A retrospective review of methylamphetamine detected in child deaths reported to the Victorian Coroner, Australia.

This study investigated methylamphetamine (MA) exposures in the deaths of children (≤ 12 years old) reported to the Coroner in the state of Victoria, Australia, between 2011 and 2020. Demographics, autopsy findings including the cause of death, self-reported prenatal or caregiver drug use, child protection services information, and toxicological findings were summarized by descriptive statistics. Validated methods of liquid chromatography-tandem mass spectrometry were used in the analysis of drugs. There were 50 child deaths with MA detected in blood, urine, and/or hair with 64% (n = 32) identified in 2018-2020. Most children were 1-365 days old (66%, n = 33) and the cause of death was unascertained in 62% (n = 31) of cases. MA was toxicologically confirmed in hair (94%, n = 47) significantly more than blood (18%, n = 9). Prenatal or caregiver drug use was self-reported in 44% (n = 22) and 42% (n = 21) of cases, respectively. Moreover, only 54% (n = 27) of deceased children were a child protection client at their time of death. These findings suggest the number of deceased children exposed to MA has increased over the past 10 years, which is consistent with the greater supply of crystal MA in the Australian community. Hair analysis provided additional means to identify cases that were unknown to child protection services and may have implications for other children in the same drug exposure environment.

Methylamphetamine toxicity and its involvement in death: A retrospective observational study of deaths reported to the Victorian Coroner, Australia.

A retrospective observational study of Victorian deaths involving MA between 2010 and 2019 was conducted to determine the prevalence and contribution of methylamphetamine (MA) toxicity to death in the absence of other factors. Demographics, autopsy findings, toxicology, and the cause of death were reviewed. Coronial cases were categorized into five groups: deaths due to MA toxicity in the absence of other factors (Group A1); deaths due to MA toxicity in the setting of other potentially contributing factors (Group A2); deaths due to MA toxicity in the setting of significant natural disease (Group B); deaths primarily due to multiple-drug toxicity (Group C); and deaths primarily due to natural causes (Group D). There were 506 deaths involving MA categorized into Group A1 (n = 1, 0.6%), Group A2 (n = 8, 1.6%), Group B (n = 28, 5.5%), Group C (n = 229, 45%), and Group D (n = 240, 47%). Significant natural disease was prevalent among deaths involving MA and mainly concerned forms of cardiovascular disease (n = 277, 55%). The MA concentration in the one death included in Group A1 was 2.1 mg/L. The median MA concentrations of Group A2 (1.6 mg/L) and Group B (0.5 mg/L) were significantly higher than Group C (0.2 mg/L) and Group D (0.2 mg/L). Additionally, many other toxicologically significant drugs were detected and mostly comprised of central nervous system depressants. Deaths due to MA toxicity in the absence of other factors were rare despite the greater availability of crystal MA in the Australian community. The study highlights the interpretative challenges of MA blood concentrations and the continuing harms of this drug in Australia.

Challenges for Detecting Valproic Acid in a Nontargeted Urine Drug Screening Method.

BACKGROUND: Valproic acid (VPA) is a widely prescribed medicine, and acute toxicity is possible. As such, it should be included in any nontargeted urine drug screening method. In many published liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS/MS) methods, VPA is usually measured using a pseudo-multiple reaction monitoring (MRM) transition. We investigate a simple ultra-high-performance liquid chromatography-quadrupole time-of-flight (QTof) approach to detect the presence of VPA with more confidence. METHODS: Three commercially sourced VPA metabolites were characterized and added to a nontargeted high-resolution MS urine drug screening method. All analyses were performed on a Waters Xevo G2-XS LC-QTof in negative electrospray ionization mode. The mass detector was operated in MS mode, and data were processed with UNIFI software. Sixty-eight patient urine samples, which were previously identified by a well-established gas chromatography-MS method as containing VPA, were analyzed on the Waters Xevo G2-XS LC-QTof, to validate this approach. RESULTS: VPA metabolite standards were characterized, and their detection data were added to the broad drug screening library. VPA metabolites were readily detectable in the urine of patients taking VPA. CONCLUSIONS: The inclusion of characterized VPA metabolites provides a simple and reliable method enabling the detection of VPA in nontargeted urine drug screening.

