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

Renal replacement modality and stroke risk in end-stage renal disease—a national registry study

Background: The risk of stroke in end-stage renal disease (ESRD) on renal replacement therapy (RRT) is up to 10-fold greater than the general population. However, whether this increased risk differs by RRT modality is unclear. Methods: We used data contained in the Scottish Renal Registry and the Scottish Stroke Care Audit to identify stroke in all adult patients who commenced RRT for ESRD from 2005 to 2013. Incidence rate was calculated and regression analyses were performed to identify variables associated with stroke. We explored the effect of RRT modality at initiation and cumulative dialysis exposure by time-dependent regression analysis, using transplant recipients as the reference group. Results: A total of 4957 patients commenced RRT for ESRD. Median age was 64.5 years, 41.5% were female and 277 patients suffered a stroke (incidence rate was 18.6/1000 patient-years). Patients who had stroke were older, had higher blood pressure and were more likely to be female and have diabetes. On multivariable regression older age, female sex, diabetes and higher serum phosphate were associated with risk of stroke. RRT modality at initiation was not. On time-dependent analysis, haemodialysis (HD) exposure was independently associated with increased risk of stroke. Conclusions: In patients with ESRD who initiate RRT, HD use independently increases risk of stroke compared with transplantation. Use of peritoneal dialysis did not increase risk on adjusted analysis

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

Coagulation and fibrinolytic activity of tenecteplase and alteplase in acute ischemic stroke

Background and Purpose—We compared the fibrinolytic activity of tenecteplase and alteplase in patients with acute ischemic stroke, and explored the association between hypofibrinogenaemia and intracerebral hemorrhage. Methods—Venous blood samples from a subgroup of participants in the Alteplase–Tenecteplase Trial Evaluation for Stroke Thrombolysis (ATTEST) study were obtained at pretreatment, 3 to 12 hours, and 24±3 hours post-intravenous thrombolysis for analyses of plasminogen, plasminogen activator inhibitor-1, D-dimer, factor V, fibrinogen, and fibrin(ogen) degradation products, in addition to routine coagulation assays. Related sample Wilcoxon signed-rank tests were used to test the within-group changes, and independent Mann–Whitney tests for between-group differences. Results—Thirty patients were included (alteplase=14 and tenecteplase=16) with similar baseline demographics. Compared with baseline, alteplase caused significant hypofibrinogenaemia (P=0.002), prolonged prothrombin time (P=0.011), hypoplasminogenaemia (P=0.001), and lower factor V (P=0.002) at 3 to 12 hours after administration with persistent hypofibrinogenaemia at 24 hours (P=0.011), whereas only minor hypoplasminogenaemia (P=0.029) was seen in the tenecteplase group. Tenecteplase consumed less plasminogen (P<0.001) and fibrinogen (P=0.002) compared with alteplase. Conclusions—In patients with acute ischemic stroke, alteplase 0.9 mg/kg caused significant disruption of the fibrinolytic system, whereas tenecteplase 0.25 mg/kg did not, consistent with the trend toward lower intracerebral hemorrhage incidence with tenecteplase in the ATTEST study

The association of atrial fibrillation and ischaemic stroke in patients on haemodialysis: a competing risk analysis

Background: Stroke is common in patients with end-stage renal disease (ESRD) treated with hemodialysis (HD) and associated with high mortality rate. In the general population, atrial fibrillation (AF) is a major risk factor for stroke and therapeutic anticoagulation is associated with risk reduction, whereas in ESRD the relationship is less clear. Objective: The purpose of this study is to demonstrate the influence of AF on stroke rates and probability in those on HD following competing risk analyses. Design: A national record linkage cohort study. Setting: All renal and stroke units in Scotland, UK. Patients: All patients with ESRD receiving HD within Scotland from 2005 to 2013 (follow-up to 2015). Measurements: Demographic, clinical, and laboratory data were linked between the Scottish Renal Registry, Scottish Stroke Care Audit, and hospital discharge data. Stroke was defined as a fatal or nonfatal event and mortality derived from national records. Methods: Associations for stroke were determined using competing risk models: the cause-specific hazards model and the Fine and Gray subdistribution hazards model accounting for the competing risk of death in models of all stroke, ischemic stroke, and first-ever stroke. Results: Of 5502 patients treated with HD with 12 348.6-year follow-up, 363 (6.6%) experienced stroke. The stroke incidence rate was 26.7 per 1000 patient-years. Multivariable regression on the cause-specific hazard for stroke demonstrated age, hazard ratio (HR) (95% confidence interval [CI]) = 1.04 (1.03-1.05); AF, HR (95% CI) = 1.88 (1.25-2.83); prior stroke, HR (95% CI) = 2.29 (1.48-3.54), and diabetes, HR (95% CI) = 1.92 (1.45-2.53); serum phosphate, HR (95% CI) = 2.15 (1.56-2.99); lower body weight, HR (95% CI) = 0.99 (0.98-1.00); lower hemoglobin, HR (95% CI) = 0.88 (0.77-0.99); and systolic blood pressure (BP), HR (95% CI) = 1.01 (1.00-1.02), to be associated with an increased stroke rate. In contrast, the subdistribution HRs obtained following Fine and Gray regression demonstrated that AF, weight, and hemoglobin were not associated with stroke risk. In both models, AF was significantly associated with nonstroke death. Limitations: Our analyses derive from retrospective data sets and thus can only describe association not causation. Data on anticoagulant use are not available. Conclusions: The incidence of stroke in HD patients is high. The competing risk of “prestroke” mortality affects the relationship between AF and risk of future stroke. Trial designs for interventions to reduce stroke risk in HD patients, such as anticoagulation for AF, should take account of competing risks affecting associations between risk factors and outcomes

Derivation and validation of a modified short form of the stroke impact scale

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. Methods and Results: We examined data from the Virtual International Stroke Trial Archive, generating derivation and validation populations. We derived a short form (SF-SIS) by selecting one 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, NIHSS, and EQ-5D visual analogue 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]; 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 QOL measures (all rho>0.70; p<0.0001). Significant associations were seen with our chosen predictors of stroke outcome in the acute group (p<0.0001). The focus group agreed with the choice of items for SF-SIS across 7/8 domains. Conclusions: Using multiple, complementary methods we have derived a short form 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

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

Inequality in Care and Differences in Outcome Following Stroke in People With ESRD

Acknowledgments: MF is funded by a Kidney Research UK Training Fellowship and is supported by a grant from Darlinda’s Charity for Renal Research.Peer reviewedPublisher PD

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