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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.forsciint.2009.01.014 Byline: Alan Wayne Jones, Fredrik C. Kugelberg, Anita Holmgren, Johan Ahlner Keywords: Alcohol; Drugs; Driving; Crash statistics; Fatalities Abstract: According to statistics provided by the Swedish National Road Administration (Vagverket), a total of 1403 drivers were killed in road-traffic crashes in Sweden between 2003 and 2007. Forensic autopsies were performed in [approximately equal to]97% of all deaths and specimens of blood and urine were sent for toxicological analysis. In 60% of cases (N =835) the toxicology results were negative and 83% of these victims were men. The blood-alcohol concentration (BAC) was above the legal limit for driving (>0.2g/L) in 22% of cases (N =315) at mean, median and highest concentrations of 1.7g/L, 1.7g/L and 4.9g/L, respectively. The proportions of male to female drivers with BAC0.2g/L were 93% vs 7% compared with 83% vs 17% for those with drugs other than alcohol in blood. Drivers with a punishable BAC were over-represented in single vehicle crashes compared with multiple vehicle crashes (67% vs 33%). The opposite held for drivers who had taken a prescription drug (39% vs 61%) and also for drug-negative cases (31% vs 69%). Drugs other than alcohol were identified in 253 cases (18%); illicit drugs only in 39 cases (2.8%), both licit and illicit in 28 cases (2.0%) and in 186 cases (13.3%) one or more therapeutic drugs were present. Amphetamine was the most common illicit drug identified at mean, median and highest concentrations of 1.5mg/L, 1.1mg/L and 5.0mg/L, respectively (N =39). Blood specimens contained a wide spectrum of pharmaceutical products (mean 2.4 drugs/person), comprising sedative-hypnotics (N =93), opiates/opioids (N =69) as well non-scheduled substances, such as paracetamol (N =78) and antidepressants (N =93). The concentrations of these substances in blood were mostly in the therapeutic range. Despite an appreciable increase (12-fold) in number of arrests made by the police for drug-impaired driving after a zero-tolerance law was introduced (July 1999), alcohol still remains the psychoactive substance most frequently identified in the blood of drivers killed in road-traffic crashes. Author Affiliation: Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Artillerigatan 12, SE-587 58 Linkoping, Sweden Article History: Received 23 October 2008; Revised 14 January 2009; Accepted 15 January 2009

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.forsciint.2008.08.010 Byline: Alan Wayne Jones, Fredrik C. Kugelberg, Anita Holmgren, Johan Ahlner Keywords: Alcohol; Ethanol; Illicit drugs; Medication; Intoxication; Sexual assault Abstract: Results of toxicological analysis of blood and urine specimens from 1806 female victims of alleged non-consensual sexual activity are reported. After making contact with the police authorities, the victims were examined by a physician for injuries and biological specimens were taken for forensic toxicology and other purposes (e.g. DNA). Urine if available or otherwise on an aliquot of blood after protein precipitation was screened for the presence of drugs by enzyme immunoassay methods (EMIT/CEDIA). All positive results from screening were verified by more specific methods, involving isotope dilution gas chromatography-mass spectrometry (GC-MS) for illicit drugs. A large number of prescription drugs were analyzed in blood by capillary column gas chromatography with a nitrogen-phosphorous (N-P) detector. Ethanol was determined in blood and urine by headspace gas chromatography and concentrations less than 0.1g/L were reported as negative. The number of reported cases of alleged sexual assault was highest during the warmer summer months and the mean age of victims was 24 years (median 20 years), with [approximately equal to]60% being between 15 and 25 years. In 559 cases (31%) ethanol and drugs were negative. In 772 cases (43% of total) ethanol was the only drug identified in blood or urine. In 215 cases (12%) ethanol occurred together with at least one other drug. The mean, median and highest concentrations of ethanol in blood (N =806) were 1.24g/L, 1.19g/L and 3.7g/L, respectively. The age of victims and their blood-alcohol concentration (BAC) were positively correlated (r =0.365, p Author Affiliation: Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Artillerigatan 12, SE-587 58 Linkoping, Sweden Article History: Received 21 May 2008; Revised 27 August 2008; Accepted 30 August 2008

Background: Multiple arrests for use of illicit drugs and/or impaired driving strongly suggests the existence of a personality disorder and/or a substance abuse problem.Methods: This retrospective study (1993-2010) used a national forensic toxicology database (TOXBASE), and we identified 3943 individuals with two or more arrests for use of illicit drugs and/or impaired driving. These individuals had subsequently died from a fatal drug poisoning or some other cause of death, such as trauma.Results: Of the 3943 repeat offenders 1807 (46%) died from a fatal drug overdose and 2136 (54%) died from other causes (p<0.001). The repeat offenders were predominantly male (90% vs 10%) and mean age of drug poisoning deaths was 5 y younger (mean 35 y) than other causes of death (mean 40 y). Significantly more repeat offenders (46%) died from drug overdose compared with all other forensic autopsies (14%) (p<0.001). Four or more drugs were identified in femoral blood in 44% of deaths from poisoning (drug overdose) compared with 18% of deaths by other causes (p<0.001). The manner of death was considered accidental in 54% of deaths among repeat offenders compared with 28% for other suspicious deaths (p<0.001). The psychoactive substances most commonly identified in autopsy blood from repeat offenders were ethanol, morphine (from heroin), diazepam, amphetamines, cannabis, and various opioids.Conclusions: This study shows that people arrested multiple times for use of illicit drugs and/or impaired driving are more likely to die by accidentally overdosing with drugs. Lives might be saved if repeat offenders were sentenced to treatment and rehabilitation for their drug abuse problem instead of conventional penalties for drug-related crimes. [ABSTRACT FROM AUTHOR]

