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Differentiation between consumption of illegal and prescription drugs remains an important aspect in forensic toxicology. While illicit amphetamine is most often racemic, the medicinal drugs marketed in Denmark for the treatment of attention-deficit hyperactivity disorder contain the pure (S)-enantiomer or a prodrug thereof. In this study, we present a simple and efficient analytical workflow to provide information about the origin of amphetamine consumed in forensic cases concerning driving under the influence of drugs (DUID). Following quantification of amphetamine and methamphetamine using our conventional multi-target ultra-high performance liquid chromatography–tandem mass spectrometry method, determination of (R)- and (S)-amphetamine was performed by reinjecting the sample extract on a Phenomenex LUX® AMP chiral column using the same analytical instrument and mobile phases. Chiral separation was performed isocratic within a run time of 6 min. The analytical workflow was applied to blood samples from 5,248 suspected DUID cases within a 2-year period. Amphetamine was detected in 18.7% of the samples, of which both enantiomers were detected in 89.5% of the cases, indicating the consumption of illegal racemic amphetamine. In 6.1% of the positive cases, both amphetamine and methamphetamine were detected, indicating either co-consumption of both amphetamines or consumption of methamphetamine. In the remaining 4.4%, only (S)-amphetamine was detected indicating the consumption of prescription drugs containing (S)-amphetamine or a prodrug thereof. Implementation of a simple and rapid chiral method in the conventional analytical workflow for routine forensic casework proved to be an efficient way to elucidate whether a positive amphetamine result originates from illegal or prescription drug consumption, without increasing turnaround time nor costs to any significant extent, as no additional sample preparation was required. [ABSTRACT FROM AUTHOR]

Therapeutic drug monitoring is a tool for optimising the pharmacological treatment of diseases where the therapeutic effect is difficult to measure or monitor. Therapeutic reference ranges and dose-effect relation are the main requirements for this drug titration tool. Defining and updating therapeutic reference ranges are difficult, and there is no standardised method for the calculation and clinical qualification of these. The study presents a basic model for validating and selecting routine laboratory data. The programmed algorithm was applied on data sets of antidepressants and antipsychotics from three public hospitals in Denmark. Therapeutic analytical ranges were compared with the published therapeutic reference ranges by the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) and in additional literature. For most of the drugs, the calculated therapeutic analytical ranges showed good concordance between the laboratories and to published therapeutic reference ranges. The exceptions were flupentixol, haloperidol, paroxetine, perphenazine, and venlafaxine + o-desmethyl-venlafaxine (total plasma concentration), where the range was considerably higher for the laboratory data, while the calculated range of desipramine, sertraline, ziprasidone, and zuclopenthixol was considerably lower. In most cases, we identified additional literature supporting our data, highlighting the need of a critical re-examination of current therapeutic reference ranges in Denmark. An automated approach can aid in the evaluation of current and future therapeutic reference ranges by providing additional information based on big data from multiple laboratories. [ABSTRACT FROM AUTHOR]

Tramadol is a commonly used opioid with a potential of addiction and abuse. Using Danish nationwide registers, we aimed to (1) characterise opioid poisonings; (2) assess the 30‐day mortality following morphine, oxycodone, and mixed poisonings compared to tramadol poisonings; and (3) assess the development in tramadol poisonings during a 12‐year period. Poisonings were identified from 2006 to 2017. A Cox proportional hazards regression model was used to estimate adjusted hazard ratios (aHRs) along with 95% confidence intervals (CIs) for 30‐day mortality following morphine, oxycodone or mixed poisonings compared to tramadol poisonings. We identified 7718 opioid poisonings among 6365 patients. The patients with a tramadol poisoning were younger and had less comorbidities than the patients with a morphine, oxycodone or mixed poisoning. Within 30 days, a total of 205 patients died. The 30‐day mortality risk was higher following morphine (aHR 3.2, 95% CI 2.0–5.1), oxycodone (aHR 2.1, 95% CI 1.2–3.6) and mixed poisonings (aHR 1.6, 95% CI 1.0–2.7) compared to tramadol poisonings. The annual number of tramadol poisonings increased from 233 in 2006 to 501 in 2013 and declined to 348 in 2017. In conclusion, despite a lower mortality risk compared to other opioid poisonings, physicians should consider the poisoning and abuse risks when prescribing tramadol. [ABSTRACT FROM AUTHOR]

