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  • 1.
    Ahlner, Johan
    et al.
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Linköping University, Faculty of Health Sciences.
    Aamo, T. O.
    Trondheims University.
    THERAPEUTIC DRUG MONITORING AND CLINICAL TOXICOLOGY2009In: in BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY, vol 105, 2009, Vol. 105, p. 16-16Conference paper (Refereed)
    Abstract [en]

    n/a

  • 2.
    Ahlner, Johan
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.
    Druid, H
    Holmgren, P
    Genotyping avseende metabolism av läkemedel och droger - betydelse i forensiska sammanhang.1999In: Nordisk Rettsmedisin, ISSN 0809-1498, Vol. 5, p. 47-48Article in journal (Other (popular science, discussion, etc.))
  • 3.
    Ahlner, Johan
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Swedish National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Holmgren, Anita
    Swedish National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Jones, A Wayne
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Swedish National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Demographics and post-mortem toxicology findings in deaths among people arrested multiple times for use of illicit drugs and/or impaired driving2016In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 265, p. 138-143Article in journal (Refereed)
    Abstract [en]

    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 amp;lt; 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 amp;lt; 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 amp;lt; 0.001). The manner of death was considered accidental in 54% of deaths among repeat offenders compared with 28% for other suspicious deaths (p amp;lt; 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. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

  • 4.
    Ahlner, Johan
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Holmgren, Anita
    National Board for Forensic Medicine, Linkoping, Sweden .
    Jones, A Wayne
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Prevalence of alcohol and other drugs and the concentrations in blood of drivers killed in road traffic crashes in Sweden2014In: Scandinavian Journal of Public Health, ISSN 1403-4948, E-ISSN 1651-1905, Vol. 42, no 2, p. 177-183Article in journal (Refereed)
    Abstract [en]

    Background: Drunk or drug-impaired drivers represent a major public health and societal problem worldwide. Because over 95% of drivers killed on the roads in Sweden are autopsied, reliable information is available about the use of alcohol and/or other drug before the crash. Methods: This retrospective 4-year study (2008-2011) used a forensic toxicology database (TOXBASE) to evaluate the concentrations of alcohol and other drugs in blood samples from drivers killed in road-traffic crashes. Results: The mean age of all victims (N = 895) was 48 +/- 20 years, and the majority were male (86%). In 504 drivers (56%), the results of toxicological analysis were negative and these victims were older; mean age (+/- SD) 47 +/- 20 years, than alcohol positive cases (35 +/- 14 years) and illicit drug users (34 +/- 15 years). In 21% of fatalities, blood-alcohol concentration (BAC) was above the statutory limit for driving (0.2 g/L), although the median BAC was appreciably higher (1.72 g/L). Illicit drugs (mainly amphetamine and cannabis) were identified in similar to 7% of victims, either alone (2.5%), together with alcohol (1.8%) or a prescription drug (2%). The psychoactive prescription drugs identified were mainly benzodiazepines, z-hypnotics and tramadol, which were found in the blood of 7.6% of crash victims. Conclusions: The high median BAC in fatally-injured drivers speaks strongly towards alcohol-induced impairment as being responsible for the crash. Compared with alcohol, the prevalence of illicit and psychoactive prescription drugs was fairly low despite a dramatic increase in the number of drug-impaired drivers arrested by the police after a zero-tolerance law was introduced in 1999.

  • 5.
    Ahlner, Johan
    et al.
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Zackrisson, Anna Lena
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Lindblom, Bertil
    Linköping University, Department of Clinical and Experimental Medicine, Forensic Genetics. Linköping University, Faculty of Health Sciences.
    Bertilsson, Leif
    Karolinska Institute.
    Editorial Material: CYP2D6, serotonin and suicide2010In: Pharmacogenomics (London), ISSN 1462-2416, E-ISSN 1744-8042, Vol. 11, no 7, p. 903-905Article in journal (Other academic)
    Abstract [en]

    n/a

  • 6. Apelqvist, G
    et al.
    Wikell, C
    Carlsson, Björn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.
    Hjorth, S
    Bergqvist, P B F
    Ahlner, Johan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Bengtsson, Finn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Dynamic and kinetic effects of chronic citalopram treatment in experimental hepatic encephalopathy2000In: Clinical neuropharmacology, ISSN 0362-5664, E-ISSN 1537-162X, Vol. 23, no 6, p. 304-317Article in journal (Refereed)
    Abstract [en]

    Chronic hepatic encephalopathy (HE) is a neuropsychiatric syndrome that arises in liver-impaired subjects. Patients with HE display various neuropsychiatric symptoms including affective disturbances and may therefore likely receive treatment with novel thymoleptics like citalopram (CIT). The simultaneous pharmacokinetic and pharmacodynamic outcome of the commonly used serotonin-selective thymoleptic drugs in liver-impaired subjects with pending chronic HE is far from understood today. We therefore investigated the effects of chronic, body-weight-adjusted (10 mg ╖ kg-1 ╖ day-1), treatment with CIT in rats with and without portacaval shunts (PCS). Open-field activity was monitored. The 5-HT, 5-HIAA, noradrenaline (NA), and dopamine (DA) output were assessed in the frontal neocortex. The racemic levels of CIT and its metabolites DCIT and DDCIT, including the S- and R-enantiomers, were determined in serum, brain parenchyma, and extracellular fluid. The rats with PCS showed higher (2-3-fold) levels of CIT than rats undergoing a sham treatment with CIT in all compartments investigated. The PCS rats also showed elevated levels of DCIT and DDCIT. No major differences in the S/R ratios between PCS rats and control rats could be detected. The CIT treatment resulted in neocortical output differences between PCS rats and control rats mainly within the 5-HT and DA systems but not within the NA system. For the 5-HT system, this change was further evidenced by outspoken elevation in 5-HT output after KCl-depolarizing challenges. Moreover, the CIT treatment to PCS rats was shown to "normalize" the metabolic turnover of 5-HT, measured as a profound lowering of a basal elevation in the 5-HIAA levels. The CIT treatment resulted in an increased or "normalized" behavioral activity in the PCS group. Therefore, a dose-equal chronic treatment with CIT in PCS rats produced pharmacokinetic and pharmacodynamic changes not observed in control rats. The results further support the contention of an altered 5-HT neurotransmission prevailing in the chronic HE condition. However, the tentatively beneficial behavioral response also seen following chronic CIT treatment to PCS rats in this study has to be viewed in relation to both the pharmacokinetic and pharmacodynamic changes observed.

  • 7.
    Bastami, Salumeh
    et al.
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Frödin, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Dermatology and Venerology in Östergötland.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Uppugunduri, Srinivas
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Chemistry.
    Topical morphine gel in the treatment of painful leg ulcers, a double-blind, placebo-controlled clinical trial: a pilot study2012In: International Wound Journal, ISSN 1742-4801, E-ISSN 1742-481X, Vol. 9, no 4, p. 419-427Article in journal (Refereed)
    Abstract [en]

    Chronic painful wounds, a major health problem, have a detrimental impact on the quality of life due to associated pain. Some clinical reports have suggested that local administration of morphine could be beneficial. The aim of this study was to evaluate the analgesic effect of topically applied morphine on chronic painful leg ulcers. Twenty-one patients were randomly assigned to receive either morphine or placebo in a randomised, placebo-controlled, crossover pilot study. Each patient was treated four times in total. Pain was measured by the visual analogue score (VAS) before application of gel, directly after and after 2, 6, 12 and 24 hours. Although an overall, clinically relevant, reduction of pain was observed upon treatment with morphine, the difference was not statistically significant. Morphine reduced pain scores more than placebo on treatment occasions 1 and 2. The difference was statistically significant only 2 hours after dressing on the first treatment occasion. Thus, our study did not demonstrate a consistent and globally significant difference in nociception in patients treated with morphine. However, the relatively small number of patients included in our study and other methodological limitations makes it difficult for us to draw general conclusions regarding efficacy of topically applied morphine as an effective treatment for some painful ulcers. Further studies are warranted to evaluate the value of topically applied morphine in the treatment of patients with chronic painful leg ulcers.

