Impact assessment of the Centre for Research Excellence in Stroke Rehabilitation and Brain Recovery.

BACKGROUND: Research impact is an emerging measure of research achievement alongside traditional academic outputs such as publications. We present the results of applying the Framework to Assess the Impact from Translational health research (FAIT) to the Centre for Research Excellence (CRE) in Stroke Rehabilitation and Brain Recovery (CRE-Stroke, 2014-2019) and report on the feasibility and lessons from the application of FAIT to a CRE rather than a discrete research project. METHODS: Data were gathered via online surveys, in-depth interviews, document analysis and review of relevant websites/databases to report on the three major FAIT methods: the modified Payback Framework, an assessment of costs against monetized consequences, and a narrative account of the impact generated from CRE-Stroke activities. FAIT was applied during the last 4 years of CRE-Stroke operation. RESULTS: With an economic investment of AU$ 3.9 million over 5 years, CRE-Stroke delivered a return on investment that included AU$ 18.8 million in leveraged grants, fellowships and consultancies. Collectively, CRE-Stroke members produced 354 publications that were accessed 470,000 times and cited over 7220 times. CRE-Stroke supported 26 PhDs, 39 postdocs and seven novice clinician researchers. There were 59 capacity-building events benefiting 744 individuals including policy-makers and consumers. CRE-Stroke created research infrastructure (including a research register of stroke survivors and a brain biobank), and its global leadership produced international consensus recommendations to influence the stroke research landscape worldwide. Members contributed to the Australian Living Stroke Guidelines: four researchers' outputs were directly referenced. Based only on the consequences that could be monetized, CRE-Stroke returned AU$ 4.82 for every dollar invested in the CRE. CONCLUSION: This case example in the developing field of impact assessment illustrates how researchers can use evidence to demonstrate and report the impact of and returns on research investment. The prospective application of FAIT by a dedicated research impact team demonstrated impact in broad categories of knowledge-gain, capacity-building, new infrastructure, input to policy and economic benefits. The methods can be used by other research teams to provide comprehensive evidence to governments and other research funders about what has been generated from their research investment but requires dedicated resources to complete.

Self-evaluation of personal needs by community-living young stroke survivors using an online English language questionnaire.

BACKGROUND: Identifying personal needs of young stroke survivors is crucial for their recovery. PURPOSE: Identify factors, burden, and significance of unmet needs of young community-living stroke survivors. MATERIALS AND METHODS: We used online advertising and word-of-mouth snowballing to recruit participants for an English language online questionnaire constructed for this purpose. Eligible participants aged 18-55 at time of stroke. Needs were classified into seven domains: Healthcare Experience, Impairments from Stroke, Everyday Activities, Work/Study, Finances, Relationships, and Social Participation. Random-effects logistic regression was used to determine the probability of unmet needs and X2 test to determine significance of distribution across domains. RESULTS: Out of 137 responses recorded: 32 did not meet inclusion criteria, 29 duplicates identified were discarded, and 76 eligible participants were analysed. Respondents were median 37 (IQR 32-47) years at time of stroke, and median 3 (1-5) years since stroke. Fifty-eight (76%) females. Modified Rankin Scale median score of 1 (1-3). Of 48 identified potential needs, 25 (IQR 19-30) were rated unmet. Twenty (IQR 15-25) considered of high significance. Unmet needs most frequently occurred in the domains: Impairments from Stroke, Finances, and Social Participation. CONCLUSIONS: There is high burden of unmet needs in community-living young stroke survivors which are spread disproportionately across the identified domains.IMPLICATIONS FOR REHABILITATIONIdentifying personal needs of young stroke survivors is crucial for their recovery.Impairments after Stroke, Finances, and Social Participation were often selected as being high burden unmet needs for community-living young people after stroke.Employing a post-stroke checklist to guide exploration of needs in young stroke may better capture which needs are unmet.

The economic and health burden of stroke among younger adults in Australia from a societal perspective.

