Stroke is a global health concern, with a significant impact on mortality and disability. Motor impairment, including upper limb impairment is particularly common following stroke. Upper limb impairment impacts on an individual’s ability to complete activities of daily living and quality of life. Effective interventions targeted at upper limb recovery are therefore important andfurther research, within this area, has been identified as necessary. However, challenges researching such complex interventions have been recognised. To attempt to overcome such difficulties the Medical Research Council (MRC) proposed a framework for the development and evaluation ofRCTs for complex interventions.In this thesis the MRC framework has been used, focusing on the processes of developing and feasibility/piloting, to provide information for a phase III randomised controlled trial (RCT) of a novel intervention targeted at upperlimb recovery following stroke.A systematic review and meta-analysis was undertaken to investigate and clarify any possible association between predictive variables and upper limbrecovery. Observational studies of stroke patients investigating at least one predictive variable and its relationship with a defined measure of upper limbrecovery at a future time point were included. For this review data analysis combined several approaches. Fifty eight studies were included and 41 predictor variables identified. Initial measures of upper limb function andimpairment were found to be the most significant predictors of upper limb recovery; odds ratio (OR) 38.62 (95% confidence interval (CI) 8.40-177.55) and OR 14.84 (95% CI 9.08-24.25) respectively. Neurophysiological factors(motor evoked potentials and somatosensory evoked potentials) were also consistently identified as strongly associated with upper limb recovery; OR 11.76 (95% CI 2.73-69.05) and OR 13.73 (95% CI 2.73-69.05) respectively. Moderate evidence of association was found for global disability and lower limb impairment. Interpretation of results is complicated by methodological factors, particularly relating to the heterogeneous nature of the included studies.In order to identify interventions which show potential for reducing impairment and/or improving upper limb function after stroke, an overview of the available evidence was completed. This systematic review and meta-analysis included Cochrane systematic reviews, other reviews and, where necessary, additional RCTs of interventions to promote upper limb recovery.Thirteen relevant interventions were found, covered by nine Cochrane systematic reviews (bilateral training, constraint-induced movement therapy (CIMT), electromyograhphic (EMG) biofeedback, electrostimulation, hands-on therapy interventions, mental practice, repetitive task training (RTT), electromechanical/robotic devices and virtual reality) and four other reviews (neurophysiological approaches, high-intensity therapy, mirror therapy andsplinting). A statistically significant result, in terms of arm recovery, was found in favour of eight of the interventions: CIMT (standardised mean difference (SMD) 0.74 95% CI 0.44-1.03), EMG biofeedback (SMD 0.41 95%CI 0.05-0.77), electrostimulation (SMD 0.40 95% CI 0.02-0.77), mental practice (SMD 1.37 95% CI 0.60-2.15), mirror therapy (SMD 0.41 95%CI 0.05-0.77), RTT (SMD 0.23 95% CI 0.06-0.41), electromechanical/robotic devices (SMD 0.30 95% CI 0.02-0.58) and virtual reality (SMD 0.52 95% CI0.25-0.78). Two out of the eleven interventions, which investigated hand function outcomes found a positive result (CIMT SMD 0.39 95% CI 0.11-0.68 and repetitive task training SMD 0.27 95% CI 0.06-0.47). Analyses were limited by a relatively small number of RCTs, which were also generally small in size. Heterogeneity of the available data and methodological limitations further impacts on the conclusions. Despite these limitations this overview provided a concise and informative summary of the available evidence. The interventions found to be beneficial, or showing promise tend to include elements of intensive, repetitive, task-specific practice.To build the evidence base for upper limb interventions, two Cochrane systematic reviews were undertaken. These reviews investigated the effects of bilateral training and home therapy programmes on upper limb recovery.Both included RCTs of stroke patients. Eighteen trials were included in the bilateral review, of which 14 were included in the analyses. Most of the included trials were considered to be at high risk of bias and the evidence was further limited by heterogeneity. No statistically significant results were found for any of the primary outcomes. One study found a statistically significant result in favour of another upper limb intervention for performance in extended ADL. No statistically significant differences were found for any of the other secondary outcomes. Four RCTs were included in the home-based therapy programmes review. No statistically significant result was found for any of the outcomes. There is currently insufficient good quality evidence to determine the effects of both the interventions studied.Following the evidence gained from the overview of interventions elements of intensive, repetitive and task-specific practice were to be included in a novel upper limb intervention. Robotic interventions, which incorporate theseprinciples, were also found to have a positive effect on upper limb outcomes.Therefore a pilot, feasibility and acceptability study of a novel device (Armeo®Spring) that included these elements was completed. Medically stable adults with a clinical diagnosis of stroke and arm deficits admitted to an acute stroke unit were recruited. Participants were randomly allocated to experimental intervention (high or low intensity training with the Armeo®Spring arm orthosis) or usual stroke unit care. Primary outcomes were feasibility and acceptability of the experimental device recorded at postintervention.Secondary outcomes were; safety and three efficacy outcomesrecorded at post-intervention, and 3 month follow-up. Patient recruitment was challenging; over eight months 393 consecutive stroke admissions were screened and 12 participants recruited. This study demonstrated that per-protocol levels of intensity were not feasible to provide in an acute stroke unit. However, higher levels of intensity could be achieved and this novel intervention was found to be acceptable to patients. This pilot trial alsofound higher change scores on the three efficacy outcomes within both intervention groups, compared to the control group. Due to small sample size and other possible confounding factors, these findings must be interpreted with caution.Using the MRC complex intervention framework as a guide I completed development and feasibility/piloting work surrounding an upper limb intervention, following stroke. Following the results of this research further development, feasibility/piloting work is suggested for the ArmeoSpringdevice prior to the undertaking of a phase III RCT. The information gained from this research could be used to inform phase III RCTs of other upper limb interventions.
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