Post-mortem Toxicological Findings Research Articles

Toxicology Screening in Sports-Related Sudden Cardiac Death: A Multinational Observational Study

BackgroundKnowledge of toxicological findings among sports-related sudden cardiac death (SrSCD) is scarce. ObjectivesThis study aimed to describe postmortem toxicology findings in a multinational cohort of young SrSCD. MethodsPatients with sudden cardiac death (SCD) aged 12 to 49 years with a complete post mortem were included from Denmark, Spain, and Australia. Postmortem findings were compared between SrSCD and non-SrSCD, and toxicology findings in SrSCD were assessed. ResultsWe included 3,189 SCD, of which 219 (7%) were sports-related. SrSCD patients were younger (36 years vs 41 years; P < 0.001) and of male predominance (96% vs 75%; P < 0.001), and their death was more often caused by structural cardiac disease (68% vs 61%; P = 0.038). Positive toxicology screenings were significantly less likely among SrSCD than non-SrSCD (12% vs 43%; P < 0.001), corresponding to 82% lower odds of a positive toxicology screening in SrSCD. Patient characteristics were similar between SrSCDs with positive and negative toxicology screenings, but deaths were more often unexplained (59% vs 34%). Nonopioid analgesics were the most common finding (3%), and SCD-associated drugs were detected in 6% of SrSCD. SUD was more prevalent among the SrSCD with positive toxicology (59% vs 34%). ConclusionsSports-related SCD mainly occurred in younger men with structural heart disease. They had a significantly lower prevalence of a positive toxicology screening compared with non-SrSCD, and detection of SCD-associated drugs was rare.

Postmortem toxicology findings from the Camden Opioid Research Initiative.

The United States continues to be impacted by decades of an opioid misuse epidemic, worsened by the COVID-19 pandemic and by the growing prevalence of highly potent synthetic opioids (HPSO) such as fentanyl. In instances of a toxicity event, first-response administration of reversal medications such as naloxone can be insufficient to fully counteract the effects of HPSO, particularly when there is co-occurring substance use. In an effort to characterize and study this multi-faceted problem, the Camden Opioid Research Initiative (CORI) has been formed. The CORI study has collected and analyzed post-mortem toxicology data from 42 cases of decedents who expired from opioid-related toxicity in the South New Jersey region to characterize substance use profiles. Co-occurring substance use, whether by intent or through possible contamination of the illicit opioid supply, is pervasive among deaths due to opioid toxicity, and evidence of medication-assisted treatment is scarce. Nearly all (98%) of the toxicology cases show the presence of the HPSO, fentanyl, and very few (7%) results detected evidence of medication-assisted treatment for opioid use disorder, such as buprenorphine or methadone, at the time of death. The opioid toxicity reversal drug, naloxone, was detected in 19% of cases, but 100% of cases expressed one or more stimulants, and sedatives including xylazine were detected in 48% of cases. These results showing complex substance use profiles indicate that efforts at mitigating the opioid misuse epidemic must address the complications presented by co-occurring stimulant and other substance use, and reduce barriers to and stigmas of seeking effective medication-assisted treatments.

Can postmortem toxicological findings be influenced by a further release of fentanyl from transdermal patches?–A pilot study using the pig model

