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Background: Nightclubs and bars are recreational settings with extensive availability and consumption of alcohol and recreational drugs., Objectives: This study aims to determine the proportion of nightclub patrons in Norway that tested positive for illicit drugs, moreover, we examined the correlation between positive test results and demographic and substance use characteristics., Methods: Patrons were recruited outside nightclubs on Friday and Saturday nights between 10:00 pm and 04:00 am. Substance use was determined by breath testing and oral fluid testing for alcohol and drugs, respectively, using accurate and specific analytical methods. Questionnaires recorded demographic and substance use characteristics., Results: Of the 1988 included nightclub patrons, 90% tested positive for alcohol, 14% for illicit drug use, and 3% for two or more illicit drugs. The proportion of patrons who tested positive for illicit drugs was highest in the early hours of the morning. Nine out of ten who tested positive for illicit drugs also consumed alcohol. Testing positive for one or more illicit drugs was most strongly correlated with being male and unemployed, using tobacco or other nicotine products, and early on-set illicit drug use; further the correlations were strongest among those who tested positive for two or more illicit drugs. Conclusions/Importance: Patrons who used illicit drugs before or during nightclub visits most often combined drug use with alcohol consumption. Substituting alcohol with cannabis or other drugs was not common in this cohort. The study results provide evidence to introduce harm-reduction prevention programs to address illicit drug and excessive alcohol consumption.

Objective: To study the prevalence of alcohol and drugs in biological samples from drivers, motorcycle riders, bicyclists, and pedestrians involved in fatal road traffic crashes (RTCs) during 2016-2018 in Norway, both among fatally injured victims and those who survived fatal RTCs., Methods: Anonymous information was extracted from police data. No personal data were recorded., Results: There were 330 fatal RTCs with 349 killed road users and 384 survivors during the study period; this included 179 passengers who were excluded from the study. In total, 90% of the studied killed road users and 67% of the survivors were investigated for alcohol or drug use by analyzing biological samples. Alcohol or drugs in concentrations above the legal limits were detected in 21% of the analyzed samples. The proportion impaired by alcohol or drugs (blood alcohol concentrations equal to or greater than 0.05%, or drug concentrations above equivalent limits) was highest among killed bicyclists (43%), higher than among killed pedestrians (24%), car and van drivers (28%) and motorcyclists (20%), and significantly higher than among drivers who survived fatal crashes (4%)., Conclusions: Impairment due to use of alcohol or drugs was often a contributing factor among bicyclists, pedestrians and motor vehicle drivers who died in RTCs. Driving under the influence of alcohol or drugs was more often a contributing factor in cases where the motor vehicle driver was killed than in cases where the driver survived.

Background: Pedestrian and cyclist injuries are a major concern globally, but especially in low-income countries. Locally conducted research is needed to measure the size of the problem and advise policy on road safety interventions. We wanted to investigate the precise circumstances of these injuries in Lilongwe, Malawi and to identify risk factors for severe injuries., Methods: Cross-sectional study of all adult pedestrian and cyclist injuries presenting to a large central hospital. This was a sub-study of a larger study with all types of road users included. All patients provided detailed information about the incidents leading to injury and were tested for alcohol., Results: There were 222 pedestrians, 183 bicycle riders and 42 bicycle passengers among the 1259 adult road traffic injury victims that were treated at Kamuzu Central Hospital during a 90-day period in 2019. Of these injuries, 60.2% occurred while the victim was walking/cycling along the road and 22.3% when the victim was trying to cross the road. The majority of the victims were men (89.1%). Helmet use for bicyclists was almost non-existent. Only 1 patient had used reflective devices when injured in the dark, despite 44.7% of these injuries occurring in reduced light conditions. There was an increased risk for serious and fatal injuries for pedestrians compared with bicyclists, and also compared with all types of road users. Patients injured in rural areas and those hit by lorries were more severely injured. Consuming alcohol before being injured was associated with more severe injuries in bicyclists. Being injured while crossing the road at painted zebra crossings was associated with an increased risk of serious and potentially fatal injuries., Conclusion: This study identified important risk factors for severe injuries in pedestrians and cyclists. Implications for preventive measures are presented in a Haddon Matrix., (© 2020 The College of Medicine and the Medical Association of Malawi.)

Purpose: To report a case of peripheral ulcerative keratitis secondary to atypical hemolytic uremic syndrome., Methods: We report the case of a 76-year-old man who presented with bilateral aggressive peripheral ulcerative keratitis. Clinical examinations and investigations are reported from the patients' admission., Results: The patient had an extended workup for autoimmune and infectious etiologies that all returned negative. The laboratory work in conjunction with renal biopsy and clinical symptoms were consistent with atypical hemolytic uremic syndrome. The patient was treated with systemic steroids for his peripheral ulcerative keratitis and underlying systemic disease. Corneal glueing and amniotic membrane grafting was also performed., Conclusions: To our knowledge, we report the first known case of peripheral ulcerative keratitis secondary to atypical hemolytic uremic syndrome. In cases where the standard workup is negative, this diagnosis should be considered because it can have significant systemic morbidity.

Background: The ratio between the concentrations of drugs in the oral fluid and blood (OF/B ratio) reflects the transfer of drugs from blood to oral fluid, which is influenced by several factors such as oral fluid contamination. OF/B drug concentration ratios for psychoactive drugs, including interindividual variation, were investigated in this study. For a portion of the material, oral fluid concentrations in both sides of the mouth were compared., Methods: Samples of whole blood and oral fluid collected using the Intercept device were obtained from 489 suspected drugged drivers. Concentrations of amphetamine, methamphetamine, THC, diazepam, N-desmethyldiazepam, clonazepam, alprazolam, oxazepam, nitrazepam, morphine, buprenorphine, and methadone were determined in blood and oral fluid samples using liquid chromatography-tandem mass spectrometry., Results: Median OF/B ratios were 18.6 for amphetamine, 13.8 for methamphetamine, 3.8 for morphine, 24.8 for buprenorphine, 3.7 for methadone, 0.026 for diazepam, 0.031 for N-desmethyldiazepam, 0.28 for alprazolam, 0.16 for clonazepam, 0.12 for oxazepam, 0.099 for nitrazepam, and 4.3 for THC. Large interindividual variations in OF/B ratios were observed. The median difference in concentrations in oral fluid from both sides of the mouth was less than 20% for all drugs, except THC and buprenorphine, which had median differences of 32%-34%., Conclusions: High OF/B ratios were found for amphetamines and opioids, reflecting a high degree of drug transfer from blood to oral fluid and a longer detection window in oral fluid than in blood. For benzodiazepines, low OF/B ratios were found. Results of the concentration measurements in oral fluid from both sides of the mouth could indicate that some remnants of THC and buprenorphine were present in the oral cavity. The large variations among individuals and between the 2 sides of the mouth suggest that drug concentrations in oral fluid do not accurately reflect drug concentrations in the blood.

