Meta-analysis of the procedural risks of carotid endarterectomy and carotid artery stenting over time.

BACKGROUND: Stroke/death rates within 30 days of carotid endarterectomy (CEA) and carotid artery stenting (CAS) in RCTs inform current clinical guidelines. However, the risks may have changed in recent years with wider use of effective stroke prevention therapies, especially statins, improved patient selection and growing operator expertise. The aim of this study was to investigate whether the procedural stroke/death risks from CEA and CAS have changed over time. METHODS: MEDLINE and Embase were searched systematically from inception to May 2016 for observational cohort studies of CEA and CAS. Studies included reported on more than 1000 patients, with 30-day outcomes after the procedure according to patients' symptom status (recent stroke or transient ischaemic attack). Restricted maximum likelihood random-effects and meta-regressions methods were used to synthesize procedural stroke/death rates of CEA and CAS according to year of study recruitment completion. RESULTS: Fifty-one studies, including 223 313 patients undergoing CEA and 72 961 undergoing CAS, were reviewed. Procedural stroke/death risks of CEA decreased over time in symptomatic and asymptomatic patients. Risks were substantially lower in studies completing recruitment in 2005 or later, both in symptomatic (5·11 per cent before 2005 versus 2·68 per cent from 2005 onwards; P = 0·002) and asymptomatic (3·17 versus 1·50 per cent; P < 0·001) patients. Procedural stroke/death rates of CAS did not change significantly over time (4·77 per cent among symptomatic and 2·59 per cent among asymptomatic patients). There was substantial heterogeneity in event rates and recruitment periods were long. CONCLUSIONS: Risks of procedural stroke/death following CEA appear to have decreased substantially. There was no evidence of a change in stroke/death rates following CAS.

Pre-operative Carotid Plaque Echolucency Assessment has no Predictive Value for Long-Term Risk of Stroke or Cardiovascular Death in Patients Undergoing Carotid Endarterectomy.

INTRODUCTION: In patients with carotid stenosis receiving medical treatment, carotid plaque echolucency has been thought to predict risk of future stroke and of other cardiovascular events. This study evaluated the prognostic value of pre-operative plaque echolucency for future stroke and cardiovascular death in patients undergoing carotid endarterectomy in the first Asymptomatic Carotid Surgery Trial (ACST-1). METHODS: In ACST-1, 1832/3120 patients underwent carotid endarterectomy (CEA), of whom 894 had visual echolucency assessment according to the Gray-Weale classification. During follow-up patients were monitored both for peri-procedural (i.e. within 30 days) death, stroke, or MI, and for long-term risk of stroke or cardiovascular death. Unconditional maximum likelihood estimation was used to calculate odds ratios of peri-procedural risk and Kaplan-Meier statistics with log-rank test were used to compare cumulative long-term risks. RESULTS: Of 894 operated patients in whom echolucency was assessed, 458 plaques (51%) were rated as echolucent and peri-procedural risk of death/stroke/MI in these patients was non-significantly higher when compared with patients with non-echolucent plaques (OR 1.48 [95% CI 0.76-2.88], p = .241). No differences were found in the 10 year risk of any stroke (30/447 [11.6%] vs. 29/433 [11.0%], p = .900) or cardiovascular (non-stroke) death (85/447 [27.9%] vs. 93/433 [32.1%], p = .301). CONCLUSION: In ACST-1, carotid plaque echolucency assessment in patients undergoing CEA offered no predictive value with regard to peri-operative or long-term stroke risk or of cardiovascular (non-stroke) death.

Diastolic Blood Pressure is a Risk Factor for Peri-procedural Stroke Following Carotid Endarterectomy in Asymptomatic Patients.

