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This study examines the presence of psychoactive drugs and alcohol in blood from apprehended drivers driving under the influence of drugs (DUID) and alcohol in Denmark in a five-year period from 2015 to 2019. Data were analysed with respect to gender, age, substances with concentrations above the Danish legal limit, arresting time of day and repeat arrest. By request of the police, the blood samples were subjected to analysis for alcohol and/or tetrahydrocannabinol (THC) alone, for "other drugs" (covering all drugs including new psychoactive substances (NPS), except THC, listed in the Danish list of narcotic drugs) or for both THC and other drugs. About the same number of alcohol traffic cases (37,960) and drug traffic cases (37,818) were submitted for analysis for the five-year period. The number of drug traffic cases per year increased from 5660 cases in 2015 to 9505 cases in 2019, while the number of alcohol traffic cases per year (average, 7600) was unchanged. Ethanol (89.2%) was the overall most frequent single substance, followed by THC (68.2%). CNS stimulants (46.8%) were the second most prevalent group of non-alcoholic drugs. Cocaine (23.8%) and amphetamine (22.9%) were the most frequent CNS stimulants. The proportion of CNS-stimulant positive drivers more than doubled in ten years. Benzodiazepines/z-hypnotics (12.7%) were the third most prevalent drug group detected, with clonazepam (8%) as the most frequent drug. Opioids were above the legal limit in 9.8% of the cases. NPS was above the legal limit in 128 cases (0.6%). Poly-drug use occurred in 40% of the DUID cases in the requested groups: other drug or other drug/THC. Young males dominated the DUID cases (median age 26). Drink-drivers (median age 39) were also mainly men, but the age distribution was equally spread over the age groups. Re-arrest occurred more often in DUID drivers (18-29%) than in drinking drivers (6-12%). DUID was evenly spread over the week, while drink-driving was most frequent on weekends. This study is an important supplement to the knowledge of drug use in Denmark. It was the well-known psychoactive substances that were detected. Only a few NPS occurred. However, the abuse pattern has changed, and CNS stimulants now account for a much higher proportion than earlier. Our results indicate a drug use problem among DUID drivers. This gives rise to concern because of a risk of traffic accidents. Treating the underlying abuse problem is therefore recommended, rather than focusing solely on prosecuting., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: Knowledge of trends of illegal drug use is vital for planning initiatives to reduce accidents and deaths among drug users. The aim of this study was to describe the cause of death, abuse pattern and geographic differences in fatal poisonings among drug users in Denmark in 2017., Methods: All fatal poisonings among drug users examined at the three institutes of forensic medicine in Denmark in 2017 were included in the study., Results: Overall, fatal poisonings declined from a maximum of 226 in 2007 to 162 in 2017. Methadone (52%) was the most common cause of death, followed by heroin/morphine (25%). A marked increase in deaths was due to stimulants (13%), especially cocaine. The abuse pattern has changed since 2012. Methadone remained the most frequently detected drug, but clonazepam and cocaine surpassed heroin/morphine, diazepam and tetrahydrocannabinol as the second-most frequently detected drugs. Ketobemidone had disappeared, whereas buprenorphine, oxycodone, fentanyl, pregabalin and gabapentin had increased. Antidepressants/antipsychotics were detected in half (47%) of the cases. Cocaine was more frequent in the areas covered by Copenhagen and Aarhus, whereas heroin/morphine was most frequently detected in the area covered by Odense. Amphetamine was more frequent in the Aarhus area., Conclusions: Methadone and heroin/morphine still account for most fatal poisonings. However, deaths due to stimulants, especially cocaine, have increased. The abuse pattern has changed and geographical differences have emerged., Funding: none., Trial Registration: not relevant., (Articles published in the DMJ are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.)

