Use of a 3-item short-form version of the Barthel Index for use in stroke: systematic review and external validation

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<0.001). Using rehabilitation trial data (n=332), SF-BI demonstrated modest correlation with quality of life measures Stroke Impact Scale and 5 domain EuroQOL (ρ≥0.50, P<0.001). Prespecified prognostic factors were associated with SF-BI outcomes (all P<0.001). Our factor analysis described a 3 factor structure, and item reduction suggested an optimal 3-item SF-BI comprising bladder control, transfer, and mobility items in keeping with 1 of the 3-item SF-BI previously described in the literature. 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

Interruption to antiplatelet therapy early after acute ischaemic stroke: a nested case-control study

Aims: Antiplatelet drugs are often discontinued early after ischaemic stroke, either because of poor compliance, complications or withdrawal of care. It is unclear whether this places patients at increased risk of recurrence. We explored the association between cardiovascular event rate and persistence with prescribed antiplatelet drugs. Methods: We used a matched case–control design using the Virtual International Stroke Trials Archive (VISTA). Cases were patients who had an acute coronary syndrome, recurrent stroke or transient ischaemic attack within 90 days post-stroke and were matched for age ± 10 years and sex with up to four controls. Antiplatelet use was categorized as persistent (used for >3 days and continued up to day 90), early cessation (used antiplatelet 3 days but stopped prior to day 90). These categories were compared in cases and controls using a conditional logistic regression model that adjusted for potential confounders. Results: A total of 970 patients were included, of whom 194 were cases and 776 were matched controls. At 90 days, 10 cases (5.2%) and 58 controls (7.5%) stopped/interrupted their antiplatelet. The risk of cardiovascular event was not different in stopped/interrupted users (adjusted odds ratio 0.70, 95% confidence interval 0.33, 1.48; P = 0.352) and early cessations (adjusted odds ratio 1.04, 95% confidence interval 0.62, 1.74; P = 0.876) when compared to persistent users. Conclusion: We found no increased risk in patients who stopped and interrupted antiplatelets early after stroke but the study was limited by a small sample size and further research is needed

Clinical selection strategies to identify ischemic stroke patients with large anterior vessel occlusion: results from SITS-ISTR (Safe Implementation of Thrombolysis in Stroke International Stroke Thrombolysis Registry)

Background and Purpose—The National Institutes of Health Stroke Scale (NIHSS) correlates with presence of large anterior vessel occlusion (LAVO). However, the application of the full NIHSS in the prehospital setting to select patients eligible for treatment with thrombectomy is limited. Therefore, we aimed to evaluate the prognostic value of simple clinical selection strategies. Methods—Data from the Safe Implementation of Thrombolysis in Stroke International Stroke Thrombolysis Registry (January 2012–May 2014) were analyzed retrospectively. Patients with complete breakdown of NIHSS scores and documented vessel status were included. We assessed the association of prehospital stroke scales and NIHSS symptom profiles with LAVO (internal carotid artery, carotid-terminus or M1-segment of the middle cerebral artery). Results—Among 3505 patients, 23.6% (n=827) had LAVO. Pathological finding on the NIHSS item best gaze was strongly associated with LAVO (adjusted odds ratio 4.5, 95% confidence interval 3.8–5.3). All 3 face–arm–speech–time test (FAST) items identified LAVO with high sensitivity. Addition of the item gaze to the original FAST score (G-FAST) or high scores on other simplified stroke scales increased specificity. The NIHSS symptom profiles representing total anterior syndromes showed a 10-fold increased likelihood for LAVO compared with a nonspecific clinical profile. If compared with an NIHSS threshold of ≥6, the prehospital stroke scales performed similarly or even better without losing sensitivity. Conclusions—Simple modification of the face–arm–speech–time score or evaluating the NIHSS symptom profile may help to stratify patients’ risk of LAVO and to identify individuals who deserve rapid transfer to comprehensive stroke centers. Prospective validation in the prehospital setting is required

Interruption to antiplatelet therapy early after acute ischaemic stroke: a nested case-control study

