How Nordic Countries Enforce Impaired Driving Legislation.

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 These clinical tests have been superseded by results derived from a comprehensive toxicological analysis of psychoactive substances in samples of the driver's blood.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.

Clinical and forensic toxicology of methanol.

Methanol has a very simple chemical structure (CH3OH) considering its potential health hazard, including the many poisoning deaths after ingestion. In countries where authentic alcoholic beverages are expensive, restricted, or banned for religious or other reasons, some people resort to purchasing alcoholic drinks made illegally. These clandestine sources of "booze" often contain high concentrations of methanol, added by the perpetrators to enhance potency and increase profits. Although an effective medical treatment for methanol poisoning exists, because most such incidents occur in socially deprived parts of the world, the hospital emergency facilities are scarce and/or inadequate. Trace amounts of methanol (median ~1.0 mg/L) are produced endogenously via certain enzymatic processes, such as one-carbon metabolism. Methanol and methyl esters are also contained in fresh fruits and vegetables as well as in alcoholic beverages. During a period of heavy drinking the blood-methanol concentration (BMC) increases and might surpass 10 mg/L, which is considered a biomarker for alcohol abuse and alcoholism. Methanol itself has a low intrinsic toxicity, but is converted in the body into two highly toxic metabolites, formaldehyde and formic acid. This metabolism is delayed by co-ingestion of ethanol, which creates a latent period of 12-24 h before toxic symptoms develop. Accordingly, when patients are admitted to hospital for diagnosis and treatment, a life-threatening metabolic acidosis has already developed and is irreversible. Symptoms of methanol poisoning include blurred vision, breathlessness, nausea, gastric pains, and acid-base disturbances and deficiency of oxygen in arterial blood. The visual disturbances might even develop into permanent blindness, owing to an interaction of toxic metabolites with the optic nerve. The minimum lethal dose of ethanol in humans is not easy to specify, because most poisonings involve co-ingestion of ethanol, which to some extent protects the patient from toxic sequelae. Effective antidotes for treatment of methanol poisoning are administration of ethanol or the therapeutic drug fomepizole (Antizol®), which is 4-methyl pyrazole (4-MP). Both treatments work by blocking the metabolism of methanol by liver alcohol dehydrogenase (ADH). The metabolic acidosis caused by the accumulation of formic acid in the body is treated with sodium bicarbonate, which helps to normalize pH in the bloodstream. Thereafter, methanol and its metabolites in the blood are removed by hemodialysis. However, the long-term prognosis for survivors of methanol poisoning is not good, because many are elderly males who are in poor health and often suffer from an alcohol-use disorder.

Increased sensitivity of higher-order laser beams to mode mismatches.

This Letter derives explicit factors linking mode-mismatch-induced power losses in Hermite-Gauss optical modes to the losses of the fundamental spatial mode. Higher-order modes are found to be more sensitive to beam parameter mismatches. This is particularly relevant for gravitational-wave detectors, where lasers employing higher-order optical modes have been proposed to mitigate thermal noise, and quantum-enhanced detectors are very susceptible to losses. This work should inform mode matching and squeezing requirements for Advanced+ and third generation detectors.

High dynamic range spatial mode decomposition.

An accurate readout of low-power optical higher-order spatial modes is of increasing importance to the precision metrology community. Mode sensors are used to prevent mode mismatches from degrading quantum and thermal noise mitigation strategies. Direct mode analysis sensors (MODAN) are a promising technology for real-time monitoring of arbitrary higher-order modes. We demonstrate MODAN with photo-diode readout to mitigate the typically low dynamic range of CCDs. We look for asymmetries in the response of our sensor to break degeneracies in the relative alignment of the MODAN and photo-diode and consequently improve the dynamic range of the mode sensor. We provide a tolerance analysis and show methodology that can be applied for sensors beyond first order spatial modes.

High Correlation between Ethanol Concentrations in Postmortem Femoral Blood and in Alternative Biological Specimens, but Large Uncertainty When the Linear Regression Model Was Used for Prediction in Individual Cases.

