Investigating the Source of Fatal Pulmonary Thromboembolism in a Coronial Postmortem Population.

ABSTRACT: The incidence of how often a deep vein thrombosis is found in the calves of the legs at coronial postmortem examination is unclear. This study retrospectively examined postmortem examination reports from Australian Coronial investigations of sudden death resulting from pulmonary thromboembolism to determine the likelihood of dissection of the deep veins of calves of the legs revealing the source of a pulmonary thromboembolism. From 450 cases taken from the National Coronial Information System (NCIS) for 2016, the postmortem reports of 327 cases were reviewed to provide demographic details of victims of sudden death from pulmonary thromboembolism. In 235 cases, it was possible to determine in 76.6% a thrombus had been found in the deep veins of the calves of the legs after dissection. In 141 cases, it was documented that both sides had been examined. From these, it was determined there was no statistically significant difference in the prevalence of thrombus in either side. However, it was shown that the presence of an abnormality of a lower limb (such as leg or hip infection, burns, surgery and nonoperated fractures, or a larger circumference) increased the likelihood that a deep vein thrombus would be found on that side.

Methamphetamine and alcohol detection in vehicle-driver fatalities in South Australia: A 10-year survey (2008-2018).

Motor vehicle driver fatalities (≥18 years) from the files at Forensic Science South Australia were reviewed from January 2008 to December 2018 for cases in which either positive blood sample for methamphetamine (MA) or an illegal blood alcohol concentration (BAC) >0.05g/100 ml were found. Three hundred driver deaths were found with MA detected in 28 cases (age range 21-62 years; ave. 37.8 years; M:F 23:5). Hundred and fifteen cases with a BAC > 0.05 g/100 ml were identified (age range 18-67 years; ave 35.7 years; M:F 95:20). No change was found in numbers of MA cases, although alcohol cases showed a significant decline (p < 0.001). Drunk driving-related fatal crashes tended to occur in the evening (5 p.m. to 11 p.m.), while MA-related fatal crashes had a longer peak extending from late evening until late morning (11 p.m. to 8 a.m.). This study has demonstrated that while roadside breath testing, legislative changes, and increased monitoring have resulted in reduced levels of drunk driving, similar safety countermeasures have had negligible effects on MA use in drivers. Continued monitoring of MA use by drivers will, therefore, be necessary to assess the possible effects, or not, of new countermeasures.

Characteristics of drowning deaths in an inner city river.

A study was undertaken of all drowning deaths that occurred over a 30-year period from 1988 to 2017 in the urban section of the River Torrens, Adelaide, South Australia, an augmented waterway that runs through the central business district. Autopsy records from Forensic Science South Australia (FSSA) were reviewed. There were 34 drownings (0-5 cases/yr) with 28 males and 6 females (M;F = 4.6:1), with an age range for males of 18-76yrs (mean 42.0; SD 18.0) and for females of 20-84yrs (mean 69.3; SD 24.5). There were 15 (44%) accidents, 11 (32%) suicides, 1 (3%) homicide and 7 (21%) undetermined. Of the 22 cases during or after 1994 with complete toxicology reports, 10 (45%) had a blood alcohol concentration (BAC) of greater than 0.05% (g/100 mL) with an illicit substance detected in 4 (18%) cases: (MDMA (3,4-methylenedioxymethamphetamine), methylamphetamine and THC (delta-9-tetrahydrocannabinol) acid). The presence of various therapeutic drugs was also detected in 10 cases (45%) including temazepam, fluoxetine, diazepam, olanzapine, amitriptyline, carbamazepine, codeine, citalopram and valproate. Although the numbers of cases were not high, the urban portion of the River Torrens had a much higher number of drowning events per kilometre compared to other inland waterways in South Australia such as the Murray River. This is most likely due to the vulnerability that exists for intoxicated individuals in the city from falls into the water and to the availability of the river as a means of suicide to members of the adjacent urban population.

The use of therapeutic magnesium for neuroprotection during global cerebral ischemia associated with cardiac arrest and cardiac surgery in adults: a systematic review.