OBJECTIVE/BACKGROUND: Carotid endarterectomy (CEA) prevents future stroke, but this benefit depends on detection and control of high peri-operative risk factors. In symptomatic patients, diastolic hypertension has been causally related to procedural stroke following CEA. The aim was to identify risk factors causing peri-procedural stroke in asymptomatic patients and to relate these to timing of surgery and mechanism of stroke. METHODS: In the first Asymptomatic Carotid Surgery Trial (ACST-1), 3,120 patients with severe asymptomatic carotid stenosis were randomly assigned to CEA plus medical therapy or to medical therapy alone. In 1,425 patients having their allocated surgery, baseline patient characteristics were analysed to identify factors associated with peri-procedural (< 30 days) stroke or death. Multivariate analysis was performed on risk factors with a p value < .3 from univariate analysis. Event timing and mechanism of stroke were analysed using chi-square tests. RESULTS: A total of 36 strokes (27 ischaemic, four haemorrhagic, five unknown type) and six other deaths occurred during the peri-procedural period, resulting in a stroke/death rate of 2.9% (42/1,425). Diastolic blood pressure at randomisation was the only significant risk factor in univariate analysis (odds ratio [OR] 1.34 per 10 mmHg, 95% confidence interval [CI] 1.04-1.72; p = .02) and this remained so in multivariate analysis when corrected for sex, age, lipid lowering therapy, and prior infarcts or symptoms (OR 1.34, 95% CI 1.05-1.72; p = .02). In patients with diastolic hypertension (> 90 mmHg) most strokes occurred during the procedure (67% vs. 20%; p = .02). CONCLUSION: In ACST-1, diastolic blood pressure was the only independent risk factor associated with peri-procedural stroke or death. While the underlying mechanisms of the association between lower diastolic blood pressure and peri-procedural risk remain unclear, good pre-operative control of blood pressure may improve procedural outcome of carotid surgery in asymptomatic patients.

Choices of Stent and Cerebral Protection in the Ongoing ACST-2 Trial: A Descriptive Study.

OBJECTIVE/BACKGROUND: Several plaque and lesion characteristics have been associated with an increased risk for procedural stroke during or shortly after carotid artery stenting (CAS). While technical advancements in stent design and cerebral protection devices (CPD) may help reduce the procedural stroke risk, and anatomy remains important, tailoring stenting procedures according to plaque and lesion characteristics might be a useful strategy in reducing stroke associated with CAS. In this descriptive report of the ongoing Asymptomatic Carotid Surgery Trial-2 (ACST-2), it was assessed whether choice for stent and use or type of CPD was influenced by plaque and lesion characteristics. METHODS: Trial patients who underwent CAS between 2008 and 2015 were included in this study. Chi-square statistics were used to study the effects of plaque echolucency, ipsilateral preocclusive disease (90-99%), and contralateral high-grade stenosis (>50%) or occlusion of the carotid artery on interventionalists' choice for stent and CPD. Differences in treatment preference between specialties were also analysed. RESULTS: In this study, 831 patients from 88 ACST-2 centres were included. Almost all procedures were performed by either interventional radiologists (50%) or vascular surgeons (45%). Plaque echolucency, ipsilateral preocclusive disease (90-99%), and significant contralateral stenosis (>50%) or occlusion did not affect the choice of stent or either the use of cerebral protection and type of CPD employed (i.e., filter/flow reversal). Vascular surgeons used a CPD significantly more often than interventional radiologists (98.6% vs. 76.3%; p < .001), but this choice did not appear to be dependent on patient characteristics. CONCLUSION: In ACST-2, plaque characteristics and severity of stenosis did not primarily determine interventionalists' choice of stent or use or type of CPD, suggesting that other factors, such as vascular anatomy or personal and centre preference, may be more important. Stent and CPD use was highly heterogeneous among participating European centres.

Driving performance of long-term users of sedating antidepressants and benzodiazepines.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Repeated conditionally automated driving on the road: How do drivers leave the loop over time?

The goal of this on the road driving study was to investigate how drivers adapt their behavior when driving with conditional vehicle automation (SAE L3) on different occasions. Specifically, we focused on changes in how fast drivers took over control from automation and how their gaze off the road changed over time. On each of three consecutive days, 21 participants drove for 50 min, in a conditionally automated vehicle (Wizard of Oz methodology), on a typical German commuting highway. Over these rides the take-over behavior and gaze behavior were analyzed. The data show that drivers' reactions to non-critical, system initiated, take-overs took about 5.62 s and did not change within individual rides, but on average became 0.72 s faster over the three rides. After these self-paced take-over requests a final urgent take-over request was issued at the end of the third ride. In this scenario participants took over rapidly with an average of 5.28 s. This urgent take-over time was not found to be different from the self-paced take-over requests in the same ride. Regarding gaze behavior, participants' overall longest glance off the road and the percentage of time looked off the road increased within each ride, but stayed stable over the three rides. Taken together, our results suggest that drivers regularly leave the loop by gazing off the road, but multiple exposures to take-over situations in automated driving allow drivers to come back into loop faster.

Keeping the driver in the loop through semi-automated or manual lane changes in conditionally automated driving.