BACKGROUND: To estimate the short term (5 years) and long term (30 years) economic burden of stroke among younger adults (18-64 years), and to calculate the loss of health-related quality of life in these individuals, in Australia. METHODS: A Markov microsimulation model was built to simulate incidence of stroke among younger adults in Australia. Younger adults with stroke commenced in the model via health states defined by the modified Rankin Scale at 12 months from the AVERT study (A Very Early Rehabilitation Trial), and transitioned through these health states. Costs in Australian dollars (AUD) were measured from a societal perspective for a 2018 reference year and categorised into medical, non-medical and indirect costs. Probabilistic sensitivity analyses were performed to test the robustness around the cost of illness estimates. The loss of health-related quality of life due to stroke among younger adults was calculated by determining the difference in estimated quality-adjusted life years (QALYs) between the stroke population and the general population. This was determined by multiplying the predicted remaining life years for the modelled stroke cohort and the age-matched general population, by their corresponding age-dependent utilities. RESULTS: The economic burden of stroke among younger adults was estimated to be AUD2.0 billion over 5 years, corresponding to a mean of $149,180 per stroke patient. Over 30 years, the economic impact was AUD3.4 billion, equating to a mean of $249,780 per case. Probabilistic sensitivity analyses revealed a mean cost per patient of $153,410 in the short term, and a mean cost per patient of $273,496 in the long term. Compared to the age-matched general population, younger adults with stroke experienced a loss of 4.58 life years and 9.21 QALYs. CONCLUSIONS: The results of our study suggests high economic and health burden of stroke among younger adults and highlights the need for preventive interventions targeting this age group. TRIAL REGISTRATION: ACTRN12606000185561 , retrospectively registered.

Gender Equity in Leadership and Conferences of the Stroke Society of Australasia.

INTRODUCTION AND AIM: Internationally, women are underrepresented as leaders in major scientific organizations and conferences. We aimed to determine gender differences in leadership roles and annual scientific conferences of the Stroke Society of Australasia (SSA). METHODS: In a retrospective review of SSA data (2014-2019), committee members were obtained through the SSA Web site, and moderators, speakers, and award recipients were identified from SSA annual scientific conference programs. Gender was determined by name inspection and Web search. Absolute numbers and proportions of women and men were recorded for all roles examined, overall and per year. Associations between representation of women in conferences and percentage of women in speaking roles were tested using multinomial regression. RESULTS: Presidential leadership of the SSA was held by men in 2014-2016 and 2019 and women in 2017-2018. SSA committee membership was predominantly women (55%), being lowest (47%) in 2014 and 2019 and highest (65%) in 2017. There was a wide gender variation at scientific conferences, with 41% of keynote speakers being women overall, from 20% in 2016 to 75% in 2015. From 2014 to 2019, 55% of all speakers were women, ranging from 32% (in 2016) to 71% (in 2015). A higher percentage of women as speakers or moderators was associated with a program committee with over a third of its members composed of women (p ≤ 0.044). CONCLUSIONS: Representation of women varied from 2014 to 2019 in the SSA organization and its conferences, although men are more often elected president in the organization and women are less often keynote speakers. When more women were included in the program committee, the representation of women as speakers increased.

Young Stroke Survivors' Preferred Methods of Meeting Their Unique Needs: Shaping Better Care.

OBJECTIVE: To determine how young stroke survivors want their unmet needs to be addressed, we undertook an international online survey of people living with stroke. METHODS: Participants self-selected to complete an online survey that included a questionnaire on demographics and stroke-related characteristics, the Young Stroke Needs Screening Tool, and a questionnaire on how they wanted their needs to be met. RESULTS: One hundred seventy-one responses were received (68% female respondents, mean age 45 years, interquartile range 36-51 years). Preferences for methods of meeting needs varied depending on the domain of need and participants' demographic and stroke-related characteristics. Face-to-face contact with a health care professional was a popular means of meeting needs, but methods outside of a traditional health care setting such as a succinct list of tips or peer support were widely acceptable and sometimes preferred. CONCLUSION: This work provides the impetus for developing alternative methods of meeting young stroke survivors' needs, many of which are not resource intensive or do not require an appointment with a health care professional.

A systematic review protocol of timing, efficacy and cost effectiveness of upper limb therapy for motor recovery post-stroke.