Ergonomics has gained increasing recognition as an integral component of career longevity in ophthalmology. Residents and fellows may encounter unique ergonomic challenges when learning surgical techniques. A systematic review of the literature, specifically looking for recommendations on optimizing ergonomics in the operating room (OR) and articles that explicitly mentioned suggestions for trainees, was conducted. Of the identified 41 pieces of literature, 31 specifically mentioned ergonomics in the OR, 10 discussed vitreoretinal surgery, 2 mentioned strabismus surgery, and 2 described ergonomics in oculoplastics surgeries. Only 9 of the 41 articles explicitly mentioned either residents or fellows. Based on this review, as well as anecdotal experience, recommendations for residents, fellows, and staff ophthalmologists while working in the OR were compiled. To help offset risk for musculoskeletal injury, recommendations related to relaxation, movement, and maintenance of ergonomic focus are proposed. In addition, methods to optimize ergonomics for the patient, surgeon, surgical bed, foot pedals, surgeon's chair, and the microscope are identified. Trainees may be at particular risk for injury owing to their placement at the surgical bed, and the fact that they may be less likely to get set up ergonomically either owing to a lack of awareness and teaching on the subject, or secondary to perceived time pressures in the OR. Ergonomics should ideally be considered across all domains of life, including in the OR, clinic, and office and at home. The earlier proper positioning is adopted and becomes habitual, the less likely potentially career-threatening musculoskeletal disorders will develop., (Copyright © 2020 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Background/aim: Drug use and risky driving is associated with sensation seeking. The aim of this study was to investigate the association between use of psychoactive substances and levels of the sensation seeking personality trait as measured with the Brief Sensation Seeking Scale 4 among drivers in Norway., Method: A cross-sectional design was applied to estimate the association between psychoactive substance use and sensation seeking behavior. Drivers in normal traffic were included in two roadside surveys: one in the north (September 2014 - October 2015) and the other in the south-east of Norway (April 2016 - April 2017). Oral fluid was analyzed for alcohol and psychoactive drugs, and data on sex, age and time of participation were recorded. Participants filled in the Brief Sensation Seeking Scale 4 questionnaire., Results: A total of 8053 drivers were included, of which 32% were women and 62% were under 40 years. The prevalence of alcohol was 0.3%, stimulants 0.6%, tetrahydrocannabinol 1.4%, benzodiazepines and/or z-hypnotics 2.0% and polydrug use 0.6%. Associations were found between the use of tetrahydrocannabinol or benzodiazepines and/or z-hypnotics and a low score on the "thrill and adventure seeking" domain of the Brief Sensation Seeking Scale 4 (OR = 1.723, 95% C.I. = 1.001-2.966). Associations were also found between the use of stimulants and the highest scores on the "experience seeking" (OR = 2.085, 95% C.I. = 1.084-4.009) and "disinhibition" (OR = 4.791, 95% C.I. =1.748-13.135) domains of the Brief Sensation Seeking Scale 4. No associations were found between sensation seeking behavior and alcohol or polydrug use., Conclusion: A high degree of sensation seeking was found among drivers who had used stimulating drugs, in contrast to drives who had used tetrahydrocannabinol and benzodiazepines and/or z-hypnotics who showed a low degree of sensation seeking. The combination of sensation seeking behavior and the use of stimulants might lead to increased risky behavior and thus traffic crashes.

Background: Alcohol consumption is a well-known risk factor for sustaining road traffic injuries worldwide. Malawi is a low-income country with a large and increasing burden of road traffic injuries. It has generally been viewed as a country with relatively little alcohol consumption. This study investigates the role of alcohol in road traffic injuries in and around the capital Lilongwe., Methods: All patients presenting to the emergency department of Kamuzu Central Hospital after being injured in road traffic crashes were asked to participate in the study. Alcohol testing was done with a breathalyzer or a saliva test. Participants were asked about alcohol use before the injury as well as hazardous drinking using the AUDIT-C questionnaire., Results: Of 1347 patients age 18 years or older who were asked to participate, 1259 gave informed consent, and data on alcohol use (alcohol test results and/or self-reported intake) were available for 1251 participants. Of those, 251 (20.1%) tested positive for alcohol, whereas 221 (17.7%) reported alcohol use before the crash; in total 311 (24.9%, 95% CI 22.5-27.3) either tested positive, reported use, or both. Females had a low prevalence of alcohol use (2.5%), while 30.6% of males had consumed alcohol before the injuries. Pedestrians had the highest prevalence at 41.8% (95% CI 35.5-48.4), while car drivers had 23.8% (95% CI 18.2-30.5). Among male pedestrians, 49.5% had used alcohol before the injury. Alcohol-associated injuries had a peak in the evening and at night, especially in the weekends. Of the patients, 63.1% reported that they had not consumed alcohol during the last year, while 21.4% had an AUDIT-C score suggesting hazardous drinking, and 66.2% of those had used alcohol before the injury., Conclusions: A large percentage of road traffic injured patients had been drinking alcohol before their injury, especially male pedestrians. A large proportion of the patients were abstaining from alcohol, but those not abstaining had a high prevalence both of alcohol use when injured and hazardous drinking identified by AUDIT-C. This has important implications for prevention.

Objective: To investigate whether the use of recommended therapeutic doses of medicinal drugs has led to suspicion of driving under the influence of drugs (DUID) after implementation of legislative limits for illicit and medicinal drugs in 2012. Methods: Data from suspected drug-impaired drivers apprehended by the police from 2013 to 2015 were selected from the Norwegian Forensic Toxicology Database. The blood samples had been analyzed for benzodiazepines (BZDs), z-hypnotics, opioids, stimulants, certain hallucinogens, and alcohol. Drivers who tested positive for one BZD or a z-hypnotic only, were included in the study. Drug concentrations measured in their blood samples were compared to the maximal obtainable steady state concentrations if the drug had been used in accordance with the recommendations set by the Norwegian Directorate of Health. Results: BZDs or z-hypnotics were found in 10 248 samples, representing 59.6% of the total number of drivers arrested for suspected DUID (n = 17 201). Only one BZD or z-hypnotic with a blood drug concentration above the legislative limit was detected in 390 (2.3%) of the total number of samples. Clonazepam was the most frequently detected BZD (n = 4656), while as a single drug above the legislative limit, it was detected in only 3.6% (n = 168) of the clonazepam-positive blood samples. For drivers testing positive for only one z-hypnotic, drug concentrations above the legislative limit were found in 27% (n = 55) of the blood samples that tested positive for zolpidem and 12.4% (n = 53) of the samples that tested positive for zopiclone. In total, 155 subjects out of 10 248 testing positive for BZDs or z-hypnotics displayed concentrations above the legislative limit but within the concentration ranges that are expected when taking recommended therapeutic drug doses, and 77 below the legislativel limit. Conclusions: The results show that the implementation of legislative limits for BZDs and z-hypnotics may have contributed to DUID suspicion for a small group of patients using therapeutic drug doses; only 1.3% of the suspected DUID offenders had concentrations of only one of those drugs in-line with recommended therapeutic dosing.

Background: Familial exudative vitreoretinopathy (FEVR) is a rare congenital disorder characterized by a lack of blood vessel growth to the periphery of the retina with secondary fibrovascular proliferation at the vascular-avascular junction. These structurally abnormal vessels cause leakage and hemorrhage, while the fibroproliferative scarring results in retinal dragging, detachment and blindness. Mutations in the FZD4 gene represent one of the most common causes of FEVR., Methods: A loss of function mutation resulting from a 10-nucleotide insertion into exon 1 of the zebrafish fzd4 gene was generated using transcription activator-like effector nucleases (TALENs). Structural and functional integrity of the retinal vasculature was examined by fluorescent microscopy and optokinetic responses., Results: Zebrafish retinal vasculature is asymmetrically distributed along the dorsoventral axis, with active vascular remodeling on the ventral surface of the retina throughout development. fzd4 mutants exhibit disorganized ventral retinal vasculature with discernable tubular fusion by week 8 of development. Furthermore, fzd4 mutants have impaired optokinetic responses requiring increased illumination., Conclusion: We have generated a visually impaired zebrafish FEVR model exhibiting abnormal retinal vasculature. These fish provide a tractable system for studying vascular biology in retinovascular disorders, and demonstrate the feasibility of using zebrafish for evaluating future FEVR genes identified in humans., (© 2019 Wiley Periodicals, Inc.)

