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Objective To establish international, multidisciplinary expert consensus on minimum participant characteristic reporting standards in aphasia research (DESCRIBE project). Methods An international, three-round e-Delphi exercise and consensus meeting, involving multidisciplinary researchers, clinicians and journal editors working academically or clinically in the field of aphasia. Results Round 1 of the DESCRIBE e-Delphi exercise ( n = 156) generated 113 items, 20 of which reached consensus by round 3. The final consensus meeting ( n = 19 participants) established DESCRIBE's 14 participant characteristics that should be reported in aphasia studies: age; years of education; biological sex; language of treatment/testing; primary language; languages used; history of condition(s) known to impact communication/cognition; history of previous stroke; lesion hemisphere; time since onset of aphasia; conditions arising from the neurological event; and, for communication partner participants, age, biological sex and relationship to person with aphasia. Each characteristic has been defined and matched with standard response options to enable consistent reporting. Conclusion Aphasia research studies should report the 14 DESCRIBE participant characteristics as a minimum. Consistent adherence to the DESCRIBE minimum reporting standard will reduce research wastage and facilitate evidence-based aphasia management by enabling replication and collation of research findings, and translation of evidence into practice.

Background We require high-quality information on the current burden, the types of therapy and resources available, methods of delivery, care pathways and long-term outcomes for people with aphasia. Aim To document and inform international delivery of post-stroke aphasia treatment, to optimise recovery and reintegration of people with aphasia. Methods & Procedures Multi-centre, prospective, non-randomised, open study, employing blinded outcome assessment, where appropriate, including people with post-stroke aphasia, able to attend for 30 minutes during the initial language assessment, at first contact with a speech and language therapist for assessment of aphasia at participating sites. There is no study-mandated intervention. Assessments will occur at baseline (first contact with a speech and language therapist for aphasia assessment), discharge from Speech and Language Therapy (SLT), 6 and 12-months post-stroke. Our primary outcome is changed from baseline in the Amsterdam Nijmegen Everyday Language Test (ANELT/Scenario Test for participants with severe verbal impairments) at 12-months post-stroke. Secondary outcomes at 6 and 12 months include the Therapy Outcome Measure (TOMS), Subjective Index of Physical and Social Outcome (SIPSO), Aphasia Severity Rating Scale (ASRS), Western Aphasia Battery Aphasia Quotient (WAB-AQ), stroke and aphasia quality of life scale (SAQoL-39), European Quality of Life Scale (EQ-5D), lesion description, General Health Questionnaire (GHQ-12), resource use, and satisfaction with therapy provision and success. We will collect demography, clinical data, and therapy content. Routine neuroimaging and medication administration records will be accessed where possible; imaging will be pseudonymised and transferred to a central reading centre. Data will be collected in a central registry. We will describe demography, stroke and aphasia profiles and therapies available. International individual participant data (IPD) meta-analyses will examine treatment responder rates based on minimal detectable change & clinically important changes from baseline for primary and secondary outcomes at 6 and 12 months. Multivariable meta-analyses will examine associations between demography, therapy, medication use and outcomes, considering service characteristics. Where feasible, costs associated with treatment will be reported. Where available, we will detail brain lesion size and site, and examine correlations with SLT and language outcome at 12 months. Conclusion International differences in care, resource utilisation and outcomes will highlight avenues for further aphasia research, promote knowledge sharing and optimise aphasia rehabilitation delivery. IPD meta-analyses will enhance and expand understanding, identifying cost-effective and promising approaches to optimise rehabilitation to benefit people with aphasia.

Background and Purpose: The factors associated with recovery of language domains after stroke remain uncertain. We described recovery of overall-language-ability, auditory comprehension, naming, and functional-communication across participants’ age, sex, and aphasia chronicity in a large, multilingual, international aphasia dataset. Methods: Individual participant data meta-analysis of systematically sourced aphasia datasets described overall-language ability using the Western Aphasia Battery Aphasia-Quotient; auditory comprehension by Aachen Aphasia Test (AAT) Token Test; naming by Boston Naming Test and functional-communication by AAT Spontaneous-Speech Communication subscale. Multivariable analyses regressed absolute score-changes from baseline across language domains onto covariates identified a priori in randomized controlled trials and all study types. Change-from-baseline scores were presented as estimates of means and 95% CIs. Heterogeneity was described using relative variance. Risk of bias was considered at dataset and meta-analysis level. Results: Assessments at baseline (median=43.6 weeks poststroke; interquartile range [4–165.1]) and first-follow-up (median=10 weeks from baseline; interquartile range [3–26]) were available for n=943 on overall-language ability, n=1056 on auditory comprehension, n=791 on naming and n=974 on functional-communication. Younger age ( Conclusions: Earlier intervention for poststroke aphasia was crucial to maximize language recovery across a range of language domains, although recovery continued to be observed to a lesser extent beyond 6 months poststroke.

Primary Objective: To identify how families experience cognitive-communication difficulties following Traumatic Brain Injury (TBI). Experiences of information, training and support for managing com...

Introduction Approaches to economic evaluations of stroke therapies are varied and inconsistently described. An objective of the European Stroke Organisation (ESO) Health Economics Working Group is to standardise and improve the economic evaluations of interventions for stroke. Methods The ESO Health Economics Working Group and additional experts were contacted to develop a protocol and a guidance document for data collection for economic evaluations of stroke therapies. A modified Delphi approach, including a survey and consensus processes, was used to agree on content. We also asked the participants about resources that could be shared to improve economic evaluations of interventions for stroke. Results Of 28 experts invited, 16 (57%) completed the initial survey, with representation from universities, government, and industry. More than half of the survey respondents endorsed 13 specific items to include in a standard resource use questionnaire. Preferred functional/quality of life outcome measures to use for economic evaluations were the modified Rankin Scale (14 respondents, 88%) and the EQ-5D instrument (11 respondents, 69%). Of the 12 respondents who had access to data used in economic evaluations, 10 (83%) indicated a willingness to share data. A protocol template and a guidance document for data collection were developed and are presented in this article. Conclusion The protocol template and guidance document for data collection will support a more standardised and transparent approach for economic evaluations of stroke care.

Stroke 53(3), 956-967 (2022). doi:10.1161/STROKEAHA.121.035216, Published by Lippincott Williams & Wilkins, Philadelphia, Pa.