BACKGROUND: Improving upper limb (UL) motor recovery after stroke represents a major clinical and scientific goal. We aim to complete three systematic reviews to estimate the (1) association between time to start of UL therapy and motor recovery, (2) relative efficacy of different UL therapy approaches post-stroke and (3) cost-effectiveness of UL therapy interventions. METHODS: We have designed a systematic review protocol to address three systematic review questions that were each registered with PROSPERO. The search will be conducted in MEDLINE, EMBASE, and Cochrane Controlled Register of Trials. We will include randomised controlled trials, non-randomised clinical trials, before-after studies and observational studies of adult stroke survivors with an average stroke onset < 6 months, undergoing hospital-based therapy to improve UL function. Eligible interventions will aim to promote UL functional recovery. Two reviewers will independently screen, select and extract data. Study risk of bias will be appraised using appropriate tools. Clinical measures of motor recovery will be investigated (primary measure Fugl Meyer UL assessment), as well as measures of health-related quality of life (primary measure EQ-5D) and all cost-effectiveness analyses completed. Secondary outcomes include therapy dose (minutes, weeks, repetitions as available) and safety (i.e. adverse events, serious adverse events). A narrative synthesis will describe quality and content of the evidence. If feasible, we will conduct random effects meta-analyses where appropriate. DISCUSSION: We anticipate the findings of this review will increase our understanding of UL therapy and inform the generation of novel, data-driven hypotheses for future UL therapy research post-stroke. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42018019367, http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42018111629, http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42018111628.

Economic evaluation of a phase III international randomised controlled trial of very early mobilisation after stroke (AVERT).

OBJECTIVES: While very early mobilisation (VEM) intervention for stroke patients was shown not to be effective at 3 months, 12 month clinical and economical outcomes remain unknown. The aim was to assess cost-effectiveness of a VEM intervention within a phase III randomised controlled trial (RCT). DESIGN: An economic evaluation alongside a RCT, and detailed resource use and cost analysis over 12 months post-acute stroke. SETTING: Multi-country RCT involved 58 stroke centres. PARTICIPANTS: 2104 patients with acute stroke who were admitted to a stroke unit. INTERVENTION: A very early rehabilitation intervention within 24 hours of stroke onset METHODS: Cost-utility analyses were undertaken according to pre-specified protocol measuring VEM against usual care (UC) based on 12 month outcomes. The analysis was conducted using both health sector and societal perspectives. Unit costs were sourced from participating countries. Details on resource use (both health and non-health) were sourced from cost case report form. Dichotomised modified Rankin Scale (mRS) scores (0 to 2 vs 3 to 6) and quality adjusted-life years (QALYs) were used to compare the treatment effect of VEM and UC. The base case analysis was performed on an intention-to-treat basis and 95% CI for cost and QALYs were estimated by bootstrapping. Sensitivity analysis were conducted to examine the robustness of base case results. RESULTS: VEM and UC groups were comparable in the quantity of resource use and cost of each component. There were no differences in the probability of achieving a favourable mRS outcome (0.030, 95% CI -0.022 to 0.082), QALYs (0.013, 95% CI -0.041 to 0.016) and cost (AUD1082, 95% CI -$2520 to $4685 from a health sector perspective or AUD102, 95% CI -$6907 to $7111, from a societal perspective including productivity cost). Sensitivity analysis achieved results with mostly overlapped CIs. CONCLUSIONS: VEM and UC were associated with comparable costs, mRS outcome and QALY gains at 12 months. Compared with to UC, VEM is unlikely to be cost-effective. The long-term data collection during the trial also informed resource use and cost of care post-acute stroke across five participating countries. TRIAL REGISTRATION NUMBER: ACTRN12606000185561; Results.

Statistical analysis plan (SAP) for the Very Early Rehabilitation in Speech (VERSE) after stroke trial: an international 3-arm clinical trial to determine the effectiveness of early, intensive, prescribed, direct aphasia therapy.

Background Limited evidence exists to support very early intensive aphasia rehabilitation after stroke. VERSE is a PROBE trial designed to determine whether two types of intensive aphasia therapy, beginning within 14 days of acute stroke, provide greater therapeutic and cost-effectiveness than usual care. Objective To publish the detailed statistical analysis plan for the VERSE trial prior to unblinding. This statistical analysis plan was based on the published and registered VERSE trial protocol and was developed by the blinded steering committee and management team, led by the trial statistician. This plan was developed using outcome measures and trial data collection forms. Results The VERSE statistical analysis plan is consistent with reporting standards for clinical trials and provides for clear and open reporting. Conclusions Publication of a statistical analysis plan serves to reduce potential trial reporting bias and outlines transparent pre-specified analyses. Australian New Zealand Clinical Trials Registry (ANZCTR) Registration number: ACTRN12613000776707; Universal Trial Number (UTN) is U1111-1145-4130.

