Karel A. Brookhuis

ObjectiveUsing benzodiazepines and certain antidepressants is associated with an increased risk of motor vehicle crashes due to impaired driving skills. Hence, several countries prohibit people who use these drugs from driving. Traffic regulations for driving under the influence of these drugs are, however, largely based on single-dose studies with healthy participants. The effects of drugs on chronic users may be different because of potential development of tolerance or by adapting behavior. In this study, we test the effects of anti-depressants, hypnotics, or anxiolytics use on driving performance in patients who use these drugs for different durations and compare the effects to healthy controls' performance.MethodsSixty-six healthy controls and 82 medication users were recruited to perform four drives in a driving simulator. Patients were divided into groups that used anti-depressants, hypnotics, or anxiolytics, for shorter or longer than 3 years (i.e. LT3- or LT3+, respectively). The minimum term of use was 6 months. Driving behavior was measured in terms of longitudinal and lateral control (speed variability and Standard Deviation of Lateral Position: SDLP), brake reaction time, and time headway. Impaired driving performance was defined as performing similar to driving with a Blood Alcohol Concentration of 0.5 parts per thousand or higher, determined by means of non-inferiority analyses.ResultsReaction time analyses revealed inconclusive findings in all groups. No significant performance differences between matched healthy controls, LT3- (n = 2), and LT3+ (n = 8) anxiolytics users were found. LT3+ antidepressants users (n = 12) did not perform inferior to their matched controls in terms of SDLP. LT3- hypnotics users (n = 6) showed more speed variability than their matched healthy controls, while this effect was not found for the LT3+ group (n = 14): the latter did not perform inferior to the healthy controls. Regarding Time Headway, no conclusions about the LT3- hypnotics group could be drawn, while the LT3+ group did not perform inferior compared to the control group.ConclusionsThe small number of anxiolytics users prohibits drawing conclusions about clinical relevance. Although many outcomes were inconclusive, there is evidence that some elements of complex driving performance may not be impaired (anymore) after using antidepressants or hypnotics longer than 3 years.

The combination of negative mental and physical symptoms which can be experienced after a single episode of alcohol consumption, starting when blood alcohol concentration (BAC) approaches zero, are collectively referred to as the alcohol hangover. Previous research revealed that 10 to 20% of drinkers claim not to experience next-day hangovers. Past studies were usually limited to single timepoint assessments. The aim of the current semi-naturalistic study was to compare the next-day effects of an evening of alcohol consumption of self-reported hangover-resistant drinkers (n = 14) with those of a group of self-reported hangover-sensitive drinkers (n = 15) at hourly timepoint throughout the day (09:30 until 15:30). Assessments of 23 hangover symptoms, mood (Profiles of Mood States-Short Form), and daytime sleepiness (Karolinska Sleepiness Scale) were made hourly after both an alcohol day and an alcohol-free control day. Additional morning assessments were made for mood (State-Trait Anxiety Inventory-Y, Beck’s Depression Inventory-II), risk-taking behavior (RT-18), past night sleep (Groningen Sleep Quality Scale), alcohol consumption, and activities during the test days. No significant differences were found regarding the amount of alcohol consumed and the total sleep time of the two groups. The hangover-sensitive group reported having a hangover as well as the presence of a variety of hangover-related symptoms, which were most severe in the morning and then gradually decreased during the day. The most frequently reported and most severe symptoms were sleepiness and fatigue, concentration problems, and headache. In contrast, the hangover-resistant group reported the absence of a hangover and the presence and severity of next-day symptoms did not significantly differ from the control day, except for increased fatigue and reduced vigor. The next-day effects on sleepiness-related complaints and vigor were significantly more pronounced among hangover-sensitive drinkers compared to hangover-resistant drinkers. In conclusion, contrary to hangover-resistant drinkers, hangover-sensitive drinkers report a variety of hangover symptoms that gradually ease during the day, but are still present in the afternoon.