This article reviews how the Nordic countries of Denmark, Finland, Norway, and Sweden enforce their legislation pertaining to driving under the influence of alcohol and/or other impairing drugs. The evidence necessary for a successful prosecution of traffic offenders has undergone radical changes over the past 50 years. The once widely used clinical tests of impairment are no longer a major element of the prosecution case and a physician is more seldom required to examine apprehended drivers and document any clinical signs and symptoms of alcohol and/or drug influence. These clinical tests have been superseded by results derived from a comprehensive toxicological analysis of psychoactive substances in samples of the driver's blood. The current statutory limits of blood-alcohol concentration (BAC) are among the lowest in the world: Norway and Sweden (0.20 g/kg) and Denmark and Finland (0.50 g/kg). Results from using evidential quality breath-alcohol instruments are accepted as evidence in drunk-driving cases and this has necessitated setting statutory breath-alcohol concentration (BrAC) limits. Laws dealing with driving under the influence of drugs (DUID) other than alcohol have also been updated and made more pragmatic for prosecution of traffic offenders. In Finland and Sweden zero-tolerance laws exist, making it illegal to drive with any quantifiable amount of a scheduled drug in the driver's blood. Prescription drugs are exempt from this zero-tolerance mandate provided the medication was used in accordance with a physician's ordination. Lacking a valid prescription or if there is a supratherapeutic concentration of the drug in blood, this will lead to a prosecution for DUID. In Denmark and Norway threshold concentration limits have been established for many psychoactive drugs, both licit and illicit. After these stricter laws for DUID were introduced, the number of suspects apprehended by the police per year increased by as much as tenfold in some Nordic countries. There is increasing evidence that many traffic delinquents in the Nordic countries suffer from a substance-use disorder, because repeat-offending is a common occurrence. This suggests that some type of treatment and rehabilitation program might be more beneficial compared with conventional penalties for people arrested for DUI and/or DUID. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: To describe the use of tramadol and other analgesics in Denmark focusing on the impact of media attention (June and December 2017) and regulatory actions (September 2017 and January 2018) on the use of tramadol., Methods: Using nationwide registries, we identified all adults who filled a prescription for tramadol and other analgesics from 2014 to 2019. We described incidence rates, prevalence proportions, and total use of tramadol and other analgesics over time. We also described switching between analgesics, treatment duration, skewness in drug use, and doctor-shopping., Results: From early 2017 until the end of 2019, total tramadol use decreased markedly while the use of morphine and oxycodone decreased slightly. The quarterly prevalence of tramadol use decreased from 32/1000 individuals in 2014 to 18/1000 at the end of 2019, dropping mainly at the time of media attention. Concomitantly, the quarterly prevalence increased for oxycodone (from 5.1 to 8.2) and morphine (from 8.5 to 9.8), mainly due to more short-term and sporadic users, and decreased for codeine (14 to 9.6). From 2014 to mid-2017, the incidence of tramadol use was stable (around 2.2/1000 person-months) but dropped in June 2017 to 1.7/1000, coinciding with the media attention. The incidence of tramadol use continued to decrease (to 1.1/1000 at the end of 2019)., Conclusion: We identified a decline in tramadol use coinciding with the media attention in 2017 and continuing during regulatory actions. There was generally no evidence of unintended effects on the utilization of opioids related to the media attention and regulatory actions.

Aim. To map and compare mortality and morbidity of poisonings in Denmark, Finland, Iceland, Norway, and Sweden in 2002 and to establish a common understanding of methods and procedures among the National Poisons Information Centres (NPIC) in order to create a Nordic toxico-epidemiological platform. Methods. Morbidity was for this study defined as acute poisonings treated in hospitals given the ICD-10 codes T36-T65 and F10-F19. The figures were extracted from the National Patient/Hospital Registers. Acute poisonings listed as main as well as side diagnoses were included. Deaths recorded as acute poisoning (using the same ICD-10 codes) were collected from the National Death Cause Registers. Results. Annual mortality of acute poisonings per 100,000 inhabitants (rate) was 16.6 in Finland and between 8.6 and 11.1 in the other Nordic countries. Morbidity rates varied between 150 and 255 per 100,000 inhabitants. Conclusion. The death rate due to acute poisoning was 50% higher in Finland compared to the rate in the other Nordic countries. The variable data between countries obtained for morbidity of acute poisonings need further elucidations to verify if the differences are real and not only due to heterogeneous procedures and practice for data collection and recording. [ABSTRACT FROM AUTHOR]