  • 8.
    Bastami, Salumeh
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Gupta, A.
    Department of Anesthesia and Intensive Care, Örebro University, Örebro, Sweden.
    Zackrisson, Anna Lena
    Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden .
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Osman, Abdimajid
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Uppugunduri, Srinivas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Influence of UGT2B7, OPRM1 and ABCB1 gene polymorphisms on morphine use2014In: Basic & Clinical Pharmacology & Toxicology, ISSN 1742-7835, E-ISSN 1742-7843, Vol. 115, no 5, p. 423-431Article in journal (Refereed)
    Abstract [en]

    Therapeutic modulation of pain with morphine and other opioids is associated with significant variation in, both, effects and adverse effects in individual patients. Many factors including gene polymorphisms have been shown to contribute to the interindividual variability in the response to opioids. The aim of this study was to investigate the significance of UGT2B7, OPRM1 and ABCB1 polymorphisms for interindividual variability in morphine induced analgesia in patients undergoing hysterectomy. The frequency of these polymorphisms was also investigated in forensic autopsy cases as morphine is also a very commonly abused drug

    Blood samples were collected from 40 patients following abdominal hysterectomy, 24 hours after initiation of analgesia through a PCA pump. Samples were genotyped and analysed for morphine and its metabolites. We also genotyped approximately 200 autopsy cases found positive for morphine in routine forensic analysis.

    Patients homozygous for UGT2B7 802C needed significantly lower dose of morphine for pain relief. The same trend was observed for patients homozygous for ABCB1 1236T and 3435T, as well as to OPRM1 118A. Dose of morphine in patients included in this study was significantly related to variation in UGT2B7 T802C. Age was significantly related to both dose and concentration of morphine in blood.

    Regression analysis showed that 30% of differences in variation in morphine dose could be explained by SNPs in these genes. The genotype distribution was similar between the forensic cases and the patients. However, the mean concentration of morphine was higher in forensic cases compared to patients.

    We conclude that gene polymorphisms contribute significantly to the variation in morphine levels observed in individual patients.

  • 9.
    Bastami, Salumeh
    et al.
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Norling, Cecilia
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Trinks, Cecilia
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Holmlund, Birgitta
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology UHL.
    Walz, Thomas M
    Department of Oncology, Karolinska University Hospital, Stockholm, Sweden.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Uppugunduri, Srinivas
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Chemistry.
    Inhibitory effect of opiates on LPS mediated release of TNF and IL-82013In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 52, no 5, p. 1022-1033Article in journal (Refereed)
    Abstract [en]

    Most patients with advanced cancer experience severe pain and are often treated with opiates. Cancer patients are especially susceptible to opportunistic infections due to treatment with immunosuppressive and cytostatic drugs. Since opiates have been demonstrated to have immunomodulatory effects, it is of clinical importance to evaluate potential differences between commonly used opiates with regard to their effect on the immune system. The aim of this study was to evaluate the effect of morphine, tramadol, fentanyl and ketobemidone on the functioning of the immune system with special reference to TNF and IL-8 release. Method. U-937 cells were preincubated with different concentrations of opioids followed by stimulation with LPS 100 μg/ml for three hours. The effect of opioids on the levels of cytokine mRNA was studied using RT-PCR. Erk and Akt phosphorylation was also measured by Western blot. Results. All opioids with the exception of fentanyl were capable of inhibiting TNF release from U-937 cells. Morphine had no effect on IL-8 release but the effect of other opiates was almost the same as the effect on TNF. All opioids with the exception of fentanyl were capable of inhibiting production of mRNA for TNF and IL-8. The observed effects of opiates were not always reversible by naloxone, suggesting that the effects might be mediated by other receptors or through a non-receptor mediated direct effect. Although preliminary evidence suggests the involvement of Erk and Akt pathways, further studies are needed to unravel the intracellular pathways involved in mediating the effects of opiates. Our data suggests that the order of potency with regard to inhibition of cytokine release is as follows: tramadol > ketobemidone > morphine > fentanyl. Conclusion. Further studies are needed to understand the clinical implications of the observed immunosuppressive effects of tramadol and ketobemidone and to improve opioid treatment strategies in patients with cancer.

  • 10.
    Bengtsson, Finn
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Ahlner, Johan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.
    Insights in stereopharmacology in modern antidepressant treatment2005In: Association of European Psychiatrists AEP Congress,2005, 2005Conference paper (Other academic)
  • 11.
    Boiso, Samuel
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Zackrisson, Anna Lena
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Jakobsen Falk, Ingrid
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Karlsson, Louise
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Carlsson, Björn
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pharmacology.
    Tillmar, Andreas
    Natl Board Forens Med, Dept Forens Genet and Forens Toxicol, Linkoping, Sweden .
    Kugelberg, Fredrik
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pharmacology.
    Green, Henrik
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    ABCB1 gene polymorphisms are associated with suicide in forensic autopsies2013In: Pharmacogenetics & Genomics, ISSN 1744-6872, E-ISSN 1744-6880, Vol. 23, no 9, p. 463-469Article in journal (Refereed)
    Abstract [en]

    Background Polymorphisms in ABCB1 have the ability to affect both the function and the expression of the transporter protein P-glycoprotein and may lead to an altered response for many drugs including some antidepressants and antipsychotics.Objective The aim of this study was to examine the impact of the ABCB1 polymorphisms 1199Gandgt;A, 1236Candgt;T, 2677Gandgt;T/A, and 3435Candgt;T in deaths by suicide.Patients and methods A total of 998 consecutive Swedish forensic autopsies performed in 2008 in individuals 18 years of age or older, where femoral blood was available and a toxicological screening had been performed, were investigated. Genotypes were assessed with pyrosequencing and information on the cause and manner of each death was obtained from the forensic pathology and toxicology databases.Results There was a significantly higher frequency of the T allele at positions 1236, 2677, and 3435 among the suicide cases compared with the nonsuicide cases.Conclusion Our result from forensic cases suggests that ABCB1 polymorphisms are associated with an increased risk for completed suicides. The biological mechanisms involved and the clinical implications for these findings are largely unknown and need to be examined further.

  • 12.
    Carlsson, Björn
    et al.
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Holmgren, A.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Forensic Science and Toxicology .
    Ahlner, Johan
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Linköping University, Faculty of Health Sciences.
    Bengtsson, Finn
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Enantioselective analysis of citalopram and escitalopram in postmortem blood together with genotyping for CYP2D6 and CYP2C192009In: Journal of Analytical Toxicology, ISSN 0146-4760, Vol. 33, no 2, p. 65-76Article in journal (Refereed)
    Abstract [en]

    Citalopram is marketed as a racemate (50:50) mixture of the S(+)-enantiomer and R(-)-enantiomer and the active S(+)-enantiomer (escitalopram) that possess inhibitory effects. Citalopram was introduced in Sweden in 1992 and is the most frequently used antidepressant to date in Sweden. In 2002, escitalopram was introduced onto the Swedish market for treatment of depression and anxiety disorders. The main objective of this study was to investigate S(+)-citalopram [i.e., the racemic drug (citalopram) or the enantiomer (escitalopram)] present in forensic autopsy cases positive for the presence of citalopram in routine screening using a non-enantioselective bioanalytical method. Fifty out of the 270 samples found positive by gas chromatography-nitrogen-phosphorus detection were further analyzed using enantioselective high-performance liquid chromatography. The 50 cases were genotyped for CYP2D6 and CYP2C19, as these isoenzymes are implicated in the metabolism of citalopram and escitalopram. In samples positive for racemic citalopram using the screening method for forensic autopsy cases, up to 20% would have been misinterpreted in the absence of an enantioselective method. An enantioselective method is thus necessary for correct interpretation of autopsy cases, after the enantiomer has been introduced onto the market. The percentage of poor metabolizers was 6% for CYP2D6 and 8% for CYP2C19.