Mortuary operations following mass fatality natural disasters: a review.

This is a critical review to discuss the best practice approaches to mortuary operations in preparation for and the response to natural, mass fatality, disaster events, as identified by a review of published articles. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) Statement guided the identification of potential articles to use in this critical review. Subsequent searches were also conducted to identify articles relating to heat wave, and flood mortality. All identified peer-reviewed studies published in English which discussed the preparation and response of mortuaries to mass fatality natural disasters occurring in developed countries were included. Using the PRISMA-P method of identifying articles, 18 articles were selected for inclusion in this review. Although there are numerous articles which describe the mortuary response to mass fatality incidents, few articles analyzed the response, or discussed the roles which supported and enabled the organization to undertake the task of identifying disaster victims. It is thus difficult to determine objectively if the actions and activities outlined in the articles represent best-practice.

An update on oxycodone: lessons for death investigators in Australia.

Oxycodone is one of the most abused prescription drugs. Iatrogenic factors that lead to oxycodone-related death, such as mis-prescribing, present an opportunity for death prevention if identified early. This study investigated deaths involving oxycodone in Australia to explore potentially inappropriate prescribing and the coroner's investigation. The National Coronial Information System identified cases from 2001 to 2011 where oxycodone was detected by toxicological analysis. There were 806 oxycodone-related deaths, with a significant increase in the 11-year period, from 21 deaths in 2001, up almost sevenfold in 2011 (139 deaths). Most deaths were caused by combined drug toxicity (63.4%) or oxycodone toxicity alone (11.8%). Most individuals were male (59.1%), aged 35-44 years (26.7%), who died unintentionally (56.4%), with mental illness (52.1%) and/or a history of acute or chronic pain (46.2%). 312 cases (39%) described a legitimate prescription for oxycodone, of which most involved non-cancer related chronic pain. About three quarters of the indications were deemed appropriate. There were at least 43 different indications treated with oxycodone that were inappropriate. The majority of oxycodone-related cases involved minor to no description of the drugs involved (n = 600; 74.4%). A moderate description of oxycodone involvement was given in 162 cases (20.1%), while only 44 cases (5.5%) involved a thorough examination and recommendations from the coroners on oxycodone and other drugs involved in death. This study emphasized the need for medical practitioners to exercise caution when prescribing oxycodone and for coroners to provide more consistent and detailed information regarding drug use, in order to identify and implement preventive strategies.

The postmortem redistribution of iso-α-acids in postmortem specimens.

Iso-α-acids (IAA) and reduced IAA can be used as beer-specific ingredient congeners to confirm beer consumption when detected in blood and other specimens using a UHPLC-MS/MS method. Recent analysis of postmortem casework demonstrated a high prevalence of beer consumption and the possibility of providing the source of alcohol in forensic casework. Research outlined in this manuscript has examined the degree to which the interval after death and quality of blood affects the concentration of IAA in postmortem cases. Postmortem whole blood and serum were analyzed in cases where natural or reduced IAA groups were detected. The trans-IAA, cis-IAA, and tetrahydro-IAA (TIAA) groups were subject to postmortem redistribution, although only weakly associated with the length of time from death to collection of specimens. Serum had threefold higher concentrations than blood for trans-IAA, cis-IAA, and TIAA. These studies confirm that although postmortem concentrations cannot be easily compared to concentrations found in living persons the presented findings do provide some understanding to assist in interpretation where the confirmation of beer consumption is required in forensic casework.

The analysis of methylamphetamine and para-hydroxy-methylamphetamine in post-mortem hair samples using liquid chromatography-tandem mass spectrometry.

