Showing papers by "Pooja Khatri published in 2017"

Treatment and Outcome of Hemorrhagic Transformation After Intravenous Alteplase in Acute Ischemic Stroke: A Scientific Statement for Healthcare Professionals From the American Heart Association/American Stroke Association

Abstract: Purpose— Symptomatic intracranial hemorrhage (sICH) is the most feared complication of intravenous thrombolytic therapy in acute ischemic stroke. Treatment of sICH is based on expert opinion and small case series, with the efficacy of such treatments not well established. This document aims to provide an overview of sICH with a focus on pathophysiology and treatment. Methods— A literature review was performed for randomized trials, prospective and retrospective studies, opinion papers, case series, and case reports on the definitions, epidemiology, risk factors, pathophysiology, treatment, and outcome of sICH. The document sections were divided among writing group members who performed the literature review, summarized the literature, and provided suggestions on the diagnosis and treatment of patients with sICH caused by systemic thrombolysis with alteplase. Several drafts were circulated among writing group members until a consensus was achieved. Results— sICH is an uncommon but severe complication of systemic thrombolysis in acute ischemic stroke. Prompt diagnosis and early correction of the coagulopathy after alteplase have remained the mainstay of treatment. Further research is required to establish treatments aimed at maintaining integrity of the blood-brain barrier in acute ischemic stroke based on inhibition of the underlying biochemical processes.

Correlation of imaging and histopathology of thrombi in acute ischemic stroke with etiology and outcome: a systematic review

Abstract: Background and purpose Studying the imaging and histopathologic characteristics of thrombi in ischemic stroke could provide insights into stroke etiology and ideal treatment strategies We conducted a systematic review of imaging and histologic characteristics of thrombi in acute ischemic stroke Materials and methods We identified all studies published between January 2005 and December 2015 that reported findings related to histologic and/or imaging characteristics of thrombi in acute ischemic stroke secondary to large vessel occlusion The five outcomes examined in this study were (1) association between histologic composition of thrombi and stroke etiology; (2) association between histologic composition of thrombi and angiographic outcomes; (3) association between thrombi imaging and histologic characteristics; (4) association between thrombi imaging characteristics and angiographic outcomes; and (5) association between imaging characteristics of thrombi and stroke etiology A meta-Analysis was performed using a random effects model Results There was no significant difference in the proportion of red blood cell (RBC)-rich thrombi between cardioembolic and large artery atherosclerosis etiologies (OR 162, 95% CI 01 to 280, p=063) Patients with a hyperdense artery sign had a higher odds of having RBC-rich thrombi than those without a hyperdense artery sign (OR 90, 95% CI 26 to 312, p<001) Patients with a good angiographic outcome had a mean thrombus Hounsfield unit (HU) of 551±31 compared with a mean HU of 484±19 for patients with a poor angiographic outcome (mean standard difference 65, 95% CI 27 to 102, p<0001) There was no association between imaging characteristics and stroke etiology (OR 113, 95% CI 032 to 400, p=085) Conclusions The hyperdense artery sign is associated with RBC-rich thrombi and improved recanalization rates However, there was no association between the histopathological characteristics of thrombi and stroke etiology and angiographic outcomes

Analyses of thrombi in acute ischemic stroke: A consensus statement on current knowledge and future directions

Abstract: Limited data exist on clot composition and detailed characteristics of arterial thrombi associated with large vessel occlusion in acute ischemic stroke Advances in endovascular thrombectomy and related imaging modalities have created a unique opportunity to analyze thrombi removed from cerebral arteries Insights into thrombus composition, etiology, physical properties and neurovascular interactions may lead to future advancements in acute ischemic stroke treatment and improved clinical outcomes Advances in imaging techniques may enhance clot characterization and inform therapeutic decision-making prior to treatment and reveal stroke etiology to guide secondary prevention Current imaging techniques can provide some information about thrombi, but there remains much to evaluate about relationships that may exist among thrombus composition, occlusion characteristics and treatment outcomes Improved pathophysiological characterization of clot types, their properties and how these properties change over time, together with clinical correlates from ongoing studies, may facilitate revascularization with thrombolysis and thrombectomy Interdisciplinary approaches covering clinical, engineering and scientific aspects of thrombus research will be key to advancing the understanding of thrombi and improving acute ischemic stroke therapy This consensus statement integrates recent research on clots and thrombi retrieved from cerebral arteries and provides a rationale for further analyses, including current opportunities and limitations

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).