This study is the seventh report on fatal poisonings among drug addicts in the Nordic countries. In this report, we analyse data from the five Nordic countries: Denmark, Finland, Iceland, Norway and Sweden. Data on gender, number of deaths, places of deaths, age, main intoxicants and substances detected in blood were recorded to obtain national and comparable Nordic data, and to allow comparison with earlier studies conducted in 1984, 1991, 1997, 2002, 2007 and 2012. The death rate (number of deaths per 100,000 inhabitants) was highest in Iceland (6.58) followed closely by Sweden (6.46) and then lowest in Denmark (4.29). The death rate increased in Finland (5.84), Iceland and Sweden and decreased in Denmark compared to earlier studies. The death rate in Norway, which has decreased since 2002, has stabilised around 5.7 as of 2017. Women accounted for 7-23% of the fatal poisonings. The percentage was lowest in Iceland and highest in Finland and Norway. The age range was 14-70 years. The median age (41 years) was highest in Denmark and Norway. The other countries had a median age between 33 and 35 years. Opioids were the main cause of death. Methadone remained the main intoxicant in Denmark, while heroin/morphine was still the main intoxicant in Norway, as was buprenorphine in Finland. However, the picture has changed in Sweden compared to 2012, where heroin/morphine caused most deaths in 2017. Sweden also experienced the highest number of deaths from fentanyl analogues (67 deaths) and buprenorphine (61 deaths). Deaths from fentanyl analogues also occurred in Denmark, Finland and Norway, but to a smaller extent. Over the years, the proportion of opioid deaths has decreased in all countries except Sweden, which has experienced an increase. This decline has been replaced by deaths from CNS stimulants like cocaine, amphetamine and methylenedioxymethamphetamine (MDMA). Cocaine deaths have occurred in all countries but most frequently in Denmark. MDMA deaths have increased in all countries but mostly in Finland. Poly-drug use was widespread, as seen in the earlier studies. The median number of detected drugs per case varied from 4-6. Heroin/morphine, methadone, buprenorphine, cocaine, amphetamine, methamphetamine, MDMA, tetrahydrocannabinol (THC) and benzodiazepines were frequently detected. Pregabalin and gabapentin were detected in all countries, especially pregabalin, which was detected in 42% of the Finnish cases. New psychoactive substances (NPS) occurred in all countries except Iceland., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: The objective of this study was to examine the frequency of psychoactive drugs and alcohol in drivers under suspicion of driving under the influence of drugs and alcohol in 2015 and 2016 in the eastern part of Denmark. The trends in the number of traffic cases sent for drug analysis since 2000 and alcohol analysis since 2011 are also discussed., Methods: Blood samples from drivers suspected of being under the influence of alcohol and/or medication and/or illicit drugs in 2015 and 2016 were investigated as requested by the police. The blood samples were screened for alcohol and/or tetrahydrocannabinol (THC) alone, for other drugs (covering all drugs, except THC, listed in the Danish list of narcotic drugs), or for THC and other drugs. Age and gender were also recorded. The number of drug traffic cases since 2000 and the number of alcohol cases since 2011 were extracted from our Laboratory Information Management System (LIMS)., Results: In total, 11,493 traffic cases were investigated. Alcohol and/or drugs exceeded the legal limit in 9,657 (84%) cases. Men constituted 95% of the drivers investigated for drugs and 88% of the alcohol cases. The drivers investigated for drugs consisted primarily of young men, whereas drivers investigated for alcohol were older. The frequency was higher for positive alcohol cases above the legal limit (87%) than for drug cases (76%) above the fixed concentration limit. THC (67-69%) was the most frequently detected drug above the legal limit, followed by cocaine (27-28.5%), amphetamine (17%), and clonazepam (6-7%) in both years. Morphine (5.4%), included among the 5 most frequent drugs in 2015, was replaced by methadone (4.6%) in 2016. Few new psychoactive drugs (NPS) were detected. The number of traffic cases sent for drug analysis has increased more than 30-fold since 2000-2006, and the number of traffic cases submitted in 2016 for drug analysis was higher than the number for alcohol analysis; the latter has decreased since 2011., Conclusion: Overall, alcohol was the most frequent compound detected above the legal limit in both years, followed by the well-known illicit drugs THC, cocaine, and amphetamine. NPS were seldom seen. One consequence of the increased focus on drugs in traffic has been an immense increase in drug traffic cases sent for analysis since 2006 in the eastern part of Denmark. Although this survey revealed only minimal changes compared to earlier investigations, surveys like this are invaluable for monitoring abuse patterns and trends in drugged and drunken driving.

Introduction: Fatal poisonings among drug addicts in Denmark in 2012 were examined. Cause of death, abuse pattern and geographic differences are discussed and data are compared with previous studies., Methods: All fatal poisonings examined at the three institutes of forensic medicine in Denmark in 2012 were included in the study., Results: A total of 188 fatal intoxications were recorded. The median age increased from 37.5 in 2007 to 41.5 in 2012. The majority were men (77%). Methadone (59%) was the main intoxicant. The decrease in the frequency of heroin/morphine deaths since 1997 (71%) continued, declining to 44% in 2002, 33% in 2007 and finally to 27% in 2012. Few deaths from central stimulants (amphetamine and cocaine) occurred. Multiple drug use was common and consisted mainly of opioids, cocaine, amphetamine, cannabis, benzodiazepines and alcohol. Heroin/morphine use was most frequent on Funen and in South Jutland. Cocaine was most frequently detected in East Denmark, while amphetamine was more frequent in West Denmark., Conclusions: The number of fatal poisonings among drug addicts has stabilised around 200. The increase in methadone deaths continued and, as in 2007, methadone was the main intoxicant. The increase in methadone deaths seems to be associated with use of methadone in substitution treatment. Nevertheless, methadone treatment also seems to save lives, as indicated by the increasing median age. Use of antidepressants and antipsychotics increased to a high level compared with 2007, indicating that a considerable number of drug addicts also have psychiatric illness., Funding: none., Trial Registration: not relevant.