BACKGROUND: Global cerebral ischemia occurs due to reduced blood supply to the brain. This is commonly caused by a cessation of myocardial activity associated with cardiac arrest and cardiac surgery. Survival is not the only important outcome because neurological dysfunction impacts on quality of life, reducing independent living. Magnesium has been identified as a potential neuroprotective agent; however, its role in this context is not yet clear. OBJECTIVES: The objective of this review was to present the best currently available evidence related to the neuroprotective effects of magnesium during a period of global cerebral ischemia in adults with cardiac arrest or cardiac surgery. INCLUSION CRITERIA TYPES OF PARTICIPANTS: The current review considered adults aged over 18 years who were at risk of global cerebral ischemia associated with cardiac arrest or cardiac surgery. Studies of patients with existing neurological deficits or under the age of 18 years were excluded from the review. TYPES OF INTERVENTION(S)/PHENOMENA OF INTEREST: The intervention of interest was magnesium administered in doses of at least of 2 g compared to placebo to adult patients within 24 hours of cardiac arrest or cardiac surgery. TYPES OF STUDIES: The current review considered experimental designs including randomized controlled trials, non-randomized controlled trials and quasi-experimental designs. OUTCOMES: The outcome of interest were neurological recovery post-cardiac arrest or cardiac surgery, as measured by objective scales, such as but not limited to, cerebral performance category, brain stem reflexes, Glasgow Coma Score and independent living or dependent living status. To enable assessment of the available data, neuroprotection was examined by breaking down neurological outcomes into three domains - functional neurological outcomes, neurophysiological outcomes and neuropsychological outcomes. SEARCH STRATEGY: The search strategy aimed to find both published and unpublished studies between January 1980 and August 2014, utilizing the Joanna Briggs Institute (JBI) three-step search strategy. Databases searched included PubMed, Embase, CINAHL, Cochrane Central Register of Controlled Trials, Australian Clinical Trials Register, Australian and New Zealand Clinical Trials Register, Clinical Trials, European Clinical Trials Register and ISRCTN Registry. METHODOLOGICAL QUALITY: The studies included in this review were of moderate-to-good-quality randomized controlled trials. Studies included measured neurological outcome using functional neurological assessment, neuropsychiatric assessment or neurophysiological assessment. DATA EXTRACTION: Data were extracted using standardized templates provided by the JBI Meta-analysis of Statistics Assessment and Review Instrument software. DATA SYNTHESIS: Quantitative data were, where possible, pooled in statistical meta-analysis using Review Manager 5.3 (The Nordic Cochrane Centre, Cochrane; Copenhagen, Denmark). Where statistical pooling was not possible, the findings were presented in narrative form, including tables and figures, to aid in data presentation, where appropriate. RESULTS: Seven studies with a total of 1164 participants were included in this review. Neurological outcome was categorized into three domains: functional neurological, neurophysiological and neuropsychological outcomes. Meta-analysis of three studies assessing the neuroprotective properties of magnesium administration post cardiac arrest found improved functional neurological outcome (odds ratio 0.44; 95% confidence interval 0.24-0.81). CONCLUSION: Magnesium may improve functional neurological outcome in patients who suffer global cerebral ischemia associated with cardiac surgery and cardiac arrest. Magnesium does not decrease neuropsychological decline.Further testing of neurological outcomes in the domains of functional outcomes, neurophysiological markers and neuropsychological tests are required to further understanding of the neuroprotective effects of magnesium. Suitable dosing regimens should be investigated prior to introduction into clinical practice. Further research is required to investigate the optimal magnesium dose.

Differential effects of 670 and 830 nm red near infrared irradiation therapy: a comparative study of optic nerve injury, retinal degeneration, traumatic brain and spinal cord injury.

Red/near-infrared irradiation therapy (R/NIR-IT) delivered by laser or light-emitting diode (LED) has improved functional outcomes in a range of CNS injuries. However, translation of R/NIR-IT to the clinic for treatment of neurotrauma has been hampered by lack of comparative information regarding the degree of penetration of the delivered irradiation to the injury site and the optimal treatment parameters for different CNS injuries. We compared the treatment efficacy of R/NIR-IT at 670 nm and 830 nm, provided by narrow-band LED arrays adjusted to produce equal irradiance, in four in vivo rat models of CNS injury: partial optic nerve transection, light-induced retinal degeneration, traumatic brain injury (TBI) and spinal cord injury (SCI). The number of photons of 670 nm or 830 nm light reaching the SCI injury site was 6.6% and 11.3% of emitted light respectively. Treatment of rats with 670 nm R/NIR-IT following partial optic nerve transection significantly increased the number of visual responses at 7 days after injury (P ≤ 0.05); 830 nm R/NIR-IT was partially effective. 670 nm R/NIR-IT also significantly reduced reactive species and both 670 nm and 830 nm R/NIR-IT reduced hydroxynonenal immunoreactivity (P ≤ 0.05) in this model. Pre-treatment of light-induced retinal degeneration with 670 nm R/NIR-IT significantly reduced the number of Tunel+ cells and 8-hydroxyguanosine immunoreactivity (P ≤ 0.05); outcomes in 830 nm R/NIR-IT treated animals were not significantly different to controls. Treatment of fluid-percussion TBI with 670 nm or 830 nm R/NIR-IT did not result in improvements in motor or sensory function or lesion size at 7 days (P>0.05). Similarly, treatment of contusive SCI with 670 nm or 830 nm R/NIR-IT did not result in significant improvements in functional recovery or reduced cyst size at 28 days (P>0.05). Outcomes from this comparative study indicate that it will be necessary to optimise delivery devices, wavelength, intensity and duration of R/NIR-IT individually for different CNS injury types.