  • 13.
    Carlsson, Björn
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Holmgren, Anita
    RMV.
    Ahlner, Johan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.
    Bengtsson, Finn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Citalopram and escitalopram in postmortem blood: Confirmation of screening results from autopsy cases with enantioselective analysis.2007In: Nordisk kollokvium Rättstoxikologi.,2007, 2007Conference paper (Other academic)
  • 14.
    Carlsson, Björn
    et al.
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Olsson, Gunilla
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Reis, Margareta
    Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Linköping University, Faculty of Health Sciences.
    Wålinder, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Psychiatry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Nordin, Conny
    Linköping University, Department of Clinical and Experimental Medicine, Psychiatry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Lundmark, Jöns
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Scordo, M. G.
    Dahl, M-L.
    Bengtsson, Finn
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Enantioselective Analysis of Citalopram and Metabolites in Adolescents2001In: Therapeutic drug monitoring, ISSN 0163-4356, Vol. 23, no 6, p. 658-664Article in journal (Refereed)
    Abstract [en]

    Studies of the antidepressant effect and pharmacokinetics of citalopram have been performed in adults, but the effects on children and adolescents have only been studied to a minor extent despite its increasing use in these age groups. The aim of this study was to investigate a group of adolescents treated for depression, with respect to the steady-state plasma concentrations of the enantiomers of citalopram and its demethylated metabolites desmethylcitalopram and didesmethylcitalopram. Moreover, the authors studied the genotypes for the polymorphic cytochrome P450 enzymes CYP2D6 and CYP2C19 in relation to the different enantiomers. The S/R ratios of citalopram and desmethylcitalopram found in this study of 19 adolescents were similar to studies involving older patients. The concentrations of the R-(-)- and S-(+)-enantiomers of citalopram and desmethylcitalopram were also in agreement with values from earlier studies, the R-(-)-enantiomer (distomer) being the major enantiomer. The results indicate that the use of oral contraceptives may have some influence on the metabolism of citalopram. This might be because of an interaction of the contraceptive hormones with the CYP2C19 enzyme.

  • 15.
    D Cherma, Maria
    et al.
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Ahlner, Johan
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Bengtsson, Finn
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Gustafsson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Child and Adolescent Psychiatry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry.
    Antidepressant Drugs in Children and Adolescents Analytical and Demographic Data in a Naturalistic, Clinical Study2011In: JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY, ISSN 0271-0749, Vol. 31, no 1, p. 98-102Article in journal (Refereed)
    Abstract [en]

    Pharmacokinetics of antidepressant drugs (ATDs), in terms of steady-state and trough values, in patients from Child and Adolescent Psychiatry centers in the midsouth-eastern part of Sweden, were evaluated, and the use of ATDs in this population were described. Patients to be prescribed an ATD were studied between 2002 and 2004. Two hundred eleven children, 64% girls and 36% boys (ages 8-20 years) were evaluated. The primary indication for the antidepressant treatment was depression in 69% of subjects. The median body mass index was 20.2 kg/m(2) (range, 12.4-38.6 kg/m(2)). Suspected adverse drug reactions were spontaneously reported in 31% (no serious). Monotherapy was indicated in 49% of request forms. The most common drug combination with the ATD was oral contraceptives. The concentrations of drugs in the patient evaluated population to referenced data for adults from the dose administered were as expected in 63%, higher than expected in 26% and lower than expected in 11%. The most prescribed ATD was sertraline (SERT). Dose-concentration relationships for SERT and metabolite desmethylsertraline (DSERT) were seen, r(s) = 0.48 and r(s) = 0.5, respectively. No relationship was found between dose and ratio DSERT/SERT. The median daily dose was 50 mg (range, 12.5-150 mg), SERT concentration 16 ng/mL (range, 3-88 ng/mL), and DSERT 33 ng/mL (range, 0-253 ng/mL). CYP2D6*4 was the most common poor metabolizer allele. Therapeutic drug monitoring may provide support to prescribing physicians to individual dose optimizing and to assess drug compliance, above all when ATDs are not well studied in pediatric patients before approval for general prescription.

  • 16.
    Dolores Cherma Yeste, Maria
    et al.
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Reis, Margareta
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Hägg, Staffan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Bengtsson, Finn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Therapeutic Drug Monitoring of Ziprasidone in a Clinical Treatment Setting2008In: Therapeutic Drug Monitoring, ISSN 0163-4356, E-ISSN 1536-3694, Vol. 30, no 6, p. 682-688Article in journal (Refereed)
    Abstract [en]

    There is limited information on the pharmacokinetics of ziprasidone (ZIP) in naturalistic clinical settings. The objective of this study was to investigate the concentrations of ZIP and its active metabolite S-methyl-dihydroziprasidone (SMDZ), and the dose-normalized concentrations, using routine therapeutic drug monitoring (TDM) data. A high-performance liquid chromatographic method for determining serum concentrations of these substances for routine clinical use was established at the TDM Laboratory in Linkoping, Sweden. This analytical service was available to all physicians in Sweden. Between January 2001 and December 2004, 545 analyses, representing samples from 370 patients, were performed. The median daily ZIP dose was 120 mg (range 20-320 mg). In all, 121 steady-state trough specimens with essential clinical information were included in the pharmacokinetic evaluation. The median (25th to 75th percentile) serum concentration of ZIP was 125 nmol/L (82-188 nmol/L). The SMDZ:ZIP ratio decreased with increasing serum concentration of ZIP. The median (25th to 75th percentile) dose-normalized concentrations (nmol L-1 mg(-1) d(-1)) for ZIP and SMDZ were 1.13 (0.74-1.77) and 0.62 (0.45-0.86), respectively, with SMDZ:ZIP ratio of 0.57 (0.42-0.79). The overall coefficients of variation for close-normalized scruin concentrations of ZIP, SMDZ, and SMDZ:ZIP ratio were 62%, 56%, and 57%, respectively (n = 121). Smoking women had lower normalized ZIP concentrations than nonsmoking women. Twenty-eight patients with repeated eligible TDM analyses were studied for intraindividual variance over time. In summary, great interindividual and intraindividual differences in ZIP concentrations were observed. TDM of ZIP maybe used for individual dose adjustments and monitoring medication adherence.

  • 17. Druid, H.
    et al.
    Holmgren, P.
    Ahlner, Johan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology .
    Flunitrazepam: An evaluation of use, abuse and toxicity2001In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 122, no 2-3, p. 136-141Article in journal (Refereed)
    Abstract [en]

    The benzodiazepine flunitrazepam is extensively prescribed to patients with insomnia in many countries, but has also become popular among alcohol- and drug abusers. Several reports indicate that it is used as a date rape drug and suggest that it may precipitate violent behavior. Furthermore, flunitrazepam is involved in many fatal intoxications in Sweden. This study was designed and conducted to explore the negative consequences of flunitrazepam abuse in Sweden, and to assess the trends in its use and abuse. The occurrence of flunitrazepam in cases referred to the Department of Forensic Chemistry in Linköping, Sweden 1992-1998, was investigated in detail. The detections were studied separately for different groups, medicolegal death investigations, drug abuse cases, driving under influence cases, and other medicolegal cases. These data were further compared with the sales, and seizures by the Swedish Customs and the Swedish Police. During 1992-1998, 641 fatalities occurred, where the cause of death was attributed to intoxication with flunitrazepam solely (130) or in combination with other drugs, or concomittant conditions (511). In 78% of all driving under influence cases, where flunitrazepam was detected, the analyses also disclosed the presence of illicit drugs. A similar association was seen in drug abuse cases. The seizures reported by the Swedish Customs revealed a substantial and increasing illegal trade. Cases, where flunitrazepam seemingly induced violent behavior were identified, and one of these is described in some detail. It is concluded that the abuse pattern and the toxicity of flunitrazepam should be kept in mind by forensic investigators and that this panorama also should be considered when decisions about the registration and classification of flunitrazepam are made in different countries. Copyright © 2001 Elsevier Science Ireland Ltd.