Background and objectives: Previous research on the toxicology of homicide has shown that about half of offenders and victims have psychoactive substances in their blood. The purpose of this study was to examine this topic in a Swedish setting. Methods: Toxicological data were sought in a database for all victims (n = 273) and perpetrators (n = 257) of homicide in Sweden from 2007 to 2009. Sufficient tests were identified for 97.1% of all victims (n = 265) and 46.7% of all offenders (n = 120). Additional information was obtained from court records and police reports. Results: A majority of individuals involved in homicides displayed positive toxicology (57.0% of victims and 62.5% of offenders). The most commonly detected substances, in both victims and offenders, were ethanol (44.9% vs. 40.8%) and benzodiazepines (8.3% vs. 19.2%). The difference between offenders and victims concerning benzodiazepines was statistically significant (OR 2.6; p = 0.002). Perpetrators of homicide-suicide had a lower prevalence of positive toxicology (30.8%) than other homicide offenders (66.4%; p = 0.04) and victims in unsolved cases more often exhibited positive drug toxicology compared to victims in solved cases (36.1% vs. 8.3%; p < 0.001). Conclusions: The results of the study support the notion that substance abuse is firmly linked to committing homicide and to becoming a victim thereof. [ABSTRACT FROM AUTHOR]

Abstract: Over-consumption of alcohol and/or abuse of other drugs are closely linked to attempted or completed suicides. In this retrospective 10-year study (2001–2010), we compared the toxicology findings in hanging suicides (n = 4551) with drug poisoning (intoxication) suicides (n = 2468). The mean age of hanging deaths was 49 ± 19 y (±SD) and 80% were male, compared with a mean age of 52 ± 17 y and 47% males for the intoxication deaths. Poly-drug use was more common in poisoning suicides with an average of 3.6 drugs/case compared with 1.8 drugs/case in hangings. Moreover, 31% of hangings were negative for alcohol and/or drugs. Alcohol was detected (>0.20 g/L) in femoral blood in 30% of hanging suicides (mean 1.39 g/L) and 36% of drug poisonings (mean 1.39 g/L). The median BACs did not depend on the person's age or gender (p > 0.05). Ethanol, paracetamol, citalopram, diazepam, propiomazine, alimemazine and zopiclone were amongst the top-ten drugs detected in both methods of suicide. With the exception of ethanol, the concentrations of drugs in blood were considerably higher in the poisoning deaths, as might be expected. Regardless of the method of suicide, antidepressants and/or antipsychotics were common findings, which could implicate mental health as a significant suicide risk factor. [Copyright &y& Elsevier]

Summary: The Swedish National Clinical Final Examination (NCFE) was established in 2007 in order to examine nursing students' clinical competence upon completing their Bachelor's degree in nursing. The NCFE constitutes an innovative method of examination, divided into two parts: a written and bedside test. The aim of this study was to evaluate nursing students' experiences of being assessed by means of the NCFE, in order to obtain information that could be used to improve the examination. A survey was conducted using a questionnaire with open-ended questions concerning the written and the bedside part of the NCFE. The answers from 577 third-year nursing students were analysed using content analysis. The nursing students regarded the NCFE as promoting further learning and as an important means of quality assurance. Its comprehensive nature was perceived to tie the education together and contributed to the students' awareness of their own clinical competence. The strengths of the NCFE especially highlighted were its high degree of objectivity and the fact that it took place in a natural setting. However, the students felt that the NCFE did not cover the entire nursing programme and that it caused stress. It thus appears to be important to reconsider the written theoretical part of the examination and to standardise the bedside part. [Copyright &y& Elsevier]

Abstract: Buprenorphine is considered to have little respiratory side effects at therapeutic doses and the partial agonistic properties should produce a “ceiling effect” for respiratory depression at higher doses. Still, there are several reports on buprenorphine related deaths. Most deaths involve drug users and the co-administration of other CNS depressant drugs as well as reduced tolerance have been suggested to be risk factors. The primary aims were to investigate if lack of tolerance and/or co-ingestion of other psychotropic drugs are significant risk factors in buprenorphine fatalities. From July 2005 to September 2009, all autopsy cases where buprenorphine or norbuprenorphine had been detected in femoral blood and where analysis of buprenorphine had been performed in urine were selected. Results from the postmortem examination and toxicology were compiled. Postmortem toxicology was performed using the routine methodology at the laboratory. In total, 97 subjects were included in the study. These were divided into four groups; Intoxication with buprenorphine (N =41), Possible intoxication with buprenorphine (N =24), Control cases where buprenorphine was not the cause of death (N =14), and Unclear (N =18). The metabolite to parent compound ratios in both blood and urine in the Intoxication group were significantly different from those in the Control and Unclear groups. An extensive poly-drug use was seen in all groups with several additional opioids in the Possible group (54%) and in the Unclear group (78%) and hypnotics or sedatives in more than 75% of the Intoxication, Possible, and Unclear cases. Illicit drugs were present in all groups but not to a great extent with amphetamine and tetrahydrocannabinol as the main findings. Interestingly, 4 cases in the Intoxication group presented with no other significant drugs in blood other than buprenorphine. We conclude that a lethal concentration of buprenorphine in blood cannot be defined. Instead the analysis of blood as well as urine can be an important tool to show that the drug was taken shortly before death and to rule out a continuous use of buprenorphine supporting the notion that abstinence is an important risk factor. The presence of alprazolam in more than 40% of the Intoxications and the presence of hypnotics and sedatives in 75% of the Intoxications suggests that these drugs interact with buprenorphine producing toxic effects that buprenorphine alone would not have produced. Still, in 10% of the Intoxications no other drugs were found indicating that under certain circumstances buprenorphine alone may produce respiratory depression resulting in death. [Copyright &y& Elsevier]

Abstract: Cancer patients with advanced disease and short-survival expectancy were given hospital-based advanced home care (AHC) or conventional care (CC), according to their preference. The two groups were compared at baseline to investigate whether there were differences between the AHC and the CC patients that may help explain their choice of care. The patients were consecutively recruited over 2½ years. Sociodemographic and medical data, and the health-related quality of life (HRQL) of the two groups were compared. HRQL was assessed using a self-reporting questionnaire, including the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30), the Impact of Event Scale (IES), five questions about social support, and two items concerning general well-being. The AHC group showed significantly poorer functioning on all the EORTC QLQ-C30 scales and an overall higher symptom burden than the CC patients. Fewer of the AHC patients were receiving cancer treatment. The AHC patients had lived longer with their cancer diagnosis, had a significantly shorter survival after study enrollment, and a significantly poorer performance status. The major differences between the two groups seemed to be related to being at different stages in their disease. The results indicate that patients are reluctant to accept home care until absolutely necessary due to severity of functioning impairments and symptom burden. These findings should be taken into consideration in planning palliative care services. [Copyright &y& Elsevier]