Background: The long-term burden of self-management in type 2 diabetes can impact quality of life. Aims: To examine associations between demographic and clinical factors, anxiety/depression and perception of health in people with type 2 diabetes. Methods: Retrospective analyses of anonymised data from completed clinical trials provided by the diabetes subsection of Virtual International Cardiovascular and Cognitive Trials Archive (VICCTA). Data on demographics, polypharmacy, HbA1c, anxiety/depression (EQ-5D-3L) and perception of health (EQ-5D-3L VAS) were extracted. Regression analyses explored associations amongst polypharmacy, HbA1c and quality of life (anxiety/depression and health perception) at baseline. Results: In 2783 participants with type 2 diabetes (median age 66 years (IQR 61–70), n=1,595 (57%) male), female sex and Caucasian/European ethnicity were each associated with increased anxiety/depression and lower EQ-5D-3L VAS scores. Following adjustment for covariates, each additional prescribed medication was associated with increased anxiety/depression: OR 1.09 (95% CI 1.04 to 1.14; p

Coordination of international aphasia research would minimise duplication of effort, support synergistic international activities across languages and multidisciplinary perspectives, and promote high-quality conduct and reporting of aphasia research, thereby increasing the relevance, transparency, and implementation of findings. The Collaboration of Aphasia Trialists (CATs) sought to develop an aphasia research agenda to direct future research activities, based on priorities shared by people with aphasia, family members, and healthcare professionals. Our established international research network spanning 33 countries contributed to this activity. Research literature reporting the priorities of stakeholders was reviewed and synthesized (phase 1). Representatives from Working Groups on Aphasia Assessment & Outcomes, Prognosis & Predictors of Recovery, Effectiveness of Interventions, and Societal Impact & Reintegration participated in a two-day research agenda-setting meeting. The CATs expert panel refined research objectives and identified constituent components of research and methodological developments required to address these research components. The objectives and research components were grouped into overarching themes (phase 2). The resultant list was then circulated to more than 180 CATs members for review, revision, and approval. Consensus on the final aphasia research agenda and roadmap was reached by CATs executive committee (phase 3). The expert panel identified five overarching research themes: (i) evidence-based interventions for people with aphasia, (ii) effective interventions to support those communicating with people with aphasia, (iii) cross-linguistic assessment and core outcomes for aphasia research, (iv) predictors of language recovery, and (v) clinical implementation of research findings. Within these broad themes, 30 research objectives and 91 individual aphasia research components were identified and sequentially ordered. This agenda builds on research priorities identified by people with aphasia and their families, and includes priorities of healthcare professionals and researchers, and will support the rehabilitation and recovery of people with aphasia. Our internationally relevant research agenda promotes rigor in methodology, considers international applicability, synergistic activities, and sharing of resources and expertise. publishedVersion

Objective: We sought to (1) identify the outcome measures currently used across stroke arm rehabilitation randomized trials, (2) identify and compare outcomes important to stroke survivors, carers and clinicians and (3) describe where existing research outcome measures capture outcomes that matter the most to stroke survivors, carers and clinicians and where there may be discrepancies. Methods: First, we systematically identified and extracted data on outcome measures used in trials within a Cochrane overview of arm rehabilitation interventions. Second, we conducted 16 focus groups with stroke survivors, carers and clinicians using nominal group technique, supplemented with eight semi-structured interviews, to identify these stakeholders’ most important outcomes following post-stroke arm impairment. Finally, we described the constructs of each outcome measure and indicated where stakeholders’ important outcomes were captured by each measure. Results: We extracted 144 outcome measures from 243 post-stroke arm rehabilitation trials. The Fugl-Meyer Assessment Upper Extremity section (used in 79/243 trials; 33%), Action Research Arm Test (56/243; 23%), and modified Ashworth Scale (53/243; 22%) were most frequently used. Stroke survivors ( n = 43), carers ( n = 10) and clinicians ( n = 58) identified 66 unique, important outcomes related to arm impairment following stroke. Between one and three outcomes considered important by the stakeholders were captured by the three most commonly used assessments in research. Conclusion: Post-stroke arm rehabilitation research would benefit from a reduction in the number of outcome measures currently used, and better alignment between what is measured and what is important to stroke survivors, carers and clinicians.

Background Approximately 418,000 people live in care homes in the UK, yet accessible, robust data on care home populations and organisation are lacking. This hampers our ability to plan, allocate resources or prevent risk. Large randomised controlled trials (RCTs) conducted in care homes offer a potential solution. The value of detailed data on residents’ demographics, outcomes and contextual information captured in RCTs has yet to be fully realised. Irrespective of the intervention tested, much of the trial data collected overlaps, in terms of structured assessments and descriptive information. Given the time and costs required to prospectively collect data in these populations, pooling anonymised RCT data into a structured repository offers benefit; secondary analyses of pooled RCT data can improve understanding of this under-researched population, and enhance future trial design. This protocol describes the creation of a repository of individual participant data (IPD) from trials conducted in care homes, to address the need for accurate, high quality IPD on this vulnerable population.Methods Informed by scoping of relevant literature, the principal investigators of RCTs conducted in adult care homes in UK since 2010 will be invited to contribute trial IPD. Contributing trialists will form a Steering Committee, who will oversee data sharing and remain gatekeepers of their own trial’s data. IPD will be cleaned and standardised in consultation with the Steering Committee for accuracy. Planned analyses include comparison of pooled IPD with point estimates from administrative sources, to assess generalisability of RCT data to the wider care home population. We will also identify key resident characteristics and outcomes from within the trial repository, which will inform development of a national minimum dataset for care homes. Following project completion, management will migrate to the Virtual Trials Archives, forming a legacy dataset which will be accessible to the wider research community for analyses. Discussion Analysis of pooled IPD has the potential to inform and direct future practice, research and policy at low cost, enhancing the value of existing data and reducing research waste. We aim to create a permanent archive for care home trial data, and welcome the contribution of emerging trial datasets.

