Prespecified dose-response analysis for a very early rehabilitation trial (AVERT)

Bernhardt, J., Churilov, L., Ellery, F., Collier, J., Chamberlain, J., Langhorne, P. , Lindley, R. I., Moodie, M., Dewey, H. and Thrift, A. G. (2016) Prespecified dose-response analysis for a very early rehabilitation trial (AVERT). Neurology, 86(23), pp. 2138-2145. (doi: 10.1212/wnl.0000000000002459) (PMID:26888985) (PMCID:PMC4898313)

Abstract

Objective: Our prespecified dose-response analyses of A Very Early Rehabilitation Trial (AVERT) aim to provide practical guidance for clinicians on the timing, frequency, and amount of mobilization following acute stroke. Methods: Eligible patients were aged ≥18 years, had confirmed first (or recurrent) stroke, and were admitted to a stroke unit within 24 hours of stroke onset. Patients were randomized to receive very early and frequent mobilization, commencing within 24 hours, or usual care. We used regression analyses and Classification and Regression Trees (CART) to investigate the effect of timing and dose of mobilization on efficacy and safety outcomes, irrespective of assigned treatment group. Results: A total of 2,104 patients were enrolled, of whom 2,083 (99.0%) were followed up at 3 months. We found a consistent pattern of improved odds of favorable outcome in efficacy and safety outcomes with increased daily frequency of out-of-bed sessions (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.09 to 1.18, p < 0.001), keeping time to first mobilization and mobilization amount constant. Increased amount (minutes per day) of mobilization reduced the odds of a good outcome (OR 0.94, 95% CI 0.91 to 0.97, p < 0.001). Session frequency was the most important variable in the CART analysis, after prognostic variables age and baseline stroke severity. Conclusion: These data suggest that shorter, more frequent mobilization early after acute stroke is associated with greater odds of favorable outcome at 3 months when controlling for age and stroke severity. Classification of evidence: This study provides Class III evidence that shorter, more frequent early mobilization improves the chance of regaining independence after stroke.

• Item Type: Articles
• Additional Information: The trial was supported by the National Health and Medical Research Council (NHMRC) of Australia (project grant nos.: 386201, 1041401). Additional funding was received from Chest Heart and Stroke Scotland (Res08/A114), Northern Ireland Chest Heart and Stroke, Table 4 Effect of intervention characteristics on death and nonfatal serious adverse events Safety Deaths Nonfatal SAEs Fatal or nonfatal neurologic SAEs Fatal or nonfatal immobility SAEs Binary OR (95% CI) p Value IRR (95% CI) p Value IRR (95% CI) p Value IRR (95% CI) p Value Model 1 Time to first mobilization (per extra hour) 0.99 (0.98–1.00) 0.07 1.0 (0.99–1.00) 0.71 1.0 (0.99–1.00) 0.45 1.00 (0.99–1.00) 0.59 Frequency, median daily sessionsa (per one extra session) 0.78 (0.70–0.88) ,0.01 0.99 (0.95–1.03) 0.55 0.89 (0.84–0.95) 0.001 0.94 (0.87–1.01) 0.11 Daily amount, medianb (per extra 5 minutes) 0.96 (0.89–1.04) 0.30 0.96 (0.93–0.99) 0.01 1.03 (0.99–1.08) 0.17 0.94 (0.89–1.00) 0.06 Model 2 Time to first mobilization (per extra hour) 0.99 (0.98–1.00) 0.07 0.99 (0.99–1.00) 0.81 1.00 (0.99–1.00) 0.35 1.00 (0.99–1.00) 0.59 Frequency, median daily sessionsa (per one extra session) 0.79 (0.71–0.88) ,0.01 0.96 (0.93–0.99) 0.02 0.93 (0.88–0.98) ,0.01 0.91 (0.85–0.97) ,0.01 Total amountb (per extra 5 minutes over intervention period) 0.99 (0.98–1.00) 0.06 1.00 (1.00–1.00) 0.49 1.00 (0.99–1.00) 0.32 1.0 (0.99–1.00) 0.41 Abbreviations: CI 5 confidence interval; IRR 5 incident rate ratio; OR 5 odds ratio; SAE 5 serious adverse event. All analyses are adjusted for age and baseline NIH Stroke Scale score. Two models are shown. Model 1 includes examination of the effect of an extra 5 minutes of out-of-bed activity per day, while model 2 includes examination of the effect of an extra 5 minutes of out-of-bed activity over the intervention period to account for differences in length of hospital stay. Immobility-related SAEs included deep vein thrombosis, pulmonary embolism, pressure sores, pneumonia, and urinary tract infection. Neurologic SAEs include stroke progression and recurrent stroke. a Frequency is derived from nursing and physiotherapist data. b Amount (minutes) is derived from physiotherapist data only. 2144 Neurology 86 June 7, 2016 Singapore Health (SHF/FG401P/2008), The Stroke Association, UK (TSA2009/09), and the National Institute of Health Research, UK (grant no.: HTA Project 12/01/16). The Florey Institute of Neuroscience and Mental Health received support from the Victorian government via the Operational Infrastructure Support Scheme.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Langhorne, Professor Peter
• Authors: Bernhardt, J., Churilov, L., Ellery, F., Collier, J., Chamberlain, J., Langhorne, P., Lindley, R. I., Moodie, M., Dewey, H., and Thrift, A. G.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Neurology
• Publisher: Lippincott Williams & Wilkins
• ISSN: 0028-3878
• ISSN (Online): 1526-632X
• Published Online: 17 February 2016
• Copyright Holders: Copyright © 2016 American Academy of Neurology
• First Published: First published in Neurology 86(23):2138-2145
• Publisher Policy: Reproduced under a Creative Commons License