Surgery (RMH) - Research Publications
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ItemQuality and safety indicators for home care recipients in Australia: development and cross-sectional analyses(BMJ PUBLISHING GROUP, 2022-08)Objectives To develop and examine the prevalence of quality and safety indicators to monitor care of older Australians receiving home care packages (HCPs), a government-funded aged care programme to support individuals to live at home independently. Design Cross-sectional. Setting Home care recipients, Australia. Participants 90 650 older individuals (aged ≥65 years old and ≥50 years old for people of Aboriginal or Torres Strait Islander descent) who received a HCP between 1 January 2016 and 31 December 2016 nationally were included. Primary and secondary outcome measures The Registry of Senior Australians developed 15 quality and safety indicators: antipsychotic use, high sedative load, chronic opioid use, antimicrobial use, premature mortality, home medicines reviews, chronic disease management plan, wait-time for HCP, falls, fractures, medication-related adverse events, weight loss/malnutrition, delirium/dementia-related hospitalisations, emergency department (ED) presentations and pressure injuries. Risk adjusted prevalence (%, 95% CI) and geographical area (statistical level 3) variation during 2016 were examined. Results In 2016, a total of 102 590 HCP episodes were included for 90 650 individuals, with 66.9% (n=68 598) level 1–2 HCP episodes (ie, for basic care needs) and 33.1% (n=33 992) level 3–4 HCP (ie, higher care needs). The most prevalent indicators included: antibiotic use (52.4%, 95% CI 52.0 to 52.7), chronic disease management plans (38.1%, 95% CI 37.8 to 38.4), high sedative load (29.1%, 95% CI 28.8 to 29.4) and ED presentations (26.4%, 95% CI 25.9 to 26.9). HCP median wait time was 134 days (IQR 41–406). Geographical variation was highest in chronic disease management plans and ED presentations (20.7% of areas outside expected range). Conclusion A comprehensive outcome monitoring system to monitor the quality and safety of care and variation for HCP recipients was developed. It provides a pragmatic, efficient and low burden tool to support evidence-based quality and safety improvement initiatives for the aged care sector.
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ItemNo Preview AvailableEfficacy of combined CDK9/13ET inhibition in preclinical models of MLL-rearranged acute leukemia(ELSEVIER, 2020-01-28)Cyclin-dependent kinase 9 and bromodomain and extraterminal inhibitors are synergistic in MLL-rearranged leukemia. Multiple AML driver genes are downregulated by the combined therapy suggesting broad applicability for this subtype.
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ItemRegistry of Older South Australians (ROSA): framework and plan(BMJ PUBLISHING GROUP, 2019-06)INTRODUCTION: Australia's ageing population puts significant demands on the aged care and healthcare sectors. To monitor the provision of aged care and healthcare services to older people, each government body has an individual data collection system. Together these systems can be the basis for creating the evidence necessary to support future allocation of resources for our ageing community. The Registry of Older South Australians (ROSA) is a cross-sector multidisciplinary (ie, aged care and healthcare) platform built to address the challenges of monitoring people in aged care settings. This protocol describes the ROSA's framework and plans. METHODS AND ANALYSIS: A registry to capture 16 000 South Australians/year undergoing an aged care eligibility assessment was designed. ROSA will contain information captured by the Commonwealth and South Australian state Health Authority, linked by two data integrating authorities, and housed on a secured data platform. ROSA will contain information on the sociodemographic, health, function, psychological, social, home and safety assessment and concerns characteristics, aged care services, general health services, and mortality of people receiving aged care services. Registered participants will be prospectively monitored until their death and yearly updates of their aged care and healthcare services information will be added to the registry. ETHICS AND DISSEMINATION: ROSA will longitudinally monitor the services provided to a population that puts costly demands on the state healthcare and aged care systems, identify unwanted variation, and underpin future research. ROSA's expected outputs include an annual report, a research agenda that focuses on high burden conditions and potentially economically impactful questions, educational materials, and risk profiling tools. ROSA was approved by the South Australian Department for Health and Ageing HREC (HREC/17/SAH/125) and the Australian Institute of Health and Welfare HREC (EO2018/2/429).