This report is a follow-up to a study on fatal poisoning in drug addicts conducted in 2012 by a Nordic working group. Here we analyse data from the five Nordic countries: Denmark, Finland, Iceland, Norway and Sweden. Data on sex, number of deaths, places of death, age, main intoxicants and other drugs detected in the blood were recorded. National data are presented and compared between the Nordic countries and with data from similar studies conducted in 1991, 1997, 2002 and 2007. The death rates (number of deaths per 100,000 inhabitants) increased in drug addicts in Finland, Iceland and Sweden but decreased in Norway compared to the rates in earlier studies. The death rate was stable in Denmark from 1991 to 2012. The death rate remained highest in Norway (5.79) followed by Denmark (5.19) and Iceland (5.16). The differences between the countries diminished compared to earlier studies, with death rates in Finland (4.61) and Sweden (4.17) approaching the levels in the other countries. Women accounted for 15-27% of the fatal poisonings. The median age of the deceased drug addicts was still highest in Denmark, and deaths of addicts >45 years old increased in all countries. Opioids remained the main cause of death, but medicinal opioids like methadone, buprenorphine, fentanyl and tramadol mainly replaced heroin. Methadone was the main intoxicant in Denmark and Sweden, whereas heroin/morphine caused the most deaths in Norway. Finland differed from the other Nordic countries in that buprenorphine was the main intoxicant with only a few heroin/morphine and methadone deaths. Deaths from methadone, buprenorphine and fentanyl increased immensely in Sweden compared to 2007. Poly-drug use was widespread in all countries. The median number of drugs per case varied from 4 to 5. Heroin/morphine, medicinal opioids, cocaine, amphetamines, benzodiazepines and alcohol were the main abused drugs. However, less widely used drugs, like gamma-hydroxybutyric acid (GHB), methylphenidate, fentanyl and pregabalin, appeared in all countries. New psychotropic substances emerged in all countries, with the largest selection, including MDPV, alpha-PVP and 5-IT, seen in Finland and Sweden., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Driving with alcohol and other psychoactive substances imposes an increased risk of severe injury accidents. In a population-based case-control design, the relative risks of severe driver injury (MAIS≥2) by driving with ten substance groups were approximated by odds ratios (alcohol, amphetamines, benzoylecgonine, cocaine, cannabis, illicit opiates, benzodiazepines and Z-drugs, i.e. zolpidem and zopiclone, medicinal opioids, alcohol-drug combinations and drug-drug combinations). Data from six countries were included in the study: Belgium, Denmark, Finland, Italy, Lithuania and the Netherlands. Case samples (N=2490) were collected from severely injured drivers of passenger cars or vans in selected hospitals in various regions of the countries. Control samples (N=15,832) were sampled in a uniform sampling scheme stratified according to country, time, road type and season. Relative risks were approximated by odds ratios and calculated by logistic regression. The estimates were adjusted for age, gender and country. The highest risk of the driver being severely injured was associated with driving positive for high concentrations of alcohol (≥0.8 g/L), alone or in combination with other psychoactive substances. For alcohol, risk increased exponentially with blood alcohol concentration (BAC). The second most risky category contained various drug-drug combinations, amphetamines and medicinal opioids. Medium increased risk was associated with medium sized BACs (at or above 0.5 g/L, below 0.8 g/L) and benzoylecgonine. The least risky drug seemed to be cannabis and benzodiazepines and Z-drugs. For male drivers, the risk of being severely injured by driving with any of the psychoactive substances was about 65% of that of female drivers. For each of the substance groups there was a decrease in the risk of severe driver injury with increasing age. It is concluded that among psychoactive substances alcohol still poses the largest problem in terms of driver risk of getting injured., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

An efficient method for analyzing illegal and medicinal drugs in whole blood using fully automated sample preparation and short ultra-high-performance liquid chromatography-tandem mass spectrometry (MS/MS) run time is presented. A selection of 31 drugs, including amphetamines, cocaine, opioids, and benzodiazepines, was used. In order to increase the efficiency of routine analysis, a robotic system based on automated liquid handling and capable of handling all unit operation for sample preparation was built on a Freedom Evo 200 platform with several add-ons from Tecan and third-party vendors. Solid-phase extraction was performed using Strata X-C plates. Extraction time for 96 samples was less than 3 h. Chromatography was performed using an ACQUITY UPLC system (Waters Corporation, Milford, USA). Analytes were separated on a 100 mm × 2.1 mm, 1.7 μm Acquity UPLC CSH C(18) column using a 6.5 min 0.1 % ammonia (25 %) in water/0.1 % ammonia (25 %) in methanol gradient and quantified by MS/MS (Waters Quattro Premier XE) in multiple-reaction monitoring mode. Full validation, including linearity, precision and trueness, matrix effect, ion suppression/enhancement of co-eluting analytes, recovery, and specificity, was performed. The method was employed successfully in the laboratory and used for routine analysis of forensic material. In combination with tetrahydrocannabinol analysis, the method covered 96 % of cases involving driving under the influence of drugs. The manual labor involved in preparing blood samples, solvents, etc., was reduced to a half an hour per batch. The automated sample preparation setup also minimized human exposure to hazardous materials, provided highly improved ergonomics, and eliminated manual pipetting.

Between 2006 and 2010, six population based case-control studies were conducted as part of the European research-project DRUID (DRiving Under the Influence of Drugs, alcohol and medicines). The aim of these case-control studies was to calculate odds ratios indicating the relative risk of serious injury in car crashes. The calculated odds ratios in these studies showed large variations, despite the use of uniform guidelines for the study designs. The main objective of the present article is to provide insight into the presence of random and systematic errors in the six DRUID case-control studies. Relevant information was gathered from the DRUID-reports for eleven indicators for errors. The results showed that differences between the odds ratios in the DRUID case-control studies may indeed be (partially) explained by random and systematic errors. Selection bias and errors due to small sample sizes and cell counts were the most frequently observed errors in the six DRUID case-control studies. Therefore, it is recommended that epidemiological studies that assess the risk of psychoactive substances in traffic pay specific attention to avoid these potential sources of random and systematic errors. The list of indicators that was identified in this study is useful both as guidance for systematic reviews and meta-analyses and for future epidemiological studies in the field of driving under the influence to minimize sources of errors already at the start of the study., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The objective of this study was to determine the presence of alcohol and drugs in drivers severely injured in traffic crashes in six European countries. Data were collected from 2492 seriously injured drivers of cars and vans in Belgium, Denmark, Finland, Italy, Lithuania, and the Netherlands, between 2007 and 2010. Toxicological analysis was performed with chromatographic techniques on whole blood for 23 substances. The percentage of drivers positive for at least one psychoactive substance ranged between 28% (Lithuania) and 53% (Belgium). Alcohol (≥0.1 g/L) was the most common finding with the highest percentage in Belgium (42.5%). Among the alcohol-positive drivers, 90.5% had a blood alcohol count (BAC) ≥0.5 g/L and 65.7% had a BAC ≥1.3 g/L. Benzodiazepines (0.0-10.2%) and medicinal opioids (0.5-7.8%) were the most prevailing medicinal drugs, but half of the concentrations were lower than therapeutic. Cannabis (0.5-7.6%) was the most prevailing illicit drug. Alcohol was found in combination with drugs in 2.3-13.2% of the drivers. Drug combinations were found in 0.5-4.3% of the drivers. This study confirms the high prevalence of psychoactive substances in injured drivers, but we observed large differences between the participating countries. Alcohol was the most common finding, followed by cannabis and benzodiazepines. Notable are the many drivers having a BAC ≥ 1.3 g/L. The majority of the substances were found in combination with another psychoactive substance, mostly alcohol. The high prevalence of high BACs and combinations (compared to roadside surveys) suggest that those drivers are most at risk and that preventive actions should target them preferentially., (Copyright © 2012 John Wiley & Sons, Ltd.)