BACKGROUND Whilst research into the wide-ranging needs of family members following traumatic brain injury (TBI) is well established, investigation into the specific needs of families in relation to supporting cognitive-communication difficulties, relationships and social participation is limited. AIMS To identify the family needs for cognitive-communication difficulties following TBI and to explore whether current services are meeting these needs. METHODS & PROCEDURES Following a successful pilot, family members from the UK and Australia were invited via posters, social media and e-mail to take part in an anonymous, communication needs survey. Data arising from the thirty two closed questions (six eligibility, nine demographic and seventeen needs questions) were analysed using SPSS descriptive statistics. Data arising from one open question were analysed using qualitative content analysis. OUTCOMES & RESULTS A total of 102 family members from the UK (n = 89, 87%) and Australia (n = 13, 13%) completed the survey. The majority of respondents were female (n = 76; 75%), between the ages of 30 and 69 (n = 88; 87%), and either a parent or a partner of the person following TBI (n = 78;76%). Respondents rated information about expected recovery from cognitive-communication difficulties and training in helpful strategies as their most important needs. The majority of respondents (more than 60%) were not satisfied that any of their cognitive-communication needs had been fully met and high levels of unmet need remained evident at three years or more post-injury. Written information, communication partner training and counselling were identified as key supports. CONCLUSIONS & IMPLICATIONS Families report high levels of unmet need for managing cognitive-communication difficulties following TBI. Access to written information and communication partner training should be available to families at various time points following TBI and not just in the early stages. What this paper adds What is already known on this subject Attempting to support a person who has cognitive-communication difficulties following TBI has been found to be highly burdensome for family members. However, few studies have asked how families perceive their needs in relation to cognitive-communication difficulties or measured how well current services are meeting their needs. What this paper adds to existing knowledge This study demonstrates that current speech and language therapy services are not yet meeting the needs of the relatives of individuals with cognitive-communication difficulties following TBI. Important insights into the information, training and support families' rate as important are identified in addition to how these needs develop over time. What are the potential or actual clinical implications of this work? Speech and language therapy service design requires to reflect the ongoing nature of familial needs for cognitive-communication difficulties following TBI. Families require access to appropriate literature, speech and language therapy support, and communication partner training in the longer term, not just in the acute phase.

Supplemental material, ESO897466 Supplemental Figure for Improving economic evaluations in stroke: A report from the ESO Health Economics Working Group by Dominique A Cadilhac, Joosup Kim, Alastair Wilson, Eivind Berge, Anita Patel, Myzoon Ali, Jeffrey Saver, Hanne Christensen, Matthieu Cuche, Sean Crews, Olivia Wu, Marine Provoyeur, Peter McMeekin, Isabelle Durand-Zaleski, Gary A Ford, Natalia Muhlemann, Philip M Bath, Azmil H Abdul-Rahim, Katharina Sunnerhagen, Atte Meretoja, Vincent Thijs, Christian Weimar, Ayrton Massaro, Annemarei Ranta and Kennedy R Lees; on behalf of the ESO Health Economics Working group in European Stroke Journal

Objectives:Underpowered trials risk inaccurate results. Recruitment to stroke rehabilitation randomised controlled trials (RCTs) is often a challenge. Statistical simulations offer an important opportunity to explore the adequacy of sample sizes in the context of specific outcome measures. We aimed to examine and compare the adequacy of stroke rehabilitation RCT sample sizes using the Barthel Index (BI) or modified Rankin Scale (mRS) as primary outcomes. Methods:We conducted computer simulations using typical experimental event rates (EER) and control event rates (CER) based on individual participant data (IPD) from stroke rehabilitation RCTs. Event rates are the proportion of participants who experienced clinically relevant improvements in the RCT experimental and control groups. We examined minimum sample size requirements and estimated the number of participants required to achieve a number needed to treat within clinically acceptable boundaries for the BI and mRS. Results:We secured 2350 IPD (18 RCTs). For a 90% chance of statistical accuracy on the BI a rehabilitation RCT would require 273 participants per randomised group. Accurate interpretation of effect sizes would require 1000s of participants per group. Simulations for the mRS were not possible as a clinically relevant improvement was not detected when using this outcome measure. Conclusions:Stroke rehabilitation RCTs with large sample sizes are required for accurate interpretation of effect sizes based on the BI. The mRS lacked sensitivity to detect change and thus may be unsuitable as a primary outcome in stroke rehabilitation trials.

Background: Aphasia is a language disorder resulting from acquired brain injury which affects one-third of stroke survivors. National clinical guidelines recommend referring people with aphasia to ...

Background and Purpose— There may be a potential to reduce the number of items assessed in the Barthel Index (BI), and shortened versions of the BI have been described. We sought to collate all existing short-form BI (SF-BI) and perform a comparative validation using clinical trial data. Methods— We performed a systematic review across multidisciplinary electronic databases to find all published SF-BI. Our validation used the VISTA (Virtual International Stroke Trials Archive) resource. We describe concurrent validity (agreement of each SF-BI with BI), convergent and divergent validity (agreement of each SF-BI with other outcome measures available in the data set), predictive validity (association of prognostic factors with SF-BI outcomes), and content validity (item correlation and exploratory factor analyses). Results— From 3546 titles, we found 8 articles describing 6 differing SF-BI. Using acute trial data (n=8852), internal reliability suggested redundancy in BI (Cronbach α, 0.96). Each SF-BI demonstrated a strong correlation with BI, modified Rankin Scale, National Institutes of Health Stroke Scale (all ρ≥0.83; P P P Conclusions— There is redundancy in the original BI; we have demonstrated internal and external validity of a 3-item SF-BI that should be simple to use.