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ItemHealth status and healthcare trends of individuals accessing Australian aged care programmes over a decade: the Registry of Senior Australians historical cohort(WILEY, 2021-05)BACKGROUND: Understanding the health profile, service and medicine use of Australians in the aged care sector will help inform appropriate service provision for our ageing population. AIMS: To examine the 2006-2015 trends in (i) comorbidities and frailty of individuals accessing aged care, and (ii) health services, medicine use and mortality after entry into long-term care. METHODS: Cross-sectional and population-based trend analyses were conducted using the Registry of Senior Australians. RESULTS: From 2006 to 2015, 509 944 individuals accessed permanent residential care, 206 394 home care, 283 014 respite and 124 943 transition care. Over this time, the proportion of individuals accessing permanent residential care with high frailty scores (≥0.3) increased (19.7-49.7%), as did the proportion with 5-9 comorbidities (46.4-54.5%), with similar trends observed for those accessing other services. The median number of medicines dispensed in the year after entering permanent residential care increased from 9 (interquartile range (IQR) 6-12) to 10 (IQR 7-14), while remaining stable in home care (2006: 9, IQR 5-12, 2015: 9, IQR 6-13). Short-term (within 100 days) mortality in those accessing permanent care was higher in 2006 (15.6%, 95% CI 15.2-16.0) than 2015 (14.6%, 95% CI 14.3-14.9). Longer term (101-1095 days, 2006: 44.3%, 95% CI 43.7-45.0, 2015: 46.4%, 95% CI 45.8-46.9) mortality was higher in 2015 compared to 2006. Mortality in individuals accessing home care did not change. CONCLUSION: The health of older Australians accessing aged care programmes has declined while frailty increased, with an increasing use of medicine and worse long-term mortality in some. Funding and care models need to adapt to this changing profile.
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ItemA novel, somatic, transforming mutation in the extracellular domain of Epidermal Growth Factor Receptor identified in myeloproliferative neoplasm(NATURE PORTFOLIO, 2017-05-26)We describe a novel ERBB1/EGFR somatic mutation (p. C329R; c.985 T > C) identified in a patient with JAK2V617F Polycythaemia Vera (PV). This substitution affects a conserved cysteine residue in EGFR domain 2 and leads to the formation of a ligand-independent covalent receptor dimer, associated with increased transforming potential. Aberrant signalling from the EGFRC329R receptor is cell type-dependent and in the TF1.8 erythroid cell line expression of this mutant suppresses EPO-induced differentiation. Clonal analysis shows that the dominant JAK2V617F-positive clone in this PV patient harbors EGFRC329R, thus this mutation may contribute to clonal expansion. Somatic mutations affecting other ERBB and related receptor tyrosine kinases are observed in myeloproliferative neoplasms (MPN), and we show elevated EGFR levels in MPN samples, consistent with previous reports. Thus activation of this group of receptors, via multiple mechanisms, may contribute to clonal growth and survival of the JAK2V617F disease clone in MPN.
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ItemMitochondrial genomes reveal an explosive radiation of extinct and extant bears near the Miocene-Pliocene boundary(BMC, 2008-07-28)BACKGROUND: Despite being one of the most studied families within the Carnivora, the phylogenetic relationships among the members of the bear family (Ursidae) have long remained unclear. Widely divergent topologies have been suggested based on various data sets and methods. RESULTS: We present a fully resolved phylogeny for ursids based on ten complete mitochondrial genome sequences from all eight living and two recently extinct bear species, the European cave bear (Ursus spelaeus) and the American giant short-faced bear (Arctodus simus). The mitogenomic data yield a well-resolved topology for ursids, with the sloth bear at the basal position within the genus Ursus. The sun bear is the sister taxon to both the American and Asian black bears, and this clade is the sister clade of cave bear, brown bear and polar bear confirming a recent study on bear mitochondrial genomes. CONCLUSION: Sequences from extinct bears represent the third and fourth Pleistocene species for which complete mitochondrial genomes have been sequenced. Moreover, the cave bear specimen demonstrates that mitogenomic studies can be applied to Pleistocene fossils that have not been preserved in permafrost, and therefore have a broad application within ancient DNA research. Molecular dating of the mtDNA divergence times suggests a rapid radiation of bears in both the Old and New Worlds around 5 million years ago, at the Miocene-Pliocene boundary. This coincides with major global changes, such as the Messinian crisis and the first opening of the Bering Strait, and suggests a global influence of such events on species radiations.