This roadside study is the Danish part of the EU-project DRUID (Driving under the Influence of Drugs, Alcohol, and Medicines) and included three representative regions in Denmark. Oral fluid samples (n=3002) were collected randomly from drivers using a sampling scheme stratified by time, season, and road type. The oral fluid samples were screened for 29 illegal and legal psychoactive substances and metabolites as well as ethanol. Fourteen (0.5%) drivers were positive for ethanol (alone or in combination with drugs) at concentrations above 0.53g/l, which is the Danish legal limit. The percentage of drivers positive for medicinal drugs above the Danish legal concentration limit was 0.4%; while, 0.3% of the drivers tested positive for one or more illicit drug at concentrations exceeding the Danish legal limit. Tetrahydrocannabinol, cocaine, and amphetamine were the most frequent illicit drugs detected above the limit of quantitation (LOQ); while, codeine, tramadol, zopiclone, and benzodiazepines were the most frequent legal drugs. Middle aged men (median age 47.5 years) dominated the drunk driving group, while the drivers positive for illegal drugs consisted mainly of young men (median age 26 years). Middle aged women (median age 44.5 years) often tested positive for benzodiazepines at concentrations exceeding the legal limits. Interestingly, 0.6% of drivers tested positive for tramadol, at concentrations above the DRUID cut off; although, tramadol is not included in the Danish list of narcotic drugs. It can be concluded that driving under the influence of drugs is as serious a road safety problem as drunk driving., (Copyright © 2012. Published by Elsevier Ireland Ltd.)

The aim of this study was to find which drugs and drug combinations were most common in drivers who died, in particular, in single vehicle crashes where the responsibility for the crash would be referred to the driver killed. The study included all available blood samples from drivers, who died within 24h of the accident, in the years 2001 and 2002 in the five Nordic countries (total population about 24 million inhabitants). The samples were analysed for more than 200 different drugs in addition to alcohol, using a similar analytical programme and cut-off limits in all countries. In three countries (Finland, Norway and Sweden) blood samples were available for more than 70% of the drivers, allowing representative prevalence data to be collected. 60% of the drivers in single vehicle crashes had alcohol and/or drug in their blood samples, compared with 30% of drivers killed in collisions with other vehicles. In single vehicle accidents, 66% of the drivers under 30 years of age had alcohol and/or drugs in their blood (alcohol only - 40%; drugs only - 12%; alcohol and drugs - 14%). The drugs found were mostly illicit drugs and psychoactive medicinal drugs with warning labels (in 57% and 58% respectively of the drivers under 30 with drugs present). Similar findings were obtained for drivers 30-49 years of age (63% with alcohol and/or drugs). In drivers aged 50 years and above, killed in single vehicle crashes (48% with alcohol and/or drugs) illicit drugs were found in only one case, and psychoactive medicinal drugs were detected less frequently than in younger age groups. In 75% of single vehicle crashes, the driver was under 50 years. Thus, the majority of accidents where the drivers must be considered responsible, occurred with drivers who had recently used alcohol, or drugs, alone or in combination. The drugs involved were often illicit and/or psychoactive drugs with warning labels. Therefore a large proportion of single vehicle accidents appear to be preventable, if more effective measures against driving after intake of alcohol and drugs can be implemented., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Introduction: We investigated fatal poisonings among drug addicts in 2007. The cause of death, abuse pattern and geographic differences are presented., Material and Methods: All drug-related deaths examined at the three forensic medicine institutes in Denmark in 2007 were evaluated., Results: The number of drug-related deaths in 2007 was 226. Methadone deaths had increased since 1997 while heroin/morphine deaths decreased. In earlier studies, very few deaths from central stimulants like cocaine and amphetamines occurred (1-1.5%), but in 2007 6% of the deaths were caused by these drugs. Multiple drug use was common. Heroin/morphine, cocaine, amphetamine, cannabis, methadone, benzodiazepines and alcohol were included in the poly-drug use., Conclusion: This investigation shows stabilization in the number of fatal poisonings in drug addicts. Geographic differences were observed. Methadone was the most frequent cause of fatal poisoning and there was a continuous decrease in heroin/morphine deaths. Fatal deaths from cocaine and amphetamine have increased considerably. Multiple drug use was common., Funding: not relevant., Trial Registration: not relevant.

The frequency of medico-legally examined fatal poisonings in 2007 among drug addicts was investigated in five Nordic countries; Denmark, Finland, Iceland, Norway, and Sweden. The number of deaths, age, sex, place of death, main intoxicant, and other drugs present in blood samples were recorded to obtain national and comparable Nordic data, as well as data to compare with earlier studies in 2002, 1997, and 1991. Norway had the highest incidence of drug addict deaths by poisoning followed by Denmark, with 8.24 and 6.92 per 100,000 inhabitants, respectively. The death rates in Finland (4.02), Iceland (4.56), and Sweden (3.53) were about half that of Norway and Denmark. Compared with earlier studies, the death rates were unchanged in Denmark and Norway, but increased in Finland, Iceland, and Sweden. In all countries, fewer deaths (29-35%) were recorded in the capital area compared with earlier studies. Females accounted for 11-19% of the fatal poisonings. Iceland deviates with a more equal distribution between men and women (40%). Deaths from methadone overdoses increased in all Nordic countries, and methadone was the main intoxicant in Denmark in 2007, accounting for 51% of the poisonings. In Norway and Sweden, heroin/morphine was still the main intoxicant with a frequency of 68% and 48%, respectively. In Iceland, 3 deaths each were due to heroin/morphine and methadone, respectively. Finland differs from other Nordic countries in having a high number of poisonings caused by buprenorphine and very few caused by heroin/morphine. The total number of buprenorphine deaths in Finland doubled from 16 in 2002 to 32 in 2007, where it constituted 25% of deaths. The general toxicological screening program showed widespread multi-drug use in all countries. The median number of drugs per case varied from 3 to 5. The most frequently detected substances were heroin/morphine, methadone, buprenorphine, tramadol, amphetamine, cocaine, tetrahydrocannabinol, benzodiazepines and ethanol., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