Fatal road traffic crashes are often related to speeding, non-use of a seatbelt, and alcohol/drug-impaired driving. The aim of this study was to examine associations between driving under the influence of drugs and/or alcohol and driver-related risk factors that have been reported as significantly contributing causes of fatal road traffic crashes. The data were extracted from Norwegian road traffic crash registries and forensic toxicology databases. Drug/alcohol investigated car and van drivers and motorcycle riders fatally injured in road traffic crashes in Norway during 2005-2015 were included in this study (n = 772). Drug and alcohol concentrations corresponding to 0.5 g/kg alcohol in blood were used as the lower limits for categorising drivers/riders as impaired; 0.2 g/kg was the upper limit for being categorised as sober. Associations between driver-related risk factors and impairment from specific substance groups were calculated using multivariable logistic regression, adjusted for other substance groups, age, and sex, and were reported when the confidence intervals did not contain the value 1 or lower. Substances found in concentrations above the impairment limits were mainly alcohol (20%), medicinal drugs (10%: benzodiazepines, opioids, z-hypnotics), stimulants (5%: amphetamines, methylphenidate, and cocaine), and cannabis (4%: THC). The drug/alcohol-impaired drivers had compared to the sober drivers more often been speeding (68% versus 32%), not used a seatbelt (69% versus 30%), and been driving without a valid driver license (26% versus 1%). Logistic regression analysis showed that impairment from alcohol or stimulants (mainly amphetamines) was associated with all three risk factors, medicinal drugs with all except speeding, and impairment from cannabis (THC) with not having a valid driver license. Among motorcycle riders, drug/alcohol impairment was associated with not having a valid driver license and non-use of a helmet. At least one of the risk factors speeding, non-use of a seatbelt/helmet, and driving without a valid license were present among the vast majority of the drug/alcohol-impaired fatally injured drivers and riders, and also among more than half of the fatally injured sober drivers., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose: We aimed to study the pharmacokinetics of methadone and buprenorphine in blood and oral fluid after single-dose administration and investigate correlations between concentrations in blood and neurocognitive functions., Methods: A 5-way, double-blind, randomized, placebo-controlled, double-dummy, crossover study was performed to study the pharmacokinetics and neurocognitive effects of methadone (5 and 10 mg per oral) and buprenorphine (0.2 and 0.4 mg sublingual) in 22 healthy volunteers. Blood and oral fluid were collected throughout the test days, and drug concentrations in both matrices were analyzed using ultrahigh-performance liquid chromatography-tandem mass spectrometry. On-road driving testing, neurocognitive computerized tests, and subjective questionnaires were performed., Results: Large individual variations in concentrations of methadone and buprenorphine in blood and oral fluid, and accordingly oral fluid/blood drug concentration ratios, were observed. The mean ratio 6.5 hours after drug administration was 2.0 (range, 0.49-7.39) for methadone after both doses. Buprenorphine was not detected above the limit of quantification in blood after 6.5 hours. No significant correlation between methadone concentration in blood and effect was found. Significant correlations were found between buprenorphine concentration in blood and standard deviation of lateral position in the driving test and some measures of reaction time, divided attention, balance, alertness, contentedness. and sleepiness., Conclusions: Concentrations of methadone and buprenorphine in blood and oral fluid showed large interindividual variations. No concentration-effect correlations were found for methadone, whereas low to moderate correlations were observed between buprenorphine concentration and driving, psychomotor function, and subjective rating of sleep and alertness.

Aims: Illegal substance use at music festivals is less documented than it is in nightlife and electronic dance music settings. This study investigated such use through questionnaires, breathalysers and oral fluid drug testing. We also examined the associations between testing positive for illegal substances and demographics, self-reported substance use and measured blood alcohol concentration levels., Methods: A cross-sectional study of 1,309 festival attendees from six Norwegian music festivals taking place between July and August 2016. Logistic regression models estimated the likelihood of a positive oral fluid drug test. Covariates were male, age, education, employment, smoking status, early age for alcohol intoxication, alcohol intoxication ⩾2 times a week, past-month and past-year illegal substance use, blood alcohol concentration levels and festivals., Results: Overall, 12% reported illegal substance use in the past 30 days and 11% tested positive for illegal substances. Cannabis (6%), cocaine (3%) and MDMA/ecstasy (2%) were most commonly detected. One-third had a blood alcohol concentration ⩾0.10%. Of those with a positive test result ( n=146), 95% had detectable alcohol levels and 41% had a blood alcohol concentration above 0.10%. Those studying or working part-time were less likely to test positive compared to those who were not employed. Furthermore, those reporting daily smoking and past-year cannabis or MDMA/ecstasy use were more likely to test positive, compared to those not reporting such use., Conclusions: Illegal substance use was less prevalent than in previous nightlife and electronic dance music studies. Almost all those testing positive for illegal substances had detectable alcohol levels and 41% had a blood alcohol concentration greater than 0.10%, possibly indicating combined use.

Simultaneously collected samples of oral fluid and blood in a naturalistic setting could provide a qualitative impression of the relative detection times of drugs in oral fluid compared to blood. The aim of this study was to compare detections of different drugs in oral fluid and blood from a large material of paired samples. The study included results from 930 paired oral fluid and blood samples collected from drivers suspected for driving under the influence of drugs. Oral fluid was collected using the Intercept device. Blood samples were screened using an ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS-MS) method and positive results were confirmed and quantified with a different analytical method. Oral fluid samples were analyzed using UHPLC-MS-MS. The drugs included in the study were: amphetamine, methamphetamine, tetrahydrocannabinol (THC), diazepam, N-desmethyldiazepam, clonazepam, alprazolam, nitrazepam, oxazepam, morphine, 6-monoacetylmorphine (6-MAM), methadone and buprenorphine. The drugs detected more frequently in oral fluid compared to blood were amphetamine (497 positive in oral fluid/408 positive in blood), methamphetamine (332/232), oxazepam (106/36), morphine (65/31) and 6-MAM (19/0). The drugs detected less frequently in oral fluid compared to blood were THC (224 positive in oral fluid/407 positive in blood), diazepam (137/160), N-desmethyldiazepam (183/188), clonazepam (148/307), alprazolam (47/68), nitrazepam (16/29) and buprenorphine (31/59). For methadone, the number of detections was the same in oral fluid and in blood (23/23). The results indicate that for amphetamine, methamphetamine, morphine and 6-MAM, relative detection time is longer in oral fluid than in blood, while for benzodiazepines, the results indicate that relative detection time is shorter in oral fluid than in blood. For oxazepam and buprenorphine, the results were dependent on the cut-off limits used. Regarding THC, the detection time in oral fluid depends on the sampling method. The relative detection time was shorter than in blood when using the Intercept device., (© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Aims: The present study assessed the acute effects of methadone and buprenorphine on actual on-road driving performance and neurocognitive function., Methods: Methadone (5 and 10 mg per os) and buprenorphine (0.2 and 0.4 mg sublingual) were administered to 22 healthy volunteers in a five-way, double-blind, randomized, placebo-controlled, double-dummy, cross-over study. Driving performance was assessed with an on-road driving test. The primary outcome measure was standard deviation of lateral position (SDLP), a measure of road tracking control. Laboratory tests were used to measure cognitive function (e.g. reaction time and attention) and questionnaires were used to assess subjective measures of mood and sedation., Results: There was no significant main effect of treatment on SDLP. Yet, analysis of individual drug-placebo contrast data revealed that buprenorphine 0.4 mg significantly increased SDLP. Driving impairment was mild and below the impairment threshold of a blood alcohol concentration of 0.5 mg ml -1 . Four participants stopped their driving test while under the influence of either opioid due to sleepiness. Both opioids produced impairments of cognitive task performance and increased sleepiness particularly at the highest dose., Conclusions: Analgesic doses of buprenorphine produced mild impairing effects on driving and related cognitive skills, while methadone impaired cognitive task performance but not driving performance. Large individual variations were observed for both drugs. Patients should be informed about the possibility of driving impairment when initiating opioid treatment., (© 2018 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Objectives: The rate of deaths caused by road traffic crashes is particularly high in rural areas. It has been hypothesised that one factor that may contribute is differences in patterns of alcohol use. The aim was to compare the prevalence of psychoactive substances among crash-involved drivers arrested for suspicion of driving under the influence (DUI) who are tested for alcohol and drugs and recent random drivers in a rural area. Furthermore, we investigated the association between traffic crashes and driving after using alcohol, illicit or medicinal drugs either alone or in combination., Methods: A case-control study was carried out in which the case group consisted of crash-involved drivers arrested for suspicion of DUI from 2000 to 2015. This group was compared with a control group of randomly selected drivers recruited to a roadside survey in normal traffic from 2014 to 2015. The case group consisted of 612 individuals (542 men and 70 women) and the control group of 3027 individuals (2099 men and 927 women). Drug and alcohol screening was performed on blood samples from the cases and samples of oral fluid from the controls., Results: The proportion of psychoactive substances was 81.7% among cases and 1.6% among the controls. The prevalence of combinations of psychoactive substances was 18% among the cases and 0.3% among the controls. The multivariate regression model analysis identified significant drug interactions., Conclusion: The prevalence of alcohol and drugs was high among the crash-involved drivers arrested for suspicion of DUI by the police. In contrast to earlier published research combinations of different psychoactive substances did not increase the OR for traffic crash involvement more than the single drug with highest OR. The statistical methodology presented in this study should be allied in future studies with greater statistical power to confirm these findings., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Road traffic crashes (RTCs) are responsible for a large number of deaths worldwide, but low- and middle-income countries frequently present higher rates of deaths; for example, Norway, a high-income country, has a rate of 2.0 drivers killed per 100,000 inhabitants, whereas Brazil, a middle-income country, has a rate of 18.4. A significant fraction of RTCs are related to use of psychoactive substances, especially alcohol, due to its availability, legality, and relatively low price. The aim of the present study was to evaluate differences in alcohol-related fatal RTCs in Sao Paulo, the largest city in Brazil, and Norway during an 11-year period (2005-2015). Methods: The authors compared databases of drivers killed in RTCs in Sao Paulo and in Norway, a country renowned for its success in reducing traffic fatalities and keeping them at a low level. Results: In total, 772 victims from Norway (11 years, 2005 to 2015) and 584 victims from Sao Paulo (2 years, 2005 and 2015) were analyzed. Sao Paulo presented higher proportions of motorcycle drivers, men involved in RTCs, and blood alcohol concentration (BAC)-positive cases. The mean BAC for alcohol-positive cases was similar in both sites. For both regions, the percentage of alcohol-positive cases decreased during the study period (from 45.6% to 35.3% in Sao Paulo and from 24.4% to 15.8% in Norway) but remained higher for Sao Paulo. Conclusions: The study shows a different profile of RTC victims and higher alcohol consumption among drivers in Sao Paulo. The differences between the sites can possibly be attributed to public policies regarding traffic safety and alcohol control, which could be further improved by following the Norwegian model in Sao Paulo.