External contamination is a well-recognized limitation of hair analysis for drugs of abuse like methylamphetamine (MA), and there are no guidelines regarding the analysis of specific metabolites of MA to assist interpretation. We developed an analytical method to detect MA, amphetamine (AMP), and para-hydroxy-methylamphetamine (p-OH-MA) in hair and present their concentrations among a cohort of deceased persons positive for MA in blood (n = 63). Hair samples (≤ 3 cm) were washed with dichloromethane and water prior to extraction using a methanolic micro-pulverization. The reconstituted hair extracts were separated on a UCT Selectra® Aqueous C18 HPLC Column (100 × 2.1 mm, 3 µm) by gradient elution and detected using a Sciex Triple Quad 6500+ system. Validation was satisfactory, and the lower limits of quantitation were 0.01 ng/mg for MA and AMP and 0.001 ng/mg for p-OH-MA. The median hair concentrations of MA, AMP, and p-OH-MA were 13 ng/mg (range = 0.015-49; n = 51), 1.1 ng/mg (range = 0.018-44; n = 60), and 0.020 ng/mg (range = 0.0012-0.38, n = 62), respectively. These concentrations in hair were strongly positively correlated (r = .7202 to .8641, p < .001), suggesting similar modes of incorporation. Moreover, the wash/hair ratios were indicative of external contamination, especially among the soiled group of hair samples. Therefore, further studies are necessary to determine concentrations of p-OH-MA in living MA users and confirm if this metabolite constitutes a potential marker of MA consumption.

The rapid identification and quantification of iso-α-acids and reduced iso-α-acids in blood using UHPLC-MS/MS: validation of a novel marker for beer consumption.

A method for the detection of iso-α-acid (IAA) type ingredient congeners that are derived from the hop plant (Humulus lupulus L.) was developed to detect recent consumption of beer in blood. Three structurally similar but chemically altered IAA, also used as beer-specific ingredients, are known as "reduced IAA", consisting of the rho-, tetrahydro-, and hexahydro-IAA were also targeted. The use of a simple protein precipitation extraction and ultrahigh-performance liquid chromatography system coupled with a tandem mass spectrometer system enabled detection of these analytes in both antemortem and postmortem blood. Extracts were injected onto a C18 solid-core column under gradient elution to achieve separation of isobaric analogs and isomers within a 10-min run time. Electrospray ionization in negative multiple reaction monitoring mode was used to monitor three transitions for each of the analytes that were ultimately grouped together to form a calibration curve for quantification of each of the four IAA groups. The method was fully validated according to international guidelines that included extraction efficiency, matrix effects, process efficiency, ion suppression/enhancement of co-eluting analytes, selectivity, crosstalk, accuracy and precision, stabilities, and lower limits of quantification. Finally, applicability of the method described was demonstrated by the detection of IAA ingredient congeners in the blood of a volunteer following the consumption of a relatively small amount of beer in a pilot study.

Recent increase in detection of alprazolam in Victorian heroin-related deaths.

OBJECTIVES: To examine the rate of detection of alprazolam among cases of heroin-related death (HRD) in Victoria, including the relationship between alprazolam supply and HRDs. DESIGN AND SETTING: Population-based study of community alprazolam supply in Victoria and HRDs reported to the Victorian coroner from January 1990 to December 2010. MAIN OUTCOME MEASURES: Number of prescriptions for alprazolam supplied; defined daily dose (DDD) per 1000 population per 04 of alprazolam; number of cases of HRD in which alprazolam was detected through postmortem toxicological testing. RESULTS: Alprazolam supply increased by 1426%, from 0.42 DDD/1000/04 in 1990, to 6.41 in 2010. For every 1 unit increase in DDD/1000/04, the proportion of cases of HRD in which alprazolam was detected increased at an incidence rate ratio of 2.4 (95% CI, 2.1-2.8; P < 0.001). Alprazolam was detected among increasing proportions of HRDs, from 5.3% in 2005 to a peak of 35.3% in 2009. CONCLUSION: The increase in detection of alprazolam among cases of HRD, particularly since 2005, and the disproportionate increase in prescribing of the high-dose 2 mg formulation compared with other formulations suggest a need to examine alprazolam prescribing and to identify inappropriate prescribing and the circumstances of diversion from licit to illicit use.

