Physiotherapy - Research Publications

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    Structural MRI markers of brain aging early after ischemic stroke
    Werden, E ; Cumming, T ; Li, Q ; Bird, L ; Veldsman, M ; Pardoe, HR ; Jackson, G ; Donnan, GA ; Brodtmann, A (LIPPINCOTT WILLIAMS & WILKINS, 2017-07-11)
    OBJECTIVE: To examine associations between ischemic stroke, vascular risk factors, and MRI markers of brain aging. METHODS: Eighty-one patients (mean age 67.5 ± 13.1 years, 31 left-sided, 61 men) with confirmed first-ever (n = 66) or recurrent (n = 15) ischemic stroke underwent 3T MRI scanning within 6 weeks of symptom onset (mean 26 ± 9 days). Age-matched controls (n = 40) completed identical testing. Multivariate regression analyses examined associations between group membership and MRI markers of brain aging (cortical thickness, total brain volume, white matter hyperintensity [WMH] volume, hippocampal volume), normalized against intracranial volume, and the effects of vascular risk factors on these relationships. RESULTS: First-ever stroke was associated with smaller hippocampal volume (p = 0.025) and greater WMH volume (p = 0.004) relative to controls. Recurrent stroke was in turn associated with smaller hippocampal volume relative to both first-ever stroke (p = 0.017) and controls (p = 0.001). These associations remained significant after adjustment for age, sex, education, and, in stroke patients, infarct volume. Total brain volume was not significantly smaller in first-ever stroke patients than in controls (p = 0.056), but the association became significant after further adjustment for atrial fibrillation (p = 0.036). Cortical thickness and brain volumes did not differ as a function of stroke type, infarct volume, or etiology. CONCLUSIONS: Brain structure is likely to be compromised before ischemic stroke by vascular risk factors. Smaller hippocampal and total brain volumes and increased WMH load represent proxies for underlying vascular brain injury.
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    STROKOG (stroke and cognition consortium): An international consortium to examine the epidemiology, diagnosis, and treatment of neurocognitive disorders in relation to cerebrovascular disease.
    Sachdev, PS ; Lo, JW ; Crawford, JD ; Mellon, L ; Hickey, A ; Williams, D ; Bordet, R ; Mendyk, A-M ; Gelé, P ; Deplanque, D ; Bae, H-J ; Lim, J-S ; Brodtmann, A ; Werden, E ; Cumming, T ; Köhler, S ; Verhey, FRJ ; Dong, Y-H ; Tan, HH ; Chen, C ; Xin, X ; Kalaria, RN ; Allan, LM ; Akinyemi, RO ; Ogunniyi, A ; Klimkowicz-Mrowiec, A ; Dichgans, M ; Wollenweber, FA ; Zietemann, V ; Hoffmann, M ; Desmond, DW ; Linden, T ; Blomstrand, C ; Fagerberg, B ; Skoog, I ; Godefroy, O ; Barbay, M ; Roussel, M ; Lee, B-C ; Yu, K-H ; Wardlaw, J ; Makin, SJ ; Doubal, FN ; Chappell, FM ; Srikanth, VK ; Thrift, AG ; Donnan, GA ; Kandiah, N ; Chander, RJ ; Lin, X ; Cordonnier, C ; Moulin, S ; Rossi, C ; Sabayan, B ; Stott, DJ ; Jukema, JW ; Melkas, S ; Jokinen, H ; Erkinjuntti, T ; Mok, VCT ; Wong, A ; Lam, BYK ; Leys, D ; Hénon, H ; Bombois, S ; Lipnicki, DM ; Kochan, NA ; STROKOG, (Wiley, 2017)
    INTRODUCTION: The Stroke and Cognition consortium (STROKOG) aims to facilitate a better understanding of the determinants of vascular contributions to cognitive disorders and help improve the diagnosis and treatment of vascular cognitive disorders (VCD). METHODS: Longitudinal studies with ≥75 participants who had suffered or were at risk of stroke or TIA and which evaluated cognitive function were invited to join STROKOG. The consortium will facilitate projects investigating rates and patterns of cognitive decline, risk factors for VCD, and biomarkers of vascular dementia. RESULTS: Currently, STROKOG includes 25 (21 published) studies, with 12,092 participants from five continents. The duration of follow-up ranges from 3 months to 21 years. DISCUSSION: Although data harmonization will be a key challenge, STROKOG is in a unique position to reuse and combine international cohort data and fully explore patient level characteristics and outcomes. STROKOG could potentially transform our understanding of VCD and have a worldwide impact on promoting better vascular cognitive outcomes.
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    Does left ventricular hypertrophy affect cognition and brain structural integrity in type 2 diabetes? Study design and rationale of the Diabetes and Dementia (D2) study
    Patel, SK ; Restrepo, C ; Werden, E ; Churilov, L ; Ekinci, EI ; Srivastava, PM ; Ramchand, J ; Wai, B ; Chambers, B ; O'Callaghan, CJ ; Darby, D ; Hachinski, V ; Cumming, T ; Donnan, G ; Burrell, LM ; Brodtmann, A (BMC, 2017-04-07)
    BACKGROUND: Cognitive impairment is common in type 2 diabetes mellitus, and there is a strong association between type 2 diabetes and Alzheimer's disease. However, we do not know which type 2 diabetes patients will dement or which biomarkers predict cognitive decline. Left ventricular hypertrophy (LVH) is potentially such a marker. LVH is highly prevalent in type 2 diabetes and is a strong, independent predictor of cardiovascular events. To date, no studies have investigated the association between LVH and cognitive decline in type 2 diabetes. The Diabetes and Dementia (D2) study is designed to establish whether patients with type 2 diabetes and LVH have increased rates of brain atrophy and cognitive decline. METHODS: The D2 study is a single centre, observational, longitudinal case control study that will follow 168 adult patients aged >50 years with type 2 diabetes: 50% with LVH (case) and 50% without LVH (control). It will assess change in cardiovascular risk, brain imaging and neuropsychological testing between two time-points, baseline (0 months) and 24 months. The primary outcome is brain volume change at 24 months. The co-primary outcome is the presence of cognitive decline at 24 months. The secondary outcome is change in left ventricular mass associated with brain atrophy and cognitive decline at 24 months. DISCUSSION: The D2 study will test the hypothesis that patients with type 2 diabetes and LVH will exhibit greater brain atrophy than those without LVH. An understanding of whether LVH contributes to cognitive decline, and in which patients, will allow us to identify patients at particular risk. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ( ACTRN12616000546459 ), date registered, 28/04/2016.