Implementing a protocol for a research impact assessment of the Centre for Research Excellence in Stroke Rehabilitation and Brain Recovery.

BACKGROUND: There is growing recognition that the wider benefits of research (economic, social and health impacts) should be assessed and valued alongside traditional research performance metrics such as peer-reviewed papers. Translation of findings into policy and practice needs to accelerate and pathways to impact need to be better understood. This research protocol outlines a mixed methods study to apply the Framework to Assess the Impact from Translational health research (FAIT) to the Centre for Research Excellence in Stroke Rehabilitation and Brain Recovery (CRE-Stroke). FAIT is purpose-designed to encourage research translation and assess research impact but lacks validation. METHODS/DESIGN: Phase 1 involves application of the FAIT-modified programme logic model to each CRE-Stroke research stream including identifying process, output and impact metrics, as well as end users of the research. A scoping review will inform potential impacts anticipated from CRE-Stroke. In Phase 2, audit and feedback on achievements against plans will track and encourage research translation. Logic models will be updated to account for changes in the research pathways over time. In Phase 3, three proven methods for measuring research impact - Payback, economic assessment and narratives - will be applied to each research stream and the data triangulated and reported in Phase 4. The feasibility of applying FAIT will also be assessed as part of Phase 3. DISCUSSION: Use of prospective, comprehensive research impact frameworks for large interdisciplinary programmes of research is rare. FAIT's application to CRE-Stroke will provide opportunity for the impact of CRE-Stroke to be assessed and a range of impacts beyond standard academic achievements to be reliably reported. The feasibility of FAIT's application will also be assessed and, if necessary, refined. The usefulness of FAIT for encouraging research translation will also be described and may prove useful for other programmes looking to implement a research impact framework.

Validity of Multisensor Array for Measuring Energy Expenditure of an Activity Bout in Early Stroke Survivors.

Introduction. Stroke survivors use more energy than healthy people during activities such as walking, which has consequences for the way exercise is prescribed for stroke survivors. There is a need for wearable device that can validly measure energy expenditure (EE) of activity to inform exercise prescription early after stroke. We aimed to determine the validity and reliability of the SenseWear-Armband (SWA) to measure EE and step-counts during activity <1 month after stroke. Materials and Methods. EE was measured using the SWA and metabolic cart and steps-counts were measured using the SWA and direct observation. Based on walking ability, participants performed 2x six-minute walks or repeated sit-to-stands. Concurrent validity and test-retest reliability were determined by calculating intraclass and concordance correlation coefficients. Results and Discussion. Thirteen participants walked; nine performed sit-to-stands. Validity of the SWA measuring EE for both activities was poor (ICC/CCC < 0.40). The SWA overestimates EE during walking and underestimated EE during sit-to-stands. Test-retest agreement showed an ICC/CCC of <0.40 and >0.75 for walking and sit-to-stand, respectively. However, agreement levels changed with increasing EE levels (i.e., proportional bias). The SWA did not accurately measure step-counts. Conclusion. The SWA should be used with caution to measure EE of activity of mild to moderate stroke survivors <1 month after stroke.

The Energy Cost of Steady State Physical Activity in Acute Stroke.

OBJECTIVE: Cardiorespiratory fitness levels are very low after stroke, indicating that the majority of stroke survivors are unable to independently perform daily activities. Physical fitness training improves exercise capacity poststroke; however, the optimal timing and intensity of training is unclear. Understanding the energy cost of steady-state activity is necessary to guide training prescription early poststroke. We aimed to determine if acute stroke survivors can reach steady state (oxygen-uptake variability ≤2.0 mL O2/kg/min) during physical activity and if the energy cost of steady state activity differs from healthy controls. MATERIAL AND METHODS: We recruited 23 stroke survivors less than 2 weeks poststroke. Thirteen were able to walk independently and performed a 6-minute walk (median age 78 years, interquartile range [IQR] 70-85), and 7 who were unable to walk independently performed 6 minutes of continuous sit-to-stands (median age 78 years, IQR 74-79) and we recruited 10 healthy controls (median age 73 years, IQR 70-77) who performed both 6 minutes of walking and sit-to-stands. Our primary outcome was energy cost (oxygen-uptake) during steady state activity (i.e., walking and continuous) sit-to-stands, measured by a mobile metabolic cart. RESULTS: All stroke survivors were able to reach steady state. Energy costs of walking was higher in stroke than in controls (mean difference .10 mL O2/kg/m, P = .02); the difference in energy costs during sit-to-stands was not significant (mean difference .11 mL O2/kg/sts, P = .45). CONCLUSIONS: Acute stroke survivors can reach a steady state during activity, indicating they are able to perform cardiorespiratory exercise. Acute stroke survivors require more energy per meter walked than controls.