Background and Objectives: Even though nightlife studies with potentially intoxicated participants provide the much needed information on drug use, they face additional methodological challenges. This study aimed to explore the utility of such studies by (i) classifying nightlife attendees based on their self-reported drug use and by (ii) examining whether these classifications were meaningful when assessed against other sources of data, including oral fluid drug tests., Methods: Self-reported questionnaires, oral fluid samples and blood alcohol concentration readings were collected in a sample of 1,085 nightlife patrons recruited outside 12 popular nightclubs in Oslo, Norway, in 2014. Patrons were classified using multiple approaches, including latent class analysis. Group differences were examined by logistic regression models., Results: Participants were classified into 5 mutually exclusive groups: 2 among current non-users ("Never-users"; "Previous users"), 2 among current users ("Multiple drugs"; "Cannabis mainly") and one "Incomplete information" group. Meaningful differences across these groups were observed. For instance, positive tests for any illicit drug were more common in "Multiple drugs" group than in "Cannabis mainly" (62.7 vs. 29.1%, adjusted OR [aOR] 3.77 [2.42-5.84]) or "Incomplete information" groups (62.7 vs. 34.4%, aOR 2.46 [1.26-4.79]). Despite their self-declared non-use, illicit substances were detected in oral fluids of "Never-users" (13.1%; 95% CI 9.9-17.2) and "Previous users" (7.9%; 95% CI 5.1-12.1)., Conclusions: Despite some discrepancies between self-reports and biological tests, self-reports proved both suitable and useful in identification of substantively different drug-user typologies, potentially informing targeted policy responses. Still, methodological challenges associated with onsite studies of illicit drug use should be further explored., (© 2019 S. Karger AG, Basel.)

Background: Use of illicit substances is often under-reported. Testing positive in oral fluid provides an objective confirmation of recent intake., Objectives: To examine the agreement between oral fluid test results and self-reported substance use among music festival attendees, and factors associated with reporting past 48 h drug use among users identified by drug testing., Methods: One thousand three hundred nine participants were recruited from six music festivals in Norway (June-August 2016). They completed a questionnaire and provided oral fluid samples analyzed for amphetamines, MDMA, tetrahydrocannabinol (cannabis), and cocaine. Additionally, their blood alcohol levels were measured., Results: Overall, 5.5% reported use of amphetamines, cannabis, cocaine, and/or MDMA during past 48 h in the questionnaire, whereas 10.8% tested positive in oral fluid. Only 16.7% of identified cocaine users and 31.1% of identified MDMA users reported past 48 h cocaine or MDMA use, respectively. Higher proportions of identified cannabis and amphetamine users reported past 48 h use (53.8% and 55.6%, respectively). Multivariable logistic regression analysis showed that among participants who tested positive, those reporting weekly illicit substance use (Adjusted Odds Ratio [AOR] 30.6; 95% Confidence Interval [CI] 6.3-147.9), and using such substances when younger than 18 years (AOR 5.0; 95% CI 1.9-13.4) were more likely to report past 48 h use. Conclusions/Importance: Oral fluid testing appears to be an important tool when studying illicit substance use among music festival attendees, as significant under-reporting was observed. Among those testing positive, regular, and experienced users were more likely to report recent use, compared to less regular and experienced users.

Background: Self-reported data are commonly used when investigating illicit substance use. However, self-reports have well-known limitations such as limited recall and socially desirable responding. Mislabeling or adulteration of drugs on the illicit market may also cause incorrect reporting. Objectives: We aimed to examine what could be gained in terms of illicit drug use findings among music festival attendees when including biological sample test results in the assessment. Methods: We included 651 attendees at three music festivals in Norway from June to August 2016. Self-reported drug use was recorded using questionnaires, and samples of oral fluid were analyzed to detect use of illicit drugs. In addition, we analyzed samples of pooled urine from portable toilets at each festival. Results: All methods identified cannabis, MDMA, and cocaine as the most commonly used drugs. Overall, 6.6% of respondents reported use of illicit substances during the previous 48 hours. Oral fluid testing identified a larger number of drug users as 12.6% tested positive for illicit drugs. In oral fluid testing, we identified ketamine and three new psychoactive substances (NPS) that had not been reported on the questionnaire. In pooled urine testing, we identified amphetamine and three additional NPS that were neither reported used nor found in oral fluid samples. Conclusions/Importance: Drug testing of biological samples proved to be an important supplement to self-reports as a larger number of illicit substances could be detected.

Objective: Truck drivers represent a group that is susceptible to the use of stimulant substances to reduce the symptoms of fatigue, which may be caused by a stressful and exhausting work environment. The use of psychoactive substances may increase the risk for involvement in road traffic crashes. Previous studies have demonstrated that amphetamine, cocaine, and cannabis are the 3 main drugs used by Brazilian truck drivers. We studied the prevalence of amphetamine, benzoylecgonine (indicating use of cocaine), and Δ-9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH; indicating use of cannabis) in urine samples from truck drivers in the state of São Paulo, Brazil, using the same methodology during 8 years (2009-2016)., Methods: Samples were collected during a health program supported by the Federal Highway Police. Toxicological analyses were performed using immunoassays and gas chromatography-mass spectrometry., Results: The total prevalence of illicit drugs was 7.8%. Benzoylecgonine was the most prevalent substance (3.6%), followed by amphetamine (3.4%) and THC-COOH (1.6%). We found the highest drug prevalence in 2010 (11.3%) and the lowest in 2011 (6.1%). We could detect a slight change in the pattern of stimulant use: until 2010, amphetamine was the most prevalent substance; however, in 2011 benzoylecgonine became the most frequently detected substance. This lasted until 2015, probably due to changes in Brazilian legislation regarding appetite suppressants; the most common one is metabolized to amphetamine., Conclusion: These data show that the use of psychoactive substances by truck drivers in Brazil did not decrease during the study period. This reinforces the need for further preventive measures to reduce drug use among drivers, which could lead to a decrease in traffic crashes in Brazil.