Red/near-infrared irradiation therapy for treatment of central nervous system injuries and disorders.

Irradiation in the red/near-infrared spectrum (R/NIR, 630-1000 nm) has been used to treat a wide range of clinical conditions, including disorders of the central nervous system (CNS), with several clinical trials currently underway for stroke and macular degeneration. However, R/NIR irradiation therapy (R/NIR-IT) has not been widely adopted in clinical practice for CNS injury or disease for a number of reasons, which include the following. The mechanism/s of action and implications of penetration have not been thoroughly addressed. The large range of treatment intensities, wavelengths and devices that have been assessed make comparisons difficult, and a consensus paradigm for treatment has not yet emerged. Furthermore, the lack of consistent positive outcomes in randomised controlled trials, perhaps due to sub-optimal treatment regimens, has contributed to scepticism. This review provides a balanced précis of outcomes described in the literature regarding treatment modalities and efficacy of R/NIR-IT for injury and disease in the CNS. We have addressed the important issues of specification of treatment parameters, penetration of R/NIR irradiation to CNS tissues and mechanism/s, and provided the necessary detail to demonstrate the potential of R/NIR-IT for the treatment of retinal degeneration, damage to white matter tracts of the CNS, stroke and Parkinson's disease.

Severity-dependent expression of pro-inflammatory cytokines in traumatic spinal cord injury in the rat.

The post-traumatic inflammatory response in acute spinal cord contusion injury was studied in the rat. Mild and severe spinal cord injury (SCI) was produced by dropping a 10 g weight from 3 and 12 cm at the T12 vertebral level. Increased immunoreactivity of TNF-alpha in mild and severe SCI was detected in neurons at 1 h post-injury, and in neurons and microglia at 6 h post-injury, with a less significant increase in mild SCI. Expression was short-lived and declined sharply by 1 d post-injury. RT-PCR showed an early significant up-regulation of IL-1 beta, IL-6 and TNF-alpha mRNAs, maximal at 6 h post-injury with return to control levels by 24 h post-injury, the changes being less statistically significantly in mild SCI. Western blot showed early transient increases of IL-1 beta, IL-6 and TNF-alpha proteins in severe SCI but not mild SCI. Immunocytochemical, western blotting and RT-PCR analyses suggest that endogenous cells (neurons and microglia) in the spinal cord, not blood-borne leucocytes, contribute to IL-1 beta, IL-6 and TNF-alpha production in the post-traumatic inflammatory response and that their up-regulation is greater in severe than mild SCI.

Recent advances in the development of multifactorial therapies for the treatment of traumatic brain injury.

Traumatic brain injury (TBI) is one of the leading causes of death and disability in the industrialised world and remains a major health problem with serious socioeconomic consequences. So far, despite encouraging preclinical results, almost all neuroprotection trials have failed to show any significant efficacy in the treatment of clinical TBI. This may be due, in part, to the fact that most of the therapies investigated have targeted an individual injury factor. It is now recognised that TBI is a very heterogeneous type of injury that varies widely in its aetiology, clinical presentation, severity and pathophysiology. The pathophysiological sequelae of TBI are mediated by an interaction of acute and delayed molecular, biochemical and physiological events that are both complex and multifaceted. Accordingly, a successful TBI treatment may have to simultaneously attenuate many injury factors. Recent efforts in experimental TBI have, therefore, focused on the development of neuropharmacotherapies that target multiple injury factors and thus improve the likelihood of a successful outcome. This review will focus on three such novel compounds that are currently being assessed in clinical trials; progesterone, dexanabinol and dexamethasone, and provide an update on the progress of both magnesium and cyclosporin A.