A Very Early Rehabilitation Trial after stroke (AVERT): a Phase III, multicentre, randomised controlled trial.

BACKGROUND: Mobilising patients early after stroke [early mobilisation (EM)] is thought to contribute to the beneficial effects of stroke unit care but it is poorly defined and lacks direct evidence of benefit. OBJECTIVES: We assessed the effectiveness of frequent higher dose very early mobilisation (VEM) after stroke. DESIGN: We conducted a parallel-group, single-blind, prospective randomised controlled trial with blinded end-point assessment using a web-based computer-generated stratified randomisation. SETTING: The trial took place in 56 acute stroke units in five countries. PARTICIPANTS: We included adult patients with a first or recurrent stroke who met physiological inclusion criteria. INTERVENTIONS: Patients received either usual stroke unit care (UC) or UC plus VEM commencing within 24 hours of stroke. MAIN OUTCOME MEASURES: The primary outcome was good recovery [modified Rankin scale (mRS) score of 0-2] 3 months after stroke. Secondary outcomes at 3 months were the mRS, time to achieve walking 50 m, serious adverse events, quality of life (QoL) and costs at 12 months. Tertiary outcomes included a dose-response analysis. DATA SOURCES: Patients, outcome assessors and investigators involved in the trial were blinded to treatment allocation. RESULTS: We recruited 2104 (UK, n = 610; Australasia, n = 1494) patients: 1054 allocated to VEM and 1050 to UC. Intervention protocol targets were achieved. Compared with UC, VEM patients mobilised 4.8 hours [95% confidence interval (CI) 4.1 to 5.7 hours; p < 0.0001] earlier, with an additional three (95% CI 3.0 to 3.5; p < 0.0001) mobilisation sessions per day. Fewer patients in the VEM group (n = 480, 46%) had a favourable outcome than in the UC group (n = 525, 50%) (adjusted odds ratio 0.73, 95% CI 0.59 to 0.90; p = 0.004). Results were consistent between Australasian and UK settings. There were no statistically significant differences in secondary outcomes at 3 months and QoL at 12 months. Dose-response analysis found a consistent pattern of an improved odds of efficacy and safety outcomes in association with increased daily frequency of out-of-bed sessions but a reduced odds with an increased amount of mobilisation (minutes per day). LIMITATIONS: UC clinicians started mobilisation earlier each year altering the context of the trial. Other potential confounding factors included staff patient interaction. CONCLUSIONS: Patients in the VEM group were mobilised earlier and with a higher dose of therapy than those in the UC group, which was already early. This VEM protocol was associated with reduced odds of favourable outcome at 3 months cautioning against very early high-dose mobilisation. At 12 months, health-related QoL was similar regardless of group. Shorter, more frequent mobilisation early after stroke may be associated with a more favourable outcome. FUTURE WORK: These results informed a new trial proposal [A Very Early Rehabilitation Trial - DOSE (AVERT-DOSE)] aiming to determine the optimal frequency and dose of EM. TRIAL REGISTRATION: The trial is registered with the Australian New Zealand Clinical Trials Registry number ACTRN12606000185561, Current Controlled Trials ISRCTN98129255 and ISRCTN98129255. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 54. See the NIHR Journals Library website for further project information. Funding was also received from the National Health and Medical Research Council Australia, Singapore Health, Chest Heart and Stroke Scotland, Northern Ireland Chest Heart and Stroke, and the Stroke Association. In addition, National Health and Medical Research Council fellowship funding was provided to Julie Bernhardt (1058635), who also received fellowship funding from the Australia Research Council (0991086) and the National Heart Foundation (G04M1571). The Florey Institute of Neuroscience and Mental Health, which hosted the trial, acknowledges the support received from the Victorian Government via the Operational Infrastructure Support Scheme.

