Medicine (RMH) - Research Publications

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    The Australian Multiple Sclerosis (MS) Immunotherapy Study: A Prospective, Multicentre Study of Drug Utilisation Using the MSBase Platform
    Jokubaitis, VG ; Spelman, T ; Lechner-Scott, J ; Barnett, M ; Shaw, C ; Vucic, S ; Liew, D ; Butzkueven, H ; Slee, M ; Oreja-Guevara, C (PUBLIC LIBRARY SCIENCE, 2013-03-19)
    OBJECTIVE: To prospectively characterise treatment persistence and predictors of treatment discontinuation in an Australian relapsing-remitting multiple sclerosis (RRMS) population. METHODS: Tertiary MS treatment centres participating in the MSBase registry prospectively assessed treatment utilisation, persistence, predictors of treatment discontinuation and switch rates. Multivariable survival analyses were used to compare treatment persistence between drugs and to identify predictors of treatment discontinuation. RESULTS: 1113 RRMS patients were studied. Patients persisted on their first disease-modifying therapy (DMT) for a median of 2.5 years. Treatment persistence on GA was shorter than on all IFNβ products (p<0.03). Younger age at treatment initiation and higher EDSS were predictive of DMT discontinuation. Patients persisted on subsequent DMTs, for 2.3 years. Patients receiving natalizumab (NAT) as a subsequent DMT persisted longer on treatment than those on IFNβ or GA (p<0.000). The primary reason for treatment discontinuation for any drug class was poor tolerability. Annualised switch or cessation rates were 9.5-12.5% for individual IFNβ products, 11.6% for GA and 4.4% for NAT. CONCLUSION: This multicentre MS cohort study is the first to directly compare treatment persistence on IFNβ and GA to NAT. We report that treatment persistence in our Australian RRMS population is short, although patients receiving IFNβ as a first DMT persisted longer on treatment than those on GA. Additionally, patients receiving NAT as a subsequent DMT were more likely to persist on treatment than those switched to IFNβ or GA. EDSS and age at DMT initiation were predictive of DMT discontinuation. Treatment intolerance was the principal reason for treatment cessation.
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    Perfusion CT in acute stroke: A comprehensive analysis of infarct and penumbra
    BIVARD, ANDREW ; LEVI, CHRISTOPER ; SPRATT, NEIL ; PARSONS, MARK ( 2013)
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    Systematic review of multidisciplinary rehabilitation in patients with multiple trauma
    Khan, F ; Amatya, B ; Hoffman, K (WILEY, 2012-01-01)
    BACKGROUND: Multiple trauma is a cause of significant disability in adults of working age. Despite the implementation of trauma systems for improved coordination and organization of care, rehabilitation services are not yet routinely considered integral to trauma care processes. METHODS: MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine, Physiotherapy Evidence Database, Latin American and Caribbean Literature on Health Sciences and Cochrane Library databases were searched up to May 2011 for randomized clinical trials, as well as observational studies, reporting outcomes of injured patients following multidisciplinary rehabilitation that addressed functional restoration and societal reintegration based on the International Classification of Functioning, Disability and Health. RESULTS: No randomized and/or controlled clinical trials were identified. Fifteen observational studies involving 2386 participants with injuries were included. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach assessed methodological quality as 'poor' in all studies, with selection and observer bias. Although patients with low functional scores showed improvement after rehabilitation, they were unable to resume their pretrauma level of activity. Their functional ability was significantly associated with motor independence on admission and early acute rehabilitation, which contributed to a shorter hospital stay. Injury location, age, co-morbidity and education predicted long-term functional consequences. Trauma care systems were associated with reduced mortality. The gaps in evidence include: rehabilitation settings, components, intensity, duration and types of therapy, and long-term outcomes for survivors of multiple trauma. CONCLUSION: Rehabilitation is an expensive resource and the evidence to support its justification is needed urgently. The issues in study design and research methodology in rehabilitation are challenging. Opportunities to prioritize trauma rehabilitation, disability management and social reintegration of multiple injury survivors are discussed.
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    Defining the Extent of Irreversible Brain Ischemia Using Perfusion Computed Tomography
    Bivard, A ; McElduff, P ; Spratt, N ; Levi, C ; Parsons, M (KARGER, 2011-01-01)
    BACKGROUND: Perfusion computed tomography (PCT) shows promise in acute stroke assessment. However, the accuracy of CT perfusion thresholds in defining the acute infarct core remains uncertain. METHOD: Concurrent PCT and MRI-DWI performed 3-6 h after symptoms onset were assessed in 57 ischemic stroke patients. PCT was compared to DWI images to define the infarct core using a pixel-based receiver operating characteristic curve analysis to calculate the area under the curve (AUC) for thresholds from PCT maps that were co-registered with the DWI slice location. RESULTS: A relative cerebral blood flow (CBF) of 45% of the contralateral hemisphere was found to be the most accurate threshold for describing the infarct core (AUC 0.788), and it was also by far the most frequent threshold with the highest AUC across patients. CONCLUSION: CBF thresholds on PCT define the acute infarct core more accurately than do other PCT thresholds, including a cerebral blood volume of 2 ml/100 g.
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    Home Time Is Extended in Patients With Ischemic Stroke Who Receive Thrombolytic Therapy A Validation Study of Home Time as an Outcome Measure
    Mishra, NK ; Shuaib, A ; Lyden, P ; Diener, H-C ; Grotta, J ; Davis, S ; Davalos, A ; Ashwood, T ; Wasiewski, W ; Lees, KR (LIPPINCOTT WILLIAMS & WILKINS, 2011-04-01)
    BACKGROUND AND PURPOSE: "Home time" (HT) refers to the number of days over the first 90 after stroke onset that a patient spends residing in their own home or a relative's home versus any institutional care. It is an accessible and objective parameter, free from subjective bias, with potential as an outcome measure in acute stroke trials. We sought to validate HT and assess treatment responsiveness using independent data. METHODS: We estimated HT in the Stroke Acute Ischemic NXY Treatment (SAINT) I neuroprotection trial. We compared outcomes between thrombolyzed (T) and nonthrombolyzed comparators (C) using HT and the modified Rankin Scale. For our primary analysis, we adjusted for baseline covariates that significantly influence HT and in sensitivity analyses considered all variables that differed between groups at baseline. We report ordinal logistic regression and analysis of covariance with 95% CIs. We describe the relationship of HT with baseline National Institutes of Health Stroke Scale and its components and with Day 90 modified Rankin Scale and Barthel Index. RESULTS: SAINT I included 1699 patients from 23 countries, of whom 28.7% received alteplase. HT correlated with age, baseline severity, alteplase use, side of ischemic lesion, presence of diabetes, and country of patient enrollment (each P<0.05). We found an association between use of alteplase with better adjusted outcomes by either measure (OR for extended HT, 1.36; 95% CI, 1.08 to 1.72; P=0.009; analysis of covariance P=0.007 with a 5.5-day advantage; OR for more favorable modified Rankin Scale, 1.6; 95% CI, 1.28 to 2.00; P<0.0001; Cochran-Mantel-Haenszel P=0.046). HT was significantly associated with baseline National Institutes of Health Stroke Scale and each component of the National Institutes of Health Stroke Scale except level of consciousness, dysarthria, and ataxia. HT was significantly associated with Day 90 modified Rankin Scale and Barthel Index. CONCLUSIONS: HT is a responsive measure for use in multinational acute stroke trials. Its inclusion as a complementary outcome is reasonable. We propose treatment effects are adjusted for age, baseline National Institutes of Health Stroke Scale, side of stroke lesion, country of enrollment, and the presence of diabetes.