Due to its high potency, fentanyl is increasingly misused by drug addicts. Yet, interpretation of PM toxicological results is challenging due to different issues leading to falsified higher fentanyl concentrations in blood. On the one hand, fentanyl has a high tendency for PM redistribution (PMR). On the other hand, a PM drug release from applied transdermal patches (TP) can alter blood concentrations. However, the latter has not yet been examined in a controlled manner. Thus, it should be investigated whether fentanyl is released from TP into adipose tissue (AT) or even blood near to or under a TP applied PM. In the context of another study, two fentanyl TP (TP 1: 100 μg/h and TP 2: 25 μg/h) were sticked PM to one pig each. TP 1 was applied to a shaved area on the left shoulder, TP 2 near the right groin. After 24, 48 and 72 h, AT was collected with a distance of approx. 5 (close), 10 (middle) and 15 cm (far) to the patch, respectively. In addition, peripheral blood (PB) and heart blood (HB) were sampled. After 72 hours, the TP was removed and AT was collected under the patch. HB and PB were analyzed after protein precipitation applying a one-point calibration. Regarding AT, quantification of fentanyl was performed after evaporation of the homogenates using a standard addition approach. All extracts were analyzed by LC-MS/MS. Highest fentanyl concentrations were detected in AT collected under the TP after 72 h, with concentrations of approx. 2,700 ng/g (TP 1) and 9,900 ng/g (TP 2). Regarding AT retrieved with a distance to TP 1, fentanyl could be found in every specimen collected after 24 h with highest concentrations of approx. 6.1 ng/g close to the TP, followed by 0.25 (middle) and 0.44 ng/g (far). After 48 h, analysis of AT was only positive for fentanyl in samples collected with a close (0.56 ng/g) and middle (0.19 ng/g) distance to the TP. Applying TP 2, only AT specimen retrieved after 48 were positive for fentanyl. Additionally, fentanyl could be detected in PB drawn after 48 h (0.14 ng/mL) applying TP 2. Screening of HB using patches 1 and 2 went negative for fentanyl. Independent of the dose, fentanyl appears to be released PM from TP into the underlying AT, with higher concentrations applying TP 2 despite a lower fentanyl releasing concentration. This effect might be explained by the respective skin conditions at the application sites, possibly leading to a different permeability of fentanyl. A small amount of the drug is distributed into surrounding AT. Yet, this effect seems to be more pronounced using TP with high releasing concentrations. Additionally, verification of fentanyl in PB could only be obtained after 48 h applying TP 2. The present study shows that fentanyl is released PM from sticked TP. This effect should be considered when interpreting PM findings. In addition, if fentanyl TP are applied chronically, PM blood concentrations of samples collected near to the TP could further be increased due to the subcutaneous fentanyl depot. In future studies, the extent of PMR after an antemortem application of fentanyl TP should be investigated to complement the data on interpretation of PM toxicological findings.

Suicidal Behavior and Its Relationship with Postmortem Forensic Toxicological Findings.

Suicide affects all sociodemographic levels, age groups, and populations worldwide. The factors that can increase the risk of suicidal tendencies are widely studied. The aim of this study was to analyze the types and combinations of toxics found in fatal suicide victims with different suicide mechanisms. A total of 355 autopsies were retrospectively studied, and 26 toxics were determined and related to mechanisms of suicide. Hanging (55%), drug overdose (22.7%), and jumping from a height (17.8%) were most represented suicide mechanisms with positive toxicology. Hanging was the most represented in men (50.3%; p = 0.019), while jumping from a height was more represented in women (29.7%, p = 0.028). Drugs of abuse were the most frequent toxics found in men (55.5%; p < 0.001), while medicines were the most frequent type found in women (70.3%, p < 0.001). Alcohol, nordiazepam, cocaine, and venlafaxine were the most consumed toxics. Benzodiazepines and venlafaxine were found in suicides involving drug overdose, hanging, and jumping from a height. In conclusion, most suicides were associated with drug abuse in men. Hanging was more represented in men and jumping from a height in women. Alcohol was present in combination with other toxics and medicines. The toxicological analysis is fundamental to understanding consumption patterns and establishing strategies and protocols for detecting and preventing suicide.

Using death scene and toxicology evidence to define involvement of heroin, pharmaceutical morphine, illicitly manufactured fentanyl and pharmaceutical fentanyl in opioid overdose deaths, 38 states and the District of Columbia, January 2018-December 2019.

Tracking specific drugs contributing to drug overdose deaths is limited when relying on death certificate (DC) data alone. This study aimed to determine whether integrating DC data with medical examiner/coroner reports, including postmortem toxicology and death investigation findings, would enhance identification of (1) heroin and pharmaceutical morphine involvement in overdose deaths and (2) fentanyl source (illicitly manufactured versus pharmaceutical). Retrospective analysis of heroin, pharmaceutical morphine, illicitly manufactured fentanyl (IMF) and pharmaceutical fentanyl involvement in fatal overdoses. DC and toxicology data were compared with enhanced definitions integrating overdose scene, witness and toxicology evidence. United States: 38 states and the District of Columbia, participating in Centers for Disease Control and Prevention (CDC)-funded opioid overdose death surveillance. Opioid overdose decedents from funded jurisdictions; deaths during 1 January 2018-31 December 2019. Using medical examiner/coroner report data, deaths with 6-acetylmorphine and/or morphine detected by postmortem toxicology were defined as confirmed, probable or suspected heroin deaths, or probable pharmaceutical morphine deaths. Fentanyl was defined as probable or suspected IMF or probable pharmaceutical fentanyl. The enhanced definition defined 18 393 deaths as confirmed, probable, or suspected heroin deaths (including 2678 with morphine listed as cause of death on the DC) and 404 as probable pharmaceutical morphine deaths. Among deaths with fentanyl detected, 89.3% were defined as probable or suspected IMF and 1.0% as probable pharmaceutical fentanyl. Fentanyl source could not be determined for 9.7% of deaths. Integrating drug overdose scene, witness and toxicology findings can improve identification of specific drugs contributing to overdose deaths and enhance overdose intervention targeting.