  • 18.
    Druid, H
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Forensic Medicine.
    Holmgren, P
    Carlsson, B
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Ahlner, Johan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.
    Cytochrome P450 2D6 (CYPP2D6) genotyping on postmortem blood as a supplementary tool for interpretation of forensic toxicological results.  1999In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 99, p. 25-34Article in journal (Refereed)
  • 19.
    Fazel, S.
    et al.
    Department of Psychiatry, University of Oxford, Oxford, United Kingdom, Centre for Violence Prevention, Karolinska Institute, Stockholm, Sweden, University Department of Psychiatry, Warneford Hospital, Oxford OX3 7JX, United Kingdom.
    Grann, M.
    Centre for Violence Prevention, Karolinska Institute, Stockholm, Sweden.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Goodwin, G.
    Department of Psychiatry, University of Oxford, Oxford, United Kingdom.
    Suicides by violent means in individuals taking SSRIs and other antidepressants: A postmortem study in Sweden, 1992-20042007In: Journal of Clinical Psychopharmacology, ISSN 0271-0749, E-ISSN 1533-712X, Vol. 27, no 5, p. 503-506Article in journal (Refereed)
    Abstract [en]

    A number of reports have linked consumption of selective serotonin reuptake inhibitors (SSRIs) with suicide by violent methods. We aimed to determine whether suicides with postmortem evidence of SSRI consumption are more likely to have used violent methods compared with suicides with no detectable antidepressants. Blood samples from all suicides in Sweden during 1992-2004 were examined. Suicides were classified into those who died by violence and nonviolent (self-poisoning) methods using information from police records and autopsy. In addition, we investigated proportions of violent suicide in individuals who died with detectable levels of tricyclic and other antidepressants.The sample consisted of 14,691 suicides. Of the 1958 suicides with detectable levels of SSRIs, 1247 were by violent means (63.7%) compared with 7835 of 11,045 suicides (70.9%) in antidepressant-free group (?1 = 7.6, P < 0.01). We found no significant differences in the proportion of violent suicides in the SSRI group compared with the antidepressant-free group by sex or age band (15-24, 25-39, and over 40 years). When subdivided by gender and age-bands, we found specific groups with significantly lower proportions of violent suicides compared with the antidepressants-free group, including men aged 15-24 years. © 2007 Lippincott Williams & Wilkins, Inc.

  • 20.
    Fazel, Seena
    et al.
    Univ Oxford, Dept Psychiat, Oxford, England.
    Grann, Martin
    Karolinska Inst, Ctr Violence Prevent, Stockholm, Sweden.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Goodwin, Guy
    Univ Oxford, Dept Psychiat, Oxford, England.
    Letter: SSRI-induced violent suicide: Does forensic toxicology hold the answer? Reply to comments by Mr Carlin and Mr Hardisty2008In: Journal of Clinical Psychopharmacology, ISSN 0271-0749, E-ISSN 1533-712X, Vol. 28, no 4, p. 477-477Article in journal (Other academic)
    Abstract [en]

    n/a

  • 21.
    Forsman, M.
    et al.
    National Board of Forensic Medicine, Department of Forensic Genetics and Forensic Toxicology, Artillerigatan 12, SE 587 58, Linköping, Sweden.
    Nystrom, I.
    National Board of Forensic Medicine, Department of Forensic Genetics and Forensic Toxicology, Artillerigatan 12, SE 587 58, Linköping, Sweden.
    Roman, M.
    National Board of Forensic Medicine, Department of Forensic Genetics and Forensic Toxicology, Artillerigatan 12, SE 587 58, Linköping, Sweden.
    Berglund, L.
    National Board of Forensic Medicine, Department of Forensic Genetics and Forensic Toxicology, Artillerigatan 12, SE 587 58, Linköping, Sweden.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Kronstrand, Robert
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Urinary detection times and excretion patterns of flunitrazepam and its metabolites after a single oral dose2009In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 33, no 8, p. 491-501Article in journal (Refereed)
    Abstract [en]

    We investigated the excretion profiles of flunitrazepam metabolites in urine after a single dose. Sixteen volunteers received either 0.5 or 2.0 mg flunitrazepam. Urine samples were collected after 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 240, and 336 h. Samples were screened using CEDIA (300 µg/L cutoff) and quantitated using liquid chromatography-tandem mass spectrometry. The cutoff was 0.5 µg/L for flunitrazepam, N-desmethylflunitrazepam, 7-aminoflunitrazepam, 7-aminodesmethylflunitrazepam, 7-acetamidoflunitrazepam, and 7-acetamidodesmethylflunitrazepam. None of the subjects receiving 0.5 mg were screened positive, and only 23 of 102 samples from the subjects given 2.0 mg were positive with CEDIA. The predominant metabolites were 7-aminoflunitrazepam and 7-aminodesmethylflunitrazepam. For all subjects given the low dose, 7-aminoflunitrazepam was detected up to 120 h, and for two subjects for more than 240 h. Seven subjects given the high dose were positive up to 240 h for 7-aminoflunitrazepam. We conclude that the ratio 7-aminodesmethylflunitrazepam to 7-aminoflunitrazepam increased with time, independent of dose, and may be used to estimate the time of intake. For some low-dose subjects, the metabolite concentrations in the early samples were low and a chromatographic method may fail to detect the intake. We think laboratories should consider this when advising police and hospitals about sampling as well as when they set up strategies for analysis.

  • 22. Fugelstad, A
    et al.
    Ahlner, Johan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.
    Brandt, L
    Ceder, G
    Eksborg, S
    Rajs, J
    Beck, O
    Use of morphine and 6-monoacetylmorphine in blood for the evaluation of possible risk factors for sudden death in 192 heroin users2003In: Addiction, ISSN 0965-2140, E-ISSN 1360-0443, Vol. 98, no 4, p. 463-470Article in journal (Refereed)
    Abstract [en]

    Aims: To detect risk factors for sudden death from heroin injection. Design: Evaluation of data from forensic investigations of all fatal cases of suspected heroin death in a metropolitan area. Only cases with detectable morphine and 6-monoacetylmorphine (6-MAM) in blood were included in order to select heroin intoxication cases. Setting: Stockholm, Sweden. Measurements: Autopsy investigation and toxicological analysis of blood and urine: and police reports. Findings: In two-thirds of the 192 cases, death occurred in public places, and mostly without any time delay. Blood concentrations of morphine ranged from 50 to 1200 ng/g, and of 6-MAM from 1 to 80 ng/g. Codeine was detected in 96% of the subjects. In the majority of cases the forensic investigation indicated polydrug use, the most common additional findings being alcohol and benzodiazepines. However, in one-quarter of the cases other drug combinations were found. Previous abstinence from heroin and use of alcohol were identified as risk factors. For 6-MAM there was also a correlation with the presence of THC and benzodiazepines. Despite a high frequency of heart abnormalities (e.g. myocarditis and focal myocardial fibrosis), these conditions did not correlate with morphine or 6-MAM blood concentrations. Conclusions: We confirm that alcohol intake and loss of tolerance are risk factors for death from heroin use, whereas no connection to heart pathology was observed. Further, prospective, studies should focus on other possible risk factors.

  • 23.
    Hedlund, Jonatan
    et al.
    National Board Forens Med, Sweden; Karolinska Institute, Sweden.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Kristiansson, Marianne
    National Board Forens Med, Sweden; Karolinska Institute, Sweden.
    Sturup, Joakim
    National Board Forens Med, Sweden; Karolinska Institute, Sweden.
    A population-based study on toxicological findings in Swedish homicide victims and offenders from 2007 to 20092014In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 244, p. 25-29Article in journal (Refereed)
    Abstract [en]

    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 less than 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.

  • 24.
    Hedlund, Jonatan
    et al.
    National Board Forens Med, Sweden; Karolinska Institute, Sweden.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Kristiansson, Marianne
    National Board Forens Med, Sweden; Karolinska Institute, Sweden.
    Sturup, Joakim
    National Board Forens Med, Sweden; Karolinska Institute, Sweden.
    Correction: A population-based study on toxicological findings in Swedish homicide victims and offenders from 2007 to 2009 (vol 244, pg 25, 2014)2014In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 245, p. 161-161Article in journal (Other academic)
    Abstract [en]

    n/a

  • 25.
    Hoffmann, Mikael
    et al.
    Linköping University, Department of Medicine and Care, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Hammar, Mats
    Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Kjellgren, Karin
    Linköping University, Faculty of Health Sciences. The Sahlgrenska Academy at Göteborg University, Sweden.
    Lindh-Åstrand, Lotta
    Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Ahlner, Johan
    National Board of Forensic Medicine, Linköping, Sweden.
    Risk communication in consultations about hormone therapy in the menopause: concordance in risk assessment and framing due to the context2006In: Climacteric, ISSN 1369-7137, E-ISSN 1473-0804, Vol. 9, no 5, p. 347-354Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    It is important for the physician and the patient to have a mutual understanding of the possible consequences of different treatment alternatives in order to achieve a partnership in decision-making.