In connection with medicolegal autopsies peripheral blood (e.g. from a femoral vein) is the specimen of choice for toxicological analysis, although alternative specimens are also sometimes submitted, such as bile, cerebrospinal fluid (CSF), vitreous humor (VH), bladder urine, pleural effusions and/or lung fluid. Ethanol concentrations were determined in duplicate in femoral blood and in various alternative biological specimens by headspace gas chromatography. The analysis was carried out on two different fused silica capillary columns furnishing different retention times for ethanol and both n-propanol and t-butanol were used as internal standards. The results were evaluated by linear regression using blood alcohol concentration (BAC) as dependent or outcome variable and the concentrations in an alternative specimen as independent or predictor variable. The Pearson correlation coefficients were all statistically highly significant (P < 0.001); r = 0.94 (bile), r = 0.98 (CSF), r = 0.97 (VH), r = 0.92 (urine), r = 0.94 (lung fluid) and r = 0.96 (pleural cavity effusions). When the regression model was used to predict femoral BAC from the mean concentration in an alternative specimen the mean and 95% prediction intervals were 1.12 ± 0.824 g/L (bile), 1.41 ± 0.546 g/L (CSF), 1.15 ± 0.42 g/L (VH), 1.29 ± 0.780 g/L (urine), 1.25 ± 0.772 g/L (lung fluid) and 0.68 ± 0.564 g/L (pleural cavity effusions). This large uncertainty for a single new observation needs to be considered when alcohol-related deaths are evaluated and interpreted. However, the analysis of alternative specimens is recommended in medical examiner cases to provide supporting evidence with regard to the origin of ethanol, whether this reflects antemortem (AM) ingestion or postmortem (PM) synthesis.

Driving under the influence of psychoactive substances - A historical review.

Important events in the history of driving under the influence of alcohol (DUI) and/or other drugs (DUID) are reviewed covering a period of approximately 100 years. This coincides with major developments in the pharmaceutical industry and the exponential growth in motor transportation worldwide. DUID constitutes an interaction between the driver, the motor-driven vehicle, and one or more psychoactive (mind-altering) substances. In this connection, it is important to differentiate between drugs intended and used for medical purposes (prescription or licit drugs) and recreational drugs of abuse (illicit drugs). All chemicals with a mechanism of action in the central nervous system (brain and spinal cord) are potentially dangerous to use when skilled tasks, such as driving, are performed. The evidence necessary to charge a person with drug-impaired driving has evolved over many years and initially rested on a driver's own admissions and observations made about the driving by police officers or eyewitnesses. Somewhat later, all suspects were examined by a physician, whose task was to ask questions about any recent ingestion of alcohol and/or other drugs and to administer various clinical tests of impairment. By the 1940s-1950s, the driver was asked to provide samples of blood, breath, or urine for toxicological analysis, although the test results served only to verify the type of drug causing impairment of the driver. The current trend in DUID legislation is toward zero-tolerance or concentration per se statutes, which are much more pragmatic, because behavioral evidence of impairment is no longer a lynchpin in the prosecution case. This legal framework puts considerable emphasis on the results of toxicological analysis; therefore, the methods used must be accurate, precise, and fit for forensic purposes. Many traffic delinquents charged with DUI or DUID suffer from a substance use and/or personality disorder, with high recidivism rates. In addition to conventional penalties and sanctions for drug-related traffic crimes, many offenders would probably benefit from a medical intervention, such as counseling, rehabilitation, and treatment for substance use disorder, which often coexists with a mental health problem.

The effects of bovine colostrum supplementation on in vivo immunity following prolonged exercise: a randomised controlled trial.