Analysis of 17 fentanyls in plasma and blood by UPLC-MS/MS with interpretation of findings in surgical and postmortem casework

The opioid crisis is linked to an increased misuse of fentanyl as well as fentanyl analogs that originate from the illicit drug market. Much of our current understanding of fentanyl and fentanyl analog use in our communities comes from postmortem toxicology findings. In the clinical settings of addiction medicine and pain management, where the opioid abuse potential is high, the use of fentanyl, as well as specific fentanyl analogs, may be underestimated due to limited plasma testing and limited availability of assays with suitable analytical sensitivity and selectivity to detect misuse of fentanyls. We report plasma and blood assays for 17 fentanyls (these include fentanyl, fentanyl analogs, fentanyl metabolites and synthetic precursors) in clinical, and medical examiner, casework. A mixed-mode solid phase extraction of diluted plasma or precipitated blood was optimized for maximum recovery of the fentanyls with minimized matrix effects. Analysis was performed using a Waters ACQUITY UPLC I-Class interfaced with a Waters Xevo TQ-S micro tandem quadrupole mass spectrometer. Method parameters were optimized and validated for precision, accuracy, carryover, linearity and matrix effects. Application studies were performed in postmortem blood obtained in 44 fentanyl-related fatalities and in serial plasma samples from 18 surgical patients receiving intravenous fentanyl therapy while undergoing parathyroidectomy. Fentanyls found in postmortem cases included fentanyl, norfentanyl, despropionyl-fentanyl (4-ANPP), beta-hydroxy fentanyl (β-OH fentanyl), acetyl fentanyl, acetyl norfentanyl, methoxyacetyl fentanyl, furanyl fentanyl, cyclopropyl fentanyl, and para-fluorobutyryl fentanyl, with fentanyl, norfentanyl, 4-ANPP and β-OH fentanyl predominating in frequency. Fentanyl concentrations ranged from 0.2 to 56 ng/mL and fentanyl was nearly always found with 4-ANPP, norfentanyl and β-OH fentanyl. Concentrations of other fentalogs ranged from <1 to 84 ng/mL (extrapolated). In the surgical cases, fentanyl was detected and quantified along with norfentanyl and β-OH fentanyl, but without detection of 4-ANPP in any of the samples. The association and relative concentrations of β-OH fentanyl, fentanyl and norfentanyl in the postmortem and clinical studies indicated a metabolic, rather than an illicit, source of β-OH fentanyl.

Pattern of Suicide Methods and Postmortem Toxicological Findings in Suicide-Related Deaths: A Retrospective 7-Year Forensic-Based Study in Iran.

Suicide is a public health threat that leads to morbidity and mortality worldwide. In this study, we evaluated postmortem toxicological finding among forensic autopsies on suicidal deaths from 2010 to 2016 at the Legal Medicine Center of Zanjan Province (northwest of Iran). All suicide fatal cases were investigated to define the cause and manner of death. Toxicological analyses were performed using thin-layer chromatography, high-performance liquid chromatography, gas chromatography/mass spectrometry, headspace gas chromatography, and gas chromatography equipped with nitrogen phosphorus detector. Demographic data (age, sex, educational level, residential location, and marital status), cause of death, and postmortem toxicological findings were extracted from forensic reports and were entered into the designed questioners. During this period, a total of 181 cases of suicide deaths were investigated. Among them, 74% were male. The most often used suicide method was hanging, followed by self-poisoning in young people. Aluminum phosphide was the most frequent poison detected in the fatal suicidal cases (33 cases), followed by opioids. Hanging and self-poisoning were the frequent suicidal method in young male population. It seems that psychological and social supports in young people along with restriction to easy access to drugs and poisons should be considered by policy making and healthcare authorities.