This study investigated immunological changes during an alcohol hangover, and the possible difference between hangover-resistant and hangover-sensitive drinkers in terms of immune reactivity. Using a semi-naturalistic design, N = 36 healthy social drinkers (18 to 30 years old) provided saliva samples on a control day (after drinking no alcohol) and on a post-alcohol day. Hangover severity was rated directly after saliva collection. Cytokine concentrations, interleukin (IL)-1β, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-α, and hangover severity were compared between both test days and between hangover-sensitive and -resistant drinkers. Data from N = 35 drinkers (17 hangover-sensitive and 18 hangover-resistant) were included in the statistical analyses. Relative to the control day, there were significant increases in saliva IL-6 and IL-10 concentrations on the post-alcohol day. No significant differences in cytokine concentrations were found between hangover-sensitive and hangover-resistant drinkers, nor did any change in cytokine concentration correlate significantly with hangover severity. In line with previous controlled studies assessing cytokines in blood, the current naturalistic study using saliva samples also demonstrated that the immune system responds to high-level alcohol intake. However, further research is warranted, as, in contrast to previous findings in blood samples, changes in saliva cytokine concentrations did not differ significantly between hangover-sensitive and hangover-resistant drinkers, nor did they correlate significantly with hangover severity.

Objective To assess driving performance and neurocognitive skills of long-term users of sedating antidepressants, in comparison to healthy controls. Methods Thirty-eight long-term (>6 months) users of amitriptyline (n= 13) and mirtazapine (n= 25) were compared to 65 healthy controls. Driving performance was assessed using a 1-h standardised highway driving test in actual traffic, with road-tracking error (standard deviation of lateral position [SDLP]) being the primary measure. Secondary measures included neurocognitive tasks related to driving. Performance differences between groups were compared to those of blood alcohol concentrations of 0.5 mg/ml to determine clinical relevance. Results Compared to controls, mean increase in SDLP of all antidepressant users was not significant, nor clinically relevant (+0.75 cm, 95% CI: -0.83 cm; +2.33 cm). However, users treated less than 3 years (n= 20) did show a significant and clinically relevant increase in SDLP (+2.05 cm). No significant effects were observed on neurocognitive tasks for any user group, although large individual differences were present. Most results from neurocognitive tests were inconclusive, while a few parameters confirmed non-inferiority for users treated longer than 3 years. Conclusion The impairing effects of antidepressant treatment on driving performance and neurocognition mitigate over time following long-term use of 3 years.

To prevent single-bicycle crashes, this study is the first to evaluate effects of slanted kerbstones, edge lines, shoulder strips, and edge strips on cycling behaviour of cyclists ≥50 years. In Experiment 1, 32 participants cycled on a control path and paths with edge lines, slanted kerbstones, and three types of 0.5 m wide shoulder strips (with grey artificial grass, green artificial grass, or concrete street-print). In Experiment 2, 30 participants cycled a different route including a control path and paths with edge lines or 0.3 m white edge strips. Cyclists rode closer to the main cycle path’s edge in the shoulder strips conditions, although the presence of these strips resulted in a larger total distance to the verge compared to the control condition. Furthermore, cyclists cycled further from the verge in the edge strip condition than the control condition. Safety implications of the shoulder and edge strips are considered to be positive. Practitioner Summary: Older cyclists have a high risk for single-bicycle crashes (e.g. riding into the verge). In two experiments, cyclists ≥50 years cycled a route where different treatments were applied on a cycle path. Shoulder and edge strip treatments were related to more efficient path use and safer distances from the verge. Abbreviations: AGS: artificial grass strip; CL: control location; CSS: concrete street-print strip; ELC: edge line continuous; ELI: edge line intermittent; LP: lateral position; SDLP: standard deviation of the lateral position; SK: slanted kerbstones; WCES: white chippings edge strip

Objective: The aim of this study is to compare actual driving performance and skills related to driving of patients using benzodiazepine anxiolytics or hypnotics for at least 6 months to that of healthy controls.Methods: Participants were 44 long‐term users of benzodiazepine and benzodiazepine‐related anxiolytics (n = 12) and hypnotics (n = 32) and 65 matched healthy controls. Performance was assessed using an on‐the‐road driving test measuring standard deviation of lateral position (SDLP, in cm) and a battery of neurocognitive tasks. Performance differences between groups were compared with a blood alcohol concentration of 0.5 mg/ml to determine clinical relevance.Results: Compared with controls, SDLP was significantly increased in hypnotic users (+1.70 cm) but not in anxiolytic users (+1.48 cm). Anxiolytic and hypnotic users showed significant and clinically relevant impairment on neurocognitive task measuring executive functioning, vigilance, and reaction time. For patients using hypnotics for at least 3 years, no significant driving impairment was observed.Conclusion: Impairing effects of benzodiazepine hypnotics on driving performance may mitigate over time following longer term use (i.e. 3 years or more) although neurocognitive impairments may remain.