    OBJECTIVE:

    The aim of this study was to explore to which degree first-time consultations for discussion of climacteric discomfort achieved shared understanding of the risks and benefits associated with hormone therapy in the menopausal transition.

    METHODS:

    Analysis of structure and content of transcribed consultations (n = 20), and follow-up interviews of the women (n = 19 pairs of consultations and interviews), from first-time visits for discussion of climacteric discomfort and/or HT with five physicians at three different outpatient clinics of gynecology in Sweden.

    RESULTS:

    Four distinctively different interpretations of risk, depending on whether or not benefits were discussed in the same context, emerged from the analysis. On average, five advantages (range 0-11) and two (0-3) disadvantages were mentioned during the consultations. In the interviews, the women expressed on average four advantages (0-7) and one disadvantage (0-3). There were major variations between advantages and disadvantages expressed in the consultation and the following interview.

    CONCLUSION:

    Even though the consultations scored high in patient involvement, the information in most consultations was not structured in a way that made it possible to achieve a shared or an informed decision-taking.

  • 26.
    Hoffmann, Mikael
    et al.
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Linköping University, Faculty of Health Sciences.
    Hammar, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology . Linköping University, Faculty of Health Sciences.
    Lindh-Åstrand, Lotta
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology . Linköping University, Faculty of Health Sciences.
    Ahlner, Johan
    Department of Forensic Chemistry, National Board of Forensic Medicine, Linköping, Sweden.
    Risk communication in consultations about hormone therapy in the menopause – concordance in risk assessment and framing due to the context2006In: Climacteric, ISSN 1369-7137, E-ISSN 1473-0804, Vol. 9, no 5, p. 347-354Article in journal (Refereed)
    Abstract [en]

    Background

    It is important for the physician and the patient to have a mutual understanding of the possible consequences of different treatment alternatives in order to achieve a partnership in decision making.

    Objective

    The aim of this study was to explore to which degree first-time consultations for discussion of climacteric discomfort achieved shared understanding of the risks and benefits associated with hormone therapy in the menopausal transition (HT).

    Methods

    Analysis of structure and content of transcribed consultations (n=20), and follow-up interviews of the women (n=19 pairs of consultations and interviews), from first-time visits for discussion of climacteric discomfort and/or HT with five physicians at three different out-patient clinics of gynaecology in Sweden.

    Results

    Four distinctively different interpretations of risk, depending on whether or not benefits were discussed in the same context, emerged from the analysis. On average 5 advantages (range 0-11) and 2 (0-3) disadvantages were mentioned during the consultations. In the interviews the women expressed on average 4 advantages (0-7) and 1 disadvantage (0-3). There were major variations between advantages and disadvantages expressed in the consultation and the following interview.

    Conclusion

    Even though the consultations scored high in patient involvement, the information in most consultations was not structured in a way that made it possible to achieve a shared or an informed decision making.

  • 27.
    Hoffmann, Mikael
    et al.
    Linköping University, Department of Medicine and Care, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Lindh-Åstrand, Lotta
    Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Ahlner, Johan
    National Board of Forensic Medicine, Linköping, Sweden.
    Hammar, Mats
    Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Kjellgren, Karin I.
    Faculty of Health and Caring Sciences, Institute of Nursing, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden.
    Hormone replacement therapy in the menopause - structure and content of risk talk2005In: Maturitas, ISSN 0378-5122, E-ISSN 1873-4111, Vol. 50, no 1, p. 8-18Article in journal (Refereed)
    Abstract [en]

    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.

  • 28. Holmgren, A
    et al.
    Holmgren, P
    Kugelberg, Fredrik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.
    Jones, A Wayne
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Ahlner, Johan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.
    Predominance of illicit drugs and poly-drug use among drug-impaired drivers in Sweden2007In: Traffic Injury Prevention, ISSN 1538-9588, E-ISSN 1538-957X, Vol. 8, no 4, p. 361-367Article in journal (Refereed)
    Abstract [en]

    Objective. After Sweden's zero-tolerance law came into force (1 July 1999), the number of cases of driving under the influence of drugs (DUID) submitted by the police for toxicological analysis increased more than 10-fold. This prompted an in-depth investigation into the kinds of drugs used by DUID offenders, whether licit or illicit, and the frequency of their occurrence. Methods. All blood samples from DUID suspects sent by the police for toxicological analysis over a 4-year period (2001-2004) were investigated (N = 22,777 cases). Specimens of blood or urine were subjected to a broad screening analysis by immunoassay methods aimed at detecting amphetamines, cannabis, opiates, cocaine metabolite, and the major benzodiazepines. All positive results from the screening stage were verified by use of more specific analytical methods (e.g., GC-MS, LC-MS, GC-FID, and GC-NPD). Results. Between 80 and 85% of all the blood samples contained at least one banned substance and many contained two or more therapeutic and/or illicit drugs. About 15% of cases were negative for drugs, although these frequently (30-50%) contained ethanol above the legal limit for driving in Sweden, which is 0.20 mg/g (0.02 g%). Amphetamine was the most prominent illicit drug seen in 55-60% of cases either alone or together with other drugs of abuse. Stimulants like cocaine and/or its metabolite were infrequently encountered (1.2% of cases). The next most prevalent illicit drug was cannabis, with positive results for tetrahydrocannabinol (THC) in blood either alone (4%) or together with other psychoactive substances (20%). Morphine, codeine, and/or 6-acetyl morphine were identified in 2% of all DUID suspects, being indicative of heroin abuse. The major prescription drugs identified in blood were benzodiazepines (10%) as exemplified by diazepam, alprazolam, nitrazepam, and flunitrazepam. Drugs for treating insomnia, zolpidem and zopiclone, were also identified in blood samples from DUID suspects over the study period. Other therapeutic agents were encountered in only 1-2% of all cases. Conclusions. The dramatic increase in DUID after the zero-tolerance law came into force probably reflects enhanced police activity and more enthusiasm to apprehend and charge individuals for this offence. Illicit drugs, particularly amphetamine and cannabis, and poly-drug use were predominant compared with use of scheduled prescription drugs. The typical DUID offender in Sweden abuses central stimulants, particularly amphetamine, and has probably done so over many years. Options for treating offenders for their underlying substance abuse problem should be considered instead of the more conventional penalties for drug-impaired driving.

  • 29.
    Holmgren, Anita
    et al.
    Department of Forensic Genetics and Forensic Toxicology National Board of Forensic Medicine, Linköping.
    Holmgren, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.
    Kugelberg, Fredrik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology.
    Jones, A Wayne
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry.
    Ahlner, Johan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology.
    High re-arrest rates among drug-impaired drivers despite zero-tolerance legislation2008In: Accident Analysis and Prevention, ISSN 0001-4575, E-ISSN 1879-2057, Vol. 40, no 2, p. 534-540Article in journal (Refereed)
    Abstract [en]

    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 0.2 mg/g (∼0.02 g%). 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 1.5 mg/g (∼0.15 g%), which suggests a dominance of heavy drinkers. The median BAC was even higher in recidivists (1.6-1.7 mg/g). The median concentration of amphetamine in blood was 1.0 mg/L in recidivists compared with 0.5 mg/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. © 2007 Elsevier Ltd. All rights reserved.

