Summary Background Intravenous saline is recommended in clinical practice guidelines as the cornerstone for preventing contrast-induced nephropathy in patients with compromised renal function. ...However, clinical-effectiveness and cost-effectiveness of this prophylactic hydration treatment in protecting renal function has not been adequately studied in the population targeted by the guidelines, against a group receiving no prophylaxis. This was the aim of the AMACING trial. Methods AMACING is a prospective, randomised, phase 3, parallel-group, open-label, non-inferiority trial of patients at risk of contrast-induced nephropathy according to current guidelines. High-risk patients (with an estimated glomerular filtration rate eGFR of 30–59 mL per min/1·73 m2 ) aged 18 years and older, undergoing an elective procedure requiring iodinated contrast material administration at Maastricht University Medical Centre, the Netherlands, were randomly assigned (1:1) to receive intravenous 0·9% NaCl or no prophylaxis. We excluded patients with eGFR lower than 30 mL per min/1·73 m2 , previous dialysis, or no referral for intravenous hydration. Randomisation was stratified by predefined risk factors. The primary outcome was incidence of contrast-induced nephropathy, defined as an increase in serum creatinine from baseline of more than 25% or 44 μmol/L within 2–6 days of contrast exposure, and cost-effectiveness of no prophylaxis compared with intravenous hydration in the prevention of contrast-induced nephropathy. We measured serum creatinine immediately before, 2–6 days, and 26–35 days after contrast-material exposure. Laboratory personnel were masked to treatment allocation. Adverse events and use of resources were systematically recorded. The non-inferiority margin was set at 2·1%. Both intention-to-treat and per-protocol analyses were done. This trial is registered with ClinicalTrials.gov , number NCT02106234. Findings Between June 17, 2014, and July 17, 2016, 660 consecutive patients were randomly assigned to receive no prophylaxis (n=332) or intravenous hydration (n=328). 2–6 day serum creatinine was available for 307 (92%) of 332 patients in the no prophylaxis group and 296 (90%) of 328 patients in the intravenous hydration group. Contrast-induced nephropathy was recorded in eight (2·6%) of 307 non-hydrated patients and in eight (2·7%) of 296 hydrated patients. The absolute difference (no hydration vs hydration) was −0·10% (one-sided 95% CI −2·25 to 2·06; one-tailed p=0·4710). No hydration was cost-saving relative to hydration. No haemodialysis or related deaths occurred within 35 days. 18 (5·5%) of 328 patients had complications associated with intravenous hydration. Interpretation We found no prophylaxis to be non-inferior and cost-saving in preventing contrast-induced nephropathy compared with intravenous hydration according to current clinical practice guidelines. Funding Stichting de Weijerhorst.
The risk of "hangover" effects, e.g. residual daytime sleepiness and impairment of psychomotor and cognitive functioning the day after bedtime administration, is one of the main problems associated ...with the use of hypnotics. However, the severity and duration of these effects varies considerably between hypnotics and is strongly dependent on the dose administered. This article reviews epidemiological evidence on the effect of hypnotics on patients' risk for accidents such as traffic accidents, falls and hip fractures (i.e. end-points for residual effects). Information on the duration and severity of residual effects of 11 hypnotics (flunitrazepam, flurazepam, loprazolam, lormetazepam, midazolam, nitrazepam, temazepam, triazolam, zaleplon, zolpidem and zopiclone) was derived from expert ratings, a meta-analysis and actual driving studies. Epidemiological studies show that the risks of an accident increase with increasing half-life of the hypnotic, but that the use of hypnotics with a short half-life, such as triazolam, zopiclone and zolpidem, can also be associated with increased risks. A summary of results from experimental studies should enable prescribing clinicians to compare residual effects of the various hypnotics at different doses and select the one considered most favourable in this respect for the individual patient. This information should also enable them to inform patients more adequately about the likelihood and duration of residual effects of a specific hypnotic dose.
•Alcohol can be used as a benchmark of impairment for other drugs.•Sensitivity and reliability of tests measuring driving related skills were reviewed.•A cued go/no-go task and a divided attention ...test were reliably sensitive.•Simulated driving tests should be compared head to head with actual driving tests.
Laboratory tests assessing driving related skills can be useful as initial screening tools to assess potential drug induced impairment as part of a standardized behavioural assessment. Unfortunately, consensus about which laboratory tests should be included to reliably assess drug induced impairment has not yet been reached. The aim of the present review was to evaluate the sensitivity of laboratory tests to the dose dependent effects of alcohol, as a benchmark, on performance parameters. In total, 179 experimental studies were included. Results show that a cued go/no-go task and a divided attention test with primary tracking and secondary visual search were consistently sensitive to the impairing effects at medium and high blood alcohol concentrations. Driving performance assessed in a simulator was less sensitive to the effects of alcohol as compared to naturalistic, on-the-road driving. In conclusion, replicating results of several potentially useful tests and their predictive validity of actual driving impairment should deserve further research. In addition, driving simulators should be validated and compared head to head to naturalistic driving in order to increase construct validity.