Supplemental material, Supplemental_Material for Outcome measures in post-stroke arm rehabilitation trials: do existing measures capture outcomes that are important to stroke survivors, carers, and clinicians? by Julie Duncan Millar, Frederike van Wijck, Alex Pollock and Myzoon Ali in Clinical Rehabilitation

Introduction: Short‐form versions of the Montreal Cognitive Assessment (SF‐MoCA) are increasingly used to screen for dementia in research and practice. We sought to collate evidence on the accuracy of SF‐MoCAs and to externally validate these assessment tools. Methods: We performed systematic literature searching across multidisciplinary electronic literature databases, collating information on the content and accuracy of all published SF‐MoCAs. We then validated all the SF‐MoCAs against clinical diagnosis using independent stroke (n = 787) and memory clinic (n = 410) data sets. Results: We identified 13 different SF‐MoCAs (21 studies, n = 6477 participants) with differing test content and properties. There was a pattern of high sensitivity across the range of SF‐MoCA tests. In the published literature, for detection of post stroke cognitive impairment, median sensitivity across included studies: 0.88 (range: 0.70‐1.00); specificity: 0.70 (0.39‐0.92). In our independent validation using stroke data, median sensitivity: 0.99 (0.80‐1.00); specificity: 0.40 (0.14‐0.87). To detect dementia in older adults, median sensitivity: 0.88 (0.62‐0.98); median specificity: 0.87 (0.07‐0.98) in the literature and median sensitivity: 0.96 (range: 0.72‐1.00); median specificity: 0.36 (0.14‐0.86) in our validation. Horton's SF‐MoCA (delayed recall, serial subtraction, and orientation) had the most favorable properties in stroke (sensitivity: 0.90, specificity: 0.87, positive predictive value [PPV]: 0.55, and negative predictive value [NPV]: 0.93), whereas Cecato's “MoCA reduced” (clock draw, animal naming, delayed recall, and orientation) performed better in the memory clinic (sensitivity: 0.72, specificity: 0.86, PPV: 0.55, and NPV: 0.93). Conclusions: There are many published SF‐MoCAs. Clinicians and researchers using a SF‐MoCA should be explicit about the content. For all SF‐MoCA, sensitivity is high and similar to the full scale suggesting potential utility as an initial cognitive screening tool. However, choice of SF‐MoCA should be informed by the clinical population to be studied.

Objectives: There are limited data as to what degree of early neurologic change best relates to outcome in acute intracerebral hemorrhage. We aimed to derive and validate a threshold for early postintracerebral hemorrhage change that best predicts 90-day outcomes. Design: Derivation: retrospective analysis of collated clinical stroke trial data (Virtual International Stroke Trials Archive). Validation: retrospective analysis of a prospective multicenter cohort study (Prediction of haematoma growth and outcome in patients with intracerebral haemorrhage using the CT-angiography spot sign [PREDICT]). Setting: Neurocritical and ICUs. Patients: Patients with acute intracerebral hemorrhage presenting less than 6 hours. Derivation: 552 patients; validation: 275 patients. Interventions: None. Measurements and Main Results: We generated a receiver operating characteristic curve for the association between 24-hour National Institutes of Health Stroke Scale change and clinical outcome. The primary outcome was a modified Rankin Scale score of 4–6 at 90 days; secondary outcomes were other modified Rankin Scale score ranges (modified Rankin Scale, 2–6, 3–6, 5–6, 6). We employed Youden’s J Index to select optimal cut points and calculated sensitivity, specificity, and predictive values. We determined independent predictors via multivariable logistic regression. The derived definitions were validated in the PREDICT cohort. Twenty-four–hour National Institutes of Health Stroke Scale change was strongly associated with 90-day outcome with an area under the receiver operating characteristic curve of 0.75. Youden’s method showed an optimum cut point at –0.5, corresponding to National Institutes of Health Stroke Scale change of greater than or equal to 0 (a lack of clinical improvement), which was seen in 46%. Early neurologic change accurately predicted poor outcome when defined as greater than or equal to 0 (sensitivity, 65%; specificity, 73%; positive predictive value, 70%; adjusted odds ratio, 5.05 [CI, 3.25–7.85]) or greater than or equal to 4 (sensitivity, 19%; specificity, 98%; positive predictive value, 91%; adjusted odds ratio, 12.24 [CI, 4.08–36.66]). All definitions reproduced well in the validation cohort. Conclusions: Lack of clinical improvement at 24 hours robustly predicted poor outcome and showed good discrimination for individual patients who would do poorly. These findings are useful for prognostication and may also present as a potential early surrogate outcome for future intracerebral hemorrhage treatment trials.

Background: People with aphasia present with different of demographic, language, stroke, and impairment profiles. A Cochrane review found that two-thirds of included trials had comparison data on p...

Finding, testing and demonstrating efficacy of new treatments for stroke recovery is a multifaceted challenge. We believe that to advance the field, neurorehabilitation trials need a conceptually rigorous starting framework. An essential first step is to agree on definitions of sensorimotor recovery and on measures consistent with these definitions. Such standardization would allow pooling of participant data across studies and institutions aiding meta-analyses of completed trials, more detailed exploration of recovery profiles of our patients and the generation of new hypotheses. Here, we present the results of a consensus meeting about measurement standards and patient characteristics that we suggest should be collected in all future stroke recovery trials. Recommendations are made considering time post stroke and are aligned with the international classification of functioning and disability. A strong case is made for addition of kinematic and kinetic movement quantification. Further work is being undertaken by our group to form consensus on clinical predictors and pre-stroke clinical data that should be collected, as well as recommendations for additional outcome measurement tools. To improve stroke recovery trials, we urge the research community to consider adopting our recommendations in their trial design.

Background Aphasia and dysarthria have major implications for activities of daily living and social participation following stroke. Few studies describe recovery in the acute stroke setting. We described the evolution of aphasia and dysarthria by three-months poststroke. Methods We conducted a retrospective analysis of pooled clinical trial data from the Virtual International Stroke Trials Archive. We defined aphasia and dysarthria at baseline as a score of ≥1 on the Best Language (Item 9) and Dysarthria (Item 10) domains of the National Institutes of Health Stroke Scale, respectively. We described recovery from these impairments by three-months. Covariate adjusted analyses described the associations between aphasia, dysarthria, and functional outcome using the modified Rankin Scale at three-months following stroke. Results At baseline, 4039/8904 (45·4%) people presented with aphasia and 6192 (69·5%) with dysarthria; 2639 (29·6%) had both impairments. By three-months, aphasia and dysarthria had resolved in 1292/7219 (17·9%) and 2892/7219 (40·1%) survivors, respectively, but persisted in 1713/7219 (23·7%) and 1940/7219 (27%), respectively. Age and severity of initial stroke were associated with poor recovery, whereas thrombolysis was associated with improved recovery. Aphasia at baseline [ P = 0·049, odds ratio = 0·89, 95% confidence interval (0·79,1·00)] and persistent aphasia at three-months [ P < 0·0001, odds ratio = 0·31, 95% confidence interval (0·27, 0·35)] were each associated with poorer modified Rankin Scale scores at three-months. Conclusion Aphasia or dysarthria persisted in at least a quarter of people in our dataset at three-months following stroke. The association between persistent aphasia at three-months and poor modified Rankin Scale renders this impairment a major therapeutic target for recovery and restitution.

