Medicine (Austin & Northern Health) - Research Publications
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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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ItemIMPLEMENTATION OF "GOALS OF PATIENT CARE" MEDICAL TREATMENT ORDERS IN RESIDENTIAL AGED CARE FACILITIES: A RANDOMISED CONTROLLED TRIAL(OXFORD UNIV PRESS, 2016-09)INTRODUCTION: Systematic reviews demonstrate that advance care planning (ACP) has many positive effects for residents of aged care facilities, including decreased hospitalisation. The proposed Residential Aged Care Facility (RACF) 'Goals of Patient Care' (GOPC) form incorporates a resident's prior advance care plan into medical treatment orders. Where none exists, it captures residents' preferences. This documentation helps guide healthcare decisions made at times of acute clinical deterioration. METHODS AND ANALYSIS: This is a mixed methods study. An unblinded cluster randomised controlled trial is proposed in three pairs of RACFs. In the intervention arm, GOPC forms will be completed by a doctor incorporating advance care plans or wishes. In the control arm, residents will have usual care which may include an advance care plan. The primary hypothesis is that the GOPC form is superior to standard ACP alone and will lead to decreased hospitalisation due to clearer documentation of residents' medical treatment plans. The primary outcome will be an analysis of the effect of the GOPC medical treatment orders on emergency department attendances and hospital admissions at 6 months. Secondary outcome measurements will include change in hospitalisation rates at 3 and 12 months, length of stay and external mortality rates among others. Qualitative interviews, 12 months post GOPC implementation, will be used for process evaluation of the GOPC and to evaluate staff perceptions of the form's usefulness for improving communication and medical decision-making at a time of deterioration. DISSEMINATION: The results will be disseminated in peer review journals and research conferences. This robust randomised controlled trial will provide high-quality data about the influence of medical treatment orders that incorporate ACP or preferences adding to the current gap in knowledge and evidence in this area. TRIAL REGISTRATION NUMBER: ACTRN12615000298516, Results.
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ItemClinical course, therapeutic responses and outcomes in relapsing MOG antibody-associated demyelination(BMJ PUBLISHING GROUP, 2018-02)OBJECTIVE: We characterised the clinical course, treatment and outcomes in 59 patients with relapsing myelin oligodendrocyte glycoprotein (MOG) antibody-associated demyelination. METHODS: We evaluated clinical phenotypes, annualised relapse rates (ARR) prior and on immunotherapy and Expanded Disability Status Scale (EDSS), in 218 demyelinating episodes from 33 paediatric and 26 adult patients. RESULTS: The most common initial presentation in the cohort was optic neuritis (ON) in 54% (bilateral (BON) 32%, unilateral (UON) 22%), followed by acute disseminated encephalomyelitis (ADEM) (20%), which occurred exclusively in children. ON was the dominant phenotype (UON 35%, BON 19%) of all clinical episodes. 109/226 (48%) MRIs had no brain lesions. Patients were steroid responsive, but 70% of episodes treated with oral prednisone relapsed, particularly at doses <10 mg daily or within 2 months of cessation. Immunotherapy, including maintenance prednisone (P=0.0004), intravenous immunoglobulin, rituximab and mycophenolate, all reduced median ARRs on-treatment. Treatment failure rates were lower in patients on maintenance steroids (5%) compared with non-steroidal maintenance immunotherapy (38%) (P=0.016). 58% of patients experienced residual disability (average follow-up 61 months, visual loss in 24%). Patients with ON were less likely to have sustained disability defined by a final EDSS of ≥2 (OR 0.15, P=0.032), while those who had any myelitis were more likely to have sustained residual deficits (OR 3.56, P=0.077). CONCLUSION: Relapsing MOG antibody-associated demyelination is strongly associated with ON across all age groups and ADEM in children. Patients are highly responsive to steroids, but vulnerable to relapse on steroid reduction and cessation.
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ItemNo Preview AvailableAcoustic monitoring of speech impairment in motor neuron disease associated with frontotemporal dementia: a case series(European Journal of Neurology, 2016)Frontotemporal dementia is the second most common form of younger onset dementia. A subset of people with this disorder develop motor neuron disease (MND) with associated speech impairment (dysarthria). Here, we aim to measure the progression of dysarthria in a case of FTD-MND with acoustic analysis. Four individuals with FTD (one developing concomitant MND) were longitudinally assessed over two years. Two acoustic measures demonstrated capacity to objectively monitor dysarthria in FTD-MND. These preliminary data highlight potential for the clinical use of these methods to identify the initial signs of bulbar onset motor neuron disease. Index terms: acoustics, disease monitoring, dysarthria, frontotemporal dementia, motor neuron disease.
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ItemNo Preview AvailableQuantification of motor speech in primary progressive aphasia and frontotemporal dementia(WILEY-BLACKWELL, 2016-08-01)Frontotemporal dementia (FTD) and primary progressive aphasia (PPA) are two groups of related disorders which are classified into the behavioural (bvFTD), semantic (svPPA), nonfluent/agrammatic (nfvPPA) and logopaenic (lvPPA) variants. Each variant presents with characteristic impairments of communication or behaviour, and the defining features of the syndromes are under ongoing debate in the literature. Researchers and clinicians usually assess speech with listener-based rating scales, which pose a challenge for identifying subtle changes to speech. Objective measures of speech may therefore improve characterisation of speech impairments in the literature and assist in clinical diagnosis and management. In this study, speech samples were taken from 43 people with PPA or FTD (8 svPPA, 4 nfvPPA, 9 lvPPA, 22 bvFTD) and 24 healthy controls. Speech was analysed perceptually using a 5-point rating scale across all speech subsystems. Speech was objectively quantified with measures of lexical stress (the pairwise variability index, PVI), vowel production, timing, voice quality and diadochokinetic (DDK) speech rate. The ability of speech measures to predict regions of neurodegeneration was assessed by comparison of speech to calculations of cortical thickness and subcortical volume derived from participants’ clinical magnetic resonance imaging (MRI) scans. Longitudinal speech investigations were conducted for a subgroup of participants to investigate the capacity of the measures to track disease progression. Group comparisons indicated that several speech measures differentiate pathological groups from controls, including measures of speech timing, DDK rate, and PVI. PVI and DDK also differentiated the nfvPPA group from other subtypes. Case studies of longitudinal data highlight measures which reflect motor speech changes in a case of bvFTD progressing to motor neurone disease (MND), and in two cases of nfvPPA. Findings add to the documentation of speech production in PPA and FTD by establishing acoustic correlates which differ from the healthy population. Longitudinal case studies demonstrate the potential for these measures to be used clinically to improve monitoring of disease progression.