Abstract: 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 p...

Selection of patients for intra-arterial treatment for acute ischaemic stroke: development and validation of a clinical decision tool in two randomised trials

Abstract: Objective To improve the selection of patients with acute ischaemic stroke for intra-arterial treatment using a clinical decision tool to predict individual treatment benefit. Design Multivariable regression modelling with data from two randomised controlled clinical trials. Setting 16 hospitals in the Netherlands (derivation cohort) and 58 hospitals in the United States, Canada, Australia, and Europe (validation cohort). Participants 500 patients from the Multicenter Randomised Clinical Trial of Endovascular Treatment for Acute Ischaemic Stroke in the Netherlands trial (derivation cohort) and 260 patients with intracranial occlusion from the Interventional Management of Stroke III trial (validation cohort). Main outcome measures The primary outcome was the modified Rankin Scale (mRS) score at 90 days after stroke. We constructed an ordinal logistic regression model to predict outcome and treatment benefit, defined as the difference between the predicted probability of good functional outcome (mRS score 0-2) with and without intra-arterial treatment. Results 11 baseline clinical and radiological characteristics were included in the model. The externally validated C statistic was 0.69 (95% confidence interval 0.64 to 0.73) for the ordinal model and 0.73 (0.67 to 0.79) for the prediction of good functional outcome, indicating moderate discriminative ability. The mean predicted treatment benefit varied between patients in the combined derivation and validation cohort from −2.3% to 24.3%. There was benefit of intra-arterial treatment predicted for some individual patients from groups in which no treatment effect was found in previous subgroup analyses, such as those with no or poor collaterals. Conclusion The proposed clinical decision tool combines multiple baseline clinical and radiological characteristics and shows large variations in treatment benefit between patients. The tool is clinically useful as it aids in distinguishing between individual patients who may experience benefit from intra-arterial treatment for acute ischaemic stroke and those who will not. Trial registration clinicaltrials.govNCT00359424 (IMS III) and isrctn.com ISRCTN10888758 (MR CLEAN).

Sex-specific stroke incidence over time in the Greater Cincinnati/Northern Kentucky Stroke Study.

Abstract: Objective: Recent data suggest stroke incidence is decreasing over time, but it is unknown whether incidence is decreasing in women and men to the same extent. Methods: Within our population of 1.3 million, all incident strokes among residents ≥20 years old were ascertained at all hospitals during July 1993–June 1994 and calendar years 1999, 2005, and 2010. A sampling scheme was used to ascertain out-of-hospital cases. Sex-specific incidence rates per 100,000 among black and white participants, age- and race-adjusted, were standardized to the 2000 US Census population. Trends over time by sex were compared; a Bonferroni correction was applied for multiple comparisons. Results: Over the 4 study periods, there were 7,710 incident strokes; 57.2% (n = 4,412) were women. Women were older than men (mean ± SE 72.4 ± 0.34 vs 68.2 ± 0.32, p p p = 0.15). Similar sex differences were seen for ischemic stroke (men, 238 [223–257] to 165 [153–177], p p = 0.09). Incidence of all strokes and of ischemic strokes was similar between women and men in 2010. Incidence of intracerebral hemorrhage and subarachnoid hemorrhage were stable over time in both sexes. Conclusions: Decreases in stroke incidence over time are driven by a decrease in ischemic stroke in men. Contrary to previous study periods, stroke incidence rates were similar by sex in 2010. Future research is needed to understand why the decrease in ischemic stroke incidence is more pronounced in men.