Objective: Norway introduced a "Vision Zero" strategy in 2001, using multiple approaches, aiming toward a future in which no one will be killed or seriously injured in road traffic crashes (RTCs). Official statistics show that the number of fatally injured road users has declined substantially from 341 deaths in 2000 to 117 in 2015. In-depth crash investigations of all fatal RTCs started in Norway in 2005. The aim of this study was to investigate whether fatal crash characteristics, vehicle safety features, and prevalence of drugs and/or alcohol among fatally injured drivers and riders has changed during 2005-2015, accompanying the reduction in road fatalities. Methods: Data on all car/van drivers and motorcycle/moped riders fatally injured in RTCs during 2005-2015 were extracted from Norwegian road traffic crash registries and combined with forensic toxicology data. Results: The proportion of cars and motorcycles with antilock braking systems and cars with electronic stability control, increased significantly during the study period. The prevalence of nonuse of seat belts/helmets and speeding declined among both fatally injured drivers and riders. In addition, the prevalence of alcohol declined, though no significant change in the total prevalence of other substances was noted. Conclusion: The observed changes toward more safety installations in cars and motorcycles and lower prevalence of driver-related risk factors like alcohol use, speeding, and nonuse of seat belts/helmets among fatally injured drivers/riders may have contributed to the decrease in road traffic deaths.

Purpose: To determine and discuss common weaknesses and errors in case-control studies on the association between drug use and road traffic crash injury among drivers and recommend improvements for future studies., Methods: A search for case-control studies published between 2000 and 2016 was performed using PubMed and other databases in addition to manual search. The used methodologies were compared with requirements and recommendations for case-control studies as well as current knowledge on the interpretation of drug concentrations in biological samples., Results: Seventeen studies were identified. The major difficulties in the studies were related to likely selection bias, information bias, and confounding. In some studies, the definition of drug exposure was different for controls than for cases, generating potentially serious errors in the odds ratio estimations. Other weaknesses include lacking explanation of the assessment of drug exposure, missing covariates, lacking description of statistical methods, and lack of discussion of bias and confounding., Conclusions: Many of the observed challenges and weaknesses can be overcome or reduced. Recommendations for future studies are presented., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Cocaine is a potent stimulant drug widely abused that exists in two forms: as a hydrochloride salt and as a free base (crack). Cocaine and the inactive metabolite benzoylecgonine can be determined to reveal any kind of cocaine use, whereas the pyrolysis product anhydroecgonine methyl ester (AEME) can be determined to reveal crack smoking. There are many bioanalytical LC-MS/MS methods used for the determination of cocaine, metabolites and AEME. In these methods, chromatographic separation is usually performed by HPLC and sample preparation by solid phase extraction. For the first time, an UHPLC-MS/MS method for the simultaneous determination of cocaine, benzoylecgonine, cocaethylene and AEME in blood using a sample preparation by liquid-liquid extraction was developed and validated. Extraction recoveries were approximately 80%, 40%, 80% and 80%, respectively, obtained by using a mixture of MTBE/2-propanol (70:30, v:v). Chromatographic separation was performed on a core shell biphenyl UHPLC column (100×2.1mm ID, 1.7μm particles). Method validation showed that the method is precise, accurate, robust and sensitive for its purposes. Limit of quantification (LOQ) concentrations were 0.7-1.5ng/mL. The method was used to determine cocaine, benzoylecgonine, cocaethylene and AEME in 22 blood samples collected from victims of sudden, unexpected or violent death in Sao Paulo (Brazil). Concentrations ≥LOQ were observed in 19, 21, 10 and 10 of these samples, respectively., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Reliable field testing devices for psychoactive drugs would be useful tools for the police for detecting drug-impaired drivers. The Norwegian Mobile Police Service (NMPS) started using Dräger DrugTest 5000 (DDT5000) in 2015 as an on-site screening instrument for drugs in samples of oral fluid. The aim of this study was to compare the results of field testing of DDT5000 with drug findings in blood and oral fluid samples taken from drivers suspected for driving under the influence of drugs (DUID). In total, 369 drivers were included in this field testing; blood samples were obtained from all of them, while oral fluid samples were collected with the Intercept device from 301 of them. The median time from field testing with DDT5000 and collection of blood and oral fluid samples was 50 min. The proportions of false positive results with DDT5000 compared to findings in blood samples above the Norwegian legal per se limits were for cannabis 14.5%, amphetamine 23.2%, methamphetamine 38.4%, cocaine 87.1%, opiates 65.9% and benzodiazepines 36.4%. The proportions of false negatives were for cannabis 13.4%, amphetamine 4.9%, methamphetamine 6.1%, cocaine 0.0%, opiates 0.0% and benzodiazepines 18.8%. Among drivers who had drug concentrations above the legal limits in blood, the proportion who tested positive using DDT5000 was 82.9% for THC, 90.8% for amphetamine, 75.7% for methamphetamine, 100.0% for cocaine, 100.0% for opiates and 37.2% for benzodiazepines. In cases with false-positive DDT5000 results compared to blood, traces of drugs were most often found in oral fluid. The DDT5000 did not absolutely correctly identify DUID offenders due to fairly large proportions of false-positive or false-negative results compared to drug concentrations in blood. The police reported that DDT5000 was still a valuable tool in identifying possible DUID offenders, resulting in more than doubling the number of apprehended DUID offenders.

Driver fatalities in motor vehicle collisions (MVCs) encompass accidents, suicides, and natural deaths when driving. The objective of this study was to determine the significance of pathology and other autopsy findings for drivers in fatal MVCs. Forensic autopsy records of driver fatalities in southeast Norway between 2000 and 2014 were studied retrospectively. Data from individual police and collision investigation reports were also collected and analyzed. In 406 driver fatalities, the male/female ratio was 340/66; 9% died from natural causes, 9% were suicides, 65% were culpable accidental deaths, 14% were nonculpable deaths, and 3% were undetermined deaths. Head injuries and thoracic injuries were the most common causes of death. A seatbelt had been worn in 50% of the fatalities, and its prevalence did not differ between accidental deaths and suicides. Blood levels of alcohol and/or drugs that indicated impairment at the time of the collision were found in 40% (105/262) of all culpable accidental deaths but in 50% (64/127) of drivers aged up to 35 years. Pathology (most often cardiovascular disease) suggestive of sudden incapacitation before the collision was present in 24% (62/264) of drivers who were culpable in the accident and in 70% (46/66) of culpable drivers older than 55 years. A substantial proportion of drivers are killed in accidental collisions that may have occurred as a result of either alcohol/drug impairment or preexisting disease. Suicides and natural deaths both constitute significant proportions of MVC fatalities and may be misclassified unless a full inquest including an autopsy is performed.

Competing Interests: Competing interests: None declared.

Objective: The objective of this study was to study the association between self-reported road traffic crashes (RTCs) and recent use of alcohol and medicinal and illicit drug use and self-reported speeding in the previous 2 years., Methods: During the period from April 2016 to April 2017, drivers of cars, vans, motorcycles, and mopeds were stopped in a Norwegian roadside survey performed in collaboration with the police. Participation was voluntary and anonymous. The drivers were asked to deliver an oral fluid sample (mixed saliva), which was analyzed for alcohol and 39 illicit and medicinal drugs and metabolites. In addition, data on age, sex, and self-reported speeding tickets and RTCs during the previous 2 years were collected., Results: A total of 5,031 participants were included in the study, and 4.9% tested positive for the use of one or more illicit or medicinal drugs or alcohol. We found a significant, positive association between the use of cannabis and RTC involvement (odds ratio [OR] = 1.93; 95% confidence interval [CI], 1.05-3.57; P = 0.035) and also between previous speeding tickets and RTC involvement (OR = 1.39; 95% CI, 1.08-1.80; P = 0.012). In addition, older age groups were found to have a significant, negative association with RTC involvement, with ORs equal to or less than 0.49, when using the age group 16-24 as reference., Conclusion: Speeding, as an indicator of risk behavior, and the use of cannabis were associated with previous RTC involvement, whereas increasing age was significantly associated with lower risk. This is consistent with previous studies on RTCs.