•Current crowd management practices from 10 crowd managers are presented.•Limitations and requirements of technology to support crowd management operations are analyzed.•Recommendations for ...communication, sensing, and decision-support technologies within a techno-social system framework are provided.
Recent accidents (News, 2006, 2010, 2013, 2015) show that crowded events can quickly turn into tragedies. The goal of crowd management is to avoid such accidents through careful planning and implementation. Crowd management practices are collaborative efforts between the different actors of the crowd management team and the crowd that depend on effective handling, sharing, and communication of information. Safety and comfort of a crowd depend on the success of such efforts. We have studied current practices and the role of technology through interviews to crowd managers. Our findings show that event planning and monitoring can be complex and sophisticated, but are operated with little support from technology. Crowd managers intend to increase their use of technology, but they have been so far dissatisfied by existing solutions. We provide recommendations for a bigger role of technology in crowd management.
Abstract Background In many European countries, Canada, and Japan, the nonbenzodiazepine zopiclone is now among the most frequently prescribed hypnotic drugs. This finding can be explained by the ...growing view among physicians that zopiclone is more effective and safer than conventional benzodiazepines. However, in 4 studies using similar procedures, it has been shown that zopiclone 7.5 mg causes moderate to severe impairment in driving performance. Objective The goal of the present article was to review these studies and analyze the pooled data to determine whether the severity of effects is modified by the sex and age of the subjects. Methods The driving data of the placebo and zopiclone 7.5 mg evening treatment periods from a total of 4 studies conducted at Maastricht University were included in this pooled analysis. All studies were conducted according to balanced double-blind, crossover designs. The effects on driving were always measured the next morning, between 10 and 11 hours after administration, by using a standardized highway driving test. A total of 101 healthy volunteers of both sexes in equal proportions (with no reports of insomnia) participated. Subjects comprised young volunteers (age range, 21–45 years) in 3 studies and older volunteers (age range, 55–75 years) in the fourth study. Results Results show that zopiclone 7.5 mg has significant and clinically relevant performance-impairing effects on driving in the morning, until 11 hours after bedtime ingestion. The effects did not differ between male and female subjects and did not increase with age, at least until 75 years. The effects of zopiclone 7.5 mg are comparable to the effects of a mean blood alcohol concentration between 0.5 and 0.8 mg/mL, which has been associated with a 2- to 3-fold increase in the risk of becoming involved in a traffic accident. Conclusions We concluded that patients using an evening dose of zopiclone 7.5 mg should avoid activity in skilled work and participation in traffic the morning after intake. General practitioners’ beliefs regarding the beneficial safety profile of zopiclone may need adjustment, and patients using zopiclone 7.5 mg should be warned accordingly. There is no need to differentiate warnings about zopiclone’s residual impairing effects depending on the sex of the patient.
Introduction
The on-the-road highway driving test is generally regarded as a gold standard for assessing drug-induced driving impairment. The primary outcome measure is the standard deviation of ...lateral position (SDLP), a measure of road tracking error or “weaving”. The test has been calibrated for incremental doses of alcohol almost 30 years ago in order to define the impact of drug-induced impairment in terms of blood alcohol concentration (BAC) equivalents. Drug-induced changes in SDLP exceeding 2.4 cm have been evaluated as clinically relevant ever since. The present analysis was conducted to assess the robustness of the alcohol effect in a range of on-the-road driving studies which have been conducted since the initial alcohol calibration study.
Methods
The present study pooled data of 182 participants from nine placebo-controlled crossover studies who performed the highway driving test, while their BAC was at or just below the legal limit for drivers (i.e., 0.5 g/L).
Results
Overall, mean SDLP increased with 2.5 cm (95% CI 2.0–2.9 cm). Equivalence testing showed that the clinical relevance criterion value of 2.4 cm fell well within the 95% CI in each individual study. Gender did not affect alcohol-induced changes in SDLP.
Discussion
These results demonstrate the robustness and validity of the clinical relevance criterion for SDLP as measured during on-the-road driving.
•Sleep deprivation and time on task induce real highway driving impairments.•Time on task effects during real driving are more evident after sleep deprivation.•Time on task effects on theta activity ...are more evident after sleep deprivation.•Electroencephalography is not appropriate to predict on-the-road driving performance.