Introduction: \ud Traditional approaches to clinical research have, as yet, failed to provide effective treatments for vascular dementia (VaD). Novel approaches to collation and synthesis of data may allow for time and cost efficient hypothesis generating and testing. These approaches may have particular utility in helping us understand and treat a complex condition such as VaD.\ud \ud Methods: \ud We present an overview of new uses for existing data to progress VaD research. The overview is the result of consultation with various stakeholders, focused literature review and learning from the group’s experience of successful approaches to data repurposing. In particular, we benefitted from the expert discussion and input of delegates at the 9th International Congress on Vascular Dementia (Ljubljana, 16-18th October 2015).\ud \ud Results: \ud We agreed on key areas that could be of relevance to VaD research: systematic review of existing studies; individual patient level analyses of existing trials and cohorts and linking electronic health record data to other datasets. We illustrated each theme with a case-study of an existing project that has utilised this approach.\ud \ud Conclusions: \ud There are many opportunities for the VaD research community to make better use of existing data. The volume of potentially available data is increasing and the opportunities for using these resources to progress the VaD research agenda are exciting. Of course, these approaches come with inherent limitations and biases, as bigger datasets are not necessarily better datasets and maintaining rigour and critical analysis will be key to optimising data use.

Background: Early Neurological Worsening (ENW) is common after ICH, and predicts poor outcome. However, there is limited data as to what degree of ENW best relates to outcome. We used two ICH cohorts to refine and validate a definition of ENW that best predicted 90-day outcomes. Methods: We generated receiver operating characteristic (ROC) curves for the association between 24-hour NIHSS change and ICH outcomes using data from the VISTA collaboration. Primary outcome was poor outcome at 90 days (mRS 4-6); secondary outcomes were other mRS cutpoints (mRS 2-6, 3-6, 5-6, 6). We tested the commonly used NIHSS≥4 definition and in addition employed Youden’s J Index to select optimal cutpoints and calculated sensitivity, specificity, and predictive values. Independent predictors of poor outcome were determined via multivariable logistic regression. Definitions were validated in the prospectively collected PREDICT-ICH cohort. Results: Using 552 patients from the VISTA cohort, ROC curves of 24hr NIHSS change had an area under the curve of 0.75. NIHSS change of ≥0 at 24hrs was seen in 46.4%. Youden’s method showed an optimum cutoff at -0.5. Based on this, ENW defined as >0 (Sens 43%, Spec 91%, PPV 83%, aOR 7.13 [CI:4.05-12.55]), ≥0 (Sens 65%, Spec 73%, PPV 70%, aOR 5.05 [CI:3.25-7.85]), or ≥-1 (Sens 78%, Spec 59%, PPV 65%, aOR 6.04 [CI:3.75-9.71]) all accurately predicted poor outcome. PPV increased with higher NIHSS cutoffs, but at the cost of lower sensitivities. Regression confirmed that all definitions independently predicted outcome at all mRS cutpoints. ENW definitions reproduced well in the validation cohort of 275 patients. Conclusion: All NIHSS cut-offs for ENW predict clinical outcome, regardless of outcome definition. In particular, lack of clinical improvement at 24 hours (i.e. NIHSS is the same or higher) robustly predicted poor outcome, but may not be sufficiently reliable to determine clinical management.

Supplemental material, Measurement_Supplementary_Tables for Standardized Measurement of Sensorimotor Recovery in Stroke Trials: Consensus-Based Core Recommendations from the Stroke Recovery and Rehabilitation Roundtable* by Gert Kwakkel, Natasha A. Lannin, Karen Borschmann, Coralie English, Myzoon Ali, Leonid Churilov, Gustavo Saposnik, Carolee Winstein, Erwin E. H. van Wegen, Steven L. Wolf, John W. Krakauer and Julie Bernhardt in Neurorehabilitation and Neural Repair

Background Aphasia affects up to a third of the stroke population and is associated with poor social participation and quality of life. Yet people with aphasia may be excluded from some types of stroke research due to challenges in informing, consenting, and conducting follow-up in this population. Aims and/or hypothesis We described the representation of those with aphasia in acute stroke clinical research, the level of inclusion across international trial sites, and whether there have been improvements in the inclusion of this population in recent clinical trials. Methods We conducted a retrospective analysis of clinical trial data from the Virtual International Stroke Trials Archive (VISTA), defining aphasia using the Best Language (item 9) domain of the National Institutes of Health Stroke Scale. We used proportional odds modeling, adjusting for age, gender, ethnicity, stroke severity, medical history, hemisphere affected by stroke, and trial eligibility criteria, to examine the associations between year, location of enrollment, inclusion, and attrition of those with aphasia. Results Data were available for 8904 patients from 10 trials; no trials listed aphasia as an exclusion criterion. At baseline, aphasia was present in 4039 (45·4%); severe/global aphasia was present in 2688 (30·2%). We observed no geographic or longitudinal disparity in the attrition of these patients at three-months. Centers in the Philippines recruited fewer people [ P = 0·05, odds ratio = 0·5, 95% confidence interval (0·2, 1·0)], while centers in Central and South America included more people with severe/global aphasia [ P = 0·0004, odds ratio = 2·4, 95% confidence interval (1·3, 4·3)], when compared with centers in the USA and Canada. Conclusion Acute stroke trials have demonstrated the feasibility of including people with aphasia in stroke research; we observed geographic variations that were not entirely explained by case mix or trial eligibility criteria. Similar levels of inclusion should be sought in nonemergency stroke trials to improve the applicability of research findings to this population.