Background: Reference concentrations of drugs in post-mortem femoral blood furnishes useful information when poisoning (intoxication) deaths are investigated. However, few publications compare the concentrations of drugs in single-drug fatalities with multi-drug intoxications. This article attempts to fill this gap in knowledge.Methods: We searched a national forensic toxicology database (TOXBASE) and found N=13,963 deaths attributed by pathologists to intoxication by drugs (poisoning). The manner of death, whether accidental, suicidal or undetermined intent, was also available. To compare drug concentrations in living and deceased persons, we used information from people arrested for driving under the influence of drugs (DUID).Results: The percentage of drug intoxication deaths classified as undetermined intent decreased and accidental overdose deaths increased during the study period. In 2010 manner of death was considered accidental, suicidal or undetermined, in 41%, 30% and 28% of victims, respectively. Most of the deceased had taken multiple drugs (mean three drugs/case) and four or more drugs were identified in 35% of deaths. In single-drug fatalities ethanol (1585), morphine (114), citalopram (28), propoxyphene (51), flunitrazepam (70), propiomazine (46), tramadol (20) and zopiclone (15) were most prevalent. Alprazolam and diazepam were common findings in multi-drug deaths, although these benzodiazepines were rarely encountered in mono-drug intoxication deaths. Median blood concentrations were appreciably higher (2-10 fold) in single-drug fatalities compared with multi-drug deaths. The blood concentrations in DUID suspects were mostly lower than in the multi-drug poisoning deaths.Conclusion: This compilation of femoral blood concentrations of drugs in poisoning deaths provides a useful reference material, because we have distinguished between mono-drug intoxication deaths and poisoning with multiple-drugs. [ABSTRACT FROM AUTHOR]

Abstract: 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 (0.24mg/L, N =766) compared with apprehended drivers with 6-MAM in blood (0.15mg/L, N =124, p <0.05), and appreciably higher than in drivers with 6-MAM in urine but not in blood (0.03mg/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 (0.24mg/L, N =703) as heroin-only deaths (0.25mg/L, N =63). The concentration of morphine in drug overdose deaths (median 0.25mg/L, N =669) was about the same as in traumatic deaths among heroin users (0.23mg/L, N =97). However, the concentration of morphine was lower when the deceased had consumed alcohol (0.18mg/L, N =104) compared with taking a benzodiazepine (0.32mg/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. [Copyright &y& Elsevier]

Abstract: Zopiclone is a short-acting hypnotic drug used for treatment of insomnia and its stability has been described in some detail. However, data especially on short-term pre-analytical stability is missing. This study investigated zopiclone stability differences between spiked and authentic whole blood from subjects dosed with zopiclone. In this way influence from physiological factors such as drug interactions, matrix composition and plasma protein levels were minimized. Nine volunteers participated in the study. Whole blood was obtained before and after oral administration of 10mg Imovane®. Aliquots of 1g of authentic and spiked blood were after initial measuring, stored at 20°C during 5 days, 5 or −20°C during 3 months, and zopiclone was measured by gas chromatography with nitrogen phosphorus detection. The results showed no stability differences between authentic and spiked blood but confirmed the very short stability in whole blood at ambient temperature. In summary, the stability was less than 1 day at 20°C, less than 2 weeks at 5°C but stable for 3 months at −20°C. This study demonstrates the importance of controlling pre-analytical conditions from sampling to analysis to avoid misinterpretation of toxicological results. [Copyright &y& Elsevier]

Abstract: During the years 2000–2002, alcohol, pharmaceuticals and illicit drugs were analysed in blood samples from fatally injured drivers in Sweden. The total number of drivers was 920 and in 855 of these, corresponding to 93%, a toxicological investigation was performed. About 85% of the drivers were men and 15% were women. All but three women (96%) were car drivers while the corresponding figure for men was about 78% and about 13% were motorcyclists. The number of positive cases increased from 38.9% in year 2000 to 45.9% in year 2002 and alcohol was the most common drug with frequencies of 19.8%, 25.0% and 21.8% for the studied years 2000, 2001 and 2002, respectively. The median blood alcohol concentration ranged from 1.6 to 2.0mg/mL for men and from 1.2 to 1.8mg/mL for women. There was a decrease in cases where alcohol was the only drug detected, from 52 out of 58 cases (90%) in year 2000 to 41 out of 61 cases (67%) in 2002. At the same time there was an increase, from 5.4% to 10.0% of illicit drugs, mainly amphetamine, and the cases with multiple drug intake increased from 10% to 26%. The prevalence of pharmaceuticals as the only drug or drugs detected decreased from 14.0% to 10.4% and in the majority of these cases the drug concentrations were within the therapeutic range. [Copyright &y& Elsevier]

Objective: To investigate how risks and benefits of hormone replacement therapy (HRT) are communicated to women in clinical practice. To evaluate the usefulness of a risk classification based on context framing, i.e. whether the risk is discussed for one or several alternative treatments, and/or in the same context as possible benefits. Design: Analysis of structure and content of transcribed consultations (n=20) from first-time visits for discussion of climacteric discomfort and/or HRT with five physicians at three different out-patient clinics of gynecology. Results: All women received a prescription of HRT. An alternative to HRT was discussed in seven of the consultations. No decision aids were used. Risk discussion was dominated by the physicians giving information about long-time risk and benefits. The decision to prescribe was made either before the risk discussion was initiated, or before it was finished, in 8 of the 18 consultations where risk discussion was present. Risk classification according to context framing was performed and indicated use of different communication strategies by the physicians. Conclusions: The perspective of the physicians was mainly on prevention while the women were more focused on symptom alleviation. Each physician had a strategy of his/her own for the risk discussion. Thus, the major differences found between the consultations were between physicians, and not between the women. Risk discussion seemed to be aimed at motivating the woman to follow the physician’s decision rather than to help her participate in the decision-making process. [Copyright &y& Elsevier]