BACKGROUND: Bovine colostrum (COL) has been advocated as a nutritional countermeasure to exercise-induced immune dysfunction, but there is a lack of research with clinically relevant in vivo measures. AIM: To investigate the effects of COL supplementation on in vivo immunity following prolonged exercise using experimental contact hypersensitivity (CHS) with the novel antigen diphenylcyclopropenone (DPCP). METHODS: In a double-blind design, 31 men were randomly assigned to COL (20 g/day) or placebo (PLA) for 58 days. Participants ran for 2 h at 60% maximal aerobic capacity on day 28 and received a primary DPCP exposure (sensitisation) 20 min after. On day 56, participants received a low-dose-series DPCP challenge to elicit recall of in vivo immune-specific memory (quantified by skinfold thickness 24 and 48 h later). Analysis of the dose-response curves allowed determination of the minimum dose required to elicit a positive response (i.e., sensitivity). RESULTS: There was no difference in summed skinfold thickness responses between COL and PLA at 24 h (p = 0.124) and 48 h (p = 0.405). However, sensitivity of in vivo immune responsiveness was greater with COL at 24 h (p < 0.001) and 48 h (p = 0.023) with doses ~ twofold greater required to elicit a positive response in PLA. CONCLUSIONS: COL blunts the prolonged exercise-induced decrease in clinically relevant in vivo immune responsiveness to a novel antigen, which may be a mechanism for reduced illness reports observed in the previous studies. These findings also suggest that CHS sensitivity is highly relevant to host defence.

Relationship Between Postmortem Urine and Blood Concentrations of GHB Furnishes Useful Information to Help Interpret Drug Intoxication Deaths.

This article reports the concentrations of gamma-hydroxybutyrate (GHB) in femoral blood and bladder urine in a case series of drug intoxication deaths (N = 37). GHB was determined in blood (B-GHB) and urine (U-GHB) by a GC-FID-GBL method and 30 mg/L was used as a cut-off concentration for reporting positive results. The mean (median) and range of GHB concentrations in bladder urine were 2,818 mg/L (1,900 mg/L) and 120-13,000 mg/L, respectively. These concentrations were appreciably higher than those in femoral blood, 637 mg/L (260 mg/L) and 30-9,200 mg/L, respectively. Urine/blood ratios of GHB were highly variable (mean 8.99, median 5.33 and range 0.16-29.3). GHB is rapidly metabolized and cleared from the bloodstream, whereas there is no metabolism occurring in the urinary bladder. In five autopsy cases, U-GHB was lower than B-GHB, which suggests that these individuals died before equilibration of the drug in all body fluids and tissues. In the other 32 deaths, U-GHB was higher than B-GHB, sometimes appreciably higher, which points towards a longer survival time after intake or administration of GHB. The analysis of urine extends the window of detection of GHB by several hours compared with blood samples, depending in part on when the bladder was last voided before death. Furthermore, the urinary concentration of GHB gives a hint about the concentration in blood during the time that the urine was produced in the kidney and stored in the bladder since the previous void.

Decreases in blood ethanol concentrations during storage at 4 °C for 12 months were the same for specimens kept in glass or plastic tubes.

BACKGROUND: The stability of ethanol was investigated in blood specimens in glass or plastic evacuated tubes after storage in a refrigerator at 4 °C for up to 12 months. METHODS: Sterile blood, from a local hospital, was divided into 50 mL portions and spiked with aqueous ethanol (10% w/v) to give target concentrations of 0.20, 1.00, 2.00 and 3.00 g/L. Ethanol was determined in blood by headspace gas chromatography (HS-GC) with an analytical imprecision of <3% (coefficient of variation, CV%). Aliquots of blood were re-analysed after 2, 7, 14, 28, 91, 182 and 364 days of storage at 4 °C. RESULTS: The standard deviation (SD) of analysis by HS-GC was 0.0059 g/L at 0.20 g/L and 0.0342 g/L at 3.00 g/L, corresponding to CVs of 2.9% and 1.1%, respectively. The decreases in blood ethanol content were analytically significant after 14-28 days of storage for both glass and plastic tubes The mean (lowest and highest) loss of ethanol after 12 months storage was 0.111 g/L (0.084-0.129 g/L) for glass tubes and 0.112 g/L (0.088-0.140 g/L) for plastic tubes. The corresponding percentage losses of ethanol were 43-45% at a starting concentration of 0.20 g/L and 3.9-4.1% at 3.00 g/L. CONCLUSION: The concentration of ethanol in blood gradually decreases during storage at 4 °C. After 12 months storage the absolute decrease in concentration was ~0.11 g/L when the starting concentration ranged from 0.20 to 3.0 g/L. Decreases in ethanol content were the same for specimens kept in glass or plastic evacuated tubes.