Objective: The objective of this study was to study the use of alcohol and drugs among the general driving population in the southeastern part of Norway and to compare the findings with the results from a similar roadside survey in 2008-2009., Methods: A roadside survey of drivers of cars, vans, motorcycles, and mopeds was performed from April 2016 to April 2017 in collaboration with the Mobile Police Service. Oral fluid was collected using the Quantisal device and analyzed for alcohol, illicit drugs, and psychoactive medicinal drugs. Age, sex, time, and geographical region were recorded., Results: Of the 5,556 drivers who were asked to participate in the study, 518 drivers (9.3%) declined to participate, and 4 samples contained insufficient volume of oral fluid to be analyzed; thus, 5,034 drivers were included. Fifteen drivers (0.3%) suspected by the police for driving under the influence of alcohol or drugs refused to participate in the study, so the alcohol and drug findings represent minimum values. The weighted prevalence of alcohol concentrations above the legal limit of 0.2 g/L was 0.2%, which is similar to the finding in the 2008-2009 survey. The weighted prevalences of medicinal drugs and illicit drugs were 3.0 and 1.7%, respectively; those numbers included more drugs than the 2008-2009 survey and are therefore not comparable. The most prevalent illicit and medicinal drugs were tetrahydrocannabinol (1.3%) and zopiclone (1.4%). The prevalences of benzodiazepines and amphetamines were significantly lower than detected in the 2008-2009 survey. Only one sample tested positive for a new psychoactive substance., Conclusions: The proportion of samples that tested positive for alcohol had not changed since 2008-2009, and the proportions that tested positive for benzodiazepines and amphetamines were lower. There are several possible reasons for the reduction: Implementation of legal limits for 28 drugs in 2012-2016, increased use of drug recognition tests, implementation of drug screening instruments, and automatic number plate recognition by the police since 2010; more focused enforcement of the driving under the influence (DUI) law; better information provided to drivers; and changes in drug prescriptions.

Objective: The availability of cannabis in Norway seems to have increased according to seizures by customs and police. On the other hand, national population surveys have not found any increase in self-reported use of cannabis. This investigation aimed at studying trends in cannabis use among suspected drug-impaired drivers apprehended by the police in Norway., Methods: A time series observational study of cannabis use among all drivers tested for drugs during 2000-2015 was performed. Descriptive analyses of trends in frequencies and combined use of cannabis with other drugs or alcohol for different age groups and gender were conducted., Results: Tetrahydrocannabinol (THC) is the main psychoactive substance in cannabis and was detected in blood samples from 18,767 suspected drug-impaired drivers. The annual number of THC findings increased during the years 2000-2015 for all age groups. For cannabis-only users, young drivers aged 20-29 years dominated during the whole period, whereas for multidrug-cannabis users the median age increased steadily during 2000-2015. After 2009, the annual increase in THC findings escalated; THC-only findings increased the most., Conclusions: Increasing numbers of THC-positive drivers were found among all age groups and genders; the strongest trend was observed between 2009-2015 for young drivers testing positive only for THC.

This study describes trends in drug use among drivers suspected of driving under the influence of drugs, apprehended by the police in Norway during 1990-2015. Chromatographically determined toxicological findings in blood samples were retrospectively investigated. Drug findings above defined cut-off concentrations were considered positive; hence making the annual prevalence comparable during the 26 years studied. Blood samples from 112,348 drivers were included, of which 63% were positive for drugs; 43% had combined drug with alcohol or other drugs. In total, 87% of the drug-positive drivers were men, and a higher proportion of them were positive for illicit drugs compared to the women. Benzodiazepines and related drugs were found in 57% of the drug-positive drivers, stimulants in 51%, cannabis (tetrahydrocannabinol, THC) in 34%, and opioids in 18%. The types of benzodiazepines and opioids changed over time. The age distribution also changed; the proportion of drug-positive drivers above 40 years of age increased for all drug classes. The annual number of suspected drug-impaired drivers increased by 122% from 1990 to 1999, and by 54% from 2000 to 2015; the annual number of drug-positive samples increased by 260% from 1990 to 1999, and by 60% from 2000 to 2015. During 2000-2015, an increasing prevalence of amphetamines was found among suspected drug-impaired drivers above age 30; the highest rate of increase was observed among those at or above age 40. In the same period, the prevalence of benzodiazepines and related drugs decreased among all age groups, whereas the prevalence of THC increased; the highest prevalence and rate of increase were among suspected drug-impaired drivers under the age of 30. The results from this study indicate a slight change in the types of drugs used by drivers in Norway., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: The objective of this study was to determine the prevalence of alcohol and potentially impairing drugs among the general driving population in Finnmark and to compare the prevalence among Norwegian, Russian, and other foreign drivers by analyzing samples of oral fluid., Methods: In collaboration with local police, drivers were selected for a voluntary and anonymous study using a multistage cluster sampling procedure (selection of roads, time intervals, and drivers within each interval) from September 2014 to October 2015. Age, gender, citizenship, time, and geographical site were recorded. Samples of oral fluid were collected using the Quantisal device. The samples were analyzed for alcohol with an enzymatic method and for 12 illicit drugs and 16 medicinal drugs and some metabolites using ultra-high-performance liquid chromatography with tandem mass spectrometry detection., Results: A total of 3,228 drivers were asked to participate in the study. The refusal rate was 6.2%. Of the 3,027 participants in the study, 111 (3.7%) were Russian and 204 (6.7%) had citizenship other than Norwegian or Russian. The total prevalence of psychoactive substances was 4.3%. Alcohol was detected in 0.3%, psychoactive medicinal drugs in 2.5%, and illicit drugs in 1.6% of the samples. The most commonly found substances were the sleeping agent zopiclone (1.1%), tetrahydrocannabinol (THC; 1.1%), and the analgesic agent codeine (0.6%). Illicit drugs were detected significantly more often in samples from drivers of citizenship other than Norwegian or Russian. The prevalence of alcohol was somewhat higher among Russian drivers but not statistically significant. There were large differences between age groups and genders concerning illicit drugs and psychoactive medicinal drugs; illicit drugs were more frequently in samples from young male drivers, whereas psychoactive medicinal drugs were more frequently in samples from elderly female drivers., Conclusion: The total prevalence of alcohol and drugs among the general driving population in Finnmark was low and similar to previous Norwegian roadside surveys. Illicit drugs were detected significantly more often in samples from drivers with citizenship other than Russian and Norwegian and among young male drivers.

