Medicine (Austin & Northern Health) - Research Publications
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ItemNo Preview AvailableIS QUALITY OF LIFE RECOVERY ASSOCIATED WITH LOWER MORTALITY 5 YEARS POST-FRACTURE IN COMMUNITY-DWELLING OLDER ADULTS?(SPRINGER LONDON LTD, 2022-04)
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ItemOne-year risk of stroke after transient ischemic attack or minor stroke in Hunter New England, Australia (INSIST study)(CSIRO PUBLISHING, 2021-08-06)
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ItemExamining maintenance care following infliximab salvage therapy for acute severe ulcerative colitis(WILEY, 2018-01)BACKGROUND AND AIM: Data supporting the optimal maintenance drug therapy and strategy to monitor ongoing response following successful infliximab (IFX) induction, for acute severe ulcerative colitis (ASUC), are limited. We aimed to evaluate maintenance and monitoring strategies employed in patients post-IFX induction therapy. METHODS: Patients in six Australian tertiary centers treated with IFX for steroid-refractory ASUC between April 2014 and May 2015 were identified via hospital IBD and pharmacy databases. Patients were followed up for 1 year with clinical data over 12 months recorded. Analysis was limited to patient outcomes beyond 3 months. RESULTS: Forty one patients were identified. Five of the 41 (12%) patients underwent colectomy within 3 months, and one patient was lost to follow-up. Six of 35 (17%) of the remaining patients progressed to colectomy by 12 months. Maintenance therapy: Patients maintained on thiopurine monotherapy (14/35) versus IFX/thiopurine therapy (15/35) were followed up. Two of 15 (13%) patients who received combination maintenance therapy underwent a colectomy at 12 months, compared with 1/14 (7%) patients receiving thiopurine monotherapy (P = 0.610). Monitoring during maintenance: Post-discharge, thiopurine metabolites were monitored in 15/27 (56%); fecal calprotectin in 11/32 (34%); and serum IFX levels in 4/20 (20%). Twenty of 32 (63%) patients had an endoscopic evaluation after IFX salvage with median time to first endoscopy of 109 days (interquartile range 113-230). CONCLUSION: Following IFX induction therapy for ASUC, the uptake of maintenance therapy in this cohort and strategies to monitor ongoing response were variable. These data suggest that the optimal maintenance and monitoring strategy post-IFX salvage therapy remains to be defined.
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ItemCerebrovascular disease, Alzheimer's disease biomarkers and longitudinal cognitive decline(WILEY-BLACKWELL, 2016-06)
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ItemInsulin-responsive autonomic neurons in rat medulla oblongata(WILEY, 2018-11-01)Low blood glucose activates brainstem adrenergic and cholinergic neurons, driving adrenaline secretion from the adrenal medulla and glucagon release from the pancreas. Despite their roles in maintaining glucose homeostasis, the distributions of insulin-responsive adrenergic and cholinergic neurons in the medulla are unknown. We fasted rats overnight and gave them insulin (10 U/kg i.p.) or saline after 2 weeks of handling. Blood samples were collected before injection and before perfusion at 90 min. We immunoperoxidase-stained transverse sections of perfused medulla to show Fos plus either phenylethanolamine N-methyltransferase (PNMT) or choline acetyltransferase (ChAT). Insulin injection lowered blood glucose from 4.9 ± 0.3 mmol/L to 1.7 ± 0.2 mmol/L (mean ± SEM; n = 6); saline injection had no effect. In insulin-treated rats, many PNMT-immunoreactive C1 neurons had Fos-immunoreactive nuclei, with the proportion of activated neurons being highest in the caudal part of the C1 column. In the rostral ventrolateral medulla, 33.3% ± 1.4% (n = 8) of C1 neurons were Fos-positive. Insulin also induced Fos in 47.2% ± 2.0% (n = 5) of dorsal medullary C3 neurons and in some C2 neurons. In the dorsal motor nucleus of the vagus (DMV), insulin evoked Fos in many ChAT-positive neurons. Activated neurons were concentrated in the medial and middle regions of the DMV beneath and just rostral to the area postrema. In control rats, very few C1, C2, or C3 neurons and no DMV neurons were Fos-positive. The high numbers of PNMT-immunoreactive and ChAT-immunoreactive neurons that express Fos after insulin treatment reinforce the importance of these neurons in the central response to a decrease in glucose bioavailability.