Association of QT-Prolonging Medications With Risk of Autopsy-Defined Causes of Sudden Death

QT-prolonging medications (QTPMs) are a reported risk factor for sudden cardiac death (SCD) when defined by consensus criteria that presume an arrhythmic cause. The effect of QTPM on autopsy-defined sudden arrhythmic death (SAD) is unknown. To evaluate the association between QTPM and autopsy-defined SAD vs nonarrhythmic cause of sudden death. This prospective countywide case-control study included World Health Organization-defined (presumed) SCD cases who underwent autopsy as part of the San Francisco Postmortem Systematic Investigation of Sudden Cardiac Death Study (POST SCD) to determine arrhythmic or nonarrhythmic cause, and control deaths due to trauma (hereinafter referred to as trauma controls) in San Francisco County, California, from February 1, 2011, to March 1, 2014. Multivariate regression was used to evaluate the association of QTPM with the risk of presumed SCD, autopsy-defined SAD, and non-SAD compared with trauma controls. Medication exposure, determined by prescription lists and postmortem toxicologic findings, was used to calculate a summative QTPM exposure score (range, 0-20). Data were analyzed from September 1, 2018, to June 15, 2019. QT-prolonging medication exposure, as measured by QTPM score (1 indicated low; 2-4, moderate; and >4, high). Death due to trauma, presumed SCD, and autopsy-defined non-SAD and SAD with no postmortem findings of extracardiac cause. A total of 629 patients (mean [SD] age, 61.4 [15.7] years; 439 men [69.8%]) were included, 525 with presumed SCDs and 104 traumatic death controls. Individuals with presumed SCDs had higher exposure and were more likely to be taking any QTPM (291 [55.4%] vs 28 [26.9%]; P < .001) than trauma controls. Use of QTPMs was associated with increased risk of presumed SCD in low (odds ratio [OR], 2.25 [95% CI, 1.03-4.96]; P = .04) and high (OR, 6.70 [95% CI, 1.47-30.67]; P = .01) exposure groups. After autopsy adjudication, use of QTPMs was associated with increased risk of non-SAD (low-risk OR, 2.88 [95% CI, 1.18-6.99; P = .02]; moderate-risk OR, 2.62 [95% CI, 1.20-5.73; P = .02]; and high-risk OR, 14.22 [95% CI, 2.91-69.30; P = .001]) but not SAD in all exposure groups. This association was attenuated by the exclusion of occult overdose non-SADs in the highest exposure group. These findings confirm the association between QTPMs and presumed SCD; however, after autopsy, this risk was specific for nonarrhythmic causes of sudden death. Studies using consensus SCD criteria may overestimate the association of QTPMs with the risk of SAD.

Post-mortem Redistribution of Alprazolam in Rats.

The post-mortem toxicological findings may be misinterpreted, if the drug undergoes substantial post-mortem redistribution. As alprazolam is one of the most frequently evaluated drug for legal/forensic reasons in drug-related fatalities, we studied possible changes in alprazolam distribution after death in a rat model. Rats were sacrificed 30 minutes after alprazolam administration. Blood and tissue samples from 8 animals per sampling time were collected at 0, 2, 6, and 24 h after death. The experimental samples were assayed for alprazolam using validated UHPLC-PDA method. Median blood alprazolam concentrations increased approximately 2 times compared with ante-mortem levels due to the redistribution during early post-mortem phase and then slowly decreased with a half-life of 60.7 h. The highest alprazolam tissue concentrations were found in fat and liver and the lowest levels were observed in lungs and brain. The median amount of alprazolam deposited in the lungs was relatively stable over the 24-h post-mortem period, while in heart, liver and kidney the deposited proportion of administered dose increased by 43-48% in comparison with ante-mortem values indicating continuous accumulation of alprazolam into these tissues. These results provide evidence needed for the interpretation of toxicological results in alprazolam-related fatalities and demonstrate modest alprazolam post-mortem redistribution.

