•Variation in speed and lateral position are suitable to assess driving impairment.•Adopted distance to other vehicles measures higher level driving impairment.•Reaction time to a traffic light is ...sensitive to higher level driving impairment.•Measures that allow freedom of choice need more in depth research.
The influence of psychoactive substances on driving performance and traffic safety has been extensively studied. Research on the influence of alcohol at the control level of behaviour (i.e. automated processes) has been well established and has shown that the ability to operate a vehicle decreases with rising alcohol levels. However, results one level higher at the manoeuvring level (i.e. conscious processes), are inconsistent. The current study aimed to replicate findings on the influence of alcohol on the control level of behaviour and investigate effects on the manoeuvring level in order to find suitable measures to assess driving impairment.
The study was double-blind, placebo-controlled with a counterbalanced treatment order and a two-way crossover design. Thirty participants performed tasks in a driving simulator under the influence of alcohol (0.5‰) and a placebo. In the driving tasks the control level of behaviour (swerving, average speed, and speed variation) was investigated, as well as the manoeuvring level of behaviour (distance to other traffic during an overtaking manoeuvre, reaction time to a traffic light turning amber, and response to a suddenly merging car).
As expected, alcohol affected the control level of behaviour negatively. Participants swerved more and showed more speed variation after alcohol intake. The manoeuvring level of driving behaviour was also affected by alcohol. The distance to other drivers during an overtaking manoeuvre was smaller under the influence of alcohol. Results on reaction time were however less straightforward. Reaction time increased significantly under the influence of alcohol when reacting to a traffic light but not in reaction to a car unexpectedly merging into traffic. When analysing behaviour in reaction to these different events in more detail it became clear that they were responded to in varying manners, making it difficult to find an average impairment measure.
The deteriorating effect of alcohol at the control level of driving behaviour was replicated, confirming the suitability of the standard deviation of lateral position and the variation in speed as measures of impairment. At the manoeuvring level, the kept distance to the leading car during an overtaking manoeuvre appeared to be a suitable measure to assess impairment as well as reaction time to a traffic light. The current study also confirms the difficulties in evaluating complex driving behaviour and the need for more research on this subject.
Rationale
The driving simulator provides a safe and controlled environment for testing driving behaviour efficiently. The question is whether it is sensitive to detect drug-induced effects.
Objective
...The primary aim of the current study was to investigate the sensitivity of the driving simulator for detecting drug effects. As a case in point, we investigated the dose-related effects of oral ∆
9
-tetrahydrocannabinol (THC), i.e. dronabinol, on simulator and on-the-road driving performance in equally demanding driving tasks.
Method
Twenty-four experienced driver participants were treated with dronabinol (Marinol®; 10 and 20 mg) and placebo. Dose-related effects of the drug on the ability to keep a vehicle in lane (weaving) and to follow the speed changes of a lead car (car following) were compared within subjects for on-the-road versus in-simulator driving. Additionally, the outcomes of equivalence testing to alcohol-induced effects were investigated.
Results
Treatment effects found on weaving when driving in the simulator were comparable to treatment effects found when driving on the road. The effect after 10 mg dronabinol was however less strong in the simulator than on the road and inter-individual variance seemed higher in the simulator. There was, however, a differential treatment effect of dronabinol on reactions to speed changes of a lead car (car following) when driving on the road versus when driving in the simulator.
Conclusion
The driving simulator was proven to be sensitive for demonstrating dronabinol-induced effects particularly at higher doses. Treatment effects of dronabinol on weaving were comparable with driving on the road but inter-individual variability seemed higher in the simulator than on the road which may have potential effects on the clinical inferences made from simulator driving. Car following on the road and in the simulator were, however, not comparable.
Using 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.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.Sixty-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‰ or higher, determined by means of non-inferiority analyses.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‰ or higher, determined by means of non-inferiority analyses.Reaction 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.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.The 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.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.
Analysis of dried blood spots is an increasingly accepted method in therapeutic drug monitoring, whereas its application by analogy to forensic samples has not been studied in detail. Therefore, we ...investigated whether determination of 3,4-methylenedioxymethamphetamine (MDMA) and its main metabolite 3,4-methylendioxyamphetamine (MDA) from dried blood spots (DBS) is as reliable as that from whole blood specimens. Analysis was performed by liquid chromatography-tandem mass spectrometry following liquid-liquid extraction of blood and corresponding DBS samples from 20 volunteers participating in a controlled driving experiment under the influence of MDMA. The assay was checked for carryover, ion suppression/enhancement, linearity of response, lower limits of detection (LLOD) and quantitation, extraction efficiency and the within-run and between-run assay imprecision for both whole blood and DBS. The LLODs were 2.0 and 1.6 ng/mL for MDMA in whole blood and DBS, respectively, using a volume of 100 µL. LLODs of MDA were determined to be 0.25 ng/mL in whole blood specimens and 0.12 ng/mL in DBS. Extraction efficiency and imprecision did not differ significantly between the two methods for both MDMA and MDA. The mean concentration ratio of corresponding whole blood and DBS samples, t-test, and the Bland-Altman difference plot were used to test hypothesis of equality. Statistical analyses revealed that methods did not significantly differ for MDMA or MDA. Thus, DBS analysis has potential as a precise and inexpensive alternative to whole blood analysis of MDMA.