In the current study we investigated if drivers of conditionally automated vehicles can be kept in the loop through lane change maneuvers. More specifically, we examined whether involving drivers in lane-changes during a conditionally automated ride can influence critical take-over behavior and keep drivers' gaze on the road. In a repeated measures driving simulator study (n = 85), drivers drove the same route three times, each trial containing four lane changes that were all either (1) automated, (2) semi-automated or (3) manual. Each ride ended with a critical take-over situation that could be solved by braking and/or steering. Critical take-over reactions were analyzed with a linear mixed model and parametric accelerated failure time survival analysis. As expected, semi-automated and manual lane changes throughout the ride led to 13.5% and 17.0% faster maximum deceleration compared to automated lane changes. Additionally, semi-automated and manual lane changes improved the quality of the take-over by significantly decreasing standard deviation of the steering wheel angle. Unexpectedly, drivers in the semi-automated condition were slowest to start the braking maneuver. This may have been caused by the drivers' confusion as to how the semi-automated system would react. Additionally, the percentage gaze off-the-road was significantly decreased by the semi-automated (6.0%) and manual (6.6%) lane changes. Taken together, the results suggest that semi-automated and manual transitions may be an alarm-free instrument which developers could use to help maintain drivers' perception-action loop and improve automated driving safety.

The MMSE should not be the sole indicator of fitness to drive in mild Alzheimer's dementia.

Since Alzheimer's disease may affect driving performance, patients with Alzheimer's disease are assessed on fitness to drive. On-road driving assessments are widely used, and attempts have also been made to develop strategies to assess fitness to drive in a clinical setting. Preferably, a first indication of fitness to drive is obtained quickly after diagnosis using a single test such as the Mini-Mental State Examination (MMSE). The aim of this study is to investigate whether the MMSE can be used to predict whether patients with Alzheimer's disease will pass or fail an on-road driving assessment. Patients with Alzheimer's disease (n = 81) participated in a comprehensive fitness-to-drive assessment which included the MMSE as well as an on-road driving assessment [PLoS One 11(2):e0149566, 2016]. MMSE cutoffs were applied as suggested by Versijpt and colleagues [Acta Neurol Belg 117(4):811-819, 2017]. All patients with Alzheimer's disease who scored below the lower cutoff (MMSE ≤ 19) failed the on-road driving assessment. However, a third of the patients with Alzheimer's disease who scored above the upper cutoff (MMSE ≥ 25) failed the on-road driving assessment as well. We conclude that the MMSE alone has insufficient predictive value to correctly identify fitness to drive in patients with very mild-to-mild Alzheimer's disease implicating the need for comprehensive assessments to determine fitness to drive in a clinical setting.

Comparing treatment effects of oral THC on simulated and on-the-road driving performance: testing the validity of driving simulator drug research.

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.

Exercise-induced syncope as late consequence of radiotherapy.

This report describes a 34-year-old female with an exercise-induced atrioventricular block resulting from transient ischemia caused by a radiation-induced ostial stenosis of the right coronary artery. Patient first underwent coronary artery surgery with a right internal mammary artery to the right coronary artery. After 18 months she was readmitted with exercise-induced syncope due to graft occlusion. This time a successful rotablator procedure was performed on the ostial stenosis.

An experimental study to evaluate the effectiveness of different methods and intensities of law enforcement on driving speed on motorways.

Two field experiments were conducted to establish the most effective method of enforcement in reducing driving speed and to establish the most efficient strategy in terms of police force personnel required. In the first experiment, the effect of three variables on driving speed on motorways was studied. The first variable, intensity of enforcement, was manipulated by creating three different objective levels of apprehension for detected speeding drivers. The second variable was method of enforcement. On-view stopping and ticketing of offenders was compared to mailing of fines on the basis of the car's licence plate number. The third variable manipulated was the time delay in the mailing of fines. Time delay between detection of the offence and feedback to the driver was shortened in one condition. In a second experiment, police enforcement effort was optimized by relating intensity level of enforcement to the proportion of speeding vehicles. In the first experiment, police enforcement was applied for four weeks; in the second experiment, enforcement activities were continued for 12 consecutive weeks. In both cases the main dependent variable was driving speed. Before, during, and after the application of enforcement, speed was registered using induction loops. In addition, driver opinion about speeding and speed enforcement was studied using postal questionnaire surveys. The results show the largest and longest lasting reduction in driving speed in the highest intensity level-condition, giving support for a relation between objective chance of apprehension and speed choice. On-view stopping of offenders was shown to be a more effective method to reduce driving speed than mailing of fines. Some of these results are discussed in the light of game theory. The questionnaire surveys indicated that most drivers did not notice the recurrence in enforcement activities due to infrequent passing of the sections of motorways studied. The preventive effect of police enforcement appeared to be far more substantial than its repressive effect. Enforcement primarily deters the current nonoffender from speeding.