Aims: Antiplatelet drugs are often discontinued early after ischaemic stroke, either because of poor compliance, complications or withdrawal of care. It is unclear whether this places patients at increased risk of recurrence. We explored the association between cardiovascular event rate and persistence with prescribed antiplatelet drugs. Methods: We used a matched case–control design using the Virtual International Stroke Trials Archive (VISTA). Cases were patients who had an acute coronary syndrome, recurrent stroke or transient ischaemic attack within 90 days post-stroke and were matched for age ± 10 years and sex with up to four controls. Antiplatelet use was categorized as persistent (used for >3 days and continued up to day 90), early cessation (used antiplatelet 3 days but stopped prior to day 90). These categories were compared in cases and controls using a conditional logistic regression model that adjusted for potential confounders. Results: A total of 970 patients were included, of whom 194 were cases and 776 were matched controls. At 90 days, 10 cases (5.2%) and 58 controls (7.5%) stopped/interrupted their antiplatelet. The risk of cardiovascular event was not different in stopped/interrupted users (adjusted odds ratio 0.70, 95% confidence interval 0.33, 1.48; P = 0.352) and early cessations (adjusted odds ratio 1.04, 95% confidence interval 0.62, 1.74; P = 0.876) when compared to persistent users. Conclusion: We found no increased risk in patients who stopped and interrupted antiplatelets early after stroke but the study was limited by a small sample size and further research is needed

Antiplatelet therapy following ischaemic stroke: continue or change pre-existing therapy?

Introduction: Antiplatelet therapy is routinely prescribed early after ischaemic stroke. Many patients will already be taking antiplatelet therapy and it is unknown whether these patients should continue the same antiplatelet treatment or switch to a different regimen. Methods:We selected patients with ischaemic stroke from the Virtual International Stroke Trials Archive database who were prescribed antiplatelets both before and after their stroke and who had detailed records of adverse events after stroke. We compared patients who changed to a new antiplatelet regimen after their stroke to those who continued the same regimen. The primary outcome was recurrent ischaemic stroke within 90 days after their index stroke and the secondary outcome was intracranial haemorrhage (ICH) or extracranial haemorrhage (ECH). We used logistic regression analysis and adjusted for age and baseline NIHSS. Results: A total of 1129 participants were included. Of these, 538 subjects changed antiplatelet regimen post stroke and 591 continued the same regimen. A recurrent ischaemic event occurred in 4.1% of subjects who changed regimen and 4.3% who continued unchanged (adjusted OR¼0.93; 95% CI 0.54–1.75, p¼0.929). The incidence of ICH and ECH within the first 90 days was similar in both groups (2.4% vs. 2.6% (adjusted OR¼1.02; 95% CI 0.48–2.18, p¼0.955) and 4.7% vs. 2.9% (adjusted OR¼1.82; 95% CI 0.96–3.43, p¼0.065), respectively). Discussion: The analysis was performed using a non-randomised registry data. Conclusion: In patients who suffer ischaemic stroke whilst taking antiplatelets, a change in antiplatelet regimen was not associated with an altered risk of early recurrent ischaemic stroke rate or bleeding. However, the results must be interpreted in view of the low event rates

Dependency and health utilities in stroke: data to inform cost-effectiveness analyses

Introduction: Health utilities (HU) assign preference weights to specific health states and are required for costeffectiveness analyses. Existing HU for stroke inadequately reflect the spectrum of post-stroke disability. Using international stroke trial data, we calculated HU stratified by disability to improve precision in future cost-effectiveness analyses. Materials and methods: We used European Quality of Life Score (EQ-5D-3L) data from the Virtual International Stroke Trials Archive (VISTA) to calculate HU, stratified by modified Rankin Scale scores (mRS) at 3 months. We applied published value sets to generate HU, and validated these using ordinary least squares regression, adjusting for age and baseline National Institutes of Health Stroke Scale (NIHSS) scores. Results: We included 3858 patients with acute ischemic stroke in our analysis (mean age: 67.5+-12.5, baseline NIHSS: 12+-5). We derived HU using value sets from 13 countries and observed significant international variation in HU distributions (Wilcoxon signed-rank test p<0.0001, compared with UK values). For mRS=0, mean HU ranged from 0.88 to 0.95; for mRS=5, mean HU ranged from -0.48 to 0.22. OLS regression generated comparable HU (for mRS=0, HU ranged from 0.9 to 0.95; for mRS=5, HU ranged from -0.33 to 0.15). Patients’ mRS scores at 3 months accounted for 65–71% of variation in the generated HU. Conclusion: We have generated HU stratified by dependency level, using a common trial endpoint, and describing expected variability when applying diverse value sets to an international population. These will improve future cost-effectiveness analyses. However, care should be taken to select appropriate value sets

Online tool to improve stratification of adverse events in stroke clinical trials