Adherence to psychotropic medication in completed suicide in Sweden 2006\u20132013: a forensic-toxicological matched case-control study

ObjectiveTo investigate the influence of adherence to psychotropic medications upon the risk of completed suicide by comparing person-level prescriptions and postmortem toxicological findings among complete-suicide cases and non-suicide controls in Sweden 2006–2013.MethodsUsing national registries with full coverage on dispensed prescriptions, results of medico-legal autopsies, causes of death, and diagnoses from inpatient care, estimated continuous drug use for 30 commonly prescribed psychotropic medications was compared with forensic-toxicological findings. Subjects who had died by suicide (cases) were matched (1:2) with subjects who had died of other causes (controls) for age, sex, and year of death. Odds ratios were calculated using logistic regression to estimate the risk of completed suicide conferred by partial adherence and non-adherence to pharmacotherapy. Adjustments were made for previous inpatient care and the ratio of initiated and discontinued dispensed prescriptions, a measure of the continued need of treatment preceding death.ResultsIn 5294 suicide cases and 9879 non-suicide controls, after adjusting for the dispensation ratio and other covariates, partial adherence and non-adherence to antipsychotics were associated with 6.7-fold and 12.4-fold risks of completed suicide, respectively, whereas corresponding risk estimates for antidepressant treatment were not statistically significant and corresponding risk increases for incomplete adherence to antidepressant treatment were lower (1.6-fold and 1.5-fold, respectively) and lacked statistical significance.ConclusionAfter adjustment for the need of treatment, biochemically verified incomplete adherence to antipsychotic pharmacotherapy was associated with markedly increased risks of completed suicide.

A case of suicide by double gunshot wounds to the head: the ability to act after the first shot

A single gunshot (or multiple) does (do) not necessarily lead to immediate loss of consciousness or rapid neurological deficits, so the victim may be able to repeatedly pull the trigger before achieving the lethal effect. Despite multiple gunshot wounds can lead to the suspicious participation of other person to the death of the victim, in the medico-legal literature suicides with multiple gunshot wounds are reported, demonstrating the ability of the victim to act after two or more gunshots. In this case, a 47-years-old man was found dead in a pool of blood in the kitchen of his house. According to findings and analysis, the victim modified a single-shot, pneumatic toy gun branded "Condor" Cal. 7 mm (a gun that is made mainly with "ZAMAK" zinc-based alloy, designed to shoot one soft-polymer bullet at a time, with an initial kinetic energy lower than 1 Joule) into an improvised firearm weapon. With this gun, the victim achieved shooting of two bullets into his head, both entering from the right temporal region of his head, with one stopped in the left occipital lobe and the other one in the left temporal lobe. His death was caused by cranium-meningo-encephalic gunshot wounds. The conditions supporting the hypothesis that the victim was able to fire two shots to his head before the onset of incapacitation (the type of bullets used, the location of injuries and their consequences) and the characteristics that typically allow to distinguish the manner of death (suicide vs homicide) were evaluated. Based on all the collected elements, it was possible to confirm that suicide was the manner of death. This case underlines the importance of evaluating all available elements (post-mortem imaging, autopsy and toxicological findings, ballistics and neuropathological evaluations) to distinguish suicide from homicide and to prevent incorrect conclusions.

Adherence to Psychotropic Medication in Completed Suicide in Sweden 2006-2013: A Forensic-Toxicological Matched Case-Control Study