The potential health and economic impact of improving stroke care standards for Australia.

Background Evidence of the burden of suboptimal stroke care should expedite quality improvement. We aimed to estimate the health and economic impact of improving acute stroke management to best practice standards using Australia as a case study. Methods Hospital performance in Australia was estimated using data from the National Stroke Audit of Acute Services 2013. The percentage of patients provided evidence-based therapies in all hospitals was compared to that achieved in the aggregate of top performing benchmark hospitals (that included between them, a minimum contribution of 15% of all cases audited). The number of additional patients who would receive therapies if this performance gap was rectified was applied to a standardized economic simulation model that comprised stroke rates and resource-use estimates from the North East Melbourne Stroke Incidence Study applied to the 2013 Australian population. Results In 2013, 41,398 patients were estimated to have been hospitalized with stroke. If acute care was improved to that of Australian benchmarks, there would be an additional 15,317 patients accessing stroke units; 1960 receiving thrombolysis; and 4007 being treated with antihypertensive medication, 3082 with antiplatelet medication, 2179 with anticoagulant medication, and 3514 with lipid-lowering therapy. Approximately 9329 disability-adjusted life years could be avoided. This additional care provided would be cost effective at AUD 3304 per disability adjusted life year avoided. Conclusion The benefits of reducing evidence-practice gaps in Australia are considerable. Further investment in initiatives to optimize hospital care is justified.

Carers' Experiences, Needs, and Preferences During Inpatient Stroke Rehabilitation: A Systematic Review of Qualitative Studies.

OBJECTIVE: To report and synthesize the experiences, needs, and preferences of carers of stroke survivors undergoing inpatient rehabilitation. DATA SOURCES: MEDLINE, CINAHL, Embase, PsycINFO, and Web of Science were searched to March 2016. Reference lists of relevant publications were searched. No language restrictions were applied. STUDY SELECTION: Eligible qualitative studies reported the experiences of carers of stroke survivors who underwent inpatient rehabilitation. The search yielded 3532 records; 93 full-text publications were assessed for eligibility, and 34 documents (33 studies) were included. Comprehensiveness of reporting was assessed using the Consolidated Criteria for Reporting Qualitative Health Research framework. DATA EXTRACTION: Data on the characteristics of included studies were independently extracted by 2 authors. Differences in data extraction between authors were resolved through discussion or by a third author. All text in studies' results and discussion sections were extracted for analysis. DATA SYNTHESIS: Extracted texts were analyzed inductively using thematic synthesis. Seven analytical themes were developed that related to the carers' experiences, needs, and preferences: (1) overwhelmed with emotions; (2) recognition as a stakeholder in recovery; (3) desire to be heard and informed; (4) persisting for action and outcomes; (5) being legitimate clients; (6) navigating an alien culture and environment; and (7) managing the transition home. CONCLUSIONS: This systematic review provides new insights into the experiences, needs, and preferences of carers of stroke survivors undergoing inpatient rehabilitation. Carers experienced distress as they navigated a foreign culture and environment without adequate communication and processes in place for their inclusion. We recommend deliberate efforts to provide a more inclusive environment that better supports and prepares carers for their new role.

A randomized controlled trial of very early rehabilitation in speech after stroke.