Influence of 4 weeks of bovine colostrum supplementation on neutrophil and mucosal immune responses to prolonged cycling.

Bovine colostrum (COL) has been advocated as a nutritional countermeasure to exercise-induced immune dysfunction. The aims of this study were to identify the effects of 4 weeks of COL supplementation on neutrophil responses and mucosal immunity following prolonged exercise. In a randomized double-blind, parallel group design, participants [age 28 ± 8 years; body mass 79 ± 7 kg; height 182 ± 6 cm; maximal oxygen uptake (V̇O2max) 55 ± 9 mL/kg/min] were assigned to 20 g per day of COL (n = 10) or an isoenergetic/isomacronutrient placebo (PLA; n = 10) for 4 weeks. Venous blood and unstimulated saliva samples were obtained before and after 2.5 h of cycling at 15% Δ (∼55-60% V̇O2max). A significantly greater formyl-methionyl-leucyl phenylalanine-stimulated oxidative burst was observed in the COL group compared with PLA group (P < 0.05) and a trend toward a time × group interaction (P = 0.06). However, there was no effect of COL on leukocyte trafficking, phorbol-12-myristate-13-acetate-stimulated oxidative burst, bacterial-stimulated neutrophil degranulation, salivary secretory IgA, lactoferrin or lysozyme (P > 0.05). These findings provide further evidence of the beneficial effects of COL on receptor-mediated stimulation of neutrophil oxidative burst in a model of exercise-induced immune dysfunction.

Cause and manner of death and phase of the blood alcohol curve.

In a large number of forensic autopsies (N = 28,184) the concentrations of ethanol in femoral blood and bladder urine were determined and the urine-to-blood concentration ratios of ethanol were calculated. Based on the differences in ethanol concentration between urine and blood, the deaths were classified as having occurred during the absorptive, the peak or the post-absorptive phase of the blood­alcohol curve. Most people died in the post-absorptive phase, N = 24,223 (86%), whereas 1538 individuals (5.5%) were still absorbing alcohol and 2423 (8.6%) were at or close to the peak BAC at time of death. Both blood­alcohol concentration (BAC) and urine­alcohol concentration (UAC) were significantly higher in the post-absorptive phase (p < 0.001). The proportions of people dying in the absorptive and peak phases increased with advancing age. The cause of death (CoD) and manner of death (MoD) according to death certificates were compared with phase of the blood­alcohol curve using a multinomial regression model with and without making adjustment for possible effects of age, gender and BAC. The relative risk (RR) and relative risk ratios (RRR) showed some associations between CoD and phase of the blood­alcohol curve. Undetermined MoD was significantly higher in the absorptive phase compared with the post-absorptive phase (RRR = 2.12). Deaths related to esophagus, stomach and duodenum (RRR = 2.04) and alcoholic liver diseases (RRR = 1.85) were significantly higher at or close to peak phase compared to the post-absorptive phase. Road-traffic fatalities were more prevalent in the peak BAC phase (RRR = 1.33) and deaths by accidental falls were less in the absorptive phase (RRR = 0.58) compared with the post-absorptive phase. The phase of alcohol intoxication seems relevant to consider by forensic experts when alcohol-related deaths are investigated.

Utility of urinary ethyl glucuronide analysis in post-mortem toxicology when investigating alcohol-related deaths.

Use and abuse of alcohol are common findings when unnatural deaths are investigated as evidenced by high blood- and urine- alcohol concentrations (BAC and UAC) at autopsy. Because ethanol is metabolized in the liver until the time of death, the autopsy BAC or UAC might be negative even though the deceased had consumed alcohol in the immediate ante-mortem period. Analysis of the non-oxidative metabolite of ethanol [ethyl glucuronide (EtG)] offers a more sensitive test of recent drinking. In this paper, we determined the concentrations of ethanol and EtG in urine samples from 972 consecutive forensic autopsies. In 425 cases (44%) both EtG and ethanol were positive, which supports ante-mortem drinking. In 342 cases (35%), both EtG and ethanol was negative, which speaks against any consumption of alcohol just before death. In 181 cases, ethanol was negative in urine (<0.2 g/kg), whereas EtG was positive (>0.5 mg/L), which points towards ingestion of alcohol some time before death. In these cases, mean and median concentrations of EtG were 53.2 mg/L and 23.7 mg/L, respectively, although there was no mention of alcohol on 131 of the death certificates. Alcohol was mentioned on death certificates as an underlying or immediate cause of death or a contributing factor in 435 (45%) cases, which rose to 566 (58%) cases when positive EtG results were included. This article demonstrates the usefulness of EtG analysis in routine post-mortem toxicology when ante-mortem drinking and alcohol-related deaths are investigated.