Background: The aim of the study was to investigate how incomplete adherence to psychotropic medication influences the risk of completed suicide by comparing person-level information regarding dispensed prescriptions and postmortem toxicological findings among complete-suicide cases and non-suicide controls in Sweden 2006-2013. Method: Using national registries with full coverage on dispensed prescriptions, results of medico-legal autopsies, causes of death, diagnoses from inpatient care and continuous drug use, estimated by the prescription-based algorithm PRE2DUP, psychotropic drug use was compared with forensic-toxicological findings for 30 commonly prescribed psychotropic medications. Subjects who had died by suicide (cases) were matched (1:2) with subjects who had died from other causes (controls) for age, sex, and year of death. Odds ratios were calculated using logistic regression to estimate risk of completed suicide conferred by partial adherence and non-adherence to pharmacotherapy. Adjustments were made for previous inpatient psychiatric and somatic care, and ratio of initiated and discontinued prescriptions prior to death. Outcome: In data from autopsies performed in 5294 suicide cases and 9879 non-suicide controls, dispensation ratios for psychotropic medications (postulated as a measure of continued need of treatment) increased in cases, yet decreased in controls, the months prior to death. After adjustments for the ratio and other covariates, partial adherence and non-adherence to antipsychotics were associated with 6·7-fold and 12·4-fold risks, respectively, of completed suicide. The effect sizes for antidepressants were smaller and not statistically significant. Interpretation: After adjustment for continued need of treatment, biochemically verified incomplete adherence to antipsychotic pharmacotherapy was associated with markedly increased risks of completed suicide. Funding Statement: The study has in part been funded by Psykiatrifonden. Funders of the study had no role in study design, data collection, analysis, and interpretation, or the writing of the report. The corresponding author had full access to all data and final responsibility for the decision to submit the report for publication. Declaration of Interests: HT, JT and AT have participated in research projects funded by Janssen-Cilag and Eli Lilly, with grants paid to the institution where they were employed. AT is a member of the JanssenCilag advisory board. JT has served as a consultant to the European Medical Agency and the Finnish Medicines Agency and has received lecture fees from Eli Lilly, Janssen-Cilag, Lundbeck, and Otsuka, and grants from the Stanley Foundation and the Sigrid Juselius Foundation. JF and TM have no conflict of interest. All studied pharmacological products in this paper were generic substances without exclusive ownership by any company. Ethics Approval Statement: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. In this registry-based postmortem study, all personal information was anonymized, rendering unnecessary the need for formal consent or ethical approval. The study was nonetheless reviewed and approved by the Regional Ethical Review Board in Stockholm (2013/1411‐31/5).

Post-mortem toxicology in young sudden cardiac death victims: a nationwide cohort study.

Several drugs increase the risk of ventricular fibrillation and sudden cardiac death (SCD). We aimed to investigate in detail the toxicological findings of all young SCD throughout Denmark. Deaths in persons aged 1-49 years were included over a 10-year period. Death certificates and autopsy reports were retrieved and read to identify cases of sudden death and establish cause of death. All medico-legal autopsied SCD were included and toxicological reports collected. Positive toxicology was defined as the presence of any substance (licit and/or illicit). All toxicological findings had previously been evaluated not to have caused the death (i.e. lethal concentrations were excluded). We identified 620 medico-legal autopsied cases of SCD, of which 77% (n = 477) were toxicologically investigated post-mortem, and 57% (n = 270) had a positive toxicology profile. Sudden cardiac death with positive toxicology had higher rates of sudden arrhythmic death syndrome (SADS), compared with SCD with negative toxicology (56% vs. 42%, P < 0.01). In total, 752 agents were detected, and polypharmacy (defined as the presence of more than one drug) was present in 61% (n = 164), all substances combined. Psychotropic drugs were the most frequent (62%, n = 467), and 82% (n = 385) were in pharmacological or subpharmacological levels. We found that more than half of all toxicologically investigated SCD victims have positive post-mortem toxicological findings, and polypharmacy is displayed in a considerable proportion. SCD with positive toxicology had higher rate of SADS, suggesting that the compounds may play a proarrhythmic role in these cases.

Misuse of prescription drugs and overdose deaths

Aims. This study examined overdose deaths involving benzodiazepines and prescription opioids, and studied associated factors. Methods. In a retrospective registry study of drug-overdose deaths (n = 167) with post-mortem toxicological findings of benzodiazepines and/or opioids/carisoprodol (strong analgesics) in Oslo, Norway, from 2006 to 2008, prescribing and dispensing patterns were investigated, and factors associated with benzodiazepines and/or strong analgesics in post-mortem toxicology where these medications were not prescribed were identified. Results. Among deceased with toxicological findings of only benzodiazepines, 28.1% (20.7–36.9) had been dispensed benzodiazepines four weeks prior to death; only strong analgesics, 33.3% (13.0–61.3) had been dispensed strong analgesics; both benzodiazepines and strong analgesics, 58.3% (36.9–77.2) had been dispensed benzodiazepines and/or strong analgesics. Also, 33.0% of the deceased had five or more different prescribing physicians of either benzodiazepines or strong analgesics in the year prior to death. Doses of both dispensed benzodiazepines and strong analgesics were higher than recommended. Younger age and residing outside Oslo were associated with having benzodiazepines and/or strong analgesics in the toxicological findings when these medications had not been dispensed (p = 0.006 and p = 0.039, respectively). Conclusion. The majority of benzodiazepines and strong analgesics detected in overdose deaths were non-prescribed and/or associated with less than optimal prescribing practices by some treating physicians.

