Medicine, Dentistry & Health Sciences Collected Works - Research Publications
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ItemIncidence and outcomes of sepsis in Aboriginal and Torres Strait Islander and non-Indigenous residents of New South Wales: population-based cohort study(AUSTRALASIAN MED PUBL CO LTD, 2021-09)Objective: To estimate the incidence and outcomes of sepsis hospitalisations in Aboriginal and Torres Strait Islander and non-Indigenous residents of New South Wales. Design and participants: Prospective cohort study of residents aged 45 years and older, recruited between 2006 and 2009, and followed for hospitalisation for sepsis. Main outcome measures: Incidence and hazard ratio (HR) of sepsis hospitalisation and intensive care unit (ICU) admission identified using International Classification of Diseases (10th revision) coding on discharge data. Length of stay, readmission and mortality in those admitted for sepsis. Results: Of 264 678 participants, 1928 (0.7%) identified as Aboriginal and/or Torres Strait Islander. Sepsis hospitalisation was higher in Aboriginal and Torres Strait Islander participants (8.67 v 6.12 per 1000 person-years; age- and sex-adjusted HR, 2.35; 95% CI, 1.98-2.80) but was attenuated after adjusting for sociodemographic factors, health behaviour and comorbidities (adjusted HR, 1.56; 95% CI, 1.31-1.86). Among those hospitalised for sepsis, after adjusting for age and sex, there were no differences between the proportions of Aboriginal and Torres Strait Islander and non-Indigenous participants admitted to an ICU (18.0% v 16.1%; P = 0.42) or deceased at 1 year (36.1% v 36.8%; P = 0.92). Aboriginal and Torres Strait Islander participants had shorter lengths of hospital stay (9.98 v 11.72 days; P < 0.001) and ICU stay (4.38 v 6.35 days; P < 0.001) than non-Indigenous participants. Overall, more than 70% of participants were readmitted to hospital within 1 year. Conclusion: We found that the rate of sepsis hospitalisation in NSW was higher for Aboriginal and Torres Strait Islander adults. Culturally appropriate, community-led strategies targeting chronic disease prevention and the social determinants of health may reduce this gap. Preventing readmission following sepsis is a priority for all Australians.
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ItemAssociation of adiposity with diabetes: A national research among Chinese adults(WILEY, 2021-07)BACKGROUND: Adiposity is an established risk factor for diabetes. The different measurements of adiposity for predicting diabetes have been compared in recent studies in Western countries. However, similar researches among Chinese adults are limited. METHODS: Data were collected from a national survey conducted during September 2014 and May 2015 Among Chinese adults aged 40 years and older across 30 China's provinces. Multilevel model analysis was performed to examine the impacts of different obesity indices [body mass index (BMI), waist circumference (WC), lipid accumulation product index (LAP), visceral adiposity index (VAI), and body adiposity index (BAI)] on the risk of diabetes. RESULTS: A total of 162 880 participants were included in this study. Of them, 54.47% were female. With an increase in BMI, WC, LAP, VAI, and BAI, the prevalence of diabetes significantly grew (P < 0.001). The multilevel model analysis showed that WC has the strongest impact on diabetes prevalence, while BAI was the weakest. For one SD increment in BMI, WC, LAP, VAI, and BAI, the prevalence of diabetes increased by 27.0% (Odds Ratio (OR) = 1.270, 95% Confidence interval (CI) = 1.251-1.289), 37.4% (OR = 1.374, 95% CI = 1.346-1.401), 28.1% (OR = 1.281, 95% CI = 1.266-1.297), 22.0% (OR = 1.220, 95% CI = 1.204-1.236), and 17.4% (OR = 1.174, 95% CI = 1.151-1.192), respectively. CONCLUSION: Obesity indicators of BMI, WC, LAP, VAI, and BAI have significant positive relationships with the risk of diabetes. WC has the strongest impact on diabetes, while BAI has the weakest.
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ItemThe Creeping Concept of Trauma( 2020-09)Over the past century the concept of trauma has substantially broadened its meanings in academic and public discourse. We document four directions in which this semantic expansion has occurred at different times: from somatic to psychic, extraordinary to ordinary, direct to indirect, and individual to collective. We analyse these expansions as instances of ‘concept creep’, the progressive inflation of harm-related concepts, and present evidence for the rising cultural salience and semantic enlargement of trauma in recent decades. Expansive concepts of trauma may have mixed blessings for personal and collective identity.