The present study mainly aimed to assess whether and how sleepiness due to sleep deprivation interacts with Time on Task (ToT) effects both on electroencephalography (EEG) measures and driving performance in real driving conditions. Healthy participants performed a one hour on-the-road monotonous highway driving task while EEG was recorded continuously after one night of normal sleep and after one night of total sleep deprivation. The main outcome parameter in the highway driving test was the Standard Deviation of Lateral Position (SDLP). SDLP and EEG indices (i.e alpha and theta power spectra) increased after sleep deprivation and varied with ToT. The latter was more pronounced after sleep deprivation. Beta power spectra did not differ between conditions but increased with ToT. Changes in SDLP and EEG did not correlate significantly. We conclude that driving performance as well as fatigue and sleepiness fluctuations with ToT were more evident after sleep deprivation as compared to normal sleep.
The aim of this study was to assess the effects of a novel antidepressant, vortioxetine 10 mg, on driving, cognitive, and psychomotor performance in 24 healthy subjects in a double‐blind, ...placebo‐controlled, three‐way crossover design. Mirtazapine 30 mg was included as an active comparator. Drugs were administered in the evening of 15 consecutive days. Performance was measured in the morning of days 2 and 16, using standardized tests measuring on‐the‐road driving, memory, tracking, divided attention, and vigilance. The statistical analysis on the primary measure of driving, i.e., SD of lateral position showed noninferiority of vortioxetine on days 2 and 16, and inferiority for mirtazapine on day 2. Vortioxetine did not cause cognitive or psychomotor impairment. Mirtazapine, however, impaired cognitive and psychomotor performance on day 2. Most of these effects disappeared after multiple doses of mirtazapine. To conclude, vortioxetine did not impair driving, cognitive, or psychomotor performance after single or multiple doses.
Clinical Pharmacology & Therapeutics (2013); 93 6, 493–501. doi:10.1038/clpt.2013.39
Objective
Screening of drug-induced performance impairment is needed to provide meaningful information for users and prescribers regarding the impact of drugs on driving. The main objective was to ...assess the effects of oxazepam 10 mg (OXA10), oxazepam 30 mg (OXA30), and diazepam 10 mg (DIA10) on standard deviation of lateral position (SDLP) in a highway driving test in actual traffic and to determine the ability of eight neurocognitive tests to detect comparable effects.
Methods
Twenty-three healthy volunteers participated in a four-way double-blind, placebo-controlled, crossover study. The highway driving test was conducted between 4 and 5 h after drug intake. A range of neurocognitive tests was conducted before and after driving, 2 and 6 h post-treatment, respectively.
Results
Mean SDLP increased by 1.83, 3.03, and 7.57 cm after OXA10, DIA10, and OXA30, respectively. At 2 h post-treatment, all neurocognitive tests, except the useful field of view, showed performance impairment in all active treatments. Effect sizes (ES) were moderate for OXA10, large ES for DIA10, and largest ES for OXA30. Modest correlations were found between changes in SDLP and performance in the attention network test (ANT), the divided attention test (DAT), and the psychomotor vigilance test (PVT).
Conclusion
OXA10 caused minor, DIA10 moderate, and OXA30 severe driving impairment. No neurocognitive test was both dose dependently sensitive and able to be associated with driving impairment. No neurocognitive test can replace the on-the-road highway driving test.
Background
Standard deviation of lateral position (SDLP) has been accepted as a reliable parameter for measuring driving impairment due to lowered vigilance caused by sleepiness or the use of ...sedating drugs. Recently, lane drifts were proposed as an additional outcome measure quantifying momentary lapses of attention. The purpose of this study was to validate lane drifts as outcome measure of driver impairment in a large data pool from two independent research centers.
Methods
Data from 11 placebo-controlled studies that assessed the impact of alcohol, hypnotics, and sleep deprivation on actual driving performance were pooled. In total, 717 on-the-road tests performed by 315 drivers were subjected to an automated algorithm to detect occurrences of lane drifts. Lane drifts were defined as deviations > 100 cm from the mean (LD
mlp
) and from the absolute lateral position (LD
alp
) for 8 s.
Results
The number of LD
mlp
was low and did not differ between treatments and baseline, i.e., 14 vs. 3 events, respectively. LD
alp
were frequent and significantly higher during treatment relative to baseline, i.e., 1646 vs. 470 events. The correlation between LD
alp
and SDLP in the treatment conditions was very high (r
s
= 0.77). The frequency of the occurrence of treatment-induced lane drifts however depended on baseline SDLP of drivers, whereas treatment-induced changes in SDLP occurred independent of baseline SDLP.
Conclusion
LD
mlp
is not useful as an outcome measure of driver impairment due to its rare occurrence, even when treatment-induced increments in SDLP are evident. Treatment effects on LD
alp
and SDLP are closely related.
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