The protein disulfide isomerases PDIA4 and PDIA6 mediate resistance to cisplatin-induced cell death in lung adenocarcinoma.

Intrinsic and acquired chemoresistance are frequent causes of cancer eradication failure. Thus, long-term cis-diaminedichloroplatine(II) (CDDP) or cisplatin treatment is known to promote tumor cell resistance to apoptosis induction via multiple mechanisms involving gene expression modulation of oncogenes, tumor suppressors and blockade of pro-apoptotic mitochondrial membrane permeabilization. Here, we demonstrate that CDDP-resistant non-small lung cancer cells undergo profound remodeling of their endoplasmic reticulum (ER) proteome (>80 proteins identified by proteomics) and exhibit a dramatic overexpression of two protein disulfide isomerases, PDIA4 and PDIA6, without any alteration in ER-cytosol Ca(2+) fluxes. Using pharmacological and genetic inhibition, we show that inactivation of both proteins directly stimulates CDDP-induced cell death by different cellular signaling pathways. PDIA4 inactivation restores a classical mitochondrial apoptosis pathway, while knockdown of PDIA6 favors a non-canonical cell death pathway sharing some necroptosis features. Overexpression of both proteins has also been found in lung adenocarcinoma patients, suggesting a clinical importance of these proteins in chemoresistance.

PGC-1ß mediates adaptive chemoresistance associated with mitochondrial DNA mutations.

Primary mitochondrial dysfunction commonly leads to failure in cellular adaptation to stress. Paradoxically, however, nonsynonymous mutations of mitochondrial DNA (mtDNA) are frequently found in cancer cells and may have a causal role in the development of resistance to genotoxic stress induced by common chemotherapeutic agents, such as cis-diammine-dichloroplatinum(II) (cisplatin, CDDP). Little is known about how these mutations arise and the associated mechanisms leading to chemoresistance. Here, we show that the development of adaptive chemoresistance in the A549 non-small-cell lung cancer cell line to CDDP is associated with the hetero- to homoplasmic shift of a nonsynonymous mutation in MT-ND2, encoding the mitochondrial Complex-I subunit ND2. The mutation resulted in a 50% reduction of the NADH:ubiquinone oxidoreductase activity of the complex, which was compensated by increased biogenesis of respiratory chain complexes. The compensatory mitochondrial biogenesis was most likely mediated by the nuclear co-activators peroxisome proliferator-activated receptor gamma co-activator-1α (PGC-1α) and PGC-1ß, both of which were significantly upregulated in the CDDP-resistant cells. Importantly, both transient and stable silencing of PGC-1ß re-established the sensitivity of these cells to CDDP-induced apoptosis. Remarkably, the PGC-1ß-mediated CDDP resistance was independent of the mitochondrial effects of the co-activator. Altogether, our results suggest that partial respiratory chain defects because of mtDNA mutations can lead to compensatory upregulation of nuclear transcriptional co-regulators, in turn mediating resistance to genotoxic stress.

Concentration ratios of methamphetamine to amphetamine in blood can help to distinguish use of methamphetamine from various mixtures of the two stimulants.