  • 30.
    Holmgren, Per
    et al.
    Linköping University, Department of Medical and Health Sciences, Forensic Science and Toxicology . Linköping University, Faculty of Health Sciences.
    Carlsson, Björn
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Zackrisson, Anna-Lena
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Lindblom, Bertil
    Linköping University, Department of Clinical and Experimental Medicine, Forensic Genetics. Linköping University, Faculty of Health Sciences.
    Dahl, Marja-Liisa
    Department of Medical Sciences, Clinical Pharmacology, University Hospital, Uppsala, Sweden.
    Scordo, Maria Gabriella
    Department of Medical Laboratory Sciences and Technology, Division of Clinical Pharmacology, Karolinska Institutet, University Hospital, Stockholm, Sweden.
    Druid, Henrik
    National Board of Forensic Medicine and Department of Forensic Medicine, Karolinska Institutet, Solna, Sweden.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Forensic Science and Toxicology . Linköping University, Faculty of Health Sciences.
    Enantioselective analysis of citalopram and its metabolites in postmortem blood and genotyping for CYD2D6 and CYP2C192004In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 28, no 2, p. 94-104Article in journal (Refereed)
    Abstract [en]

    Citalopram, a selective serotonin reuptake inhibitor, is one of the most commonly found drugs in Swedish forensic autopsy cases. Citalopram is a racemic drug with 50:50 of the S- and R- enantiomers. Enantioselective analysis of citalopram and its metabolites desmethylcitalopram and didesmethylcitalopram were performed in femoral blood from 53 autopsy cases by a chiral high-performance liquid chromatography (HPLC) method. The mean (± standard deviation) S/R ratio for citalopram was 0.67 ± 0.25 and for desmethylcitalopram, 0.68 ± 0.20. We found increasing S/R ratios with increasing concentrations of citalopram. We also found that high citalopram S/R ratios were associated with a high parent drug-to-metabolite ratio and may be an indicator of recent intake. Citalopram is metabolized by cytochrome P450 (CYP) 3A4, 2C19, and 2D6. Genotyping for the polymorphic CYP2C19 and CYP2D6 revealed no poor metabolizers regarding CYP2C19 and only 2 (3.8%) poor metabolizers regarding CYP2D6. The presence of drugs metabolized by and/or inhibiting these enzymes in several of the cases suggests that such pharmacokinetic interactions are a more important (practical) problem than metabolic deficiency. Enantioselective analysis of citalopram and its metabolites can provide additional information when interpreting forensic toxicology results and might be a necessity in the future.

  • 31.
    Holmgren, Per
    et al.
    Linköping University, Department of Medical and Health Sciences, Forensic Science and Toxicology . Linköping University, Faculty of Health Sciences.
    Druid, Henrik
    Department of Forensic Medicine, Karolinska Institutet, Stockholm, Sweden.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Forensic Science and Toxicology . Linköping University, Faculty of Health Sciences.
    Drug interactions: a challenge in interpreting postmortem toxicology results and a problem in the clinical practiceManuscript (preprint) (Other academic)
    Abstract [en]

    Objective: Multiple drug intake is a problem in tbe clinical setting with potential to adverse drug reactions and certainly a problem in interpretation of forensic toxicology results. The aims of this investigation were to study the incidence of concomitant drugs in autopsy cases where citalopram or zopiclone were detected in femoral blood and to evaluate the potential of drug interactions.

    Methods: All medico-legal autopsy cases in Sweden during 1992 to 2003 where citalopram or zopiclone were detected in femoral blood at the toxicological analyses were selected. The number and occurrences of concomitant drugs were recorded together with the concentrations as well as the cause of death.

    Results: In the 2405 cases with citalopram, 123 different drugs, metabolites excluded, were detected 4679 times giving an average of 1.9 concomitant drugs and 1099 different dmg combinations were identified. The corresponding figures for the cases with zopiclone were 1557 cases, 118 different drugs detected 3984 times giving an average of 2.6 concomitant drugs and 977 different combinations. We found a strong positive correlation between the number of drugs detected and the frequency of cases judged to be intoxication.

    Conclusions: Pharmacokinetic and pharmacodynamic interactions are a potential problem when interpreting forensic toxicological results and the conclusions about the cause and manner of death in the single case must be based on all available information from the investigation and tbe autopsy and on tbe knowledge of tbe pharmacology of included drugs. A better control of prescriptions of what different drugs an individual is given together with a comprehensive therapy control may reduce the risks of adverse drug reactions and unintended or accidental intoxications.

  • 32.
    Holmgren, Per
    et al.
    Linköping University, Department of Medical and Health Sciences, Forensic Science and Toxicology . Linköping University, Faculty of Health Sciences.
    Druid, Henrik
    National Board of Forensic Medicine, Department of Forensic Medicine, Karolinska Institutet, Stockholm, Sweden.
    Holmgren, Anita
    Linköping University, Department of Medical and Health Sciences, Forensic Science and Toxicology . Linköping University, Faculty of Health Sciences.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Forensic Science and Toxicology . Linköping University, Faculty of Health Sciences.
    Stability of drugs in stored postmortem femoral blood and vitreous humor2004In: Journal of Forensic Sciences, ISSN 0022-1198, E-ISSN 1556-4029, Vol. 49, no 4, p. 820-825Article in journal (Refereed)
    Abstract [en]

    The stability of 46 drugs in postmortem femoral blood stored for one year at -20°C was investigated. The drugs included benzodiazepines, antidepressants, analgetics and hypnotics. For seven drugs we found a significant change in the concentration between the first and second analysis. Five substances; ethanol, desmethylmianserin, 7-amino-nitrazepam, THC and zopiclone showed a decrease in the concentration whereas the concentrations of two substances; ketobemidone and thioridazine increased. However, the changes observed were not of such an order that it would affect the interpretation in normal forensic casework. We also investigated the possible influence of potassium fluoride on the concentrations of the 46 drugs in vitreous humor after storage for one year. For two substances, ethanol and zopiclone, there were significantly lower concentrations in the samples without potassium fluoride. Furthermore, we also studied the correlation between the concentrations in femoral blood and vitreous humor. For 23 substances there was a significant difference between the concentrations in the vitreous humor and femoral blood. Significant correlations between the concentrations in these two specimens were found for 23 substances, indicating that vitreous humor can be an alternative specimen when blood samples are not available, provided that such correlation exists for the particular substance. Statistical analysis also revealed a correlation between the degree of protein binding of the different drugs and percentage of vitreous/femoral blood concentrations.

  • 33.
    Holmgren, Per
    et al.
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Linköping University, Faculty of Health Sciences.
    Holmgren, A
    Nationall Board of Forensic Medicine.
    Ahlner, Johan
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Linköping University, Faculty of Health Sciences.
    Alcohol and drugs in drivers fatally injured in traffic accidents in Sweden during the years 2000-20022005In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 151, no 1, p. 11-17Article in journal (Refereed)
    Abstract [en]

    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 2.0 mg/mL for men and from 1.2 to 1.8 mg/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.

  • 34.
    Holmgren, Per
    et al.
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Linköping University, Faculty of Health Sciences.
    Norden-Pettersson, Lotta
    National Board of Forensic Medicine.
    Ahlner, Johan
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Linköping University, Faculty of Health Sciences.
    Caffeine fatalities - four case reports2004In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 139, no 1, p. 71-73Article in journal (Refereed)
    Abstract [en]

    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.

  • 35.
    Isacsson, G.
    et al.
    Karolinska Institute.
    Holmgren, Anita
    National Board for Forensic Medicine.
    Osby, U.
    Karolinska Institute.
    Ahlner, Johan
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Linköping University, Faculty of Health Sciences.
    Decrease in suicide among the individuals treated with antidepressants: a controlled study of antidepressants in suicide, Sweden 1995-20052009In: Acta Psychiatrica Scandinavica, ISSN 0001-690X, E-ISSN 1600-0447, Vol. 120, no 1, p. 37-44Article in journal (Refereed)
    Abstract [en]

    Objective: Ecological studies have demonstrated a substantial decrease in suicide in parallel with an increase in the use of antidepressants. Causality cannot, however, be inferred from such studies. The aim of this study was to test on the individual level the hypothesis that treatment with antidepressant medication has been a substantially contributing cause of the decrease in suicide. Method: Time trends in the detection of antidepressants and five control medications in the forensic toxicological screening of 16 937 suicides and 33 426 controls in Sweden 1995-2005. Results: The expected number of antidepressant-positive suicides in 2005 was 409 if the hypothesis was true and 603 if it was false. The observed number in 2005 was 420. The control medications were detected to the extent that was expected if not preventing suicide. Conclusion: The observed trend in the number of suicides with antidepressants was well predicted by the hypothesis that the increased use of antidepressants has been a substantially contributing cause of the decrease in suicide.