Compilations of substances detected in fatal intoxications are important in order to observe changes in intoxication patterns, to monitor effects of preventive work and to discover new trends in drug usage. The aim of the present study was to describe the current pattern of substances detected in fatal intoxications in Sweden. Fatal intoxications investigated at the Department of Forensic Chemistry, Linköping, Sweden, during 1992–2002, were analysed. All suicides, uncertain cases and accidents where the cause of death were fatal intoxications (ICD-9: E950, E980 and E859) were included and substances detected in more than 50 fatal intoxications (in femoral blood) were listed. For each substance, a cut off value was set, above which concentrations were considered toxic. Fatal intoxications were detected by forensic-chemical analyses in 12% (6998/60,314) of the forensic autopsies during the study period. Among the suicides, an average of 3.8 substances were detected per case, the corresponding figure for uncertain cases and accidents were 3.5 and 4.1 substances, respectively. Ethanol was by far the most frequently detected substance, detected in 43% (3039) of the fatal intoxications, of which 32% (960) had toxic concentrations, followed by propoxyphene, detected in 27% (1863) of the fatal intoxications of which 74% (1370) had toxic concentrations. The number of cases where ethanol and propoxyphene were detected decreased during the study period. Moreover, other CNS-active drugs such as antidepressants, analgesics and anxiolytics were also frequently detected. The drugs with high proportions of cases with toxic concentrations detected were propoxyphene, amitriptyline, zolpidem, carisoprodol, alprazolam, thioridazine, methadone and ketobemidone. Selective serotonin reuptake inhibitors (SSRI) and tricyclic antidepressants (TCA) were detected in 12% (833) and 10% (665), respectively. A significantly (P<0.001) higher proportion of cases where TCA were detected had toxic concentrations when compared with cases where SSRI were detected (64% versus 31%). [Copyright &y& Elsevier]

• An accurate and generic LC–MS/MS method for determination of testosterone in serum and saliva. • Low testosterone measurement in biological matrices. • Clinical and forensic applications over a wide range of concentrations. A highly sensitive and accurate electrospray liquid chromatography tandem-mass spectrometry (ESI-LC–MS/MS) method for determination of testosterone in human serum and saliva was developed and validated. Accurate quantification of testosterone in human matrices is essential in diagnosis and management of androgen status in men, women and children, and in forensic investigations of suspected abuse of anabolic androgenic steroids. Chromatography was performed on an HSS-T3 C18 column with a total run-time of 5.5 min. The tandem mass spectrometry was operated in positive electrospray ionization mode with multiple reaction monitoring. Serum and saliva samples of 200 μL, were prepared by solid-phase extraction using a 96-well plate following precipitation with 200 μL methanol. 13C labeled testosterone was used as internal standard for quantification. The standard curve was linear within the range of 4−1000 pg/mL and the limit of quantification of both serum and salivary testosterone was 4 pg/mL. Accuracy were 99–101 % and 93–95 % with between-run imprecision in serum and saliva, respectively, and inter- and intra-assay coefficients of variation were less than 9.2 %. The method proved to be applicable for determination of testosterone over a wide range of concentrations in serum and saliva samples from clinical patients with various androgen disorders, healthy male and female adults as well as from forensic cases. [ABSTRACT FROM AUTHOR]

Four cases of fatal intoxications with caffeine are described. Caffeine is widely available in beverages and in different OTC-products, in many of them in combinations with other drugs like ephedrine. Caffeine is not as harmless as one might believe. An overdose of caffeine alone, intentional or not, might be deadly. It seems to be warranted to include caffeine in the drug-screening of forensic autopsy cases. It is not motivated from a medical point of view to sell pure caffeine over the counter. [Copyright &y& Elsevier]

Background& Objectives: To improve the interpretation of fatal intoxications by establishing fatal and non-fatal reference concentrations of metformin in postmortem femoral blood and to further evaluate risk factors associated with fatal metformin intoxication.Methods: All forensic autopsies in Sweden where metformin was detected in femoral blood 2011-2016 were identified in the National Board of Forensic Medicine databases (NFMD). The cases were classified as single substance intoxications, A (n = 22), multiple substance intoxications, B (N = 7) and postmortem controls, C (N = 13). The control group consisted of cases where metformin was detected, but the cause of death excluded the incapacitation by metformin or other substances. Strict inclusion criteria were used, and all postmortem cases were assessed by two independent reviewers. All other cases where the inclusion criteria of groups A-C where not met formed group O (N = 78). The forensic findings logged in the NFMD where linked to national registers whereby information on comorbidities, dispensed drugs and clinical data could be obtained.Results: The mean age was 66 ± 10 years in the total study population and did not differ between the groups. The proportion of men was 64% in group A, 71% in B, 77% in C and 74% in group O. The median values of metformin in group A (48.5 μg/g; range 13.0-210 μg/g) and B (21.0 μg/g; range 4.40-95.0 μg/g) were significantly (p < 0.001 and p = 0.015 respectively) higher than those of the control group C (2.30 μg/g ; range 0.70-21.0 μg/g). The median concentration of metformin in group A and B was also significantly higher than in group O (4.60 μg/g; range 0.64-54.0 μg/g) (p < 0.001 and p = 0.040 respectively). The results suggest that intoxication with metformin as a cause of death should be considered when the postmortem femoral blood level exceeds about 10 μg/g, although higher levels may be seen in postmortem in cases without incapacitation. The metformin intoxication was confirmed to be intentional in 23% (n = 5) of the single intoxications. Underlying factors identified as important for the remaining fatal metformin intoxications included living alone, any contraindication for the use of metformin, known alcohol abuse and a history of stroke or cardiovascular disease.Conclusions: The reported post mortem femoral blood concentrations of metformin can hopefully contribute to a better interpretation of results in suspected poisonings and obscure cases. Living in a single household, history of cardiovascular disease and contraindications, predominantly alcohol abuse, were associated with fatal metformin intoxication. [ABSTRACT FROM AUTHOR]

The E3 ubiquitin-protein ligase TRIM21, of the RINGcontaining tripartite motif (TRIM) protein family, is a major autoantigen in autoimmune diseases and a modulator of innate immune signaling. Together with ubiquitin-conjugating enzyme E2 E1 (UBE2E1), TRIM21 acts both as an E3 ligase and as a substrate in autoubiquitination. We here report a 2.82-Å crystal structure of the human TRIM21 RING domain in complex with the human E2-conjugating UBE2E1 enzyme, in which a ubiquitin-targeted TRIM21 substrate lysine was captured in the UBE2E1 active site. The structure revealed that the direction of lysine entry is similar to that described for human proliferating cell nuclear antigen (PCNA), a small ubiquitin-like modifier (SUMO)-targeted substrate, and thus differs from the canonical SUMO-targeted substrate entry. In agreement, we found that critical UBE2E1 residues involved in the capture of the TRIM21 substrate lysine are conserved in ubiquitin-conjugating E2s, whereas residues critical for SUMOylation are not conserved. We noted that coordination of the acceptor lysine leads to remodeling of amino acid side-chain interactions between the UBE2E1 active site and the E2-E3 direct interface, including the so-called “linchpin" residue conserved in RING E3s and required for ubiquitination. The findings of our work support the notion that substrate lysine activation of an E2-E3-connecting allosteric path may trigger catalytic activity and contribute to the understanding of specific lysine targeting by ubiquitinconjugating E2s. [ABSTRACT FROM AUTHOR]