Interpretation of postmortem forensic toxicology results for injury prevention research.

Forensic toxicological data provides valuable insight into the potential contribution of alcohol and drugs to external-cause deaths. There is a paucity of material that guides injury researchers on the principles that need to be considered when examining the presence and contribution of alcohol and drugs to these deaths. This paper aims to describe and discuss strengths and limitations of postmortem forensic toxicology sample selection, variations in analytical capabilities and data interpretation for injury prevention research. Issues to be considered by injury researchers include: the circumstances surrounding death (including the medical and drug use history of the deceased person); time and relevant historical factors; postmortem changes (including redistribution and instability); laboratory practices; specimens used; drug concentration; and attribution of contribution to death. This paper describes the range of considerations for testing and interpreting postmortem forensic toxicology, particularly when determining impairment or toxicity as possible causal factors in injury deaths. By describing these considerations, this paper has application to decisions about study design and case inclusion in injury prevention research, and to the interpretation of research findings.

The toxicology and comorbidities of fatal cases involving quetiapine.

The use of quetiapine in Australia has increased rapidly in recent years. Anecdotal and post-marketing surveillance reports indicate an increase in quetiapine misuse in prisons as well as an increase in its availability on the black-market. This study examined a cohort of quetiapine-associated deaths occurring in Victoria, Australia, between 2001 and 2009, to determine the prevalence of deaths associated with this drug and to determine whether misuse represents a legitimate concern. Case details were extracted from the National Coronial Information System. There were 224 cases with an average age of 43 years of age (range 15-87 years). The cause of death was mostly drug toxicity (n = 114, 51 %), followed by natural disease (n = 60, 27 %), external injury (n = 31, 14 %) and unascertained causes (n = 19, 8 %). Depression and/or anxiety were common, observed in over a third of the cohort (80 cases, 36 %). About 20 % of cases did not mention a psychiatric diagnosis at all which raises the question of whether quetiapine had been prescribed correctly in these cases. Cardiovascular disease was the most commonly reported illness after mental disease. Quetiapine ranged in concentration from the limit of reporting (0.01 mg/L) to 110 mg/L. The median concentration of quetiapine was much lower in the natural disease deaths (0.25 mg/L) compared with drug caused deaths (0.7 mg/L). The most commonly co-administered drug was diazepam in 81 (36 %) cases. There were a small number of cases where quetiapine contributed to a death where it had not apparently been prescribed, including the death of a 15 year old boy and one of a 34 year old female. Overall, misuse of quetiapine did not appear to be a significant issue in this cohort; use of the drug only occasionally led to fatalities when used in excess or concomitantly with interacting drugs. However, considering that it is a recent social concern, it is possible that analysis of cases post 2009 would reveal more cases of quetiapine abuse. Close monitoring of quetiapine is therefore advised to prevent adverse outcomes, particularly in vulnerable populations such as substance abusers.

Alcohol congener analysis and the source of alcohol: a review.

For many decades traditional alcohol congener analysis has provided the concentrations of fermentation by-product congeners found in blood, to ascertain if the claims of an individual regarding the alcoholic beverage(s) they have consumed were feasible, assisting in cases where after-drinking is involved. However, this technique does not provide information on the exact alcoholic beverage(s) consumed. More recently, ingredient biomarker congeners specific to certain alcoholic beverages have been detected in blood, making it possible to identify the particular alcoholic beverage consumed and therefore the source of alcohol (albeit only for a limited number of beverages). This novel approach may reduce current limitations that exist with traditional methods of detecting fermentation by-product congeners, which restrict the use of alcohol congener analysis internationally and for other medico-legal scenarios. This review examines the forensic application of alcohol congener analysis in determining the source of alcohol and other techniques.

False-Positive Amphetamines in Urine Drug Screens: A 6-Year Review.