Objective
Previous research reported cognitive and psychomotor impairments in long‐term users of benzodiazepine receptor agonists (BZRAs). This article explores the role of acute intoxication and ...clinical complaints.
Methods
Neurocognitive and on‐road driving performance of 19 long‐term (≥6 months) regular (≥twice weekly) BZRA users with estimated plasma concentrations, based on self‐reported use, exceeding the therapeutic threshold (CBZRA+), and 31 long‐term regular BZRA users below (CBZRA−), was compared to that of 76 controls.
Results
BZRA users performed worse on tasks of response speed, processing speed, and sustained attention. Age, but not CBZRA or self‐reported clinical complaints, was a significant covariate. Road‐tracking performance was explained by CBZRA only. The CBZRA + group exhibited increased mean standard deviation of lateral position comparable to that at blood‐alcohol concentrations of 0.5 g/L.
Conclusions
Functional impairments in long‐term BZRA users are not attributable to self‐reported clinical complaints or estimated BZRA concentrations, except for road‐tracking, which was impaired in CBZRA + users. Limitations to address are the lack of assessment of objective clinical complaints, acute task related stress, and actual BZRA plasma concentrations. In conclusion, the results confirm previous findings that demonstrate inferior performance across several psychomotor and neurocognitive domains in long‐term BZRA users.
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.
This paper describes the application of image analysis combined with a quantitative staining method for the analysis of cervical specimens. The image analysis is carried out with the Leyden ...Television Analysis System, LEYTAS, of which two versions are described. LEYTAS-1 as well as LEYTAS-2 have both been designed with a high degree of flexibility and interaction facilities. A much wider range of image analysis programs is however, possible with LEYTAS-2, enabling many applications. LEYTAS-1, the earlier version, consists of a Leitz microscope with automated functions, a TV camera, the Texture Analysis System (TAS, Leitz), a four-bit grey value memory and a minicomputer (PDP 11/23). Using this instrumentation 1,500 cervical smears prepared from cell suspensions and stained with acriflavin-Feulgen-Sits have been analysed in a completely automated procedure. Image transformations working in parallel on entire fields, have been used for cell selection and artefact rejection. Resulting alarms, consisting of selected single cells and non-rejected artefacts are stored in the grey value memory, which is displayed on a TV monitor. This option allows visual interaction after the machine diagnosis has been made. The machine diagnosis was correct in 320 out 321 specimens with a severe dysplasia or more serious lesion. The false positive rate in 561 morphologically negative specimens (normal and inflammation) was 16% (machine diagnosis). Visual interaction by subtracting the visually recognized false alarms from the total number of alarms reduces the false positive rate to 11%.
The subcellular localizations of gamma-aminobutyrate transaminase (EC 2.6.1.19) and glutamate dehydrogenase (EC 1.4.1.2) in brain tissue of adult rats were compared with each other and with those of ...NAD+-isocitrate dehydrogenase (EC 1.1.41) and monoamine oxidase (EC 1.4.3.4; kynuramine as substrate). Crude mitochondrial fractions from brain tissue were centrifuged in continuous sucrose density gradients. gamma-Aminobutyrate transaminase and glutamate dehydrogenase were always found at a higher density than NAD+-isocitrate dehydrogenase and monoamine oxidase. When centrifuged for 1 h at 53 000gav., there was a slight difference between the distribution profiles of glutamate dehydrogenase and gamma-aminobutyrate transaminase. This difference was larger when the centrifugation time was only 15 min. It is concluded that there are subpopulations of brain mitochondria with differing proportions of gamma-aminobutyrate transaminase and glutamate dehydrogenase. The results are discussed in relation to evidence obtained with labelled precursors in vivo that there are at least two small glutamate compartments in adult brain.
Texture parameters of the nuclear chromatin pattern can contribute to the automated classification of specimens on the basis of single cell analysis in cervical cytology. Current texture parameters ...are abstract and therefore hamper understanding. In this paper texture parameters are described that can be derived from the chromatin pattern after segmentation of the nuclear image. These texture parameters are more directly related to the visual properties of the chromatin pattern. The image segmentation procedure is based on a region grow algorithm which specifically isolates high chromatin density. The texture analysis method has been tested on a data set of images of 112 cervical nuclei on photographic negatives digitized with a step size of 0.125 micron. The preliminary results of a classification trial indicate that these visually interpretable parameters have promising discriminatory power for the distinction between negative and positive specimens.
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