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    CHRISTMAS 2015: PROFESSIONAL CONSIDERATIONS AVERT2 (a very early rehabilitation trial, a very effective reproductive trigger): retrospective observational analysis of the number of babies born to trial staff
    Bernhardt, J ; Lindley, RI ; Lalor, E ; Ellery, F ; Chamberlain, J ; Van Holsteyn, J ; Collier, JM ; Dewey, HM ; Parsons, B ; Moodie, M ; Lennon, S ; Donnan, GA ; Thrift, AG ; Churilov, L ; Langhorne, P (BMJ PUBLISHING GROUP, 2015-12-11)
    OBJECTIVE: To report the number of participants needed to recruit per baby born to trial staff during AVERT, a large international trial on acute stroke, and to describe trial management consequences. DESIGN: Retrospective observational analysis. SETTING: 56 acute stroke hospitals in eight countries. PARTICIPANTS: 1074 trial physiotherapists, nurses, and other clinicians. OUTCOME MEASURES: Number of babies born during trial recruitment per trial participant recruited. RESULTS: With 198 site recruitment years and 2104 patients recruited during AVERT, 120 babies were born to trial staff. Births led to an estimated 10% loss in time to achieve recruitment. Parental leave was linked to six trial site closures. The number of participants needed to recruit per baby born was 17.5 (95% confidence interval 14.7 to 21.0); additional trial costs associated with each birth were estimated at 5736 Australian dollars on average. CONCLUSION: The staff absences registered in AVERT owing to parental leave led to delayed trial recruitment and increased costs, and should be considered by trial investigators when planning research and estimating budgets. However, the celebration of new life became a highlight of the annual AVERT collaborators' meetings and helped maintain a cohesive collaborative group. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry no 12606000185561. DISCLAIMER: Participation in a rehabilitation trial does not guarantee successful reproductive activity.
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    Efficacy and safety of very early mobilisation within 24 h of stroke onset (AVERT): a randomised controlled trial
    Bernhardt, J ; Langhorne, P ; Lindley, RI ; Thrift, AG ; Ellery, F ; Collier, J ; Churilov, L ; Moodie, M ; Dewey, H ; Donnan, G (ELSEVIER SCIENCE INC, 2015-07-04)
    BACKGROUND: Early mobilisation after stroke is thought to contribute to the effects of stroke-unit care; however, the intervention is poorly defined and not underpinned by strong evidence. We aimed to compare the effectiveness of frequent, higher dose, very early mobilisation with usual care after stroke. METHODS: We did this parallel-group, single-blind, randomised controlled trial at 56 acute stroke units in five countries. Patients (aged ≥18 years) with ischaemic or haemorrhagic stroke, first or recurrent, who met physiological criteria were randomly assigned (1:1), via a web-based computer generated block randomisation procedure (block size of six), to receive usual stroke-unit care alone or very early mobilisation in addition to usual care. Treatment with recombinant tissue plasminogen activator was allowed. Randomisation was stratified by study site and stroke severity. Patients, outcome assessors, and investigators involved in trial and data management were masked to treatment allocation. The primary outcome was a favourable outcome 3 months after stroke, defined as a modified Rankin Scale score of 0-2. We did analysis on an intention-to-treat basis. The trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12606000185561. FINDINGS: Between July 18, 2006, and Oct 16, 2014, we randomly assigned 2104 patients to receive either very early mobilisation (n=1054) or usual care (n=1050); 2083 (99%) patients were included in the 3 month follow-up assessment. 965 (92%) patients were mobilised within 24 h in the very early mobilisation group compared with 623 (59%) patients in the usual care group. Fewer patients in the very early mobilisation group had a favourable outcome than those in the usual care group (n=480 [46%] vs n=525 [50%]; adjusted odds ratio [OR] 0·73, 95% CI 0·59-0·90; p=0·004). 88 (8%) patients died in the very early mobilisation group compared with 72 (7%) patients in the usual care group (OR 1·34, 95% CI 0·93-1·93, p=0·113). 201 (19%) patients in the very early mobilisation group and 208 (20%) of those in the usual care group had a non-fatal serious adverse event, with no reduction in immobility-related complications with very early mobilisation. INTERPRETATION: First mobilisation took place within 24 h for most patients in this trial. The higher dose, very early mobilisation protocol was associated with a reduction in the odds of a favourable outcome at 3 months. Early mobilisation after stroke is recommended in many clinical practice guidelines worldwide, and our findings should affect clinical practice by refining present guidelines; however, clinical recommendations should be informed by future analyses of dose-response associations. FUNDING: National Health and Medical Research Council, Singapore Health, Chest Heart and Stroke Scotland, Northern Ireland Chest Heart and Stroke, UK Stroke Association, National Institute of Health Research.