Traffic accidents are responsible for 1.25 million deaths worldwide and are the most common cause of death among those aged 15-29 years. In Brazil, traffic accidents caused more than 44,000 deaths in 2014. The use of psychoactive drugs is an important risk factor for being involved in traffic accidents. Previous studies have found that psychoactive substances are commonly used by truck drivers in Brazil to maintain their extensive work schedule and stay awake while driving during nighttime hours. The state of Sao Paulo is one of the most important states regarding goods transportation. Important highways cross through Sao Paulo to other regions from Brazil and to other countries in Latin America. This study aims to determine the prevalence of illicit drug use by truck drivers in the state of Sao Paulo through toxicological analyses of oral fluid. Truck drivers were randomly stopped by police officers on federal roads during morning hours. Oral fluid samples were collected using the Quantisal™ device. In addition, a questionnaire concerning sociodemographic characteristics and health information was administered. Oral fluid samples were screened for amphetamine, cocaine, and tetrahydrocannabinol (Δ9-THC) by ELISA and the confirmation was performed using ultra performance liquid chromatography with tandem mass spectrometry detection (UPLC-MS/MS). Of the 764 drivers stopped, 762 agreed to participate. The participants were driving an average of 614km and 9.4h a day. Of the total samples, 5.2% (n=40) tested positive for drugs. Cocaine was the most frequently found drug (n=21), followed by amphetamine (n=16) and Δ9-THC (n=8). All drivers were men with an average age of 42.5 years. With these results we were able to verify that many truck drivers were still consuming psychoactive drugs while driving, and cocaine was the most prevalent one. This reinforces the need for preventive measures aimed at controlling the use of illicit drugs by truck drivers in Brazil., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The aim of this study was to investigate psychoactive drug use among nightclub patrons by analysing samples of oral fluid and compare with findings in blood samples from criminal suspects. We hypothesized that the profile of illicit drug use among nightclub patrons is different from what we observe in those forensic cases. Research stations were established outside nine popular nightclubs with different profiles and patron-characteristics in downtown Oslo. Data and sample collection was conducted on Fridays and Saturdays in March and May 2014. Individuals and groups who entered defined recruitment zones from 23:00 to 03:30 were invited to participate in this voluntary and anonymous study. Oral fluid was collected using the Intercept Oral Fluid Sampling Device. Methanol was added to increase the recovery of cannabinoids from the device. Sample preparation was performed using liquid-liquid extraction with ethyl acetate/heptane (4:1) after adding internal standards, ammonium carbonate buffer pH 9.3 and Triton X100. The first 80 samples were analysed for 122 substances, which included psychoactive medicinal drugs, classical illicit drugs and new psychoactive substances (NPS). Based on the findings and discussions with police and customs authorities, the remaining oral fluid samples were analysed for 46 substances. Among the 500 samples collected during the study period, we found illicit drugs in 25.4% and medicinal drugs in 4.2% of the samples. The most prevalent substances were: cocaine 14.6%, THC 12.4%, amphetamine/methamphetamine 2.8%, diazepam 1.2% and clonazepam 1.0%. Various NPS were found in 1.4% of the samples. The prevalence of drugs in blood samples from criminal suspects were for cocaine 3.4%, THC 34.7%, amphetamine/methamphetamine 37.0%, diazepam 12.0%, and clonazepam 29.3%. Multi-drug use was more common among criminal suspects (41.3%) than among club patrons (6.8%). The results showed that the drug use pattern among nightclub patrons was substantially different from the drug use pattern manifested by individuals apprehended by the police suspected for criminal conduct., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Clonazepam, nitrazepam and flunitrazepam are frequently used benzodiazepines, both as prescribed medication and as drugs of abuse. Little is, however, known about how these drugs are excreted in oral fluid. It has been claimed that the parent drugs are more likely to be detected in oral fluid than the 7-amino metabolites. The aim of this study was to investigate whether the parent drugs or the 7-amino metabolites of the nitrobenzodiazepines were most frequently detected in authentic oral fluid samples. Oral fluid samples were collected from patients undergoing opioid maintenance treatment. Cases where clonazepam, nitrazepam, flunitrazepam and/or their metabolites were detected were included. The samples were collected using the Intercept Oral Specimen Collection Device. A cutoff concentration of 1 nM (∼0.3 ng/mL) in oral fluid-buffer mixture was applied for all the substances. A total of 1,001 oral fluid samples were positive for clonazepam and/or 7-aminoclonazepam; both substances were detected in 707 samples, only the parent drug in 64 cases and only the metabolite in 230 cases. For nitrazepam, both substances were detected in 139 samples; only the parent drug in 16 cases and only the metabolite in 56 cases. Flunitrazepam only was not detected in any sample; both substances were detected in one of these cases, and only the metabolite in three cases. This study revealed that 7-amino metabolites were more likely to be detected in oral fluid than the parent drugs., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Trends in the use of alcohol and drugs among motor vehicle drivers in Australia, Brazil, Norway, Spain, and the United States have been reviewed. Laws, regulations, enforcement, and studies on alcohol and drugs in biological samples from motor vehicle drivers in general road traffic and fatal road traffic crashes (RTCs) are discussed. Roadside surveys showed a reduction of drunk driving over time in the studied countries; however, the pattern varied within and between different countries. The reduction of alcohol use may be related to changes in road traffic laws, public information campaigns, and enforcement, including implementation of random breath testing or sobriety checkpoints. For non-alcohol drugs, the trend in general road traffic is an increase in use. However, drugs were not included in older studies; it is therefore impossible to assess the trends over longer time periods. Data from the studied countries, except Brazil, have shown a significant decrease in fatal RTCs per 100,000 inhabitants over the last decades; from 18.6 to 4.9 in Australia, 14.5 to 2.9 in Norway, 11.1 to 3.6 in Spain, and 19.3 to 10.3 in the United States. The number of alcohol-related fatal RTCs also decreased during the same time period. The proportion of fatal RTCs related to non-alcohol drugs increased, particularly for cannabis and stimulants. A general challenge when comparing alcohol and drug findings in biological samples from several countries is connected to differences in study design, particularly the time period for performing roadside surveys, biological matrix types, drugs included in the analytical program, and the cutoff limits used for evaluation of results. For RTC fatalities, the cases included are based on the police requests for legal autopsy or drug testing, which may introduce a significant selection bias. General comparisons between high-income countries and low- and middle-income countries as well as a discussion of possible future trends are included., (Copyright © 2016 Central Police University.)

Background: Alcohol or drug use and associated hangover may reduce workplace safety and productivity and also cause sickness absence. The aims of this study were to examine (i) the use of alcohol and drugs, and (ii) reduced efficiency at work and absence due to such use among employees., Methods: Forty-four companies were invited; half of them agreed to participate. Employees filled in a questionnaire and provided a sample of oral fluid, which was analysed for alcohol, 12 psychoactive medicinal drugs and 6 illicit drugs. Participation was voluntary and anonymous., Results: Two thousand four hundred thirty-seven employees in eight business areas agreed to participate (92 % of those invited). By combining questionnaires and oral fluid testing, we found that 5.2 % had used psychoactive medication during the last couple of days, 1.4 % had used illicit drugs, 17.0 % had used alcohol during the last 24 h but only one person (0.04 %) was positive for alcohol in oral fluid. About 25 % reported reduced efficiency at work, and 5 % reported absence from work due to alcohol use during the past 12 months. The use of illicit drugs and binge drinking resulting in reduced efficiency and absence was most common among restaurant and bar workers and more common among men than women, whereas use of psychoactive medication was most common among healthcare, transportation and storage workers., Conclusion: Impairment at work due to alcohol or drugs was rare, whereas reduced efficiency due to drinking was reported by a fairly large proportion. There were marked differences between some business areas, and across gender.

Aim: To assess whether analysis of oral fluid can be used to identify individual drivers with drug concentrations in blood above 25ng/mL for amphetamine and methamphetamine, 10ng/mL for cocaine and 1.0ng/mL for tetrahydrocannabinol (THC), which are the cut-off concentrations used in the European DRUID Project, by calculating the diagnostic accuracies when using the analytical cut-off concentrations in oral fluid as well as for the optimal cut-off concentrations., Methods: Paired samples of whole blood and oral fluid collected with the Statsure SalivaSampler were obtained from 4080 drivers in four European countries and analysed for amphetamine, methamphetamine, cocaine and THC using GC-MS or LC-MS. The vast majority (89%) were random drivers not suspected of drug-impaired driving. Receiver-Operating Characteristic analysis was used to evaluate the analytical results., Results: The prevalence of drug findings above the cut-off concentrations in blood was 1.3% for amphetamine, 1.0% for methamphetamine, 0.6% for cocaine and 1.3% for THC. The cut-off concentrations in oral fluid that gave the highest diagnostic accuracy were for amphetamine 130ng/mL (accuracy 99.8%), methamphetamine 280ng/mL (accuracy 99.9%), cocaine 570ng/mL (accuracy 99.6%), and THC 38ng/mL (accuracy 98.3%). The proportion of false positives were 0.2%, 0.1%, 0.1% and 0.9%; and the proportion of false negatives were 0.1%, 0.0%, 0.3% and 0.8%, respectively, when using those cut-offs. The positive predictive values were 87.9%, 92.9%, 84.6% and 35.7% for amphetamine, methamphetamine, cocaine and THC, respectively., Conclusions: Analysis of concentrations of illicit drugs in oral fluid could not be used to accurately identify drivers with drugs concentrations above the selected cut-offs in blood in a cohort of drivers with low prevalence of drugs., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

The aim of the study was to examine the prevalence of alcohol and drugs in blood samples from motorcycle riders who died in road crashes in Norway from 2001 to 2010. An additional aim was to compare the prevalence of alcohol and drugs in blood samples from fatally injured motorcycle riders and car drivers who died during the same time period. Blood samples from motorcycle riders who died within 24h after the accident (n=207, 63% of all killed riders), were analysed for alcohol, psychoactive drugs (medicinal and illicit drugs). The cut-off concentrations for alcohol and drugs findings in blood samples (i.e., the drug concentrations above which a finding was regarded as positive) were set according to the legislative limits under the Norwegian Road Traffic Act. Results were assessed in relation to age, sex, time of the day and week, and single versus multiple-vehicle accidents. Alcohol or drugs were found in 27.1 percent of all investigated riders. For riders killed in single or multiple-vehicle accidents, alcohol or drugs were found in 44.6 and 15.3 percent, respectively. Alcohol was the most frequently found substance for all age groups and most prevalent in samples from riders below 25 years who died in single-vehicle accidents (45.8 percent). Drugs were most often found among riders between 25 and 34 years (19.6 percent in total and 25.9% for those killed in single-vehicle crashes). The prevalence of alcohol or drugs was highest among riders killed in single-vehicle accidents during weekend days and nights (60.9 and 65.2 percent). Alcohol and drugs were less often found in samples from killed motorcycles riders than in samples from car and van drivers (40.2 percent). For single-vehicle accidents, the total prevalence of alcohol or drugs among killed motorcycles riders and car drivers was 44.6 percent and 63.8 percent, respectively. The same pattern of alcohol and drugs was found among the two groups, except that the prevalence among motorcycle riders was lower compared to car drivers in all age groups and time periods, which may be related to the fact that they are more vulnerable for fatal injury compared to car drivers in similar accidents., (Copyright © 2015. Published by Elsevier Ltd.)