Driving under the influence of alcohol is a major problem for traffic-safety and a popular defence argument is alleged consumption after driving, commonly referred to as the hip-flask defence. Forensic toxicologists are often called as expert witnesses in drinking and driving cases where the suspect has claimed the hip-flask defence, to assess the credibility of the explanation. Several approaches to help the expert have been introduced but the scientific data used to support or challenge this is solely based on data from controlled single doses of ethanol administered during a short time and in abstinent subjects. In reality, we believe that even in drinking after driving cases, the subject many times has alcohol on board at time of the hip-flask drink. This questions the applicability of the data used as basis to investigate the hip-flask defence. To fill this knowledge gap, we aimed to investigate how blood and urine ethanol kinetics vary after an initial drinking session of beer and then a subsequent hip-flask drink of three different doses of whiskey. Fifteen subjects participated in the study and each provided 10 urine samples and 17 blood samples over 7h. The initial drink was 0.51g ethanol/kg and the second was either 0.25, 0.51, or 0.85g/kg. Our data suggested that the difference between the ethanol concentrations in two consecutive urine samples is a more sensitive parameter than the ratio between urine and blood alcohol to detect a recent intake when ethanol from previous intakes are already present in the body. Twelve subjects presented results that fully supported a recent intake using the criteria developed from a single intake of ethanol. Three subjects showed unexpected results that did not fully support a recent intake. We conclude that data from one blood sample and two urine samples provide good evidence for investigating the hip-flask defence even if alcohol was on board at the time of the hip-flask drink. [ABSTRACT FROM AUTHOR]

Introduction: 3-methoxyphencyclidine (3-MeO-PCP) appeared on the illicit drug market in 2011 and is an analogue of phencyclidine, which exhibits anesthetic, analgesic and hallucinogenic properties. In this paper, we report data from a non-fatal intoxication and seven deaths involving 3-MeO-PCP in Sweden during the period March 2014 until June 2016.Case Descriptions: The non-fatal intoxication case, a 19-year-old male with drug problems and a medical history of depression, was found awake but tachycardic, hypertensive, tachypnoeic and catatonic at home. After being hospitalized, his condition worsened as he developed a fever and lactic acidosis concomitant with psychomotor agitation and hallucinations. After 22h of intensive care, the patient had made a complete recovery. During his hospitalization, a total of four blood samples were collected at different time points. The seven autopsy cases, six males and one female, were all in their twenties to thirties with psychiatric problems and/or an ongoing drug abuse.Methods: 3-MeO-PCP was identified with liquid chromatography (LC)/time-of-flight technology and quantified using LC-tandem mass spectrometry.Results: In the clinical case, the concentration of 3-MeO-PCP was 0.14μg/g at admission, 0.08μg/g 2.5h after admission, 0.06μg/g 5h after admission and 0.04μg/g 17h after admission. The half-life of 3-MeO-PCP was estimated to 11h. In the autopsy cases, femoral blood concentrations ranged from 0.05μg/g to 0.38μg/g. 3-MeO-PCP was the sole finding in the case with the highest concentration and the cause of death was established as intoxication with 3-MeO-PCP. In the remaining six autopsy cases, other medications and drugs of abuse were present as well.Conclusion: Despite being scheduled in January 2015, 3-MeO-PCP continues to be abused in Sweden. Exposure to 3-MeO-PCP may cause severe adverse events and even death, especially if the user does not receive life-supporting treatment. [ABSTRACT FROM AUTHOR]

Aims: To determine the prevalence of non-prescribed drug use among subjects suspected of drug-impaired driving with a psychoactive prescription drug, and to identify associated factors.Methods: Subjects investigated for drug-impaired driving in Sweden during 2006-2009 with a confirmed intake of diazepam, flunitrazepam, tramadol, zolpidem or zopiclone were identified using the Swedish Forensic Toxicology Database. Information on dispensed prescription drugs was retrieved from the Swedish Prescribed Drug Register. Non-prescribed use was our outcome, defined as a psychoactive prescription drug intake confirmed by toxicological analysis in a subject by whom it was not dispensed in the 12 months preceding the sampling. Prevalence proportions were calculated for each drug and logistic regression was used to identify associated factors.Results: In total, 2225 subjects were included. The median age (range) was 34 (15-80) years and 1864 (83.8%) subjects were male. Non-prescribed use was found in 1513 subjects (58.7%); for flunitrazepam 103 (76.3%), diazepam 1098 (74.1%), tramadol 192 (40.3%), zopiclone 60 (29.7%), and zolpidem 60 (21.2%) subjects, respectively. Younger age and multiple-substance use were associated with non-prescribed use, whereas ongoing treatment with other psychoactive drugs was negatively associated with non-prescribed use.Conclusions: Non-prescribed use of psychoactive prescription drugs was common in subjects suspected of drug-impaired driving and was more frequent for benzodiazepines and tramadol compared to zolpidem and zopiclone. The young and multi-substance users were more likely, whereas subjects with ongoing prescribed treatment with other psychoactive drugs were less likely, to use non-prescribed drugs. [ABSTRACT FROM AUTHOR]