Immunoassays are routinely used to provide rapid urine drug screening results in the clinical setting. These screening tests are prone to false-positive results and ideally require confirmation by mass spectrometry. In this study, we have examined a large number of urine specimens where drugs other than amphetamines may have caused a false-positive amphetamine immunoassay screening result. Urine drug screens (12,250) in a clinical laboratory that used the CEDIA amphetamine/ecstasy method were reviewed for false-positive results over a 6-year period (2015-2020). An additional 3,486 referred samples, for which confirmatory--mass spectrometry was requested, were also reviewed. About 86 in-house samples and 175 referral samples that were CEDIA false-positive screens were further analyzed by an LC-QTOF general unknown screen. Potential cross-reacting drugs were identified, and their molecular similarities to the CEDIA targets were determined. Commercial standards were also analyzed for cross-reactivity in the amphetamine/ecstasy CEDIA screen. Positive amphetamine results in 3.9% of in-house samples and 9.9% of referred tests for confirmatory analysis were false positive for amphetamines. Of these false-positive specimens, on average, 6.8 drugs were detected by the LC-QTOF screen. Several drugs were identified as possible cross-reacting drugs to the CEDIA amphetamine/ecstasy assay. Maximum common substructure scores for 70 potential cross-reacting compounds were calculated. This was not helpful in identifying cross-reacting drugs. False-positive amphetamine screens make up to 3.9-9.9% of positive amphetamine screens in the clinical laboratory. Knowledge of cross-reacting drugs may be helpful when mass spectrometry testing is unavailable.

Changing trends and characteristics of one punch deaths in Australia (2012-2018).

One-punch assaults also known as 'coward punches', are characterised by a single severe blow to the head causing the victim to lose consciousness, resulting in a secondary impact between the head and surrounding environment. Such impacts may result in brain injury leading to fatality or permanent neurological impairment. In a previous publication, there were 90 one punch deaths around Australia between 2000 and 2012, mostly involving young men drinking alcohol at a licensed venue at the weekend. This prompted a surge of public education and awareness campaigns around Australia, in addition to regulatory and legislative changes aimed at curbing social violence. This retrospective descriptive study aimed to examine one punch deaths since 2012 in Australia to determine if there has been a decrease in deaths, and whether the demographics and circumstances of these deaths have changed. A search of the National Coronial Information System was undertaken for all closed coronial cases between 1 January 2012 and 31 December 2018. Additional information was collected from medicolegal reports including toxicology, pathology and coronial findings. There were 80 one punch fatalities in Australia, almost exclusively involving males. The median age was 43.5 (range 18-71) years and there was a decreasing trend in the number of deaths annually. Most fatal assaults occurred in the state of New South Wales (28.8%) followed by Queensland (23.8%), and in metropolitan locations (64.6%) rather than regional areas (35.4%). Alcohol was the most commonly detected drug, found in 47 cases of the 71 cases where toxicology results were available (66%), with a median concentration of 0.14 and 0.19 g/100 mL in antemortem and postmortem samples, respectively (range 0.005-0.32 g/100 mL). Five deaths reported methylamphetamine, with THC detected in 21.1% of cases. Assaults more commonly occurred on a footpath or roadside (41.3%), followed by a home or dwelling (32.5%). 8.8% of assaults occurred inside hotels, bars or other licenced venues. Most transpired on a weekday, which differed from the pre-2012 period when these assaults occurred mainly on the weekend. While some trends are positive, there has been a shift in the victim demographic as well as the typical environment for fatal one punch assaults, highlighting the importance of public health surveillance in providing a current evidence base to inform policy and practice.

Quantitative analysis of tetrahydrocannabinol isomers and other toxicologically relevant drugs in blood.