Since 2005, all fatal road traffic crashes in Norway have been analyzed in-depth by multidisciplinary investigation teams organized by the Norwegian Public Roads Administration (NPRA). During the period 2005-2010, 608 drivers of cars or vans were killed in road traffic crashes. Blood samples were collected from 372 (61%) of the drivers and analyzed for alcohol and a large number of psychoactive drugs at the Norwegian Institute of Public Health (NIPH). After coupling the analytical results with the NPRA crash database, 369 drivers with a fatal outcome were identified and included. Alcohol or drug concentrations in blood above the legal limits were found in 39.8% of the drivers who were investigated for alcohol or drug impairment; 33.9% had blood alcohol concentrations above 0.5g/L or concentrations of drugs above the equivalent Norwegian legal impairment limits or concentrations of amphetamines above 200μg/L. Among drivers with a fatal outcome who had been impaired by alcohol or drugs, 64.6% were unbelted and 71.7% were speeding when the crash occurred; whereas 24.2% and 33.2% of the sober drivers were unbelted or speeding, respectively. Statistically significant associations were found between impairment by alcohol or amphetamines and driving unbelted or speeding. Excessive speeding is one of the main reasons for road traffic crashes and together with being unbelted the main reasons for a fatal outcome. This behavior might in many cases be due to increased risk-taking or negligence of safety measures as a result of alcohol or drug use., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: To investigate whether the use of the stimulants amphetamines and cocaine by truck drivers in Brazil was related to travel length., Methods: Truck drivers were randomly stopped by the Federal Highway Police on interstate roads in Sao Paulo State during morning hours from 2008 to 2011 and invited to participate in the project "Comandos de Saúde nas Rodovias" (Health Commands on the Roads). Participants were asked about the use of drugs, travel distance, and age, and gender was recorded. Samples of urine were collected and analyzed for amphetamine, benzoylecgonine (a metabolite of cocaine), and carboxytetrahydrocannabinol (THC-COOH; a metabolite of cannabis) by immunological screening and quantification by gas chromatography-mass spectroscopy., Results: Current use of amphetamine, cocaine, and cannabis was reported by 5.7%, 0.7%, and 0.3% of the truck drivers, respectively. Amphetamine, benzoylecgonine, and THC-COOH were found in urine samples from 5.4%, 2.6,% and in 1.0% of the drivers, respectively. There was a significant association between the positive cases for amphetamine and reported travel length; 9.9% of urine samples from drivers who reported travel length of more than 270 km were positive for amphetamine, and 10.9% of those drivers reported current use of amphetamines. In most cases, appetite suppressants containing amphetamines had been used, but the purpose was most often to stay awake and alert while driving. Truck drivers with travel length of more than 270 km had significantly higher odds ratio (OR) for having a urine sample that was positive for amphetamine when adjusted for age as confounding factor (OR = 9.41, 95% confidence interval [CI], 3.97-22.26). No significant association was found between the use of cocaine or cannabis and travel length., Conclusion: Truck drivers who reported driving more than 270 km had significantly higher frequencies of urine samples positive for amphetamine and reported significantly more frequent current use of amphetamines than those who reported shorter driving distances.

Background and Aims: For many years, flunitrazepam was the benzodiazepine of choice among users of illegal drugs. The aim of this study was to investigate to which extent clonazepam use has increased in this population, and whether this was related to increased prescription or because of illegal availability., Methods: We used data from three sources to study the changes in the use of clonazepam: (1) Presence and concentrations of clonazepam and flunitrazepam in blood samples collected from Norwegian drugged drivers; (2) Sales numbers (legal market) for clonazepam, extracted from the Norwegian prescription database (NorPD), and (3) Specific seizures (illegal market) for clonazepam in Norway., Results: In 2004, 13.0% of the analysed blood samples from drugged drivers contained clonazepam, whereas this proportion had increased to 27.7% in 2013. In the same period, the frequency of flunitrazepam in drugged drivers decreased from 16.6% in 2004 to 3.2% in 2013. The number of clonazepam prescriptions decreased, while the number of seized tablets containing clonazepam increased considerably from 2004 to 2013., Conclusions: For the last 10 years, a significant increase in the illegal use of clonazepam has been seen, now replacing flunitrazepam as the most used illegal benzodiazepine in Norway.

Norway introduced legislative limits for driving under the influence of drugs (DUID) February 1st, 2012, to harmonize with the legislation on driving under the influence of alcohol. Per se limits corresponding to blood alcohol concentrations (BACs) of 0.02% were established for 20 drugs and concentration limits for graded sanctions corresponding to BACs of 0.05% and 0.12% were established for 13 of these drugs as well. The new system is not applied to individuals with valid prescriptions for medicinal drugs. The aim of this study was to investigate if the implementation of legislative limits for drugs affected the number of blood samples taken from suspected drugged drivers, drug findings and the number of expert witness statement requests. The number of blood samples taken in suspected DUID cases increased by 20% after introduction of legislative limits (3320 cases in 2010 and 3970 in 2013). The number of samples with at least one drug above the per se limit corresponding to BAC of 0.02% increased by 17% (from 2646 in 2010 to 3090 in 2013), whereas the number of expert witness statements was reduced by the half (from 63.4% in 2010 and 28.7% in 2013)., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

The aim of this study was to determine the association between drug type and arrest for driving under the influence of drugs (DUID) by calculating odds ratios (ORs) using a case-control design. A DUID arrest is in most cases related to aberrant or risky driving and might therefore be regarded as a proxy for a drug related traffic crash. The 'cases' were 2738 drivers arrested on suspicion of drugged driving from April 2008 to March 2009 with blood alcohol concentrations below the legal limit of 0.2g/L; 794 were arrested due to involvement in road traffic crashes, whereas 1944 were arrested for other reasons, mainly dangerous driving, suspected impairment when stopped in traffic controls, or because of phone calls to the police from other road users or observers. The 'controls' were 9375 random drivers in normal traffic, also with alcohol concentrations below this limit. Blood samples from 'cases' and oral fluid samples from 'controls' were analyzed for 15 drugs that have legislative concentration limits in Norway, in addition to two other commonly detected psychoactive drugs. The most prevalent illicit drug in the control group was tetrahydrocannabinol (THC; 0.58%), which was also commonly found in samples from drivers arrested due to road crash (15.6%) or arrested for other reasons (21.8%). Amphetamine/methamphetamine was most prevalent among arrested drivers involved in crashes (30.6%) and drivers arrested for other reasons (56.9%), whereas only 0.18% of the control group was positive for amphetamine/methamphetamine. The single-use substances which gave highest OR for police arrest were amphetamine/methamphetamine, alprazolam, clonazepam and oxazepam. The majority of the alprazolam and clonazepam findings were probably due to non-therapeutic use of medicinal drugs purchased on the illegal market. Combinations of two or more drugs yielded higher ORs than the use of single substances; combinations of amphetamine/methamphetamine and benzodiazepines gave the highest risk., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)