In postmortem investigations of fatal intoxications it is often challenging to determine which drug/s caused the death. To improve the interpretation of postmortem blood concentrations of sedative and hypnotic drugs and/or clonazepam, all medico-legal autopsies in Sweden - where these drugs had been detected in femoral vein blood during 1992-2006 - were identified in the databases of the National Board of Forensic Medicine. For each drug, concentrations in postmortem control cases - where the cause of death was not intoxication and where incapacitation by drugs could be excluded - were compiled as well as the levels found in living subjects; drugged driving cases and therapeutic drug monitoring cases. Subsequently, fatal intoxications were assessed with regards to the primary substances contributing to death, and blood levels were compiled for single and multiple drug intoxications. The postmortem femoral blood levels are reported for 16 sedative and hypnotic drugs, based on findings in 3560 autopsy cases. The cases were classified as single substance intoxications (N = 498), multiple substance intoxications (N = 1555) and postmortem controls (N = 1507). Each autopsy case could be represented more than once in the group of multiple intoxications and among the postmortem controls if more than one of the included substances were detected. The concentration ranges for all groups are provided. Overlap in concentrations between fatal intoxications and reference groups was seen for most substances. However, the concentrations found in single and multiple intoxications were significantly higher than concentrations found in postmortem controls for all substances except alprazolam and triazolam. Concentrations observed among drugged drivers were similar to the concentrations observed among the therapeutic drug monitoring cases. Flunitrazepam was the substance with the highest number of single intoxications, when related to sales. In summary, this study provides reference drug concentrations primarily to be used for improving interpretation of postmortem drug levels in obscure cases, but which also may assist in drug safety work and in pharmacovigilance efforts. [ABSTRACT FROM AUTHOR]

We present a fatal drug poisoning case involving venlafaxine (VEN). The deceased took his medication regularly (including 150 mg VEN twice daily), and nothing in the case or autopsy findings pointed towards suicide. The toxicological assessment concluded that the cause of death was most likely due to a poisoning with a combination of VEN, oxycodone and ethanol, and the manner of death was considered to be an accident. The blood concentration of VEN was high (4.5 mg/kg), and the ratio of the VEN metabolite O-desmethylvenlafaxine (ODV) to VEN was exceptionally low (0.006). Mechanistic pharmacokinetic simulations suggested that the low metabolite ratio was the result of combined poor metabolizer (PM) status of cytochrome P450 (CYP) 2C19 and CYP2D6. This hypothesis was confirmed by genetic analysis. Simulations revealed that it was likely that the combined missing CYP2D6 and CYP2C19 activity would cause higher concentrations of VEN, but the simulations also suggested that there could be additional reasons to explain the high VEN concentration found in this case. Thus, it seems likely that the potentially toxic VEN concentration was caused by reduced metabolic capacity. The simulations combined with genotyping were considered very useful in this fatal drug poisoning case. [ABSTRACT FROM AUTHOR]

Abstract: Anabolic Androgenic Steroids (AAS) are considered drugs of abuse and are controlled substances in Sweden since 1999. Traditionally AAS have been used by elite athletes to enhance performance, but in recent years it has become an increasing problem outside elite sport among athletes, bodybuilders and criminals. Use of AAS is associated with psychiatric side effects such as aggression, depression and violent behavior. Supraphysiological doses and long term use can cause serious physical harm such as cardiovascular toxicity and even premature death. We investigated and evaluated the drug analytical findings in forensic cases from suspected perpetrators in cases from the police where a screening for AAS was requested to get information about the prevalence of AAS use and the occurrence of poly-drug abuse. The study was based on samples submitted from the police authorities to the Department of Forensic Toxicology in Sweden during the period 1999–2009. Urines were analyzed by methods based on GC–MS and LC–MS–MS. We also analyzed the prevalence of AAS use at the prison and probation services. A total number of 12,141 urine samples (6362 police cases and 5779 inmates) were analyzed and 33.5% of the cases from the police and 11.5% of the inmates were tested positive for AAS. The users of AAS were mainly in 99.2% men with a mean age of 26.2±6.2years whereas the women were 29.5±6.5years old. The most frequently used AAS was nandrolone followed by testosterone and methandienone. Other illicit and licit drugs were detected in 60% of the cases from the police, strongly indicating a frequent poly-drug abuse among users of AAS. [Copyright &y& Elsevier]

Abstract: Venlafaxine (VEN) is an antidepressant drug mainly metabolized by the cytochrome P450 (CYP) enzyme CYP2D6 to the active metabolite O-desmethylvenlafaxine (ODV). VEN is also metabolized to N-desmetylvenlafaxine (NDV) via CYP3A4. ODV and NDV are further metabolized to N,O-didesmethylvenlafaxine (DDV). VEN is a racemic mixture of the S- and R-enantiomers and these have in vitro displayed different degrees of serotonin and noradrenaline reuptake inhibition. The aim of the study was to investigate if an enantioselective analysis of VEN and its metabolites, in combination with genotyping for CYP2D6, could assist in the interpretation of forensic toxicological results in cases with different causes of deaths. Concentrations of the enantiomers of VEN and metabolites were determined in femoral blood obtained from 56 autopsy cases with different causes of death. The drug analysis was done by liquid chromatography tandem mass spectrometry (LC/MS/MS) and the CYP2D6 genotyping by PCR and pyrosequencing. The mean (median) enantiomeric S/R ratios of VEN, ODV, NDV and DDV were 0.99 (0.91), 2.17 (0.93), 0.92 (0.86) and 1.08 (1.03), respectively. However, a substantial variation in the relationship between the S- and R-enantiomers of VEN and metabolites was evident (S/R ratios ranging from 0.23 to 17.6). In six cases, a low S/R VEN ratio (mean 0.5) was associated with a high S/R ODV ratio (mean 11.9). Genotyping showed that these individuals carried two inactive CYP2D6 genes indicating a poor metabolizer phenotype. From these data we conclude that enantioselective analysis of VEN and ODV can predict if a person is a poor metabolizer genotype/phenotype for CYP2D6. Knowledge of the relationship between the S- and R-enantiomers of this antidepressant drug and its active metabolite is also important since the enantiomers display different pharmacodynamic profiles. [Copyright &y& Elsevier]