Impact of Thrombus Length on Outcomes After Intra-Arterial Aspiration Thrombectomy in the THERAPY Trial.

Abstract: Background and Purpose— Increasing thrombus length (TL) impedes recanalization after intravenous (IV) thrombolysis. We sought to determine whether the clinical benefit of aspiration thrombectomy relative to IV r-tPA (recombinant tissue-type plasminogen activator) may be greater at longer TL. Methods— THERAPY was a randomized trial of aspiration thrombectomy plus IV r-tPA versus IV r-tPA alone in large-vessel stroke patients with prospective TL measurement ≥8 mm. In this post hoc study, we evaluated the association of TL with trial end points and potential endovascular treatment effect, using univariate, multivariable, and multiplicative interaction analyses. Results— TL data were available for all 108 patients (28% internal carotid artery, 62% M1, and 10% M2). Median TL was 14.0 mm (interquartile range, 9.7–19.5 mm). Longer TL was associated with worse outcome (90-day modified Rankin Scale score: odds ratio, 1.24 per 5-mm TL increment; 95% confidence interval, 1.04–1.52; P =0.02), even after adjusting for key outcome predictors (adjusted P =0.004). Longer TL was also associated with more serious adverse events (adjusted P =0.01), more symptomatic hemorrhages (adjusted P =0.03), and increased mortality (adjusted P =0.01). No significant relationship was observed between TL and angiographic reperfusion (modified thrombolysis in cerebral ischemia 2b-3), but greater TL was associated with longer endovascular procedural times (ρ=0.36; P =0.045). Increasing TL was associated with greater aspiration thrombectomy treatment effect (interaction term P =0.03). This might be related to a potentially stronger adverse effect of increasing TL on 90-day modified Rankin Scale for patients treated with IV r-tPA (ρ=0.39; P =0.01) compared with intra-arterial therapy (ρ=0.20; P =0.165). Conclusions— Ischemic stroke patients with longer symptomatic thrombi have worse 90-day clinical outcomes but may have a greater relative benefit of aspiration thrombectomy over IV r-tPA alone. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01429350.

Endovascular Therapy of M2 Occlusion in IMS III: Role of M2 Segment Definition and Location on Clinical and Revascularization Outcomes.

Abstract: BACKGROUND AND PURPOSE: Uncertainty persists regarding the safety and efficacy of endovascular therapy of M2 occlusions following IV tPA. We reviewed the impact of revascularization on clinical outcomes in 83 patients with M2 occlusions in the Interventional Management of Stroke III trial according to specific M1-M2 segment anatomic features. MATERIALS AND METHODS: Perfusion of any M2 branch distinguished M2-versus-M1 occlusion. Prespecified modified TICI and arterial occlusive lesion revascularization and clinical mRS 0–2 end points at 90 days for endovascular therapy–treated M2 occlusions were analyzed. Post hoc analyses of the relationship of outcomes to multiple baseline angiographic M2 and M1 subgroup characteristics were performed. RESULTS: Of 83 participants with M2 occlusion who underwent endovascular therapy, 41.0% achieved mRS 0–2 at 90 days, including 46.6% with modified TICI 2–3 reperfusion compared with 26.1% with modified TICI 0–1 reperfusion (risk difference, 20.6%; 95% CI, −1.4%–42.5%). mRS 0–2 outcome was associated with reperfusion for M2 trunk (n = 9) or M2 division (n = 42) occlusions, but not for M2 branch occlusions (n = 28). Of participants with trunk and division occlusions, 63.2% with modified TICI 2a and 42.9% with modified TICI 2b reperfusion achieved mRS 0–2 outcomes; mRS 0–2 outcomes for M2 trunk occlusions (33%) did not differ from distal (38.2%) and proximal (26.9%) M1 occlusions. CONCLUSIONS: mRS 0–2 at 90 days was dependent on reperfusion for M2 trunk but not for M2 branch occlusions. For M2 division occlusions, good outcome with modified TICI 2b reperfusion did not differ from that in modified TICI 2a. M2 segment definition and occlusion location may contribute to differences in revascularization and good outcome between Interventional Management of Stroke III and other endovascular therapy studies.