Background Previous studies suggested that enlarged perivascular spaces are neuroimaging markers of cerebral small vessel disease. However, it is not clear whether enlarged perivascular spaces are associated with cognitive impairment. We aimed to determine the cross-sectional relationship between enlarged perivascular spaces and small vessel disease, and to investigate the relationship between enlarged perivascular spaces and subsequent cognitive impairment in patients with recent cerebral ischemic event. Methods Anonymized data were accessed from the virtual international stroke trial archive. We rated number of lacunes, white matter hyperintensities, brain atrophy, and enlarged perivascular spaces with validated scales on magnetic resonance brain images after the index stroke. We defined cognitive impairment as a mini mental state examination score of ≤26, recorded at one year post stroke. We examined the associations between enlarged perivascular spaces and clinical and imaging markers of small vessel disease at presentation and clinical evidence of cognitive impairment at one year using linear and logistic regression models. Results We analyzed data on 430 patients with mean (±SD) age 64.7 (±12.7) years, 276 (64%) males. In linear regression analysis, age (β = 0.24; p Conclusions Our data show that in patients with ischemic cerebral events, enlarged perivascular spaces are cross-sectionally associated with age, hypertension, and white matter hyperintensities and suggest that enlarged perivascular spaces in the basal ganglia are associated with cognitive impairment after one year.

Background The Stroke Impact Scale ( SIS ) is a stroke‐specific, quality of life measure recommended for research and clinical practice. Completion rates are suboptimal and could relate to test burden. We derived and validated a short form SIS (SF‐SIS). Methods and Results We examined data from the Virtual International Stroke Trial Archive, generating derivation and validation populations. We derived an SF ‐ SIS by selecting 1 item per domain of SIS , choosing items most highly correlated with total domain score. Our validation described agreement of SF ‐ SIS with original SIS and the SIS ‐16 and correlation with Barthel Index, modified Rankin Scale, National Institutes of Health Stroke Scale, and Euro‐QoL 5 dimensions visual analog scales. We assessed discriminative validity (associations between SF ‐ SIS and factors known to influence outcome [age, physiological parameters, and comorbidity]). We assessed face validity and acceptability by sharing the SF ‐ SIS with a focus group of stroke survivors and multidisciplinary stroke healthcare staff. From 5549 acute study patients (mean age 68.5 [ SD 13] years, mean SIS 64 [ SD 32]) and 332 rehabilitation patients (mean age 65.7 [ SD 11] years, mean SIS 61 [ SD 11]), we derived an 8‐item SF ‐ SIS that demonstrated good agreement with original SIS and good correlation with our chosen functional and quality of life measures (all ρ>0.70, P P SF ‐ SIS across 7 of 8 domains . Conclusions Using multiple, complementary methods, we have derived an SF‐ SIS and demonstrated content, convergent, and discriminant validity. This shortened SIS should allow collection of robust quality of life data with less associated test burden.

Background and Purpose— Sulfonylureas block nonselective cation channels and lower serum glucose and are neuroprotective in animal models of ischemic stroke. Human data on sulfonylureas in acute stroke are sparse and conflicting. We aimed to measure the potential neuroprotective effect of prestroke sulfonylurea use in diabetic patients. Methods— We analyzed data from a prospective cohort of individuals with diabetes mellitus (DM) enrolled in nonreperfusion ischemic stroke trials within Virtual International Stroke Trials Archive (VISTA) comprising 1050 patients, 298 with sulfonylurea use before stroke onset. The primary outcome measures were baseline National Institutes of Health Stroke Scale score and 90-day modified Rankin Scale score. Results— Compared with patients on no DM medications, those with sulfonylurea use before stroke onset presented with less severe stroke (OR, 0.69; 95% CI, 0.53 to 0.89) but had similar modified Rankin Scale scores at 90 days (OR, 0.95; 95% CI, 0.74 to 1.23). Compared with those on other DM agents, there was no difference in initial stroke severity (OR, 1.04; 95% CI, 0.73 to 1.48) nor modified Rankin Scale score at 90 days (OR, 1.00; 95% CI, 0.71 to 1.40). Compared with those using any DM medication, patients not on any treatment experienced higher initial National Institutes of Health Stroke Scale scores (OR, 1.48; 95% CI, 1.18 to 1.86) and were marginally more likely to have poor outcomes (modified Rankin Scale score >2) at 90 days (OR, 1.31; 95% CI, 0.97 to 1.77). Conclusions— Sulfonylurea use before stroke onset did not affect stroke severity or long-term functional outcome compared with other DM treatments. This finding casts doubt on the use of sulfonylureas for prophylactic neuroprotection. Furthermore, patients not using any medication for DM appear to have more severe strokes and worse outcomes.

In the last 15 years many studies have been performed on the treatment of acute stroke. The Virtual International Stroke Trials Archive (VISTA) is an investigator-initiated data base that contains prospectively collected data from patients with acute stroke recruited from controlled trials and is used to answer scientific questions. Analyses have shown that patients with very high blood pressure at the time of admission to a stroke unit have a poor prognosis. Haemorrhagic transformation of an ischaemic infarct is seen frequently in patients with cardio-embolic strokes. Haemorrhagic transformation follows a bimodal distribution with a poor prognosis when occurring late after stroke. In up to 7 % of patients with acute stroke, new onset atrial fibrillation is detected in the stroke unit. VISTA has enabled the establishment and validation of prognostic models for patients with ischaemic or haemorrhagic stroke. The most important risk factor for a poor prognosis in patients with cerebral bleeding is the growth of the initial haemorrhage. On a world-wide comparison, the prognosis of stroke patients in Germany is poorer than in many other countries.

Background and Purpose— The distribution of 3-month modified Rankin scale (mRS) scores has been used as an outcome measure in acute stroke trials. We hypothesized that hospitalization and institutional care home stays within the first 90 days after stroke should be closely related to 90-day mRS, that each higher mRS category will reflect incremental cost, and that resource use may be less clearly linked to the National Institutes of Health Stroke Scale (NIHSS) or Barthel index. Methods— We examined resource use data from the GAIN International trial comparing 90-day mRS with total length of stay in hospital or other institutions during the first 90 days. We repeated analyses using NIHSS and Barthel index scores. Relationships were examined by analysis of variance (ANOVA) with Bonferroni contrasts of adjacent score categories. Estimated costs were based on published Scottish figures. Results— We had full data from 1717 patients. Length of stay was strongly associated with final mRS ( P P Conclusions— Each mRS category reflects different average length of hospital and institutional stay. Associated costs are meaningfully different across the full range of mRS outcomes. Analysis of the full distribution of mRS scores is appropriate for interpretation of treatment effects after acute stroke and more informative than Barthel or NIHSS end points.

