Establishing the protocols for the South Australian Emergency Department Admission Blood Psychoactive Testing (EDABPT) programme for drug surveillance.

OBJECTIVE: ED presentations because of illicit use of psychotropic drugs and pharmaceuticals result in significant medical harm and resource consumption. Patient assessment is complicated by the regular emergence of new psychoactive substances, difficulties associated with their identification and a lack of information about their effects. Here we report the protocol for the Emergency Department Admission Blood Psychoactive Testing (EDABPT) programme, an observational study utilising clinical data capture and definitive drug identification to assess the medical impact and patterns of illicit drug use in the community, and their geographic and temporal fluctuations. The study provides data to an early warning system targeting an improved public health response to emerging drugs of concern. METHODS: Enrolment of adult patients presenting with suspected illicit drug use occurs at four major EDs in a single urban setting. Clinical and demographic data are collected by treating clinicians. Blood samples are collected at presentation and frozen on site prior to transport to a specialised forensic facility for comprehensive toxicological screening. RESULTS: Results are fed back to clinicians and disseminated more broadly via an existing local early warning system. Targeted warnings and public health releases are instigated where heightened risk or harm is identified. CONCLUSION: The study pairs city-wide patient enrolment with analytically confirmed toxicology results to allow broad sampling and identification of illicit drugs causing medical harm. It provides a mechanism for the identification of new agents as they emerge in the community, delivers a relevant and reliable source of information for public health agencies and clinicians and supplements existing local early warning mechanisms.

Distribution of Heparan Sulfate Oligosaccharides in Murine Mucopolysaccharidosis Type IIIA.

Heparan sulfate (HS) catabolism begins with endo-degradation of the polysaccharide to smaller HS oligosaccharides, followed by the sequential action of exo-enzymes to reduce these oligosaccharides to monosaccharides and inorganic sulfate. In mucopolysaccharidosis type IIIA (MPS IIIA) the exo-enzyme, N-sulfoglucosamine sulfohydrolase, is deficient resulting in an inability to hydrolyze non-reducing end glucosamine N-sulfate esters. Consequently, partially degraded HS oligosaccharides with non-reducing end glucosamine sulfate esters accumulate. We investigated the distribution of these HS oligosaccharides in tissues of a mouse model of MPS IIIA using high performance liquid chromatography electrospray ionization-tandem mass spectrometry. Oligosaccharide levels were compared to total uronic acid (UA), which was used as a measure of total glycosaminoglycan. Ten oligosaccharides, ranging in size from di- to hexasaccharides, were present in all the tissues examined including brain, spleen, lung, heart, liver, kidney and urine. However, the relative levels varied up to 10-fold, suggesting different levels of HS turnover and storage. The relationship between the di- and tetrasaccharides and total UA was tissue specific with spleen and kidney showing a different disaccharide:total UA ratio than the other tissues. The hexasaccharides showed a stronger correlation with total UA in all tissue types suggesting that hexasaccharides may more accurately reflect the storage burden in these tissues.

Heat-related deaths in Adelaide, South Australia: review of the literature and case findings - an Australian perspective.

Heat waves are not uncommon in Australia, but the event of 2009 was particularly severe and ranks third of the 21 recorded heat wave events in south-eastern Australia in terms of the resulting mortality and morbidity. This is a review of Coronial autopsy findings in South Australia (which has an area of nearly 1 million square kilometres with a population of 1.6 million that predominantly resides within the region of the capital: Adelaide) during the period of the 2009 heat wave. Fifty-four post-mortem examinations were performed on cases in which exposure to high ambient temperature was regarded as having caused or significantly contributed to the death. The findings (including results of toxicological and biochemical analyses, where available) are reviewed and compared with the post-mortem examination findings in 22 deaths over the same period not attributed to the effects of heat. There were no specific autopsy findings that distinguished heat-related from non heat-related deaths. The lack of specific post-mortem findings increases the reliance on scene investigation in order to be able to categorise a death as being heat-related. A checklist for scene investigators is proposed in order to assist with collection of relevant data to assist the Coronial investigation process.

Using the Excess Heat Factor (EHF) to predict the risk of heat related deaths.

Extremes of climate are not uncommon in Australia and heatwaves are not infrequent. Periods of high ambient temperature may result in clusters of heat related deaths, which may place strain on forensic facilities. This paper describes the formulation of the Excess Heat Factor using meteorological data to provide a means of predicting death resulting from periods of extreme heat stress. The 2009 South Australian heatwave had the highest ranked Excess Heat Factor in Adelaide's records. There were 58 heat related deaths, with the bulk of the heat related deaths following the peak Excess Heat Factor value (144 °C(2)). The 2008 heatwave had a lower peak Excess Heat Factor value (36 °C(2)); there was only one heat related death, which followed the peak in the Excess Heat Factor. It is proposed that calculation of the Excess Heat Factor from meteorological data could provide a means to predict and identify heat related deaths resulting from extreme weather conditions.

Characterization of sulfated oligosaccharides in mucopolysaccharidosis type IIIA by electrospray ionization mass spectrometry.

Heparan sulfate is a linear glycosaminoglycan with considerable structural diversity that binds a myriad of growth factors and proteins that play pivotal roles in a variety of biological processes. We have investigated the structural complexity of partially degraded fragments of heparan sulfate in mucopolysaccharidosis type IIIA in which there is a defect in heparan sulfate catabolism. Mono- to hexadecasaccharides were isolated from the urine of a mucopolysaccharidosis IIIA patient and shown to have non-reducing end glucosamine N-sulfate residues, reflecting the catabolic deficiency in heparan N-sulfatase (sulfamidase) activity. The use of nitrous acid digestion (pH 1.5) combined with separation by reverse-phase high-performance liquid chromatography and analysis by electrospray ionization-mass spectrometry identified multiple forms of these oligosaccharides with some N-acetylated glucosamine residues and one to three sulfates per disaccharide. Furthermore, we demonstrated that each oligosaccharide existed in multiple sulfated forms. Many structural isomers were present, suggesting a complex mixture of oligosaccharides present in the urine as a consequence of a defect in heparan sulfate degradation.