  • 36.
    Isacsson, G
    et al.
    Karolinska Institute.
    Holmgren, Per
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Linköping University, Faculty of Health Sciences.
    Ahlner, Johan
    Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Linköping University, Faculty of Health Sciences.
    Selective serotonin reuptake inhibitor antidepressants and the risk of suicide: a controlled forensic database study of 14,857 suicides2005In: Acta Psychiatrica Scandinavica, ISSN 0001-690X, E-ISSN 1600-0447, Vol. 111, no 4, p. 286-290Article in journal (Refereed)
    Abstract [en]

    To test the hypothesis that selective serotonin reuptake inhibitor (SSRI) antidepressants may have a suicide emergent effect, particularly in children and adolescents. Detections of different antidepressants in the forensic toxicological screening of 14 857 suicides were compared with those in 26 422 cases of deaths by accident or natural causes in Sweden 1992-2000. There were 3411 detections of antidepressants in the suicides and 1538 in the controls. SSRIs had lower odds ratios than the other antidepressants. In the 52 suicides under 15 years, no SSRIs were detected. In 15-19-year age group, SSRIs had lower relative risk in suicides compared with non-SSRIs. The hypothesis that treatment of depressed individuals with SSRIs leads to an increased risk of suicide was not supported by this analysis of the total suicidal outcome of the nationwide use of SSRIs in Sweden over a period of 9 years, either in adults or in children or adolescents.

  • 37.
    Isacsson, G.
    et al.
    Karolinska University Hospital, Sweden.
    Reutfors, J.
    Karolinska Institute, Sweden.
    Papadopoulos, F.C.
    University Uppsala Hospital, Sweden.
    Ösby, U.
    Karolinska University Hospital, Sweden.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Retracted articel: Antidepressant medication prevents suicide in depression2010In: Acta Psychiatrica Scandinavica, ISSN 0001-690X, E-ISSN 1600-0447, Vol. 122, no 6, p. 454-460Article in journal (Refereed)
    Abstract [en]

    Objective: Ecological studies have demonstrated a substantial decrease in suicide in parallel with an increasing use of antidepressants. To investigate on the individual level the hypothesis that antidepressant medication was a causal factor. Method: Data on the toxicological detection of antidepressants in 18 922 suicides in Sweden 1992-2003 were linked to registers of psychiatric hospitalization as well as registers with sociodemographic data. Results: The probability for the toxicological detection of an antidepressant was lowest in the non-suicide controls, higher in suicides, and even higher in suicides that had been psychiatric inpatients but excluding those who had been in-patients for the treatment of depression. Conclusion: The finding that in-patient care for depression did not increase the probability of the detection of antidepressants in suicides is difficult to explain other than by the assumption that a substantial number of depressed individuals were saved from suicide by postdischarge treatment with antidepressant medication.

  • 38.
    Jones, A Wayne
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Drug Research.
    Holmgren, A
    National Board for Forensic Medicine.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Concentrations of free-morphine in peripheral blood after recent use of heroin in overdose deaths and in apprehended drivers2012In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 215, no 1-3, p. 18-24Article in journal (Refereed)
    Abstract [en]

    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 andlt; 0.001) in both the autopsy cases (88%) and the drivers (91%), although their mean age was about the same 33-35 y (p andgt; 0.05). Concentrations of free-morphine in blood were not associated with age of heroin users in Sweden (p andgt; 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 andlt; 0.05), and appreciably higher than in drivers with 6-MAM in urine but not in blood (0.03 mg/L, N = 1823, p andlt; 0.001). The free-morphine concentration was above 0.20 mg/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.

  • 39.
    Jones, A Wayne
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Drug Research.
    Holmgren, Anita
    Nationall Board of Forensic Medicine.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Blood Methadone Concentrations in Living and Deceased Persons: Variations Over Time, Subject Demographics, and Relevance of Coingested Drugs2012In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 36, no 1, p. 12-18Article in journal (Refereed)
    Abstract [en]

    n/a

  • 40.
    Jones, A Wayne
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Drug Research.
    Holmgren, Anita
    National Board of Forensic Medicine.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Heroin poisoning deaths with 6-acetylmorphine in blood: demographics of the victims, previous drug-related offences, polydrug use, and free morphine concentrations in femoral blood2012In: FORENSIC TOXICOLOGY, ISSN 1860-8965, Vol. 30, no 1, p. 19-24Article in journal (Refereed)
    Abstract [en]

    This article discusses cases of drug-poisoning death in which 6-acetylmorphine (6-AM) was identified in blood as evidence for recent use of heroin. We report the demographics of the victims, previous drug-related offences, polydrug use, and the concentrations of free morphine in peripheral blood. After solid-phase extraction, morphine, codeine, and 6-AM were determined in blood samples by isotope-dilution gas chromatography-mass spectrometry (GC-MS) using limits of quantitation of 0.005 mg/l for each opiate. The victims of heroin poisoning were mainly men (88%), with a mean age of 35.4 +/- A 8.4 years (+/- SD) and no significant gender difference in age (men 35 +/- A 8.4 years; women 35 +/- A 8.6 years). The median concentration of free morphine in blood (n = 671) was 0.25 mg/l (66% andgt; 0.20 mg/l) and women had a higher concentration (0.30 mg/l) than men (0.24 mg/l) (P andlt; 0.05). No significant difference (P andgt; 0.05) was found for the concentration of free morphine in blood when heroin was the only drug taken (median 0.26 mg/l, n = 53) compared with multidrug deaths (median 0.24 mg/l, n = 618) (P andgt; 0.05). The coingested drugs most commonly identified in heroin-related deaths were ethanol (44%), diazepam (27%), cannabis (20%), and flunitrazepam (19%). We found that 61% of victims had previous drug-related offences ranging from 1 to 48 times. The close agreement between the concentrations of free morphine in blood when heroin was the only drug taken and multidrug deaths suggests that differences in tolerance to opiates is more important in causing death than adverse drug-drug interactions.

  • 41.
    Jones, A Wayne
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Drug Research.
    Holmgren, Anita
    National Board for Forensic Medicine.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Quantitative analysis of amphetamine in femoral blood from drug-poisoning deaths compared with venous blood from impaired drivers2011In: Bioanalysis, ISSN 1757-6180, E-ISSN 1757-6199, Vol. 3, no 19, p. 2195-2204Article in journal (Refereed)
    Abstract [en]

    Background: Amphetamine is a major drug of abuse worldwide. Here we compare the concentrations of this stimulant amine in femoral blood in drug fatalities with venous blood from impaired drivers. Method: Amphetamine was determined in blood by isotope-dilution GC-MS after liquid-liquid extraction. Results: Amphetamine was the only drug identified in 36 fatalities at mean (median) and highest concentrations of 2.0 mg/l (1.5 mg/l) and 14.0 mg/l. In multiple-drug deaths (n = 383), the concentrations were 0.94 mg/l (0.4 mg/l) and 13.3 mg/l. In impaired drivers with amphetamine as the only drug (n = 6138), the concentrations were 1.0 mg/l (0.8 mg/l) and 11.9 mg/l, compared with 0.78 mg/l (0.6 mg/l) and 22.3 mg/l in multidrug users (n = 8250). Conclusion: Fatal amphetamine poisonings cannot be identified on the basis of the concentration in blood alone, owing to the development of tolerance and the toxicity of co-ingested substances.

  • 42.
    Jones, A Wayne
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Drug Research.
    Holmgren, Anita
    National Board for Forensic Medicine, Sweden.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Toxicological analysis of blood and urine samples from female victims of alleged sexual assault2012In: Clinical Toxicology, ISSN 1556-3650, E-ISSN 1556-9519, Vol. 50, no 7, p. 555-561Article in journal (Refereed)
    Abstract [en]

    Background. The toxicological analysis of blood and urine samples from victims of alleged sexual assault represents a crucial part of the forensic evidence when this crime is investigated. Material and methods. We searched a national forensic toxicology database (TOXBASE) to find cases registered as sexual assault, rape, including date-rape that the police had requested the analysis of ethanol and other drugs. Between 2008 and 2010, N = 1460 such cases met this criteria. After immunological screening of urine or blood samples, all positive results were verified by more specific analytical methods, such as gas chromatography-mass spectrometry (GC-MS) for illicit drugs. A large number of prescription drugs and their metabolites were determined by capillary GC with nitrogen-phosphorous (N-P) detector. GC with flame ionization detector (FID) was used to analyze ethanol and gamma-hydroxybutyrate (GHB) in blood at limits of quantitation (LOQ) of 0.1 g/L and 8 mg/L, respectively. Results. The average age (+/- standard deviation) of all victims was 24 +/- 10.3 years and 72% were between 15 and 29 years. Ethanol and other drugs were not detected in 31% of cases (N +/- 459). Blood-ethanol was positive in N = 658 cases at mean, median and highest concentrations of 1.23 g/L, 1.22 g/L and 4.3 g/L, respectively. Ethanol plus drugs were present in N = 188 cases (13%) and one or more other drugs alone in N = 210 cases (14%). Cannabis (marijuana) and amphetamines were the major illicit drugs, whereas diazepam, alprazolam, zopiclone as well as newer antidepressants were the major prescription drugs identified. Conclusions. The mean age of victims of sexual assault in Sweden, the proportion of drug positive to drug negative cases, the predominance of ethanol positive cases as well as the types of other drugs showed a remarkably good agreement in two studies spanning a period of 8 years.