Hyperlipidemia is associated with lower risk of poststroke mortality independent of statin use: A population-based study

Abstract: BackgroundAlthough statin therapy is associated with reduced stroke and mortality risk, some studies report that higher lipid levels are associated with improved outcomes following ischemic stroke....

Estimated Impact of Emergency Medical Service Triage of Stroke Patients on Comprehensive Stroke Centers: An Urban Population-Based Study.

Abstract: Background and Purpose—The American Stroke Association recommends that Emergency Medical Service bypass acute stroke–ready hospital (ASRH)/primary stroke center (PSC) for comprehensive stroke cente...

Observed Cost and Variations in Short Term Cost-Effectiveness of Therapy for Ischemic Stroke in Interventional Management of Stroke (IMS) III.

Abstract: Background Examination of linked data on patient outcomes and cost of care may help identify areas where stroke care can be improved. We report on the association between variations in stroke severity, patient outcomes, cost, and treatment patterns observed over the acute hospital stay and through the 12‐month follow‐up for subjects receiving endovascular therapy compared to intravenous tissue plasminogen activator alone in the IMS (Interventional Management of Stroke) III Trial. Methods and Results Prospective data collected for a prespecified economic analysis of the trial were used. Data included hospital billing records for the initial stroke admission and subsequent detailed resource use after the acute hospitalization collected at 3, 6, 9, and 12 months. Cost of follow‐up care varied 6‐fold for patients in the lowest (0–1) and highest (20+) National Institutes of Health Stroke Scale category at 5 days, and by modified Rankin Scale at 3 months. The kind of resources used postdischarge also varied between treatment groups. Incremental short‐term cost‐effectiveness ratios varied greatly when treatments were compared for patient subgroups. Patient subgroups predefined by stroke severity had incremental cost‐effectiveness ratios of $97 303/quality‐adjusted life year (severe stroke) and $3 187 805/quality‐adjusted life year (moderately severe stroke). Conclusions Detailed economic and resource utilization data from IMS III provide powerful evidence for the large effect that patient outcome has on the economic value of medical and endovascular reperfusion therapies. These data can be used to inform process improvements for stroke care and to estimate the cost‐effectiveness of endovascular therapy in the US health system for stroke intervention trials. Clinical Trial Registration URL: . Registration number: NCT00359424.

Sex-specific stroke incidence over time in the Greater Cincinnati/Northern Kentucky Stroke Study

Abstract: Objective: Recent data suggest stroke incidence is decreasing over time, but it is unknown whether incidence is decreasing in women and men to the same extent. Methods: Within our population of 1.3 million, all incident strokes among residents ≥20 years old were ascertained at all hospitals during July 1993–June 1994 and calendar years 1999, 2005, and 2010. A sampling scheme was used to ascertain out-of-hospital cases. Sex-specific incidence rates per 100,000 among black and white participants, age- and race-adjusted, were standardized to the 2000 US Census population. Trends over time by sex were compared; a Bonferroni correction was applied for multiple comparisons. Results: Over the 4 study periods, there were 7,710 incident strokes; 57.2% (n = 4,412) were women. Women were older than men (mean ± SE 72.4 ± 0.34 vs 68.2 ± 0.32, p p p = 0.15). Similar sex differences were seen for ischemic stroke (men, 238 [223–257] to 165 [153–177], p p = 0.09). Incidence of all strokes and of ischemic strokes was similar between women and men in 2010. Incidence of intracerebral hemorrhage and subarachnoid hemorrhage were stable over time in both sexes. Conclusions: Decreases in stroke incidence over time are driven by a decrease in ischemic stroke in men. Contrary to previous study periods, stroke incidence rates were similar by sex in 2010. Future research is needed to understand why the decrease in ischemic stroke incidence is more pronounced in men.