Demographics and post-mortem toxicology findings in deaths among people arrested multiple times for use of illicit drugs and/or impaired driving

BackgroundMultiple arrests for use of illicit drugs and/or impaired driving strongly suggests the existence of a personality disorder and/or a substance abuse problem. MethodsThis 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. ResultsOf the 3943 repeat offenders 1807 (46%) died from a fatal drug overdose and 2136 (54%) died from other causes (p<0.001). The repeat offenders were predominantly male (90% vs 10%) and mean age of drug poisoning deaths was 5 y younger (mean 35 y) than other causes of death (mean 40 y). Significantly more repeat offenders (46%) died from drug overdose compared with all other forensic autopsies (14%) (p<0.001). Four or more drugs were identified in femoral blood in 44% of deaths from poisoning (drug overdose) compared with 18% of deaths by other causes (p<0.001). The manner of death was considered accidental in 54% of deaths among repeat offenders compared with 28% for other suspicious deaths (p<0.001). The psychoactive substances most commonly identified in autopsy blood from repeat offenders were ethanol, morphine (from heroin), diazepam, amphetamines, cannabis, and various opioids. ConclusionsThis 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.

Postmortem Toxicology Findings of Acetyl Fentanyl, Fentanyl, and Morphine in Heroin Fatalities in Tampa, Florida.

In the last two years, an epidemic of 40 fatal heroin overdose cases has occurred in the Tampa area of Florida. Of these cases, 14 involved fentanyl and acetyl fentanyl. Victim demographics, case histories, toxicology findings, and causes and manners of death for all 40 deaths are presented. In 26 deaths in which acetyl fentanyl or fentanyl were not involved, free and total peripheral blood morphine concentrations were consistent with fatal heroin intoxications, averaging 0.16 mg/L and 0.35 mg/L, respectively. In the heroin cases with fentanyl present (n=7), the average free morphine concentration was 0.040 mg/L, the average total morphine concentration was 0.080 mg/L, and the average fentanyl concentration was 0.012 mg/L. In the cases with heroin, fentanyl, and acetyl fentanyl (n=3), the average free morphine concentration was 0.010 mg/L, the average total morphine concentration was 0.030 mg/L, the average fentanyl concentration was 0.018 mg/L, and the average acetyl fentanyl concentration was 0.008 mg/L. In the cases involving only acetyl fentanyl (without heroin or fentanyl, n=4), the average acetyl fentanyl concentration was 0.47 mg/L and the average acetyl norfentanyl concentration was 0.053 mg/L. The presented cases, with associated drug concentrations, case histories, demographics, and causes and manners of death may help provide assistance with the interpretation of the postmortem findings. Based on case circumstances, autopsy results, and toxicology results, it is evident that fentanyl and/or acetyl fentanyl, when present, contributed to the cause of death.

Sudden cardiac death, borderline myocarditis and molecular diagnosis: evidence or assumption?

Sudden unexpected death autopsy is sometimes non-conclusive both from a macroscopic and from a histological point of view, even if carried out according to the guidelines for sudden cardiac death examination. Molecular biology techniques are required in this setting and may play a crucial role in reaching the final diagnosis. The postmortem examination and toxicology findings of the body of a young monk found dead in his cell were negative. Rare focal myocardial lymphocytic infiltrates were seen microscopically, associated with interstitial oedema. The findings were not sufficient to diagnose a myocarditis as the certain final cause of cardiac arrest. According to the recent guidelines for sudden cardiac death, a molecular investigation by polymerase chain reaction analysis was performed on samples of myocardium and spleen, with detection of parvovirus B19 DNA in the myocardium. Accordingly, a diagnosis of parvovirus B19 borderline acute myocarditis was put forward as the possible cause of sudden cardiac death. In sudden death cases in which there is lack of a cause-effect relationship with the postmortem findings, the final report should be expressed as a descriptive association of evidence, not providing unreliable certainty, as the Association for European Cardiovascular Pathology recommends.