We describe a multi-method for simultaneous identification and quantification of 12 acidic and neutral compounds in whole blood. The method involves a simple liquid-liquid extraction, and the identification and quantification are performed using liquid chromatography-tandem mass spectrometry. The method was fully validated for salicylic acid, paracetamol, phenobarbital, carisoprodol, meprobamate, topiramate, etodolac, chlorzoxazone, furosemide, ibuprofen, warfarin, and salicylamide. The method also tentatively includes thiopental, theophylline, piroxicam, naproxen, diclophenac, and modafinil, but these drugs were not included in the full validation program and are not described in detail here. Limit of quantitation was 1 mg/kg for the compounds with coefficients of variation of < 20%, except for furosemide, which had a coefficient of variation of 32% at limit of quantitation. The measuring interval was wide for most components. Extraction efficiencies were high, reflecting the high-yield capacity of the method.

Objective: Until July 2007, the driving under the influence of drugs (DUID) legislation in Denmark was based on impairment, evaluated on the basis of a clinical investigation and toxicological analyses, but in 2007 fixed concentration limits were introduced into the Danish traffic legislation. The objective for this study was to investigate the prevalence of medication and illicit drugs among Danish drivers before and after 2007., Methods: Blood samples from drivers suspected of being under the influence of medication and/or illicit drugs were investigated as requested by the police. The results for a 10-year period before and for one year after the introduction of fixed concentration limits are presented., Results: A total of 2340 blood samples were analyzed for the presence of medications and/or illicit drugs for the period 1997-2006. The average number of cases per year was 234 (213-283), and on average 87 percent of the investigated cases were positive for one or more drugs. For 2008 the number of investigated traffic cases was increased to 1176. Seventy-three percent of the cases from 2008 were positive for one or more drugs. Benzodiazepines, cannabis (THC), amphetamine, heroin/morphine, methadone, cocaine, and ecstasy were the most frequently detected drugs for the period 1997-2006 and also in 2008. The number of these cases in which an ethanol level was detected above 0.5 mg/g (the Danish legal limit) was on average 18 percent (9-26%) for the period 1997-2006 and 19 percent for 2008. The average age of the drivers ranged from 31 to 34 years for the period 1997-2006 and was 31 years for 2008. The percentage of females per year ranged from 3 to 20 percent., Conclusion: The number of traffic cases investigated for substances other than ethanol were consistently low, in the range of 200 to 300 per year during the period from 1997 to 2006, but after the introduction of fixed concentration limits in 2007 a 5-fold increase was seen already in 2008.

An ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) method for detection of 23 benzodiazepines and related compounds in whole blood was developed and validated. The method is used for screening and quantitation of benzodiazepines in whole blood received from autopsy cases and living persons. The detected compounds were alprazolam, bromazepam, brotizolam, chlordiazepoxide, demoxepam, clobazam, clonazepam, 7-aminoclonazepam, diazepam, nordiazepam, estazolam, flunitrazepam, 7-aminoflunitrazepam, lorazepam, lormetazepam, midazolam, nitrazepam, 7-aminonitrazepam, oxazepam, temazepam, triazolam, zaleplon, and zopiclone. Whole blood from drug-free volunteers was used for all experiments. Blood samples (0.200 g) were extracted with ethyl acetate at pH 9. Target drugs were quantified using a Waters ACQUITY UPLC system coupled to a Waters Quattro Premier XE triple quadrupole in positive electrospray ionization, multiple reaction monitoring mode. The use of deuterated internal standards for most compounds verified that the accuracy of the method was not influenced by matrix effects. Extraction recoveries were 73-108% for all analytes. Lower limits of quantification ranged from 0.002 to 0.005 mg/kg. Long-term imprecision (CV%) ranged from 6.0 to 18.7%. We present a fully validated UPLC-MS-MS method for 23 benzodiazepines in whole blood with a run-time of only 5 min and using only 0.200 g of whole blood.

Background: The European DRUID (Driving under the Influence of Drugs, Alcohol And Medicines) project calls for analysis of oral fluid (OF) samples, collected randomly and anonymously at the roadside from drivers in Denmark throughout 2008-2009. To analyze these samples we developed an ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for detection of 29 drugs and illicit compounds in OF. The drugs detected were opioids, amphetamines, cocaine, benzodiazepines, and Delta-9-tetrahydrocannabinol., Method: Solid-phase extraction was performed with a Gilson ASPEC XL4 system equipped with Bond Elut Certify sample cartridges. OF samples (200 mg) diluted with 5 mL of ammonium acetate/methanol (vol/vol 90:10) buffer were applied to the columns and eluted with 3 mL of acetonitrile with aqueous ammonium hydroxide. Target drugs were quantified by use of a Waters ACQUITY UPLC system coupled to a Waters Quattro Premier XE triple quadrupole (positive electrospray ionization mode, multiple reaction monitoring mode)., Results: Extraction recoveries were 36%-114% for all analytes, including Delta-9-tetrahydrocannabinol and benzoylecgonine. The lower limit of quantification was 0.5 mug/kg for all analytes. Total imprecision (CV) was 5.9%-19.4%. With the use of deuterated internal standards for most compounds, the performance of the method was not influenced by matrix effects. A preliminary account of OF samples collected at the roadside showed the presence of amphetamine, cocaine, codeine, Delta-9-tetrahydrocannabinol, tramadol, and zopiclone., Conclusions: The UPLC-MS/MS method makes it possible to detect all 29 analytes in 1 chromatographic run (15 min), including Delta-9-tetrahydrocannabinol and benzoylecgonine, which previously have been difficult to incorporate into multicomponent methods.