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ItemEarly detection of amyloid load using 18F-florbetaben PET(BMC, 2021-03-27)BACKGROUND: A low amount and extent of Aβ deposition at early stages of Alzheimer's disease (AD) may limit the use of previously developed pathology-proven composite SUVR cutoffs. This study aims to characterize the population with earliest abnormal Aβ accumulation using 18F-florbetaben PET. Quantitative thresholds for the early (SUVRearly) and established (SUVRestab) Aβ deposition were developed, and the topography of early Aβ deposition was assessed. Subsequently, Aβ accumulation over time, progression from mild cognitive impairment (MCI) to AD dementia, and tau deposition were assessed in subjects with early and established Aβ deposition. METHODS: The study population consisted of 686 subjects (n = 287 (cognitively normal healthy controls), n = 166 (subjects with subjective cognitive decline (SCD)), n = 129 (subjects with MCI), and n = 101 (subjects with AD dementia)). Three categories in the Aβ-deposition continuum were defined based on the developed SUVR cutoffs: Aβ-negative subjects, subjects with early Aβ deposition ("gray zone"), and subjects with established Aβ pathology. RESULTS: SUVR using the whole cerebellum as the reference region and centiloid (CL) cutoffs for early and established amyloid pathology were 1.10 (13.5 CL) and 1.24 (35.7 CL), respectively. Cingulate cortices and precuneus, frontal, and inferior lateral temporal cortices were the regions showing the initial pathological tracer retention. Subjects in the "gray zone" or with established Aβ pathology accumulated more amyloid over time than Aβ-negative subjects. After a 4-year clinical follow-up, none of the Aβ-negative or the gray zone subjects progressed to AD dementia while 91% of the MCI subjects with established Aβ pathology progressed. Tau deposition was infrequent in those subjects without established Aβ pathology. CONCLUSIONS: This study supports the utility of using two cutoffs for amyloid PET abnormality defining a "gray zone": a lower cutoff of 13.5 CL indicating emerging Aβ pathology and a higher cutoff of 35.7 CL where amyloid burden levels correspond to established neuropathology findings. These cutoffs define a subset of subjects characterized by pre-AD dementia levels of amyloid burden that precede other biomarkers such as tau deposition or clinical symptoms and accelerated amyloid accumulation. The determination of different amyloid loads, particularly low amyloid levels, is useful in determining who will eventually progress to dementia. Quantitation of amyloid provides a sensitive measure in these low-load cases and may help to identify a group of subjects most likely to benefit from intervention. TRIAL REGISTRATION: Data used in this manuscript belong to clinical trials registered in ClinicalTrials.gov ( NCT00928304 , NCT00750282 , NCT01138111 , NCT02854033 ) and EudraCT (2014-000798-38).
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ItemClinical outcomes following ST-elevation myocardial infarction secondary to stent thrombosis treated by percutaneous coronary intervention(WILEY, 2020-10-01)OBJECTIVES: To assess the clinical outcomes of patients presenting with ST-elevation myocardial infarction (STEMI) secondary to stent thrombosis (ST) compared to those presenting with STEMI secondary to a de novo culprit lesion and treated by percutaneous coronary intervention (PCI). BACKGROUND: ST is an infrequent but serious complication of PCI with substantial associated morbidity and mortality, however with limited data. METHODS: We studied consecutive patients who underwent PCI for STEMI from 2005 to 2013 enrolled prospectively in the Melbourne Interventional Group registry. Patients were divided into two groups: the ST group comprised patients where the STEMI was due to ST and the de novo group formed the remainder of the STEMI cohort and all patients were treated by PCI. The primary endpoint was 30-day all-cause mortality. RESULTS: Compared to the de novo group (n = 3,835), the ST group (n = 128; 3.2% of STEMI) had higher rates of diabetes, hypertension and dyslipidemia, established cardiovascular diseases, myocardial infarction, and peripheral vascular disease, all p < .01. Within the ST group, very-late ST was the most common form of ST, followed by late and early ST (64, 19, and 17%, respectively). There was no significant difference in the primary outcome between the ST group and the de novo group (4.7 vs. 7.1%, p = .29). On multivariate analysis, ST was not an independent predictor of 30-day mortality (odds ratio: 0.62, 95% confidence interval: 0.07-1.09, p = .068). CONCLUSION: The short-term prognosis of patients with STEMI secondary to ST who were treated by PCI was comparable to that of patients with STEMI due to de novo lesions.
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ItemNo Preview Available'Willingness to Pay': The Value Attributed to Program Location by Pulmonary Rehabilitation Participants(American Thoracic Society, 2020-01-01)
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ItemSUN-039 Estradiol Dose and Concentrations in Transfeminine Individuals(The Endocrine Society, 2020-05)Abstract Background: Feminizing hormone therapy with estradiol is used to align an individual’s physical characteristics with their gender identity. Australian expert consensus guidelines (1) recommend targeting estradiol concentrations of 250-600 pmol/L (68-163 pg/mL) based on local cross-sectional data (2). We aimed to establish the proportion of individuals achieving estradiol concentrations in consensus guidelines. Methods: A retrospective cross-sectional analysis was performed of transfeminine individuals attending a primary or secondary care clinic in Melbourne, Australia who were prescribed oral estradiol valerate for at least 6 months and had estradiol dose and concentration available. Estradiol concentration was measured by immunoassay. Outcomes were (1) proportion of individuals achieving target estradiol concentrations and (2) influence of estradiol dose and BMI on estradiol concentrations. Results: 259 individuals (median age 25.8(IQR 21.9,33.5) years)) had data available for analysis. Median duration of estradiol therapy was 24(15,33) months. Median estradiol concentration was 328(238,434) pmol/L (89(65,118) pg/mL) on 6(4,8) mg estradiol valerate. 172 (66%) individuals had estradiol concentrations within the target range recommended in consensus guidelines. 70 (27%) individuals had estradiol concentrations below target, and 17 (7%) above target. There was a weak positive correlation between estradiol dose and estradiol concentration (r=0.156, p=0.012). There was no correlation between BMI and estradiol concentration achieved (r=-0.063, p=0.413). Conclusions: 66% of individuals achieved estradiol concentration recommended in consensus guidelines with a relatively high oral estradiol dose. There was significant interindividual variability. Estradiol concentration should be interpreted in conjunction with clinical features of feminization and weighed against potential risks of escalating estradiol dose. References 1. Cheung AS, Wynne K, Erasmus J, Murray S, Zajac JD. Position statement on the hormonal management of adult transgender and gender diverse individuals. Med J Aust 2019; 211:127-133 2. Angus L, Leemaqz SY, Ooi O, Cundill P, Silberstein N, Locke P, Zajac JD, Cheung AS. Cyproterone acetate or spironolactone in lowering testosterone concentrations for transgender individuals receiving estradiol therapy. Endocr Connect 2019