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ItemIL-15 Preconditioning Augments CAR T Cell Responses to Checkpoint Blockade for Improved Treatment of Solid Tumors(CELL PRESS, 2020-11-04)Chimeric antigen receptor (CAR) T cell therapy has been highly successful in hematological malignancies leading to their US Food and Drug Administration (FDA) approval. However, the efficacy of CAR T cells in solid tumors is limited by tumor-induced immunosuppression, leading to the development of combination approaches, such as adjuvant programmed cell death 1 (PD-1) blockade. Current FDA-approved methods for generating CAR T cells utilize either anti-CD3 and interleukin (IL)-2 or anti-CD3/CD28 beads, which can generate a T cell product with an effector/exhausted phenotype. Whereas different cytokine preconditioning milieu, such as IL-7/IL-15, have been shown to promote T cell engraftment, the impact of this approach on CAR T cell responses to adjuvant immune-checkpoint blockade has not been assessed. In the current study, we reveal that the preconditioning of CAR T cells with IL-7/IL-15 increased CAR T cell responses to anti-PD-1 adjuvant therapy. This was associated with the emergence of an intratumoral CD8+CD62L+TCF7+IRF4- population that was highly responsive to anti-PD-1 therapy and mediated the vast majority of transcriptional and epigenetic changes in vivo following PD-1 blockade. Our data indicate that preservation of CAR T cells in a TCF7+ phenotype is crucial for their responsiveness to adjuvant immunotherapy approaches and should be a key consideration when designing clinical protocols.
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ItemPatient Rights and Practitioner Responsibilities During a Pandemic(The Federation press, 2021)
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ItemCurrent Practice of Physical Activity Counselling within Physiotherapy Usual Care and Influences on Its Use: A Cross-Sectional Survey(MDPI, 2021-05)Physical activity counselling has demonstrated effectiveness at increasing physical activity when delivered in healthcare, but is not routinely practised. This study aimed to determine (1) current use of physical activity counselling by physiotherapists working within publicly funded hospitals; and (2) influences on this behaviour. A cross-sectional survey of physiotherapists was conducted across five hospitals within a local health district in Sydney, Australia. The survey investigated physiotherapists' frequency of incorporating 15 different elements of physical activity counselling into their usual healthcare interactions, and 53 potential influences on their behaviour framed by the COM-B (Capability, Opportunity, Motivation-Behaviour) model. The sample comprised 84 physiotherapists (79% female, 48% <5 years of experience). Physiotherapists reported using on average five (SD:3) elements of physical activity counselling with at least 50% of their patients who could be more active. A total of 70% of physiotherapists raised or discussed overall physical activity, but less than 10% measured physical activity or contacted community physical activity providers. Physiotherapists reported on average 25 (SD:9) barriers influencing their use of physical activity counselling. The most common barriers were related to "opportunity", with 57% indicating difficulty locating suitable community physical activity opportunities and >90% indicating their patients lacked financial and transport opportunities. These findings confirm that physical activity counselling is not routinely incorporated in physiotherapy practice and help to identify implementation strategies to build clinicians' opportunities and capabilities to deliver physical activity counselling.
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ItemKnowledge, risk perception and preparedness towards coronavirus disease-2019 (COVID-19) outbreak among Ghanaians: a quick online cross-sectional survey(AFRICAN FIELD EPIDEMIOLOGY NETWORK-AFENET, 2020-04)INTRODUCTION: Coronavirus disease 2019 (COVID-19) is recognized as global pandemic, affecting more than 300,000 worldwide. Ghana joined the international community by confirming first two COVID-19 cases on March 12, 2020. The study aimed to assess the public knowledge, risk perception and preparedness to respond the COVID-19 in the early stage of the outbreak in Ghana. METHODS: A cross-sectional study was conducted to collect information from Ghanaian during the early stage of the outbreak from 12th to 20th March 2020. Electronic based questionnaire was developed to collected information on the public knowledge, risk perceptions and preparedness to respond the COVID-19. All people who were aged 18 years and over were invited to participate in the study. RESULTS: A total of 350 participants were recruited into the analysis; 56% were males, with the majority of the study population aged between 18-30 years (61.4%), single (68.9%) and attained tertiary education (95.1%). Regarding COVID-19, 62.7% had "good" knowledge about the outbreak, 68.3% had a high risk of contracting the COVID-19 infection and 81.4% had a moderate preparedness skill to prevent and control the disease. Internet (77.1%) was the major sources of information. Knowledge of COVID-19 was significantly associated with education (p<0.001), age (p=0.018), employment (p=0.011) and health-related occupation (P=0.001) but only religion was associated with risk perception. CONCLUSION: Though overall public knowledge was good, disparity exist among the least educated population, there was high risk perceptions and moderate preparedness skill to respond to COVID-19 among our study population. We recommend that educational campaigns through timely online update on COVID-19, van mobilization and mass media broadcasting should target all groups including those in the rural communities.