Background Mood disorders are frequent after stroke and are associated with poorer quality of life. Previous studies have reported conflicting results as to stroke subtype in the incidence of poststroke mood disorders. We explored the relationship between subcortical ischemic stroke subtype (lacunar) and presence of such symptoms at 1 year after stroke. Methods Anonymized data were accessed from the Virtual International Stroke Trials Archive. Stroke subtypes were classified according to the Trial of Org 10172 in Acute Stroke Treatment classification. Depression and anxiety symptoms were assessed using Hospital Anxiety and Depression Scale. We investigated independent predictors of depression and anxiety symptoms using a logistic regression model. Results Data were available for 2160 patients. Almost one fifth of the patients developed both anxiety and depression at 1-year follow-up. After adjusting for confounders, the lacunar subtype was least associated with both anxiety (odds ratio [OR] = .61; 95% confidence interval [CI] = .46-.80) and depression symptoms (OR = .71; CI = .55-.93) versus other stroke subtypes. Conclusions Lacunar strokes have a weaker association with presence of anxiety and depression symptoms compared with other subtypes.

The summed Alberta Stroke Program Early CT Score (ASPECTS) is useful for predicting stroke outcome. The anatomical information in the CT template is rarely used for this purpose because traditional regression methods are not adept at handling collinearity (relatedness) among brain regions. While penalized logistic regression (PLR) can handle collinearity, it does not provide an intuitive understanding of the interaction among network structures in a way that eigenvector method such as PageRank can (used in Google search engine). In this exploratory analysis we applied graph theoretical analysis to explore the relationship among ASPECTS regions with respect to disability outcome. The Virtual International Stroke Trials Archive (VISTA) was searched for patients who had infarct in at least one ASPECTS region (ASPECTS ≤ 9, ASPECTS = 10 were excluded), and disability (modified Rankin score/mRS). A directed graph was created from a cross correlation matrix (thresholded at false discovery rate of 0.01) of the ASPECTS regions and demographic variables and disability (mRS > 2). We estimated the network-based importance of each ASPECTS region by comparing PageRank and node strength measures. These results were compared with those from PLR. There were 185 subjects, average age 67.5 ± 12.8 years (55% Males). Model 1: demographic variables having no direct connection with disability, the highest PageRank was M2 (0.225, bootstrap 95% CI 0.215-0.347). Model 2: demographic variables having direct connection with disability, the highest PageRank were M2 (0.205, bootstrap 95% CI 0.194-0.367) and M5 (0.125, bootstrap 95% CI 0.096-0.204). Both models illustrate the importance of M2 region to disability. The PageRank method reveals complex interaction among ASPECTS regions with respects to disability. This approach may help to understand the infarcted brain network involved in stroke disability.

Introduction. Limited evidence suggests that visual impairments may influence outcome after stroke. The degree of recovery from these impairments is poorly characterized. Objectives. To describe recovery and to determine whether visual impairments influence functional outcome and quality of life. Methods. We extracted demographic and outcome data from the Virtual International Stroke Trials Archive (VISTA). We examined horizontal eye movement disorders and hemianopia using the Best Gaze and Visual domains of the National Institutes of Health Stroke Scale (NIHSS) and described recovery at 30 and 90 days. Proportional odds modelling was used to examine the association between impairments at baseline, modified Rankin Scale (mRS), and European Quality of Life Score (EQ-5D) at 90 days. Results. Visual impairments were reported in 7,204/11,900 (60.5%) patients at baseline. Complete recovery occurred in 1,398/3,285 (42.6%) and 3,243/7,204 (45.0%) patients by 30 and 90 days respectively. The burden of persistent visual impairment in survivors was 1,135/4,028 (28.2%) at 30 days and 1,915/9,338 (20.5%) at 90 days. Partial gaze palsy (P < .0001; OR = 0.81; 95% CI = 0.74-0.87), forced deviation (P < .0001; OR = 0.48; 95% CI = 0.43-0.53), and complete homonymous hemianopia (P < .0001; OR = 0.67; 95% CI = 0.62-0.73) at baseline were associated with poor mRS at 90 days. Conclusions. The rate of recovery was greater in the first month after stroke, suggesting a potential time frame for interventions. The associations between visual impairments and poor mRS suggest that these impairments should be considered in multidisciplinary assessments and interventions.

Background: Post-stroke hyperglycaemia (PSH) is associated with higher mortality and dependence, but further data on predictors of PSH and its evolution over time are required. We examined the prevalence, predictors, and prognosis of acute PSH using data from well-characterised clinical trials in the VISTA database.\ud \ud Methods: Data were extracted for individual participants enrolled 7.0 mmol/l. Outcome measures were: (1) prevalence of PSH; (2) predictors of PSH by binary logistic regression; (3) mortality, and (4) favourable functional outcome [modified Rankin Scale (mRS) score \ud \ud Results: For 2,649 subjects treated at a median 5.5 h after admission, PSH was present in 1,126 (42.6%, 95% CI 40.7–44.5) on admission and within the first 48 h in 1,421 (53.7%, 95% CI 51.8–55.6). PSH developed between 24 and 48 h in 19.4% (95% CI 17.5–21.4) of initially normoglycaemic subjects. Admission and 48-hour PSH were predicted predominantly by a history of diabetes (for admission PSH: OR 7.40, 95% CI 5.60–9.79) and less clearly by stroke severity. Favourable outcome (mRS \ud \ud Conclusions: Over 40% of ischaemic stroke patients are hyperglycaemic on admission, and 20% of those who are initially normoglycaemic develop hyperglycaemia within 48 h. Diabetes is the strongest predictor of acute hyperglycaemia. Hyperglycaemia within the first 48 h is independently associated with higher mortality and poorer functional outcome, with an absolute increase of 12.9%.