A multi-analyte liquid chromatography-tandem mass spectrometry (LC-MS/MS) method is described, involving the separation of delta-9-tetrahydrocannabinol (delta-9-THC) and delta-8-THC in addition to other commonly encountered drugs and metabolites. Briefly, sample preparation involved an alkaline liquid-liquid extraction (methyl tert-butyl ether) of blood (100 µl). The solvent layer was transferred, evaporated to dryness, reconstituted, and samples then separated on an Agilent Poroshell 120 EC-C18 100 Å (50 mm × 3.0 mm, 2.7 µm) analytical column using a multi-step gradient elution of 50 mM ammonium formate in water (pH 3.5) and 0.1% formic acid in methanol over 14 min. A SCIEX Triple Quad 6500+ system operating in scheduled multiple reaction monitoring and positive electrospray ionization was used for detection. There were no interferences, and matrix effects were generally acceptable (±20% of neat response). Linearity was achieved within the calibration range, including methylamphetamine (MA) (10-1000 ng/ml), 3,4-methylenedioxy-N-methylamphetamine (MDMA) (10-1,000 ng/ml), cocaine (10-1000 ng/ml), and two THC isomers (1-100 ng/ml). Accuracies of MA, MDMA, cocaine, and two THC isomers were 3.6 to 8.9%, -1.2 to 4%, -5.3 to 5.8%, and -11 to 14%, respectively; while precision estimates of the same were 1.6 to 5.4%, 1.7 to 5.3%, 1.2 to 4.5%, and 2 to 10%, respectively. Autosampler stability and dilution integrity were within acceptable limits, and no carryover was detected at the limit of detection. This validated LC-MS/MS method made the routine identification of both delta-9-THC and delta-8-THC in blood possible.

Fatal Intoxications from a Combination of 4-Fluoroamphetamine and 25C-NBOMe.

Six fatalities have occurred from the ingestion of a combination of new psychoactive substances (NPSs), 4-fluoroamphetamine (4FA) and 2-(4-chloro-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine (25C-NBOMe) over a 9-month period. Four of these fatalities (one older female and three young males) were from direct adverse effects of drugs, and one each from a fall while being intoxicated and during restraint. All cases were subject to full postmortem examinations that included collection of femoral blood. The four drug-caused fatalities had postmortem blood concentrations for 4FA and 25C-NBOMe of 330-682 ng/L (median 417) and 1.4-12 ng/mL (median 4.3), respectively. The other two cases (both young males) where death was considered to have been caused indirectly by drug intoxication had 4FA and 25C-NBOMe postmortem concentrations of 21 and 123 ng/mL, and 1.8 and 4.5 ng/mL, respectively. None of these cases showed concentrations of drugs that suggested use of high recreational doses. In one drug-caused death, capsules and a brown powder obtained from the scene were found to contain a mixture of these two NPSs. With the exception of one drug-caused death, other drugs were detected; however, the effects of the two NPSs together were regarded as the primary triggers for the deaths. There were no consistent symptoms or pathology in these cases; however, agitation/aggression was observed in two cases prior to their collapse, with seizures in possibly three cases. Pulmonary and/or cerebral edema was noted in three cases. Potentially significant natural disease (a mildly enlarged heart) was only observed in one drug-caused case. These cases illustrate a possible increased risk of sudden death with this combination of drugs, both of which can elevate serotonin concentrations as well as act as strong stimulants. These cases also illustrate the difficulty in detecting NPS in cases where no prior information is available that might suggest their use.

The incidence of asymmetrical left/right skeletal and dental development in an Australian population and the effect of this on forensic age estimations.

The prevalence of developmental asymmetry between left and right sides of the body in the third molar tooth and medial clavicular epiphysis is examined in a contemporary Australian population (92% Caucasian). The contention that differences between left and right side developmental timing is statistically insignificant, and can therefore be ignored in forensic age estimation procedures, is questioned. It was found that of a population sample of 604 individuals, 177 displayed asymmetrical timing in development between antimeres of the third molar, the medial clavicle or both. There was no correlation found between the third molar tooth and medial clavicular epiphysis in terms of left/right synchronicity. For those individuals differing in development by two or more developmental stages in either age marker or one stage in both age markers, the effect upon the accuracy of forensic age estimations can be significant. Differences in age estimates for each side were as much as 3.1 years. Age estimations based on one side only may not provide the best estimate for an individual, and more accurate results can be achieved if both sides are taken into consideration. A protocol for dealing with asymmetrical development is discussed with reference to the multifactorial age estimation method proposed by the same authors in previous research.

The role of toxicology interpretations in prevention of sudden death.