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ItemAn Agrobacterium rhizogenes mediated hairy root transformation protocol for fenugreek(ELSEVIER, 2020)•This work describes a protocol for hairy root transformation of the medicinal crop legume fenugreek (Trigonella foenum-graecum L.). Hairy root plant transformation mediated by Agrobacterium rhizogenes is an established method for the rapid genetic transformation of various dicotyledonous plants. We have adapted a hairy root transformation protocol from the model legume Medicago truncatula for use in this metabolically rich non-model crop legume. Considering the great variety and abundance of phytochemicals in fenugreek and its established use in traditional medicine, we aim for this method to become a resource for metabolic pathway identification and for production of valuable specialised metabolites via metabolic engineering approaches.•Development rapid transformation (2.5-3 weeks) of fenugreek roots via A. rhizogenes.•Marker gene cassette with suitable promoter for visual detection of transformed fenugreek roots.
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ItemIncidence of idiopathic intracranial hypertension in Southern Tasmania, Australia.(BMJ, 2021)INTRODUCTION: Anecdotally, the incidence of idiopathic intracranial hypertension (IIH) is increasing, linked to an increase in the obesity rate in Australian society. However, formal incidence and prevalence studies are rare. We therefore sought to determine the incidence and clinical features of IIH in Southern Tasmania, Australia. METHOD: Neurology discharge summaries and lumbar puncture referrals from the single tertiary referral centre in this region were screened for an IIH diagnosis. All regional neurologists were surveyed to capture patients diagnosed through private neurology clinics. A retrospective review of medical records was conducted to confirm the diagnosis and determine whether patients met the Modified Dandy Criteria (MDC). Patients were included if they were above the age of 18 years and received a new diagnosis of IIH between June 2016 and June 2018. Population statistics were obtained from the Australian Bureau of Statistics. RESULTS: IIH incidence was 5.4/100 000. All patients were females, aged between 18 and 45 years. Headache was the most commonly reported symptom, with high rates of pre-existing or concurrent migraine diagnoses. Weight loss and commencement of oral acetazolamide were the most common treatment approaches. Four patients were medically refractory and required surgical intervention. CONCLUSION: The incidence of IIH in Southern Tasmania is comparable with the incidence reported in subgroups of females of childbearing age in recent prior studies. The demographic, diagnostic and therapeutic data presented can inform future local health service provision and serve as a baseline for ongoing assessment of change in incidence and treatment of IIH at a community level.
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ItemPTEN activation contributes to neuronal and synaptic engulfment by microglia in tauopathy(SPRINGER, 2020-07)Phosphatase and tensin homolog (PTEN) regulates synaptic density in development; however, whether PTEN also regulates synapse loss in a neurodegenerative disorder such as frontotemporal lobar degeneration with Tau deposition (FTLD-Tau) has not been explored. Here, we found that pathological Tau promotes early activation of PTEN, which precedes apoptotic caspase-3 cleavage in the rTg4510 mouse model of FTLD-Tau. We further demonstrate increased synaptic and neuronal exposure of the apoptotic signal phosphatidylserine that tags neuronal structures for microglial uptake, thereby linking PTEN activation to synaptic and neuronal structure elimination. By applying pharmacological inhibition of PTEN's protein phosphatase activity, we observed that microglial uptake can be decreased in Tau transgenic mice. Finally, we reveal a dichotomous relationship between PTEN activation and age in FTLD-Tau patients and healthy controls. Together, our findings suggest that in tauopathy, PTEN has a role in the synaptotoxicity of pathological Tau and promotes microglial removal of affected neuronal structures.