The aim of this article is to investigate the effect of a physical rest-frame, habituation and age on simulator sickness in an advanced mobility scooter driving simulator. Twenty-six young and 34 older adults completed a total of 12 drives in an advanced mobility scooter driving simulator over two visits. A 2x2 crossover design was used to measure the effect of a rest frame that was added to the driving simulator on either the first or second visit. The Simulator Sickness Questionnaire was used to measure simulator sickness symptoms. A significant decrease in simulator sickness was observed between the first and the second visit. Older adults reported more severe simulator sickness symptoms compared to younger participants. No effect of rest-frame could be found. Habituation appears to be the most effective method to reduce simulator sickness in an advanced mobility scooter driving simulator. More research is needed to investigate simulator sickness in patient groups. Practitioner summary: Experiencing simulator sickness is a major problem across all types of simulators. The present experiment investigated the effect of a rest-frame, habituation and age on developing simulator sickness symptoms in an advanced mobility scooter driving simulator. Habituation appeared to be the most effective method to reduce simulator sickness.

Background: Irritable bowel syndrome (IBS) can have a significant negative impact on quality of life, mood and wellbeing. The aim of this study was to investigate the association between experiencing IBS symptoms and insomnia, and perceived health status. Method: An online survey was conducted among n = 1950 Dutch university students (83.6% women). IBS was assessed with the Birmingham IBS Symptom Questionnaire, quality of life with the WHO-5 wellbeing index, and sleep outcomes with the SLEEP-50 questionnaire. Perceived immune functioning and general health were assessed using 1-item scales. Results: IBS symptom severity was significantly associated with insomnia complaints (r = 0.32, p = 0.0001), sleep quality (r = −0.21, p = 0.0001), sleep onset latency (r = 0.11, p = 0.0001) and the number of nightly awakenings (r = 0.24, p = 0.0001). Total sleep time was not significantly associated with IBS symptom severity. Significant correlations were also found between IBS symptom severity and perceived general health (r = −0.30, p = 0.0001), perceived immune functioning (r= −0.25, p = 0.0001), and quality of life (r = −0.24, p = 0.0001). Conclusions: Experiencing IBS complaints is associated with reduced perceived immune functioning, a poorer perception of general health, and sleep disturbances. These effects are reflected in a significantly lower reported quality of life in subjects with more IBS and/or sleep complaints.

Purpose: To compare different driving parameters between visually impaired people and normal sighted controls in a mobility scooter and microcar driving simulator. Materials and methods: A mobility scooter and microcar driving simulator and different virtual environments were developed for the purpose of this experiment. Participants completed 4 drives in the microcar driving simulator and 8 drives in the mobility scooter driving simulator. Driving performance was compared between visually impaired and normal sighted participants, using the parameters speed, lateral position, time-to-collision, and number and type of collision. Results: Visually impaired participants did not differ significantly from normal sighted controls with regard to speed and overall lateral position. In contrast, number of collisions was higher in visually impaired participants in almost all drives. Time-to-collision differed in some, but not all of the drives. Small obstacles with low contrast posed the highest risk of collision for impaired drivers. Conclusions: The present findings showed that visually impaired participants were able to maintain a steady position on the street, but showed more difficulties in traffic situations that included obstacles and other traffic participants. Familiarity with the driving tasks seemed to improve performance, however, further research is necessary to confirm this observation.

Increasing evidence points at a role for the immune system in the genesis of the alcohol hangover. This study investigated the association between self-reported immune function and experiencing hangovers. Dutch students aged 18 to 30 years old were invited to complete an online survey. Eighteen items on immune-related complaints were completed to assess self-reported immune function. Alcohol consumption in the past month (with respect to usual consumption and the occasion of heaviest drinking) was also recorded. Subjects with an estimated blood alcohol concentration (eBAC) of 0.18% or higher on their heaviest drinking occasion in the prior month were included in the analyses. Self-reported immune function was compared between drinkers with a hangover and those who claimed to be hangover resistant. In total, of 481 subjects (79.2% women) with a mean (SD) age of 21.1 (1.9) years old were included in the analysis. Of these, 83.3% (n = 400) reported having hangovers and 16.8% (n = 81) claimed to be hangover resistant. Drinkers with hangovers had significantly higher self-reported overall immune function scores when compared to hangover-resistant drinkers (mean ± SD = 10.5 ± 3.6 versus 13.1 ± 4.9, p = 0.0001), indicating a poorer immune status. In conclusion, experiencing alcohol hangovers is associated with significantly poorer self-reported immune function.