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ItemSynergistic roles of climate warming and human occupation in Patagonian megafaunal extinctions during the Last Deglaciation(AMER ASSOC ADVANCEMENT SCIENCE, 2016-06)The causes of Late Pleistocene megafaunal extinctions (60,000 to 11,650 years ago, hereafter 60 to 11.65 ka) remain contentious, with major phases coinciding with both human arrival and climate change around the world. The Americas provide a unique opportunity to disentangle these factors as human colonization took place over a narrow time frame (~15 to 14.6 ka) but during contrasting temperature trends across each continent. Unfortunately, limited data sets in South America have so far precluded detailed comparison. We analyze genetic and radiocarbon data from 89 and 71 Patagonian megafaunal bones, respectively, more than doubling the high-quality Pleistocene megafaunal radiocarbon data sets from the region. We identify a narrow megafaunal extinction phase 12,280 ± 110 years ago, some 1 to 3 thousand years after initial human presence in the area. Although humans arrived immediately prior to a cold phase, the Antarctic Cold Reversal stadial, megafaunal extinctions did not occur until the stadial finished and the subsequent warming phase commenced some 1 to 3 thousand years later. The increased resolution provided by the Patagonian material reveals that the sequence of climate and extinction events in North and South America were temporally inverted, but in both cases, megafaunal extinctions did not occur until human presence and climate warming coincided. Overall, metapopulation processes involving subpopulation connectivity on a continental scale appear to have been critical for megafaunal species survival of both climate change and human impacts.
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ItemFactors associated with accessing aged care services in Australia after approval for services: Findings from the historical cohort of the Registry of Senior Australians(WILEY, 2020-09)OBJECTIVE: To evaluate the access of approved aged care services and factors associated with accessing these services. METHODS: A retrospective cohort study was conducted (1/7/2003-30/6/2013). The incidence of accessing permanent residential, home and respite care services within one year or transition care within 28 days of approval was evaluated. The association of participants' socio-demographic characteristics, limitations, health conditions and assessment characteristics with service use was evaluated. RESULTS: In 799 750 older Australians, the incidence of accessing approved permanent residential care within one year was 70.9% (95% confidence interval [CI] 70.8%-71.0%), home care 49.5% (95% CI 49.3%-49.7%) and respite 41.8% (95% CI 41.7%-41.9%). The incidence of accessing transition care at 28 days was 78.5% (95% CI 78.2%-78.7%). Aged care seekers', assessments' and assessors' characteristics are associated with service access. CONCLUSION: Monitoring the use of aged care service approvals is necessary for the identification of service access barriers to support evidence-based policy changes.
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ItemLions and brown bears colonized North America in multiple synchronous waves of dispersal across the Bering Land Bridge(WILEY, 2022-12)The Bering Land Bridge connecting North America and Eurasia was periodically exposed and inundated by oscillating sea levels during the Pleistocene glacial cycles. This land connection allowed the intermittent dispersal of animals, including humans, between Western Beringia (far northeast Asia) and Eastern Beringia (northwest North America), changing the faunal community composition of both continents. The Pleistocene glacial cycles also had profound impacts on temperature, precipitation and vegetation, impacting faunal community structure and demography. While these palaeoenvironmental impacts have been studied in many large herbivores from Beringia (e.g., bison, mammoths, horses), the Pleistocene population dynamics of the diverse guild of carnivorans present in the region are less well understood, due to their lower abundances. In this study, we analyse mitochondrial genome data from ancient brown bears (Ursus arctos; n = 103) and lions (Panthera spp.; n = 39), two megafaunal carnivorans that dispersed into North America during the Pleistocene. Our results reveal striking synchronicity in the population dynamics of Beringian lions and brown bears, with multiple waves of dispersal across the Bering Land Bridge coinciding with glacial periods of low sea levels, as well as synchronous local extinctions in Eastern Beringia during Marine Isotope Stage 3. The evolutionary histories of these two taxa underline the crucial biogeographical role of the Bering Land Bridge in the distribution, turnover and maintenance of megafaunal populations in North America.