Introduction: Visual impairment after stroke may impact overall disability, but the natural history of recovery from visual impairment (VI) after stroke is poorly characterized. We examined recovery from eye movement disorders and visual field defects after stroke. Methods: We extracted anonymised data on age, medical history, modified Rankin Score (mRS), National Institutes of Health Stroke Scale (NIHSS) and European Quality of Life Score (EQ-5D) from the Virtual International Stroke Trials Archive (VISTA). We described eye movement disorders and visual field defects using the Best Gaze and Visual domains of the NIHSS and related these to recovery at 90 days. As visual neglect was not available in our dataset, we used the Extinction domain on the NIHSS to provide a broad measure of neglect of personal, visual, tactile, auditory or spatial stimulation. We used Proportional Odds Modelling, adjusting for age, medical history, vision-unrelated NIHSS domain scores [total baseline NIHSS score - (Best Gaze + Visual Scores)], rt-PA administration and type of stroke to examine associations among VI at baseline, functional outcome (mRS) and quality of life (EQ-5D) at 90 days. Results: Eye movement disorders or visual field defects were reported in 7,123/11,623 (61.3%) patients at baseline. By 90 days, these impairments had resolved in 3,177/7,123 (44.6%) patients but persisted in 2,074/7,123 (29.1%); 1,622/7,123 (22.8%) patients had died and 250/7,123 (3.5%) patients were lost to follow up. The total burden of persistent VI at 90 days in all stroke survivors was 2,074/9,384 (22.1%). Complete homonymous hemianopia was most prevalent at both baseline (n=4,165; 35.9%) and at 90 days (n=1,071; 11.5%). Partial gaze palsy (p Conclusions: VI is arguably a major stroke-related impairment with 22% of all stroke survivors exhibiting persistent visual impairment at 90 days. The extent to which VI causes poor outcome or is simply associated with severe stroke merits further investigation. The consequences of a co-existing VI should be considered in stroke multidisciplinary rehabilitation assessments and interventions.

Response: The hypothesis that sulfonylurea agents may limit neurological injury through blockade of the SUR1 receptor, expressed under ischemic conditions, is both novel and promising. It is clearly disappointing that the largest clinical study to date to examine this hypothesis, in the robustly validated Virtual International Stroke Trial Archive (VISTA) registry of patients with acute stroke, identified no association between clinical outcome and sulfonylurea treatment.1 Foremost among the concerns raised by Simard and colleagues is the potential for misclassification regarding treatment. We analyzed a subset of VISTA in which complete information existed on concomitant medications, including start and end dates of administration, derived from trials with comprehensive data including annotated case report forms available for confirmation. These trials were subjected to rigorous monitoring and source data verification to meet worldwide regulatory standards. We identified patients on sulfonylureas at the time …

Background and purpose Haematoma expansion following intracerebral haemorrhage is a major determinant of early neurological worsening and poor clinical outcome. This has created interest in improving patient selection for therapies targeting haematoma expansion. Based on prior observations, we hypothesised that intracerebral haemorrhage volumes under 10 ml would be less likely to expand. We additionally sought to define a baseline haematoma volume below which significant growth was not observed. Methods Patient data were obtained from the Virtual International Stroke Trials Archive. Patients with intracerebral haemorrhage presented within six-hours of symptom onset had baseline clinical, radiological and laboratory data, and computed tomographic scan at 72 h and three-month follow-up. The predictor of interest was baseline haematoma volume. Primary outcomes were absolute and relative haematoma growth. Secondary outcomes were early neurological worsening, good functional outcome, and 90-day mortality. Results The final dataset consisted of 496 patients. Baseline haematoma volumes under 10 ml were associated with much lower odds of absolute expansion compared to larger haematomas. Smaller haematomas were associated with significantly decreased odds of early neurological worsening and three-month mortality, and increased odds of good functional outcome. The smallest haematoma to double in size was 3·97 ml. Among the 34 subjects with very small haematomas (Conclusions This study provides observational evidence that very small haematomas are unlikely to expand, by commonly used absolute growth definitions, and may represent a subgroup of patients with intracerebral haemorrhage destined towards good clinical outcomes.

Background Stroke rehabilitation is a complex intervention. Many factors influence the interaction between the patient and the elements of the intervention. Rehabilitation interventions are aimed at altering different domains of patient outcome including body functions, activity and participation. As a consequence, randomised clinical trials in this area are difficult to design. We developed an archive of stroke rehabilitation trials (VISTA-Rehab) to act as a resource to help trialists model and design future rehabilitation studies. Methods We developed specific eligibility criteria for the entry of stroke rehabilitation trials into the archive. We established a Steering Committee to oversee projects and publications and commenced the recruitment of rehabilitation trials into this resource. Results As of August 2009, VISTA-Rehab contains data from 23 stroke rehabilitation trials (>3400 patients). Demographic data, including age [median=73, interquartile range (63,79)], gender (male=53%) and initial dependency [median baseline Barthel index score=6, interquartile range ( 9 , 19 )], are available for all patients. Outcome measures include the modified Rankin Scale, Barthel Index, Rivermead Motor Assessment, Fugl-Meyer Assessment, General Health Questionnaire and Nottingham Extended Activities of Daily Living Scale. Conclusion VISTA-Rehab expands the Virtual International Stroke Trials Archive to include rehabilitation trials. Anonymised data can be used to examine questions specific to stroke rehabilitation and to generate novel hypotheses.

Introduction The National Institutes of Health Stroke Scale (NIHSS) and Scandinavian Stroke Scale (SSS) are both validated measures of neurologic impairment and have been used in many acute stroke trials. Methods for interconverting SSS and NIHSS are needed. Methods Conversion equations were developed using linear regression (both unadjusted, and adjusted for age and sex) using a random 50% of the data at both baseline and 90 days. The remaining 50% of data were used to test the accuracy of the models produced. Results Data from 5 acute stroke trials (2004 patients) were included. Fitted models at baseline were NIHSS=25.68 – 0.43 ∗ SSS ( R 2 = 0.57, prediction error [PE] –0.2, P = .20), and SSS=50.37 – 1.63 ∗ NIHSS ( R 2 = 0.59, PE 0.2, P = .35). The 90-day models were NIHSS=22.99 – 0.39 ∗ SSS ( R 2 = 0.82, PE –0.3, P = .001), and SSS=56.68 – 2.20 ∗ NIHSS ( R 2 = 0.80, PE –0.4, P = .08). Adjustment did not materially improve the R 2 values. Conclusion Total scores for NIHSS and SSS may be interconverted with good precision; the mathematic conversion equations may prove useful in clinical practice and in comparison of data from observational studies and randomized trials.