Using a forensic toxicology database, the authors investigated cases of driving under the influence of drugs (DUID) if methamphetamine (MA) was identified in the blood samples (N = 9,310). The concentrations of MA and amphetamine (AM) in blood were determined after liquid-liquid extraction by gas chromatography-mass spectrometry at limits of quantitation of 0.03 mg/L for both stimulants. In 814 cases, AM was negative in blood and MA was positive at mean (median) and highest concentrations of 0.19 mg/L (0.11 mg/L) and 3.4 mg/L, respectively. Both amines were present in blood in 8,496 cases at concentrations of 0.54 mg/L (0.35 mg/L) and 10.4 mg/L for AM and 0.41 mg/L (0.22 mg/L) and 5.6 mg/L for MA. However, the correlation between AM and MA was low and insignificant (r = -0.13) in the whole material. The coefficient of correlation increased to r = 0.41 (P < 0.001) when the MA/AM concentration ratio was >1. When MA/AM ratios were selected at intervals of 1.0 (e.g., >3.0 and <4.0 up to >9.0 and <10.0), the correlation between AM and MA was r = 0.99 (P < 0.001). Such cases represent the use of MA without contamination from AM, and the mean (median) and highest concentrations of this secondary amine in blood of DUID suspects were 0.72 mg/L (0.56 mg/L) and 4.2 mg/L, respectively.

Blood methadone concentrations in living and deceased persons: variations over time, subject demographics, and relevance of coingested drugs.

Concentrations of d,l-methadone were determined in blood samples from people arrested for driving under the influence of drugs (DUID), users of illicit drugs, and methadone-related deaths. In drug overdose deaths (N = 346), mean (median) and highest concentrations of methadone in femoral blood were 0.53 mg/L (0.40 mg/L) and 6.7 mg/L, compared with 0.46 mg/L (0.30 mg/L) and 3.7 mg/L in non-poisoning deaths (N = 157) (p < 0.05). In DUID suspects and users of illicit drugs (N = 909), the blood-methadone concentrations were much lower, 0.23 mg/L (0.20 mg/L) and 1.1 mg/L (p < 0.001). The median concentration of methadone in blood decreased as the number of coingested drugs increased in the overdose deaths: 0.5 mg/L with methadone the only drug compared with 0.2 mg/L with 6-9 other drugs present (p < 0.001). These coingested drugs were mainly benzodiazepines (diazepam, alprazolam, flunitrazepam) and amphetamines; THC and morphine (from heroin) were the major illicit drugs. The overlap in blood-methadone concentrations in living cases and autopsy cases makes it difficult to conclude that methadone overdose was the cause of death. Adverse drug-drug interactions and varying degrees of tolerance to opiates complicate the interpretation.

Concentrations of free-morphine in peripheral blood after recent use of heroin in overdose deaths and in apprehended drivers.

The concentration of free-morphine was determined in peripheral (femoral) blood from heroin-related deaths and compared with the concentration in venous blood from impaired drivers. The presence of 6-MAM in blood or urine served as a biomarker for recent use of heroin. Males dominated over females (p<0.001) in both the autopsy cases (88%) and the drivers (91%), although their mean age was about the same 33-35 y (p>0.05). Concentrations of free-morphine in blood were not associated with age of heroin users in Sweden (p>0.05). The median concentration of free-morphine was higher in autopsy cases (0.24 mg/L, N=766) compared with apprehended drivers with 6-MAM in blood (0.15 mg/L, N=124, p<0.05), and appreciably higher than in drivers with 6-MAM in urine but not in blood (0.03 mg/L, N=1823, p<0.001). The free-morphine concentration was above 0.20mg/L in 65% of autopsy cases, 36% of drivers with 6-MAM in blood but only 1.4% of drivers with 6-MAM in urine. Poly-drug deaths had about the same concentrations of free-morphine in blood (0.24 mg/L, N=703) as heroin-only deaths (0.25 mg/L, N=63). The concentration of morphine in drug overdose deaths (median 0.25 mg/L, N=669) was about the same as in traumatic deaths among heroin users (0.23 mg/L, N=97). However, the concentration of morphine was lower when the deceased had consumed alcohol (0.18 mg/L, N=104) compared with taking a benzodiazepine (0.32 mg/L, N=94). The concentration distributions of free-morphine in blood in heroin-related deaths overlapped with the concentrations in impaired drivers, which makes the interpretation of toxicology results difficult without knowledge about tolerance to opiates in any individual case.