Post-Mortem (Re)Distribution of 3,4-Methylenedioxymethamphetamine (MDMA, &amp;#x201C;Ecstasy&amp;#x201D;): Human and Animal Data

In this paper, the distribution and redistribution of the amphetamine derivative, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) is brought into focus. Animal experimental data were compared with internationally reported MDMA-related human fatalities: in general, these turned out to be parallel with each other. Due to its inherent properties (e.g. significant volume of distribution), MDMA is liable to postmortem redistribution. Indeed, very high concentrations have been found in cardiac blood and tissues located centrally in the body (blood-rich organs such as lungs and liver in particular). This confirms that post-mortem redistribution due to diffusion from higher to lower concentration can easily take place, mainly at longer post-mortem intervals and when putrefaction occurs. Therefore, we can conclude that for post-mortem quantitation of amphetamine and derivatives, and MDMA in particular, peripheral blood sampling (e.g. femoral vein) remains compulsory. However, if the latter is impossible, MDMA quantification in a few alternative matrices such as vitreous humour and iliopsoas muscle may provide additional information to come to a reliable conclusion. Furthermore, it should be stressed that--at present--it is impossible to estimate the individual susceptibility to the various possible adverse effects of MDMA, which implies that it is impossible to provide a "safe" or "therapeutic" blood MDMA level. Therefore, in current forensic practice, the post-mortem pathological and toxicological findings should form an entity in order to draw a well-grounded conclusion.

Toxicology Findings in Child and Adolescent Suicides in Virginia

In a follow-up report of child and adolescent suicides in Virginia, we describe postmortem toxicology findings in a subset of these youths. We analyzed "unnatural" deaths from Virginia's Office of the Chief Medical Examiner for 1987 to 2003. There were 2818 unnatural deaths in children and adolescents. We grouped unnatural deaths as accidents, homicides, and suicides. Toxicology records were available for 753 cases, of which 732 were black or white youths. There were no age differences among suicide victims and accident or homicide victims. Whites were more likely than blacks to die by accident and suicide. White females were more likely than black females to commit suicide. Black males were more likely than white males to suffer homicide. For all unexpected deaths, antidepressants were more commonly found among whites than blacks. Suicide by poisoning occurred more commonly among whites. Recreational drugs were more commonly found among blacks than whites. Suicide by gun occurred more commonly among blacks. Antidepressants were found in 39 black and white suicide victims. Anti-depressants (all tricyclic antidepressants) were causally related in 17 cases of suicide by poisoning. No other antidepressants were found in lethal levels in suicide by poisoning. Selective serotonin reuptake inhibitors (SSRIs)/venlafaxine appeared more commonly in the suicides (p < .0001) than in accidents or homicides. For suicides, SSRIs appeared no more commonly in poisoning than in gun or hanging deaths (p = .695). Antidepressants appeared more commonly among youths committing suicide than those dying by accident or homicide. SSRIs did not appear more commonly among youths committing suicide by poisoning than those committing suicide by gun or hanging. Because our data are descriptive, they are subject to over-interpretation. Cause-effect inferences should not be drawn.

Pathologic features of fatal falls from height.

Deaths due to falls from height are common in urban settings. At the time the body is found, it is often unclear whether the mode of death is accident, suicide, or homicide. To assess the injury pattern in fatal falls from height with special regard to criteria that might be helpful in discrimination between accident, suicide, and homicide, respectively, we reviewed 68 medicolegal autopsy cases (22 females, 46 males, age range 13-89 years) of fatal falls from height regarding demographic data, findings at the death scene, results of the postmortem examination, psychiatric history, and toxicologic findings. Among the 68 cases, there were 34 suicides, 23 accidents, and 11 unclarified cases, in 3 of which homicide was suspected. In general, suicides were from greater heights than accidents (mean height 22.7 m for suicides and 10.8 m for accidents, respectively; 79% of suicides from more than 16 m). Strikingly, severe head injuries predominantly occurred in falls from heights below 10 m (84%) and above 25 m (90%), whereas in the group of falls from 10 to 25 m, these lesions were seen less frequently (28%). Neck injuries like muscle bleeds and fractures of the hyoid bone were found in 33% of falls from more than 10 m and did not occur from less than 10 m. Our data stress that the evaluation of pathologic features alone is not sufficient to assess the mode of death in fatal falls from height. Instead, postmortem findings have to be considered within the framework of the subject's social, medical, and psychiatric history in conjunction with findings at the death scene and toxicology results to obtain the clearest possible picture of the circumstances of death.