple linear regression analyses, controlling for sleep quality, daytime sleepiness, and mood.
Patients performed worse on the test compared with controls. Within the patient group, worse test performance was associated with increases in momentary post-test fatigue and general fatigue, indicating convergent validity, but also with daytime sleepiness, and mood complaints, indicating a lack of divergent validity. When controlling for sleepiness and mood, the association between performance and general fatigue was no longer significant, whereas the association between performance and post-test fatigue remained.
Performance on the Psychomotor Vigilance Test cannot be used as a specific measure for fatigue, but it appears to be a more general measure of severity of symptoms including fatigue, mood, and sleepiness. Therefore, the Psychomotor Vigilance Test may be a useful measure to examine the effects of interventions aimed at reducing these symptoms.
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