Assessing driver status: a demonstration experiment on the road.

Twenty subjects completed an on-the-road experiment that consisted of two parts on two separate days. One was a one-hour driving test under the influence of alcohol (BAC less than = 0.05%), the second a two-and-a-half-hour driving test under vigilance conditions. Impairment of driving performance was measured in a car-following test as well as in a standard driving test. Changes in relevant physiological parameters, such as ECG and EEG, reflected changes in driver status and predicted driving performance impairment.

The effects of mobile telephoning on driving performance.

The effects of telephoning while driving were studied in three different traffic conditions, i.e. in light traffic on a quiet motorway, in heavy traffic on a four-lane ring-road, and in city traffic. Twelve subjects, unfamiliar with mobile telephones, drove an instrumented vehicle for one hour each day during three weeks and while in each of the three traffic conditions, had to operate the mobile telephone for a short while. To ensure a fixed "heavy traffic load" in the second condition, the subjects were instructed to follow another instrumented vehicle (at a safe distance). The results showed a significant effect of telephoning while driving as opposed to normal driving (i.e., not involving telephone conversation), on the effort subjectively measured by an effort scale and objectively measured by heartrate indices and on some of the measured parameters of driving performance. One half of the subjects had to operate the telephone manually, the other half performed the telephone task with a handsfree mobile telephone set. The subjects who operated the handsfree telephone showed better control over the test vehicle than the subjects who operated the handheld telephone, as measured by the steering wheel movements. Also, a clear improvement over time in the course of the 15 test days was found for some of the measurements. As a consequence of the results, some advice concerning mobile telephoning can be given to authorities, manufacturers, and users.

A comparison of different ways to approximate time-to-line crossing (TLC) during car driving.

Three experiments are presented in which the accuracy of different methods to approximate time-to-line crossing is assessed the first experiment TLC was computed, using a trigonometric method, during normal driving while the vehicle stayed in lane. The minima of TLC were compared with two approximations and it was found computing TLC as lateral distance divided by lateral velocity gave poor results. It was concluded that this simple approximation is not suitable for measuring TLC minima in studies of driver behaviour. A way of computing TLC that takes account of the curved path of the vehicle resulted in a good fit of TLC minima. In two other experiments the vehicle exceeded the lane boundary, either intentionally as a result of a lane change manoeuvre, or unintentionally as a result of impaired driving. In these cases no TLC minima exists since these only occur as a result of correcting steering actions to stay within the lane. In contrast to normal lane keeping, it was found that prior to crossing the lane boundary, the simple approximation resulted in more accurate estimation of available time before the lane boundary is exceeded compared to the more complex approximation. This indicates that for lane keeping support systems and systems that detect when the driver has fallen asleep and drifts out of lane, a simple algorithm for TLC estimation may give reliable results, while this algorithm is not accurate enough for more fundamental studies of driver behaviour. However, the reliability of the approximation is only satisfactory over a very short time range before the lane boundary is actual exceeded. This may result in warnings that come too late and result in too little time to respond for the driver.

Elderly and young driver's reaction to an in-car enforcement and tutoring system.

A system that contrasts driver behaviour with normative behaviour was tested in an advanced driving simulator. Drivers were provided with auditory and visual tutoring messages if deviations were detected from normative, i.e. legally allowed behaviour with respect to a selection of offences. Results showed that the system was very effective in increasing law-abiding behaviour, which has a major positive effect on traffic safety. However, driver mental effort, as indicated by self-reports and drivers' physiological states, was slightly increased in conditions where drivers received feedback. Opinion about the tutoring system was positive in terms of usefulness. Self-reports on satisfaction differed between age groups; young drivers rated it low, while elderly drivers held a positive attitude.

[Angiotensin-converting enzyme inhibitors following a myocardial infarct: clinical abd echographic indications]. / Angiotensine-'converting'-enzymremmers na een myocardinfarct: klinische en echocardiografische indicaties.