We present an oxcarbazepine-related fatality together with an overview of 26 postmortem cases involving oxcarbazepine observed during the period 2001-2006. The fatality case concerned a 27-year-old woman with epilepsy, who was found dead in her bed. Oxcarbazepine and its active metabolite, 10-hydroxycarbazepine, were the only compounds detected. The concentrations of oxcarbazepine were as follows: femoral blood, 2.9mg/kg; muscle, 1.8mg/kg; liver, 0.9mg/kg; gastric content (300ml), 860mg/kg; and vitreous humour, not detected. The concentrations of 10-hydroxycarbazepine were as follows: femoral blood, 66mg/kg; muscle, 40mg/kg; liver, 62mg/kg; gastric content, 27mg/kg; and vitreous humour, 25mg/kg. The analyses were performed by HPLC-DAD after liquid-liquid extraction. Oxcarbazepine intoxication was regarded as a possible cause of death. For the other 26 cases, the 10-hydroxycarbazepine concentrations ranged from 2.2 to 48mg/kg with a median of 25mg/kg.

Introduction: The goal of this investigation was to determine the pattern of fatal poisonings in eastern Denmark from 1998 to 2002 and compare it with similar investigations from 1979 to 1996., Materials and Methods: The material included 2,996 autopsies from eastern Denmark in which extensive forensic chemical investigations were performed., Results: Of the 2,996 autopsies, 694 cases were drug addicts, in whom 497 fatal overdoses were detected, while in the remaining 2,302 cases of nonaddicts, 443 fatal poisonings were determined. Morphine (heroine) and methadone were the main causes of death among the fatal poisonings of the drug addicts, accounting for 90% of the cases. The fatal poisonings among the nonaddicts were due mainly to medicine (73% of the cases); 13% were due to carbon monoxide and/or cyanide poisoning, and 12% were due to acute ethanol poisoning. The medicine was a wide range of strong and weak analgesics, antidepressants and antipsychotic drugs of older and newer origins. Comparison with earlier investigations from 1979 to 1996 showed that the poisoning pattern had changed, but similarities were also seen. The most frequently occurring drugs involved in fatal poisonings in eastern Denmark from 1979 to 2002 were morphine, methadone, ethanol and carbon monoxide/cyanide, of which methadone increased in occurrence over the 23-year period., Conclusion: The investigation of fatal poisonings is an important element in monitoring changes in drug abuse and poisoning patterns and levels.

This article describes an investigation of illicit drugs at street level in six selected police districts in different regions of Denmark. The investigation was carried out during a 6-year period from 1995 to 2000. During the period, a total of 1244 samples were examined, as about 200 samples were seized each year. A total of 94% of the seized samples were familiar drugs: heroin base, heroin hydrochloride, cocaine hydrochloride and amphetamine sulphate. Only 2% of the samples contained designer drugs. From having constituted 53% of the samples in 1995, the frequency of heroin base fell during the period to 27% of the samples in 2000. The frequency of heroin hydrochloride was unchanged. In the same period, the frequency of cocaine hydrochloride increased from 10% of the samples in 1995 to about 25% of the samples in 2000. Apart from a few exceptions, cocaine had the same extension in all regions of Denmark after 1996. Amphetamine was more frequent in the west of Denmark, while heroin hydrochloride was more frequent in central Denmark. The purity of heroin base was lower in the period 1997-1999 than in the other years. During the entire period, the purity of cocaine hydrochloride and amphetamine sulphate fell, while the purity of heroin hydrochloride was unchanged. No significant differences between the various regions of Denmark were detected during the period in the purity of heroin hydrochloride, heroin base, cocaine hydrochloride or amphetamine sulphate. MDMA was the most frequent designer drug, but other types of designer drugs such as MDA and MDE and the less common PMA, PMMA and MBDB were also found.

The study includes medicolegally examined fatal poisonings among drug addicts in 1997 in the five Nordic countries: Denmark, Finland, Iceland, Norway and Sweden, and the results are compared to a similar investigation from 1991. A common definition of "drug addict" was applied by the participating countries. The highest death rate by poisoning in drug addicts was observed in Denmark, where it was 6.54 per 10(5)inhabitants, followed by Norway with 6.35, Sweden with 2.21, Finland with 1.63 and Iceland with 1.20 per 10(5)inhabitants. All countries showed a higher death rate in 1997 than in 1991. For all countries the distribution of deaths according to geographical regions showed a decreasing number of drug deaths in the metropolitan area and an increasing number in other cities. Heroin/morphine dominated as the cause of death and was responsible for about 90% of the cases in Norway. In Sweden and Denmark, however, heroin/morphine caused only about 70% of the fatal poisonings. About 30% of the fatal poisonings in Denmark and Sweden were caused by other group I drugs, in Denmark mainly methadone and in Sweden mainly propoxyphene. Apart from two cases in Sweden methadone deaths were not seen in the other Nordic countries. In Finland heroin/morphine deaths have increased from about 10% in 1991 to about 40% in 1997. Forty-four percent of the fatal poisonings in Finland were caused by other group I drugs, mainly codeine and propoxyphene. The two fatal poisonings in Iceland were caused by carbon monoxide. Only few deaths in this investigation were caused by amphetamine and cocaine. A widespread use of alcohol, cannabis and benzodiazepines, especially diazepam, was seen in all the countries.