Inappropriate combinations of pharmaceutical drugs are often detected in deaths reported to a coroner. However, the involvement of drug combinations in the cause of death can be overlooked in cases when significant natural disease or external injury is also present. This study examined pathology reports and coroner's findings between January 2002 and December 2008. Cases that included exposure to a selection of serotonergic drugs were examined to determine the role of different death investigators in drug-associated deaths in Victoria, Australia. Of the 326 cases identified, the involvement of drugs in the death was discussed to some degree in 66% of cases. Recommendations by the coroner pertaining to death prevention were made in 12 cases (4%). In 16 cases (5%) the drugs were not mentioned in the findings, including at least 11 cases of probable major adverse drug interactions. Death investigations serve an important public health and safety role, however, the potential involvement of drugs in many cases is not always recognized.

The effect of the postmortem interval on the redistribution of drugs: a comparison of mortuary admission and autopsy blood specimens.

Postmortem redistribution (PMR) is an accepted toxicological phenomenon that may affect the interpretation of postmortem blood concentrations. The extent of PMR is not well understood for some drugs. This report describes the PMR of selected substances resulting from the analysis of 149 cases comparing blood specimens taken at admission of the deceased to the mortuary and then at autopsy. Blood was collected in preserved tubes containing 1 % sodium fluoride/potassium oxalate. All cases were subject to a full autopsy and blood extracts were analyzed using a targeted screen by LC-MS/MS. 30 drug or drug metabolites that were detected with an incidence of 6 or more were included in this study. The pre-autopsy interval ranged from 0.5 to 164 h (6.4 days) with an average of 64 h for the cases analyzed. The increase in drug concentration from mortuary admission to autopsy ranged from 30 % for drugs such as citalopram, mirtazapine, and sertraline to 300 % for doxylamine. Only 7 drugs of the 30 studied showed increases of greater than 20 % when comparing autopsy to mortuary admission blood irrespective of the length of the postmortem interval. Drugs including methadone, EDDP, fluoxetine, mirtazapine, and sertraline all showed statistically significant increases during the pre-autopsy interval (p < 0.05) while 6-acetylmorphine, 9-hydroxy-risperidone, and caffeine showed significant decreases (p < 0.05) from mortuary admission to autopsy. While femoral blood is thought to reduce PMR, this data shows that for some drugs significant redistribution can occur even when taking peripheral specimens irrespective of the delay in the postmortem interval.

Fire/flames mortality in Australian children 1968-2016, trends and prevention.

INTRODUCTION: Mortality attributed to fire and flame for children (0-14 years) over a fifty-year period has not been previously analyzed in Australia. The literature has focused on these deaths over a shorter time period or disaggregated with other causes of burns or deaths in one burns center. However, mortality associated with fire/flames affects this age group the greatest. The aims of this study are to: (1) develop a trends analysis of fire and flames mortality between1968 to 2016, using the Australian Bureau of Statistics (ABS) mortality database and, (2) determine the association of interventions with fire and flames mortality using the Haddon's categorical intervention framework. METHODS: International Classification of Disease (ICD) codes were extracted and code equivalencies between ICD 8, 9, 10 and the Australian Bureau of Statistics for fire/flames data between 1968--2016 were assessed. To determine whether population changes affected the risks of mortality, the frequency and, rates per 100,000 were used. A literature review was conducted that summarized the current knowledge of interventions associated with the major decreases in the fire and flames mortality rate. RESULTS: In Australia, we found was a downward trend for the period although with significant variation from year to year when compared to external cause mortality. Additionally, there were multiple successful interventions associated with a sustained decrease in mortality. After 2016, child fire-related mortality remains a problem particularly in low socioeconomic groups and indigenous peoples. A combination of research, public awareness, engineering, legal enforcement, advancements in burns care and, evidence-based policy development all have a role to play in future injury prevention initiatives. Although direct causation to an individual is not possible, associations can be drawn from interventions on a population level to decreases in mortality. CONCLUSION: We found was a steady decline in both rates and frequency of childhood fire and flames mortality from 1968 to 2016 associated with multiple interventions.