  • 43.
    Jones, A Wayne
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Drug Research.
    Kugelberg, Fredrik
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Holmgren, A
    National Board for Forensic Medicine.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Drug poisoning deaths in Sweden show a predominance of ethanol in mono-intoxications, adverse drug-alcohol interactions and poly-drug use2011In: FORENSIC SCIENCE INTERNATIONAL, ISSN 0379-0738, Vol. 206, no 1-3, p. 43-51Article in journal (Refereed)
    Abstract [en]

    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 andlt; 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 andlt; 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 3.06 g/L and 3.10 g/L, respectively. The BAC decreased as the number of additional drugs in blood increased from 2.15 g/L with one drug to 1.25 g/L with 6 or more drugs. The mean (median) concentrations of non-alcohol drugs in mono-intoxication deaths were morphine (N = 93) 0.5 mg/L (0.2 mg/L), amphetamine (N = 39) 2.0 mg/L (1.2 mg/L), dextropropoxyphene (N = 33) 3.9 mg/L (2.9 mg/L), dihydro-propiomazine (N = 32) 1.6 mg/L (1.0 mg/L) and 7-amino-flunitrazepam (N = 28), 0.4 mg/L (0.3 mg/ 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.

  • 44.
    Jones, A Wayne
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Drug Research.
    Kugelberg, Fredrik
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Holmgren, Anita
    National Board for Forensic Medicine.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Five-year update on the occurrence of alcohol and other drugs in blood samples from drivers killed in road-traffic crashes in Sweden2009In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 186, no 01-Mar, p. 56-62Article in journal (Refereed)
    Abstract [en]

    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 similar 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 (greater than0.2 g/L) in 22% of cases (N = 315) at mean, median and highest concentrations of 1.7 g/L, 1.7 g/L and 4.9 g/L, respectively. The proportions of male to female drivers with BAC greater than 0.2 g/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 1.5 mg/L, 1.1 mg/L and 5.0 mg/L, respectively (N = 39). Blood specimens contained a wide spectrum of pharmaceutical products (mean 2.4 drugs/person), comprising sedative-hypno tics (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. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

  • 45.
    Jones, A Wayne
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry.
    Kugelberg, Fredrik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology.
    Holmgren, Anita
    Department of Forensic Genetics and Forensic Toxicology National Board of Forensic Medicine, Linköping.
    Ahlner, Johan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology.
    Occurrence of ethanol and other drugs in blood and urine specimens from female victims of alleged sexual assault2008In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 181, no 1-3, p. 40-46Article in journal (Refereed)
    Abstract [en]

    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 0.1 g/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 ∼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 1.24 g/L, 1.19 g/L and 3.7 g/L, respectively. The age of victims and their blood-alcohol concentration (BAC) were positively correlated (r = 0.365, p < 0.001). Because BAC decreases at a rate of 0.10-0.25 g/(L h), owing to metabolism the concentration in blood at time of sampling is often appreciably less than when the crime was committed several hours earlier. Licit or illicit drugs were identified in blood or urine in N = 262 cases (15%). Amphetamine and tetrahydrocannabinol were the most common illicit drugs at mean (median) concentrations in blood of 0.22 mg/L (0.1 mg/L) and 0.0012 mg/L (0.0006 mg/L), respectively. Among prescription drugs, sedative-hypnotics such as diazepam and zopiclone were common findings along with SSRI antidepressants and various opiate analgesics. Interpreting the analytical results in terms of voluntary vs. surreptitious administration of drugs and the degree of incapacitation in the victim as well as ability to give informed consent for sexual activity is fraught with difficulties. © 2008 Elsevier Ireland Ltd. All rights reserved.

  • 46.
    Jones, Alan Wayne
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Holmgren, Anita
    National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    High prevalence of previous arrests for illicit drug use and/or impaired driving among drivers killed in motor vehicle crashes in Sweden with amphetamine in blood at autopsy2015In: International journal on drug policy, ISSN 0955-3959, E-ISSN 1873-4758, Vol. 26, no 8, p. 790-793Article in journal (Refereed)
    Abstract [en]

    Background: Amphetamine, and to a lesser extent the secondary amine methamphetamine, are major recreational drugs of abuse in Sweden. These central stimulant amines are identified in blood from roughly 50% of people arrested for driving under the influence of drugs (DUID). However, much less information is available about the presence of amphetamine in blood of drivers killed in road-traffic crashes.

    Methods: This retrospective 10-year study (2001-2010) used a forensic toxicology database (TOXBASE) to retrieve information about road-traffic crashes when the driver had amphetamine and/or methamphetamine in autopsy blood. Forensic toxicology results were available from over 95% of all drivers killed on Swedish roads during this 10-year period.

    Results: Amphetamine was present in the blood of 106 drivers (3.9%) either alone or together with other psychoactive substances (e.g. alcohol, cannabis, diazepam, alprazolam, etc.). The vast majority of fatalities were male (95%) with a mean age (+/- standard deviation) of 37 +/- 11.4 years (range 16-67 years). The mean (median) and highest concentrations of amphetamine in femoral blood were 1.36 mg/L (1.0 mg/L) and 6.74 mg/L, respectively. Many of the victims (75%) had been arrested previously for use of illicit drugs or DUID. The median number of previous arrests was 4 (range 0-83) and amphetamine or methamphetamine were among the drugs identified in blood samples from 89% of cases (0-100%).

    Conclusion: The high prevalence of repeat DUID offending and/or use of illicit drugs among the drivers killed in road-traffic crashes suggests that an early intervention and treatment for stimulant abuse might have been more beneficial than conventional punishments for such drug-related crimes. (C) 2015 Elsevier B.V. All rights reserved.

  • 47.
    Jones, Wayne A.
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Department of Forensic Genetics and Forensic Toxicology, National.
    Holmgren, Anita
    Natl Board Forens Med, Dept Forens Genet and Forens Toxicol, SE-58758 Linkoping, Sweden .
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Toxicology findings in suicides: Concentrations of ethanol and other drugs in femoral blood in victims of hanging and poisoning in relation to age and gender of the deceased2013In: Journal of Forensic and Legal Medicine, ISSN 1752-928X, E-ISSN 1878-7487, Vol. 20, no 7, p. 842-847Article in journal (Refereed)
    Abstract [en]

    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 (andgt;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 persons age or gender (p andgt; 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.

  • 48.
    Jornil, J
    et al.
    Aarhus University, Denmark .
    Nielsen, T S.
    Aarhus University, Denmark .
    Rosendal, I
    Aarhus University, Denmark .
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Zackrisson, Anna Lena
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Boel, L W T.
    Aarhus University, Denmark .
    Brock, B
    Aarhus University, Denmark .
    A poor metabolizer of both CYP2C19 and CYP2D6 identified by mechanistic pharmacokinetic simulation in a fatal drug poisoning case involving venlafaxine2013In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 226, no 1-3, p. E26-E31Article in journal (Refereed)
    Abstract [en]

    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.

  • 49.
    Josefsson, M
    et al.
    National Board Forensic Medicine.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Letter: Amlodipine and grapefruit juice2002In: British Journal of Clinical Pharmacology, ISSN 0306-5251, E-ISSN 1365-2125, Vol. 53, no 4, p. 405-405Article in journal (Other academic)
    Abstract [en]

    n/a

  • 50.
    Jönsson, Anna
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Ahlner, Johan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.
    Benzodiazepiner, bruk och missbruk2005In: Det förbisedda missbruket - läkemedlens del i beroendeproblematiken, Mobilisering mot narkotika,2005, 2005Conference paper (Other academic)
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