Abstract: Over a 10-year period (1998–2007) all deaths in Sweden classified by forensic pathologists as fatal drug poisonings (N =6894) were retrieved from a toxicology database (TOXBASE) belonging to the National Board of Forensic Medicine. The deaths were further classified as suicides N =2288 (33%), undetermined N =2260 (33%) and accidental N =2346 (34%). The average age (±SD) of all victims was 49.1±15.9 years and men 47.4±15.6 years were 5-year younger than women 52.2±15.8 years (p <0.01). Most of the deceased (78%) were poly-drug users although a single drug (mono-intoxications) was found in 22% of all poisoning deaths (p <0.001). The number of drugs in blood samples varied from 1 to 12 with a median of 3–4 per case. Mono-intoxication deaths were mostly ethanol-related (N =976) and the mean and median blood-alcohol concentration (BAC) was 3.06g/L and 3.10g/L, respectively. The BAC decreased as the number of additional drugs in blood increased from 2.15g/L with one drug to 1.25g/L with 6 or more drugs. The mean (median) concentrations of non-alcohol drugs in mono-intoxication deaths were morphine (N =93) 0.5mg/L (0.2mg/L), amphetamine (N =39) 2.0mg/L (1.2mg/L), dextropropoxyphene (N =33) 3.9mg/L (2.9mg/L), dihydro-propiomazine (N =32) 1.6mg/L (1.0mg/L) and 7-amino-flunitrazepam (N =28), 0.4mg/L (0.3mg/L). Elevated blood morphine in these poisoning deaths mostly reflected abuse of heroin as verified by finding 6-monoacetyl morphine (6-MAM) in the blood samples. When investigating drug poisoning deaths a comprehensive toxicological analysis is essential although the results do not reveal the extent of prior exposure to drugs or the development of pharmacological tolerance. The concentrations of drugs determined in post-mortem blood are one element in the case. The autopsy report, the police investigation, the findings at the scene and eye-witness statements should all be carefully considered when the cause and manner of death are determined. [Copyright &y& Elsevier]

Abstract: A stereoselective method is described for simultaneous determination of the S- and R-enantiomers of venlafaxine and its three demethylated metabolites in human plasma and whole blood samples. This validated method involved LC/MS/MS with positive electrospray ionization and solid phase extraction. Chromatographic separation was performed on a 250mm×2.1mm Chirobiotic V column with a total run time of 35min. In plasma, calibration curves were in the range of 1–1000nM for the S- and R-enantiomers of venlafaxine and O-desmethylvenlafaxine, and 0.5–500nM for N-desmethylvenlafaxine and N,O-didesmethylvenlafaxine. In whole blood the corresponding concentrations were 10–4000 and 5–2000nM, respectively. The intra-day precision was <6.3% and the inter-day precision was <9.9% for plasma and <15% and <19% for whole blood. LLOQ ranged between 0.25 and 0.5nM. No ion suppression/enhancement or other matrix effects were observed. The method was successfully applied for determination of venlafaxine and its metabolites in plasma from patients and whole blood samples from forensic autopsy cases. [Copyright &y& Elsevier]

Abstract: Zopiclone is a common drug in forensic cases and it is frequently analyzed in biological materials using different analytical methods. Zopiclone is unstable in certain solvents and depending on storage conditions unstable in biological fluids; however its stability in human whole blood has not yet been established in detail. Therefore, the following investigation was performed to study the stability of zopiclone in both spiked and authentic human blood. First, spiked blood samples were stored at −20°C, 5°C and 20°C and the degradation of zopiclone was investigated. Second, authentic and spiked blood samples were stored at 5°C and differences in zopiclone stability were studied. Third, processed sample stability and effect of freeze/thaw cycles were evaluated. Analyses were performed by GC-NPD and zopiclone concentrations were measured at selected time intervals. The study showed that zopiclone degrades in human blood depending on time and temperature and may not be detected after long-term storage. 2-amino-5-chloropyridine was identified as the primary degradation product from zopiclone. At refrigerator temperature zopiclone was stable less than 1 month in both spiked and authentic human blood samples. The best storage condition was at −20°C even at short storage times, as freeze–thaw had no influence on the results. In butyl acetate extracts, zopiclone was stable at least 2 days when kept in the autosampler at ambient temperature. We conclude that preanalytical factors have great impact on analytical results and should be addressed when interpreting whole blood zopiclone concentrations. [Copyright &y& Elsevier]

Abstract: Background: A zero-tolerance law for driving under the influence of drugs (DUID) in Sweden led to a 10-fold increase in the number of cases submitted by the police for toxicological analysis. The statutory blood–alcohol concentration (BAC) limit for driving is 0.2mg/g (∼0.02g%). Methods: An in-house database (TOXBASE) was used to investigate re-arrests for impaired driving over 4 years (2001–2004), which comprised 36,799 cases. The age, gender, re-arrest rate of the offenders and the concentrations of ethanol and amphetamine in blood samples were evaluated. Results: We found that 44% of individuals (N =16,277) re-offended 3.2 times on average (range 1–23 arrests). Between 85 and 89% of first-time offenders were men and there was also a male dominance among the recidivists (88–93%). The mean age of drunken drivers was ∼40 years compared with ∼35 years for driving under the influence of amphetamine, which was the drug identified in 50–60% of DUID cases, either alone or together with other licit or illicit drugs. The median BAC was 1.5mg/g (∼0.15g%), which suggests a dominance of heavy drinkers. The median BAC was even higher in recidivists (1.6–1.7mg/g). The median concentration of amphetamine in blood was 1.0mg/L in recidivists compared with 0.5mg/L in the first-time offenders. About 14% of drunken drivers re-offended 1–10 times compared with 68% of DUID suspects, who were re-arrested 1–23 times. People with only a scheduled prescription drug in blood were re-arrested much less frequently (∼17%) compared with those taking illicit drugs (68%). Conclusions: The appreciable increase in number of arrests for DUID after a zero-tolerance law might reflect a heightened enthusiasm by the police authorities armed with knowledge that a prosecution is easier to obtain. Zero-tolerance laws do not deter people from impaired driving judging by the high re-arrest rates. During the sentencing of hardcore offenders, the courts should give more consideration to the underlying substance abuse problem. [Copyright &y& Elsevier]

Abstract: Tramadol is an extensively used centrally acting analgesic and is considered a safe drug devoid of many serious adverse effects of traditional opioids. However, recently, toxicity and an abuse potential of tramadol have been reported. This study examined fatal unintentional tramadol intoxications among Swedish forensic autopsy cases between 1995 and 2005. All fatal intoxications were selected, in which toxic concentrations of tramadol (>1μg/g femoral blood) had been detected, and where the forensic pathologist considered the intoxication unintentional and the fatal outcome at least partly explained by tramadol. Toxicology analyses, police reports, autopsy protocols and medical records were scrutinized. A total of 17 cases (eleven men and six women) of fatal unintentional tramadol intoxications were identified. For these cases the median age was 44 years (range 18–78 years) and the median tramadol concentration was 2.0μg/g (range 1.1–12.0μg/g). Other pharmaceutical substances, illicit drugs or ethanol were detected in addition to tramadol in all of these cases. In fact, intoxication with multiple drugs was considered the cause of death in 10 (59%) cases. However, in seven cases tramadol was the only substance present in toxic concentrations. A history of substance abuse was identified in 14 (82%) subjects and a present tramadol abuse in 8 (47%). These results suggest that fatal intoxications with tramadol may occur unintentionally and that subjects with a history of substance abuse may be at certain risk. Precaution is therefore warranted when prescribing tramadol in such patients. [Copyright &y& Elsevier]