Background and Purpose—Knowing characteristic adverse events (AEs) and their incidence among patients participating in acute stroke trials may assist interpretation of future studies. We aimed to develop an online tool to inform stroke trial safety. Methods—We identified relevant AEs from patients within the Virtual International Stroke Trials Archive (VISTA), using receiver operating characteristic principles. We modeled their incidence on patient age, baseline National Institutes of Health Stroke Scale, and comorbidities using binary logistic regression. Models with an R2&gt;5% were deemed powerful enough to predict expected AE incidences and were included. The calculator was developed using programs R and Visual Studios. Results—Forty-eight of the most common AEs were identified and incorporated into the IschAEmic Stroke Calculator. The calculator, publicly available athttp://www.vistacollaboration.org calculates the expected incidence of AEs or groups of AEs in a trial cohort and where possible compares them with the observed incidence. Conclusions—The IschAEmic Stroke Calculator is an open access resource to support safety interpretation within acute stroke trials. Prediction of AEs with higher likelihood of occurrence may direct preventive clinical measures

Efficacy and safety of digoxin in patients with heart failure and reduced ejection fraction according to diabetes status: An analysis of the Digitalis Investigation Group (DIG) trial

Background: Digoxin is recommended in symptomatic heart failure patients with reduced ejection fraction (HF-REF) in sinus rhythm and refractory to other evidence-based therapy. Although HF-REF patients with diabetes have worse functional status than those without, the effects of digoxin have not been specifically evaluated according to diabetes status. Methods: We examined the efficacy and safety of digoxin in HF-REF patients with and without diabetes in the Digitalis Investigation Group trial. Mortality from all-cause, cardiovascular (CV) causes and heart failure (HF), along with HF hospitalisation and suspected digoxin toxicity were analyzed according to diabetes status and randomised treatment assignment. Results: Of the 6800 patients, those with diabetes (n = 1933) were older, more often women, had worse clinical status and more co-morbidity than those without diabetes. All-cause and CV mortality were higher in patients with diabetes than in those without and digoxin did not reduce mortality in either sub-group. The rate of HF hospitalization (per 100 person-years) in patients with diabetes was higher than in those without and was reduced by digoxin in both patient groups: diabetes – placebo 20.5 and digoxin 16.0 (HR 0.79, 95% CI: 0.68–0.91); no diabetes – placebo 12.7 and digoxin 8.7 (HR 0.69, 0.62–0.77); interaction p = 0.14. Suspected digoxin toxicity in patients randomised to digoxin was more common among patients with diabetes than without (6.5% versus 5.8%), as was hospitalisation for digoxin toxicity (1.4% versus 0.8%). Conclusion: Added to an ACE inhibitor, digoxin reduced HF hospitalisation in HF-REF patients with and without diabetes without a substantial risk of toxicity

Sex and stroke in thrombolyzed patients and controls

Background and Purpose—We hypothesized that any sex-related difference in outcome poststroke is explained by other prognostic factors and that the response to intravenous recombinant tissue-type plasminogen activator (r-tPA) is equal in males and females after adjustment for such factors. Methods—We accessed an independent collection of randomized clinical trials—the VISTA (Virtual International Stroke Trials Archive). Data were preprocessed by selecting complete cases (n=8028) and matching females to males (coarsened exact matching, n=4575, 24.3% r-tPA). Outcome was assessed by the 7-point modified Rankin Scale (mRS) measured at 90 days after ischemic stroke. Relationship among variables was estimated by adjusted regression analysis. Results—In nonthrombolyzed patients, ordinal analysis of mRS adjusting for stroke- and sex-related prognostic factors suggested comparable outcomes for females and males (odds ratio, 0.96; 95% confidence interval, 0.85–1.06). Females responded comparably to r-tPA as did males, irrespective of the outcome definition of mRS (ordinal: PInteraction=0.46, relative excess risk because of interaction=0). The number needed to treat was 6.8 and 11.2 for 1 female to achieve mRS score of 0 to 2 and 0 to 1, which was highly congruent with males. Analysis for a nonlinear variation of age-by-sex revealed a good outcome for females &lt;45 years with significant disadvantage thereafter (mRS score of 0–2: PInteraction=0.004). No relationship between sex, r-tPA, and bleeding complications was evident. Conclusions—Functional outcome (mRS) without r-tPA was overall similar between the sexes, as was the response to r-tPA. Nonlinear sex-by-age interaction improved estimates of functional independence; this should be considered in sex-related studies in stroke