Sex differences in cardiovascular risk profiles of ischemic stroke patients with diabetes in the Greater Cincinnati/Northern Kentucky Stroke Study

Abstract: Background We aimed to compare sex-specific associations between cardiovascular risk factors and diabetes mellitus (DM) among patients with acute ischemic stroke (AIS) in the Greater Cincinnati/Northern Kentucky Stroke Study (GCNKSS). Methods The GCNKSS ascertained AIS cases in 2005 and 2010 among adult (age ≥20 years) residents of a biracial population of 1.3 million. Past and current stroke risk factors were compared between those with and without DM using chi-square and multiple logistic regression to examine sex-specific profiles. Results There were 3515 patients with incident AIS; 1919 (55%) were female, 697 (20%) were black, and 1146 (33%) had DM. Among both women and men with DM, significantly more were obese, and had hypertension, high cholesterol, and coronary artery disease (CAD) compared with those without DM. For women with AIS, in multivariable sex-specific adjusted analyses, older age was associated with a decreased odds of having DM (aOR=0.88, 95%CI 0.80-0.98). For women with CAD, the odds of DM were increased (aOR=1.76, 95%CI 1.33-2.32). Age and CAD were not significant factors in differentiating the profiles of men with and without DM. Conclusions Women with DM had strokes at a younger age, whereas no such age difference existed in men. As opposed to men, women with DM were also more likely to have CAD compared with those without DM, suggesting a sex difference in the association between DM and vascular disease. These findings may suggest a need for more aggressive risk factor management in diabetic women.

Age, Sex, and Racial Differences in Neuroimaging Use in Acute Stroke: A Population-Based Study.

Abstract: BACKGROUND AND PURPOSE: Limited information is available regarding differences in neuroimaging use for acute stroke work-up. Our objective was to assess whether race, sex, or age differences exist in neuroimaging use and whether these differences depend on the care center type in a population-based study. MATERIALS AND METHODS: Patients with stroke (ischemic and hemorrhagic) and transient ischemic attack were identified in a metropolitan, biracial population using the Greater Cincinnati/Northern Kentucky Stroke Study in 2005 and 2010. Multivariable regression was used to determine the odds of advanced imaging use (CT angiography/MR imaging/MR angiography) for race, sex, and age. RESULTS: In 2005 and 2010, there were 3471 and 3431 stroke/TIA events, respectively. If one adjusted for covariates, the odds of advanced imaging were higher for younger (55 years or younger) compared with older patients, blacks compared with whites, and patients presenting to an academic center and those seen by a stroke team or neurologist. The observed association between race and advanced imaging depended on age; in the older age group, blacks had higher odds of advanced imaging compared with whites (odds ratio, 1.34; 95% CI, 1.12–1.61; P CONCLUSIONS: Within a large, biracial stroke/TIA population, there is variation in the use of advanced neuroimaging by age and race, depending on the care center type.

Towards personalised intra- arterial treatment of patients with acute ischaemic stroke: a study protocol for development and validation of a clinical decision aid

Abstract: Introduction Overall, intra-arterial treatment (IAT) proved to be beneficial in patients with acute ischaemic stroke due to a proximal occlusion in the anterior circulation. However, heterogeneity in treatment benefit may be relevant for personalised clinical decision-making. Our aim is to improve selection of patients for IAT by predicting individual treatment benefit or harm. Methods and analysis We will use data collected in the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) trial to analyse the effect of baseline characteristics on outcome and treatment effect. A multivariable proportional odds model with interaction terms will be developed to predict the outcome for each individual patient, both with and without IAT. Model performance will be expressed as discrimination and calibration, after bootstrap resampling and shrinkage of regression coefficients, to correct for optimism. External validation will be conducted on data of patients in the Interventional Management of Stroke III trial (IMS III). Primary outcome will be the modified Rankin Scale (mRS) at 90 days after stroke. Ethics and dissemination The proposed study will provide an internationally applicable clinical decision aid for IAT. Findings will be disseminated widely through peer-reviewed publications, conference presentations and in an online web application tool. Formal ethical approval was not required as primary data were already collected. Trial registration numbers ISRCTN10888758; Post-results and NCT00359424; Post-resultsc.