Introduction: The aim of this investigation was to examine illegal tablets and capsules seized in Jutland, the western part of Denmark, during the period 1995-1999. The drugs are described according to technical appearance (colour, logo, score, diameter) and content of synthetic drugs., Material and Methods: All illegal tablets and capsules received during the period 1995-1999 (109 cases containing 192 different samples) were examined., Results: MDMA was the most common drug and was seen during the entire period. Amphetamine was the second most common drug and has been frequently detected during the the last two years. Drugs like MDE, MBDB, BDB, and 2-CB were rarely seen and they disappeared quickly from the illegal market. MDA appeared on the market at the end of 1999. Only 53% of the tablets contained MDMA as the sole drug. Eighty-one percent of the tablets/capsules contained only one synthetic drug, whereas 13% contained a mixture of two or more synthetic drugs. Six per cent of the samples did not contain a euphoric drug/designer drug. The content of MDMA, MDE, and amphetamine in the tablets varied greatly., Discussion: MDMA is apparently the drug preferred by the users, but still only half of the tablets contained MDMA as the only drug. The rest of the tablets contained either another synthetic drug or a mixture of drugs. In conclusion, the increasing supply of various drugs with different and unpredictable effects and of miscellaneous quality brings about the risk of serious and complicated intoxications.

Introduction: The purpose of this study was to investigate fatal poisonings among drug addicts in 1997 and to compare the results to similar investigations from 1985 and 1991., Material and Methods: All fatal intoxications among drug addicts in Denmark in 1997, investigated at the three Institutes of Forensic Medicine in Denmark., Results: The number of fatal intoxications increased by 32% from 1991 to 1997, mainly outside the metropolitan area, The average age increased from 32 to 36 years. The proportion of heroin/morphine intoxications increased from 57% to 71%. The most commonly used drugs were as in 1991 heroin/morphine, diazepam and methadone. The frequency of cocaine increased from one positive case in 1991 to 14% positive cases in 1997., Discussion: This study showed an increasing number of fatal intoxications and changes in drug abuse pattern and place of death since 1991.

The aim of this investigation was to examine the deaths of drug addicts from poisoning in the county of Funen in 1995 and 1996. The cause of death was related to drugs on the illicit market. Social conditions (homelessness, involvement in crime, psychogenic disease, circumstance of death) are discussed. The study included 47 drug addicts. Median age was 34, age span: 20-43. The main cause of death was poisoning by heroin. In 28% of the drug addicts cocaine was detected and in 13% amphetamine. About half had used benzodiazepines. Few were employees, most were criminals and eight were homeless. Thirty-eight percent were found in public lavatories. Eight had a serious psychiatric diagnosis. We can conclude that the drug addicts are socially marginalized. They abused a mixture of drugs. The drugs detected in the drug addicts compared well with the drugs on the illicit market and cocaine had gained access to the market.

Citalopram was found in 92 autopsy cases and 27 cases from living persons and the concentrations are described. A range of 6.2-19 mumol/kg whole blood was found in cases where citalopram alone was the cause of death and a range of 1.9-16 mumol/kg whole blood in cases, where citalopram together with other compounds were considered to be the cause of death. In autopsy cases toxic concentrations were in the range 1.2-2.8 mumol/kg whole blood and concentrations between 0:09 and 1.9 mumol/kg were considered therapeutic. In cases from living persons the citalopram concentrations in whole blood were 0.06-0.9 mumol/kg.

A prospective and comprehensive investigation was done on 73 medico-legal autopsies in alcoholics. The results of the toxicology analyses are described. Alcohol intoxication was the cause of death in 8%, combined alcohol/drug intoxication in 15% and drugs alone in 19%. Alcoholic ketoacidosis was found to be the cause of death in 7%. Altogether toxicology analyses were necessary for determining the cause of death in 51% of the cases. In four cases the cause of death would not have been found, had this investigation not been made. It is concluded that toxicology analyses should be the rule rather than the exception in deaths in alcoholics.

Fatal poisonings among young drug addicts (15-34 years) in the five Nordic countries, Denmark, Finland, Iceland, Norway and Sweden in 1991 were investigated and compared to a similar investigation for 1984-1985 (Sweden for 1984 only). A common definition of 'drug addict' has been applied by the participating countries. In both investigations, the greatest number of drug addict deaths was seen in Denmark calculated per 10(5) inhabitants, followed in descending order by Norway, Sweden, Finland and Iceland. An increased number of deaths was observed from 1984-1985 to 1991 in all five countries. The increase in Denmark and Sweden was small while the number of deaths was more than doubled in Norway and Finland. The increased number of cases in Norway and Sweden in 1991 is mainly due to a greater number of deaths in the age group 25-34 years. In Finland, the increased number was seen mainly in the age group 15-24 years. In the two investigations heroin/morphine caused most of the fatal poisonings in Norway and Sweden. In Denmark, heroin/morphine caused about half of the fatal poisonings only, and strong analgesics other than heroin/morphine caused about one third of the deaths. In 1984-1985 it was methadone, propoxyphene and ketobemidone and in 1991 mostly methadone. The number of heroin/morphine related deaths in Finland increased from 1984-1985 to 1991, but other drugs and poisons caused a much higher proportion of the deaths. Pentobarbital caused the only fatal poisoning in Iceland in 1991.