Abstract: Compared with their contemporaries, individuals abusing illicit drugs suffer a higher risk of premature death. In Sweden, a simple protocol for registration of fatalities among abusers of alcohol, pharmaceuticals, illicit drugs, or other substances, has been used by the forensic pathologists since 2001. This routine was introduced to allow for an evaluation of the cause and manner of death, and patterns of abuse among different groups of abusers. We explored the data on drug abusers (i.e. abusers of illicit drugs) subjected to a forensic autopsy 2002–2003. The Swedish forensic pathologists examined 10,273 dead victims during the study period and 7% (743/10,273) of the cases were classified as drug abusers. Toxicological analyses were carried out in 99% (736/743) and illicit drugs were detected in 70% (514/736) of these. On average, 3.8 substances (legal or illegal) were found per case. The most common substances were ethanol and morphine, detected in 43 and 35% of the cases, respectively. When exploring the importance of the different substances for the cause of death, we found that the detection of some substances, such as fentanyl and morphine, strongly indicated a poisoning, whereas certain other substances, such as benzodiazepines more often were incidental findings. In total, 50% (372/743) died of poisoning, whereas only 22% (161/743) died of natural causes. Death was considered to be directly or indirectly due to drug abuse in 47% (346/743), whereas evidence of drug abuse was an incidental finding in 21% (153/743) or based on case history alone in 33% (244/743). We believe that this strategy to prospectively categorize deaths among drug addicts constitutes a simple means of standardizing the surveillance of the death toll among drug addicts that could allow for comparisons over time and between countries. [Copyright &y& Elsevier]

: PurposeTo evaluate the health-related quality of life (HRQL) of patients with laryngeal carcinoma in a prospective longitudinal multicenter study at diagnosis, after 1 and 5 years in relation to tumor location and treatment modality.: Subjects and methodsEighty-six patients (mean age 66 years; 84% males) with laryngeal carcinoma were evaluated with standardized HRQL questionnaires: the European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30), the EORTC QLQ-Head and Neck Cancer Module (EORTC QLQ-H&N35), and the Hospital Anxiety and Depression Scale (HADS).: ResultsSome significant changes in HRQL were found between diagnosis and 5 years after diagnosis, depending on the treatment given. The patients’ ability to speak improved whereas some general functions deteriorated and treatment-related side effects increased. When comparing HRQL at 1 and 5 years after diagnosis, it appears that most values at the 1-year follow-up assessment persist until 5 years, but a few deteriorate. The HRQL at diagnosis seems to be associated with survival rate after 5 years, and the global quality of life scale at diagnosis tends to predict HRQL after 5 years.: ConclusionsThe use of HRQL questionnaires is valuable when comparing different treatments and as an aid in predicting treatment side effects. Evaluation of HRQL at diagnosis for patients with laryngeal carcinoma seems to be of value for the prognosis of HRQL over time and for the prognosis of survival. [Copyright &y& Elsevier]

Aim: Claimed intake of alcohol after a traffic incident, called the hip-flask defence, can be objectively assessed by different methods. One of them is the use of two consecutive ethanol concentrations in urine and the ratio between ethanol concentrations in urine and blood. Another one is the concentrations of ethyl glucuronide (EtG) and ethyl sulphate (EtS) in blood and their ratio to ethanol. The experimental basis for both these models is from single dose studies only. The aim of this study was therefore to describe the kinetics of ethanol, EtG and EtS after ingestion of two repeated doses of ethanol and to investigate the usefulness of the different models for the assessment of the hip-flask defence.Methods: Thirty-five subjects ingested a first dose of 0.51 g of ethanol per kilo body weight, and two hours later a second dose (the hip-flask drink) of 0.25, 0.51 or 0.85 g of ethanol per kilo body weight. Ten urine and 17 blood samples were collected and analysed for ethanol, EtG and EtS using fully validated methods. It was investigated if all subjects fulfilled the criteria for recent drinking, according to the two different models, when using the samples collected 180-240 minutes after start of first dose drinking. According to the first model, increase in urinary ethanol concentrations and a ratio UAC/BAC below 1.3 indicated recent drinking. According to the second model, increase in blood EtG concentrations and a ratio ethanol (g/kg)/EtG (mg/L) above 1 indicated recent drinking.Results: All subjects in the high dose group fulfilled all criteria for recent drinking. One subject in the medium dose group and nine subjects in the low dose group failed to show increasing UAC and/or a UAC/BAC ratio below 1.3. One subject in the low dose group failed to show increasing concentrations of blood EtG, but all subjects showed a ratio ethanol/EtG above 1.Conclusions: The present study showed, by the use of experimental data, that both two models used to investigate the hip-flask defence can be used, but only when the hip-flask dose is sufficiently high. [ABSTRACT FROM AUTHOR]

Many commonly used pharmaceuticals such as antidepressants and neuroleptics as well as some illegal drugs are metabolised by the Cytochrome P450 enzyme debrisoquine 4-hydroxylase (CYP2D6). Seven to ten percent of Caucasians lack this enzyme which can lead to adverse reactions and in some cases to unexpected intoxication even with fatal outcome, upon administration of drugs in normal therapeutic doses. 236 individuals who had died due to intoxication of pharmaceuticals were genotyped for CYP2D6 and compared to a reference group of 281 blood donors. A single nucleotide polymorphism (SNP) method was used to identify five CYP2D6 alleles: *1 (wt), *2, *3, *4 and *6. The allele *5, a complete gene deletion, was identified by a multiplex amplification of long DNA fragments. The prevalence of the CYP2D6 PM genotype in the fatal intoxications was lower (4.7%) compared to the blood donors (8.5%). A significant decrease (p<0.005) was found in the CYP2D6*4 allele frequency among the fatal intoxications. [Copyright &y& Elsevier]