Practice Patterns for Acute Ischemic Stroke Workup: A Longitudinal Population-Based Study.

Abstract: BackgroundWe examined practice patterns of inpatient testing to identify stroke etiologies and treatable risk factors for acute ischemic stroke recurrence. Methods and ResultsWe identified stroke c...

Abstract 135: Towards Automated Incidence Rate Reporting: Leveraging Machine Learning Technologies to Assist Stroke Adjudication in a Large-scale Epidemiological Study

Abstract: Introduction: Epidemiological studies utilizing administrative databases typically use International Classification of Diseases (ICD) codes to identify stroke cases and estimate incidence rates. Ho...

Endovascular Therapy Demonstrates Benefit over Intravenous Recombinant Tissue Plasminogen Activator Based on Repeatedly Measured National Institutes of Health Stroke Scale

Abstract: Background and Purpose: The Interventional Management of Stroke (IMS) III trial was a randomized controlled trial designed to compare the effect of endovascular therapy after intravenous recombinant tissue plasminogen activator (i.v. rt-PA) as compared to i.v. rt-PA alone. The primary outcome was modified Rankin Scale at 90 days. Secondary outcomes included National Institutes of Health Stroke Scale (NIHSS), which was assessed repeatedly through 90 days. The objective of this analysis is to evaluate the treatment effect of endovascular therapy over time on NIHSS. Methods: 656 subjects were enrolled in the IMS III trial, including 434 subjects randomized to endovascular therapy and 222 to i.v. rt-PA only. NIHSS scores evaluated at 40 min, 24 h, Day 5, and Day 90 were included in the analysis. A covariance structure model was used to investigate the treatment effect on NIHSS over time, adjusting for relevant covariates including baseline stroke severity. Model assumptions were valid. Results: Based on the covariance structure model, after adjusting for relevant baseline covariates, a significant time-by-treatment interaction effect (p = 0.0137) was observed. Only NIHSS at Day 90 showed a significant treatment effect (p = 0.0473), with subjects in the endovascular arm having a lower NIHSS (less neurologic deficit) compared to the i.v. rt-PA arm. Conclusions: The IMS III trial demonstrated an endovascular treatment effect based on the secondary outcome of NIHSS. However, the magnitude of this treatment effect varied by the time of assessment. It was only at Day 90 that the endovascular arm had a significantly lower NIHSS compared to that in the i.v. rt-PA arm.

Age, Sex, and Racial Differences in Neuroimaging Use in Acute Stroke: A Population-Based Study

Abstract: BACKGROUND AND PURPOSE: Limited information is available regarding differences in neuroimaging use for acute stroke work-up. Our objective was to assess whether race, sex, or age differences exist in neuroimaging use and whether these differences depend on the care center type in a population-based study. MATERIALS AND METHODS: Patients with stroke (ischemic and hemorrhagic) and transient ischemic attack were identified in a metropolitan, biracial population using the Greater Cincinnati/Northern Kentucky Stroke Study in 2005 and 2010. Multivariable regression was used to determine the odds of advanced imaging use (CT angiography/MR imaging/MR angiography) for race, sex, and age. RESULTS: In 2005 and 2010, there were 3471 and 3431 stroke/TIA events, respectively. If one adjusted for covariates, the odds of advanced imaging were higher for younger (55 years or younger) compared with older patients, blacks compared with whites, and patients presenting to an academic center and those seen by a stroke team or neurologist. The observed association between race and advanced imaging depended on age; in the older age group, blacks had higher odds of advanced imaging compared with whites (odds ratio, 1.34; 95% CI, 1.12–1.61; P CONCLUSIONS: Within a large, biracial stroke/TIA population, there is variation in the use of advanced neuroimaging by age and race, depending on the care center type.