-Angiotensin converting enzyme (ACE) inhibitors can limit mortality and the occurrence of cardiac failure after myocardial infarction because they interfere with the ventricular remodelling process. ACE inhibitors also have anti-arrhythmic and possibly anti-ischaemic potency and therefore a primary cardioprotective effect. It is not advised to treat all patients with a myocardial infarction with an ACE inhibitor, but patients with a large anterior wall infarct, with heart failure or who had a previous infarct should be treated. After three months, the remodelling process can be reevaluated. The ACE inhibitor can be discontinued if the left ventricular function has strongly improved. There is no preference for a particular ACE inhibitor.

Studying the role of vision in cycling: critique on restricting research to fixation behaviour.

In a recent study published in Accident Analysis & Prevention, Vansteenkiste et al. (2013)--as one of the first in this field--investigated the visual control of bicycle steering. They undertook the interesting task of testing cyclists' eye fixation behaviour against Donges' two-level model of steering, i.e. the guidance level to anticipate alternations in the course of the road and the stabilization level for lane keeping. Although the laboratory experiment itself is well conducted, we believe that its results cannot be used to test the two-level model of steering as developed for driving. The test track was only 15m long, was completely straight and was known in advance. Accordingly, it did not provide adequate conditions for testing the guidance level. Furthermore, as the experimental lanes were much narrower than real-world cycling lanes, the stabilization level differed considerably from that in the real world. The study by Vansteenkiste et al. (2013) may provide valuable insight into the role of vision in 'precision steering', but, as we discuss in the paper, more elaborate research paradigms are needed to achieve more comprehensive knowledge of the role of vision in real-world cycling and cycling safety.

The use and risk of portable electronic devices while cycling among different age groups.

INTRODUCTION: In the Netherlands, a survey was set up to monitor the extent of the use of portable, electronic devices while cycling amongst different age groups of cyclists and to estimate the possible consequences for safety. METHOD: The main research questions concerned age differences in the self-reported use of electronic devices while cycling, self-reported crash involvement and risk, and self-reported compensatory behaviour. Teen cyclists (12-17 years) and young adult cyclists (18-34 years) were more frequent users, and also more indiscriminate users of portable devices while cycling than middle-aged and older adult cyclists (35-49 years; 50+ years). RESULTS: After statistical correction for influences on crash risk of urbanization level, weekly time spent cycling, and cycling in more demanding traffic situations, the odds of being involved in a bicycle crash were estimated to be higher for teen cyclists and young adult cyclists who used electronic devices on every trip compared to same age groups cyclists who never used these devices. For middle-aged and older adult cyclists, the use of portable electronic devices was not a significant predictor of bicycle crashes, but frequency of cycling in demanding traffic situations was. Possible implications for education or legal measures are discussed. IMPACT ON INDUSTRY: Results may inform researchers, policy makers, and cyclists themselves. Educational campaigns may use risk information to warn young cyclists about risk of device use while cycling.

Short-term cardiovascular responses to changing task demands.

When measuring operator states the predictive power of cardiovascular and respiratory measures in relation to mental workload has been questioned. One of the main questions is to what extent do cardiovascular measures actually reflect mental workload. This question arises because good measures of mental workload should be sensitive to changes in mental effort alone and not to other influences or at least the changes associated with mental workload should be easy to isolate. In the case of cardiovascular measures, the physiological change brought on by the baroreflex is a compensatory control effect that can potentially overshadow changes in physiology due to mental effort and therefore reduce the usefulness of cardiovascular measures. However, this does not need to be the case. Despite the effects caused by the baroreflex differences in heart rate, heart rate variability and other cardiovascular measures associated with task related effort can still be found using short-term response patterns. The short-segment analysis approach described in this paper is based on a time-frequency method in which the spectral power of the cardiovascular measures in specified spectral bands is computed from small time segments, i.e. 30 s. To demonstrate the effectiveness of this technique two studies which made use of a simulation of an ambulance dispatcher's task are described, both with easy and difficult task conditions. A short-lasting increase in task demand was found to be reflected in short-lasting increases in heart rate and blood pressure in combination with corresponding decreases in heart rate variability and blood pressure variability. These effects were larger in easy task conditions than in hard conditions, likely due to a higher overall effort-level during the hard task conditions. However, the developed measures are still very sensitive to mental effort and if this brief segmentation approach is used cardiovascular measures show promise as good candidates for reflecting mental effort during the assessment of operator state.