RATIONALE: The efficacy of rehabilitation therapy for aphasia caused by stroke is uncertain. AIMS AND HYPOTHESIS: The Very Early Rehabilitation of Speech (VERSE) trial aims to determine if intensive prescribed aphasia therapy (VERSE) is more effective and cost saving than non-prescribed, intensive (usual care-plus) and non-intensive usual care (UC) therapy when started within 15 days of stroke onset and continued daily over four weeks. We hypothesize that aphasia therapy when started very early after stroke and delivered daily could enhance recovery of communication compared with UC. SAMPLE SIZE ESTIMATES: A total of 246 participants (82 per arm) will provide 80% power to detect a 4.4% improvement on aphasia quotient between VERSE and UC plus at a significance level of α = 0.05. SETTING: Acute-care hospitals and accompanying rehabilitation services throughout Australia, 2014-2017. DESIGN: Three-arm, prospective, randomized, parallel group, open-label, blinded endpoint assessment (PROBE) trial. PARTICIPANTS: Acute stroke in previous 14 days and aphasia diagnosed by aphasia quotient (AQ) of the Western Aphasia Battery (WAB). RANDOMIZATION: Computer-generated blocked randomization procedure stratified by aphasia severity according to Western Aphasia Battery, to one of three arms. INTERVENTION: All participants receive UC-usual ward-based aphasia therapy. Arm 1: UC-no additional therapy; Arm 2: UC-plus usual ward-based therapy; Arm 3: VERSE therapy-a prescribed and structured aphasia therapy program. Arms 2 and 3 receive a total of 20 additional sessions (45-60 min, provided daily) of aphasia therapy. The additional intervention must be provided before day 50 post stroke. STUDY OUTCOME MEASURES: The aphasia quotient of Western Aphasia Battery at 12 weeks post stroke. Secondary outcomes include discourse measures, the Stroke and Aphasia Quality of Life Scale-39 and the Aphasia Depression Rating Scale at 12 and 26 weeks. ECONOMIC EVALUATION: Incremental cost-effectiveness ratios at 26 weeks will be reported. DISCUSSION: This trial is designed to test whether the intensive and prescribed VERSE intervention is effective in promoting maximum recovery and preventing costly health complications in a vulnerable population of survivors of stroke. It will also provide novel, prospective, aphasia specific cost-effectiveness data to guide future policy development for this population.

Economic Evaluation Plan (EEP) for A Very Early Rehabilitation Trial (AVERT): An international trial to compare the costs and cost-effectiveness of commencing out of bed standing and walking training (very early mobilization) within 24 h of stroke onset with usual stroke unit care.

RATIONALE: A key objective of A Very Early Rehabilitation Trial is to determine if the intervention, very early mobilisation following stroke, is cost-effective. Resource use data were collected to enable an economic evaluation to be undertaken and a plan for the main economic analyses was written prior to the completion of follow up data collection. AIM AND HYPOTHESIS: To report methods used to collect resource use data, pre-specify the main economic evaluation analyses and report other intended exploratory analyses of resource use data. SAMPLE SIZE ESTIMATES: Recruitment to the trial has been completed. A total of 2,104 participants from 56 stroke units across three geographic regions participated in the trial. METHODS AND DESIGN: Resource use data were collected prospectively alongside the trial using standardised tools. The primary economic evaluation method is a cost-effectiveness analysis to compare resource use over 12 months with health outcomes of the intervention measured against a usual care comparator. A cost-utility analysis is also intended. STUDY OUTCOME: The primary outcome in the cost-effectiveness analysis will be favourable outcome (modified Rankin Scale score 0-2) at 12 months. Cost-utility analysis will use health-related quality of life, reported as quality-adjusted life years gained over a 12 month period, as measured by the modified Rankin Scale and the Assessment of Quality of Life. DISCUSSION: Outcomes of the economic evaluation analysis will inform the cost-effectiveness of very early mobilisation following stroke when compared to usual care. The exploratory analysis will report patterns of resource use in the first year following stroke.

Upright activity within the first week after stroke is associated with better functional outcome and health-related quality of life: A Norwegian multi-site study.

OBJECTIVE: To assess the amount of early upright activity of patients managed in Norwegian stroke units and its association with functional outcome and health-related quality of life 3 months later. DESIGN: A prospective observational multi-centre study. SUBJECTS: A total of 390 acute stroke patients, mean age 76.8 years, 48.1% men, less than 14 days post-stroke, recruited from 11 Norwegian stroke units. METHODS: Time spent in different activity categories (in bed, sitting out of bed, upright) was observed with a standard method. Outcome was assessed by modified Rankin Scale (mRS), and health-related quality of life by EuroQol-5 Dimension 5 level (EQ-5D-5L) 3 months later. Ordinal logistic and linear regression analyses were used to examine the association between activity categories and mRS and EQ-5D-5L, respectively. Age, National Institute of Health Stroke Scale (NIHSS) score, premorbid mRS, sex, and hospital-site were added as covariates. RESULTS: The odds ratio (OR) (95% confidence interval (CI)) for poorer functional outcome (higher mRS) decreased as time spent in upright activities increased (OR 0.97 (95% CI 0.94-1.00)). There was also a significant positive association between time in upright activity and higher EQ-5D-5L, Beta 0.184 (95% CI 0.001- 0.008) 3 months later. CONCLUSION: This study confirms the beneficial effect of upright activity applied during hospital stay in Norwegian stroke units.

