Medicine (Austin & Northern Health) - Research Publications
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ItemNo Preview AvailableINCREASED PLASMA NEUROFILAMENT LIGHT AND CEREBRAL ATROPHY IN PATIENTS WITH TYPE 2 DIABETES AND LEFT VENTRICULAR HYPERTROPHY(LIPPINCOTT WILLIAMS & WILKINS, 2023-01)
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ItemNo Preview AvailableChampioning Better Care for Young People with Stroke: Australia's New Young Stroke Service(Sage, 2023-08)Background: The Australian Stroke Clinical Registry collects information on national acute stroke care standards. Variation in care between hospitals impacts patient outcomes. Aims: To illustrate hospital performance in four priority areas of acute stroke care (stroke unit treatment, time to neuroimaging, thrombolysis door-to-needle time (DTNT), and swallowing assessments). Methods: Across 7 states/territories, 60 adult public hospitals provided 2021 data. Adherence was determined as the percentage of eligible patients treated. Funnel plots were used identify exceptional (>3 standard deviations above national average) and poor (>3 standard deviations below national average) performance. For continuous outcomes (neuroimaging timing or DTNT), we described hospitals with performance outside of the national interquartile range. Results: Overall, 16,458 episodes of stroke were analysed (median age 75 years, 43% female, 81% ischaemic). There were 27 hospitals with exceptional adherence to stroke unit care, 13 with poor adherence and 3 with no episodes treated in a stroke unit. Stroke unit treatment was less common in regional hospitals (68% vs metropolitan 80%, p<0.001). Median time from arrival to neuroimaging was 41 minutes, 2 hospitals were above the 75th percentile (>87 minutes) and 5 hospitals were below the 25th percentile (<20 minutes). Among 1320 patients with ischaemic stroke who received intravenous thrombolysis, the median DTNT was 77 minutes. Only 5 (8%) hospitals had a median DTNT ā©½60 minutes, 4 (7%) below the 25th percentile (56.5 minutes), while 18 (30%) had DTNT above the 75th percentile (107 minutes). Only 58% of all patients had their swallowing screened/assessed prior to oral intake; and 29% within 4 hours of arrival (9 hospitals with exceptional adherence; 12 with poor adherence). Conclusion: Despite strong evidence for recommended acute stroke care practices, there remains significant variation between Australian hospitals. The standardised registry data are essential to identifying areas for improvement against national benchmarks and to support stroke unit certification.
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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/kgāi.p.) or saline after 2 weeks of handling. Blood samples were collected before injection and before perfusion at 90āmin. 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 Ā± 0.3 mmol/L to 1.7 Ā± 0.2 mmol/L (meanāĀ± 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%āĀ± 1.4% (n = 8) of C1 neurons were Fos-positive. Insulin also induced Fos in 47.2%āĀ± 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 AĪ² 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 AĪ² accumulation using 18F-florbetaben PET. Quantitative thresholds for the early (SUVRearly) and established (SUVRestab) AĪ² deposition were developed, and the topography of early AĪ² deposition was assessed. Subsequently, AĪ² accumulation over time, progression from mild cognitive impairment (MCI) to AD dementia, and tau deposition were assessed in subjects with early and established AĪ² deposition. METHODS: The study population consisted of 686 subjects (nā=ā287 (cognitively normal healthy controls), nā=ā166 (subjects with subjective cognitive decline (SCD)), nā=ā129 (subjects with MCI), and nā=ā101 (subjects with AD dementia)). Three categories in the AĪ²-deposition continuum were defined based on the developed SUVR cutoffs: AĪ²-negative subjects, subjects with early AĪ² deposition ("gray zone"), and subjects with established AĪ² 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 AĪ² pathology accumulated more amyloid over time than AĪ²-negative subjects. After a 4-year clinical follow-up, none of the AĪ²-negative or the gray zone subjects progressed to AD dementia while 91% of the MCI subjects with established AĪ² pathology progressed. Tau deposition was infrequent in those subjects without established AĪ² 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 AĪ² 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 pā<ā.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.