The study includes medicolegally examined deaths among drug addicts in 1991 in the five Nordic countries: Denmark, Finland, Iceland, Norway and Sweden. A common definition of 'drug addict' was applied by the participating countries. The greatest number of drug addict deaths per 10(5) inhabitants was observed in Denmark followed, in descending order by Norway, Sweden, Finland and finally Iceland with only four deaths. The main difference between the countries was found in the number of fatal poisonings. The distribution according to geographical regions showed that about half of all drug addict deaths occurred in the metropolitan areas. Of the capitals, the greatest number of fatal poisonings per 10(5) inhabitants was seen in Oslo, followed by Copenhagen with a similar number, Stockholm with only the half, and Helsinki with a quarter. Heroin/morphine dominated as cause of death in fatal poisonings in Norway and Sweden. In Denmark, heroin/morphine caused about half of the fatal poisonings only, and nearly one third of the fatal poisonings was caused by methadone. Except for two cases in Sweden, methadone deaths were not seen in the other Nordic countries. Amphetamine caused one tenth of the fatal poisonings in Sweden. In Finland only one tenth of the deaths were caused by heroin/morphine and more by codeine, ethylmorphine and different drugs and poisons not classified in Single Convention on Narcotic Drugs 1961 or the International Convention on Psychotropic Substances 1971. A widespread use of alcohol, cannabis and benzodiazepines, diazepam especially, was seen in all the countries.

This study includes death from poisoning among drug addicts in 1993 in the county of Funen, in all 24. The development during the last five years shows an increase, especially in the largest city in the county. The drug addicts have several problems, and several of them were well-known in the social welfare system or by the police. Half of the drug addicts had received treatment for their abuse and three persons were receiving treatment at the time of their death. A few--primarily among the youngest--had only used drugs for a short time while one third had abused drugs for several years. The greater part of the deaths were caused by heroin, which is found in different concentrations in the illegal market. Five of the dead persons had just been released from prison and three people had just left 24-hour care centres when they were found dead. Co-operation between the various, treating authorities has to be given a high priority.

This study includes all deaths among drug addicts in the years 1991 (n = 219) and 1992 (n = 214) investigated at the three institutes of forensic medicine in Denmark. The results are compared with deaths among drug addicts in 1984-1985. The number of deaths among drug addicts increased by approximately 50% in 1991-1992 compared with 1984-1985. The increase was most significant among drug addicts over 35 years of age. The cause of death was intoxication in three-quarters of the cases in 1991-1992. In half of these cases heroin/morphine had caused death, while intoxications caused by methadone accounted for approximately 30% of the cases. In the metropolitan area the frequency of methadone intoxications increased significantly compared with 1984-1985, whereas the number of heroin/morphine intoxications did not change. Outside the metropolitan area, however, a significant increase in heroin/morphine intoxications was noticed. In all parts of the country the number of propoxyphene intoxications decreased to a few annual cases. The most commonly used drugs of abuse were heroin/morphine, diazepam and methadone, often in combination with alcohol.

In the period 1987-1991 a total of 739 fatalities among drug addicts was investigated at the three University Institutes of Forensic Medicine in Denmark. The annual number rose from 130-140 in the first 4 years to 192 in 1991, and 80% were males. The mean and median age for both males and females increased by 1 year in the period. The main drug of abuse was heroin, in most cases supplemented by various other drugs, and in almost all cases taken intravenously. In about one-third of the cases each year there was information of abuse of alcohol in addition. In the poisoning cases, the main drug of poisoning was morphine/heroin, constituting 35-55% of the cases each year. As regards methadone-poisoning cases, the number increased significantly in 1991 compared to the first 4 years. Furthermore, the number and proportion of addicts dying while in methadone treatment increased during the 5-year period. In about half of the methadone poisoning cases, there was information of methadone treatment at the time of death. The other half obviously obtained the methadone completely illegally. Ketobemidone was the third most frequent drug of poisoning, while propoxyphene and barbituric acid only were found in a very few cases each. The results are compared to those from an earlier investigation concerning drug deaths in Denmark in 1968-1986. The importance of registering drug deaths is emphasized.

In a 3-year period (1989-1991) a non-selected, consecutive series of 62 deaths in drug addicts was autopsied at the Forensic Institute in Odense. The kidney sections from these addicts were examined for the presence of renal myoglobin using immunohistochemical methods. A reference group consisting of a non-selected, non-consecutive series of 58 autopsied non-addicts was likewise investigated for the presence of renal myoglobin. No major differences were demonstrated between the two groups. The presence of renal myoglobin probably indicates a prolonged course of events prior to death (unconsciousness, immobilization, hypovolemia). In sufficient amounts, renal myoglobin may be of importance as a cause of death or a contributing factor to death in both drug addicts and non-addicts.

Deaths among drug addicts in Funen and in the south part of Jutland in the period 1989-1991 are described with respect to sex, age, social conditions, cause of death etc. The material included 62 drug addict deaths. The mean age was 31 years, range 15-49 years. Seventy-seven percent died from poisoning. A heroin overdose was the cause of death in 65% of these cases. There were two (3%) deaths from methadone. In 34 of the cases we found benzodiazepines, and in 29 cases alcohol. It appeared from information from family/friends that 45 had an abuse pattern involving multiple substances, so it seems that such abuse is common.

Studies of zinc status in insulin-dependent diabetes mellitus (IDDM) have shown contradictory results. Zinc is essential for many enzymes involved in the human metabolism and may play a role in the biosynthesis and storage of insulin in the B-cell. We therefore prospectively followed 26 patients (14 males and 12 females) with newly diagnosed IDDM in order to determine the plasma zinc variation at the time of diagnosis and after 1, 3, 6, 12 and 24 months. Seventy-two healthy persons (36 males and 36 females) served as controls. Only minor differences in plasma zinc were demonstrated during the first 2 years of IDDM. A sex difference was found in healthy controls but only after 24 months in the diabetics. Quantitative changes of the B-cell function, development of insulin antibodies, age, body weight and serum albumin did not correlate with the course of plasma zinc.