Energy Expenditure and Cost During Walking After Stroke: A Systematic Review.

OBJECTIVES: To systematically review the evidence to determine energy expenditure (EE) in volume of oxygen uptake (V̇O2) (mL/kg/min) and energy cost in oxygen uptake per meter walked (V̇O2/walking speed; mL/kg/m) during walking poststroke and how it compares with healthy controls; and to determine how applicable current exercise prescription guidelines are to stroke survivors. DATA SOURCES: Cochrane Central Register of Controlled Trials, MEDLINE, Embase, and CINAHL were searched on October 9, 2014, using search terms related to stroke and EE. Additionally, we screened reference lists of eligible studies. STUDY SELECTION: Two independent reviewers screened titles and abstracts of 2115 identified references. After screening the full text of 144 potentially eligible studies, we included 29 studies (stroke survivors: n=501, healthy controls: n=123), including participants with confirmed stroke and a measure of V̇O2 during walking using breath-by-breath analysis. Studies with (9 studies) and without (20 studies) a healthy control group were included. DATA EXTRACTION: Two reviewers independently extracted data using a standard template, including patient characteristics, outcome data, and study methods. DATA SYNTHESIS: Mean age of stroke survivors was 57 years (range, 40-67y). Poststroke EE was highly variable across studies and could not be pooled because of high heterogeneity. EE during steady-state overground walking at matched speeds was significantly higher in stroke survivors than healthy controls (mean difference in V̇O2, 4.06 mL/kg/min; 95% confidence interval [CI], 2.21-5.91; 1 study; n=26); there was no significant group difference at self-selected speeds. Energy cost during steady-state overground walking was higher in stroke survivors at both self-selected (mean difference, .47 mL/kg/m; 95% CI, .29-.66; 2 studies; n=38) and matched speeds compared with healthy controls (mean difference, .27 mL/kg/m; 95% CI, .03-.51; 1 study; n=26). CONCLUSIONS: Stroke survivors expend more energy during walking than healthy controls. Low-intensity exercise as described in guidelines might be at a moderate intensity level for stroke survivors; there is a need for stroke-specific exercise guidelines.

Carers' experiences, needs and preferences during inpatient stroke rehabilitation: a protocol for a systematic review of qualitative studies.

BACKGROUND: Large numbers of people provide carer roles for survivors of stroke. Person-centred stroke rehabilitation must consider the perspectives of carers, as stroke affects not only the stroke survivor but also the quality of life and health of the carers. There is little collective knowledge about stroke carers' experiences, needs and preferences during the inpatient stroke rehabilitation process to then inform person-centred service improvements. Our objective is to report and synthesise experiences, needs and preferences of the carers of stroke survivors undergoing rehabilitation in inpatient settings. METHODS/DESIGN: We will conduct a systematic review of qualitative studies using a thematic synthesis methodology. We will follow the Enhancing Transparency in Reporting the Synthesis of Qualitative Research Guidelines (ENTREQ) and search the following databases for relevant articles: MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, Embase, and Web of Science. No language or publication date constraints will be applied. Eligible studies will have to use qualitative methods of data collection and analysis and reported data from the carers of stroke survivors who underwent inpatient stroke rehabilitation. Studies will be eligible for inclusion if they report the experiences, needs and preferences of carers regarding inpatient rehabilitation environments, organisation, care systems, therapeutic interventions, information exchange, carer training, discharge and community service planning and other issues of relevance to their roles as carers. Study selection and assessment of quality will be performed independently by two reviewers. Any disagreement will be resolved by a third reviewer. Data will be extracted by one reviewer, tabled, and checked for accuracy by another reviewer. All text reported in studies' results, discussion and conclusion sections will be entered into the NVivo software for analysis. Extracted texts will be inductively coded independently by two reviewers and analysed in three phases using thematic synthesis. Descriptive and analytical themes will be developed. DISCUSSION: This study is expected to provide new insights into the perspectives of stroke survivors' carers. Increased knowledge about carer perspectives and preferences will inform person-centred improvements in stroke rehabilitation. STUDY REGISTRATION: PROSPERO registration number: CRD42015017315 .