Dataset Information

Development and Testing of Thrombolytics in Stroke.

ABSTRACT: Despite recent advances in recanalization therapy, mechanical thrombectomy will never be a treatment for every ischemic stroke because access to mechanical thrombectomy is still limited in many countries. Moreover, many ischemic strokes are caused by occlusion of cerebral arteries that cannot be reached by intra-arterial catheters. Reperfusion using thrombolytic agents will therefore remain an important therapy for hyperacute ischemic stroke. However, thrombolytic drugs have shown limited efficacy and notable hemorrhagic complication rates, leaving room for improvement. A comprehensive understanding of basic and clinical research pipelines as well as the current status of thrombolytic therapy will help facilitate the development of new thrombolytics. Compared with alteplase, an ideal thrombolytic agent is expected to provide faster reperfusion in more patients; prevent re-occlusions; have higher fibrin specificity for selective activation of clot-bound plasminogen to decrease bleeding complications; be retained in the blood for a longer time to minimize dosage and allow administration as a single bolus; be more resistant to inhibitors; and be less antigenic for repetitive usage. Here, we review the currently available thrombolytics, strategies for the development of new clot-dissolving substances, and the assessment of thrombolytic efficacies in vitro and in vivo.

SUBMITTER: Nikitin D

PROVIDER: S-EPMC7900387 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Development and Testing of Thrombolytics in Stroke.

Nikitin Dmitri D Choi Seungbum S Mican Jan J Toul Martin M Ryu Wi-Sun WS Damborsky Jiri J Mikulik Robert R Kim Dong-Eog DE

Journal of stroke 20210131 1

Despite recent advances in recanalization therapy, mechanical thrombectomy will never be a treatment for every ischemic stroke because access to mechanical thrombectomy is still limited in many countries. Moreover, many ischemic strokes are caused by occlusion of cerebral arteries that cannot be reached by intra-arterial catheters. Reperfusion using thrombolytic agents will therefore remain an important therapy for hyperacute ischemic stroke. However, thrombolytic drugs have shown limited effica ...[more]

PMID: 33600700

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Project description:BackgroundAdministrative data are frequently used in stroke research. Ensuring accurate identification of patients who had an ischaemic stroke, and those receiving thrombolysis and endovascular thrombectomy (EVT) is critical to ensure representativeness and generalisability. We examined differences in patient samples based on mode of identification, and propose a strategy for future patient and procedure identification in large administrative databases.MethodsWe used non-public administrative data from the state of California to identify all patients who had an ischaemic stroke discharged from an emergency department (ED) or inpatient hospitalisation from 2010 to 2017 based on International Classification of Disease (ICD-9) (2010-2015), ICD-10 (2015-2017) and Medicare Severity-Diagnosis-related Group (MS-DRG) discharge codes. We identified patients with interhospital transfers, patients receiving thrombolytics and patients treated with EVT based on ICD, Current Procedural Terminology (CPT) and MS-DRG codes. We determined what proportion of these transfers and procedures would have been identified with ICD versus MS-DRG discharge codes.ResultsOf 365 099 ischaemic stroke encounters, most (87.70%) had both a stroke-related ICD-9 or ICD-10 code and stroke-related MS-DRG code; 12.28% had only an ICD-9 or ICD-10 code and 0.02% had only an MS-DRG code. Nearly all transfers (99.99%) were identified using ICD codes. We identified 32 433 thrombolytic-treated patients (8.9% of total) using ICD, CPT and MS-DRG codes; the combination of ICD and CPT codes identified nearly all (98%). We identified 7691 patients treated with EVT (2.1% of total) using ICD and MS-DRG codes; both MS-DRG and ICD-9/ICD-10 codes were necessary because ICD codes alone missed 13.2% of EVTs. CPT codes only pertain to outpatient/ED patients and are not useful for EVT identification.ConclusionsICD-9/ICD-10 diagnosis codes capture nearly all ischaemic stroke encounters and transfers, while the combination of ICD-9/ICD-10 and CPT codes are adequate for identifying thrombolytic treatment in administrative datasets. However, MS-DRG codes are necessary in addition to ICD codes for identifying EVT, likely due to favourable reimbursement for EVT-related MS-DRG codes incentivising accurate coding.

Project description:BackgroundSurrogate decision makers of stroke patients are often unprepared to make critical decisions on life-sustaining treatments. We describe the development process and key features for the Understanding Stroke web-based decision support tool.MethodsWe used multiple strategies to develop a patient-centered, tailored decision aid. We began by forming a Patient and Family Advisory Council to provide continuous input to our multidisciplinary team on the development of the tool. Additionally, focus groups consisting of nurses, therapists, social workers, physicians, stroke survivors, and family members reviewed key elements of the tool, including prognostic information, graphical displays, and values clarification exercise. To design the values clarification exercise, we asked focus groups to provide feedback on a list of important activities of daily living. An ordinal prognostic model was developed for ischemic stroke and intracerebral hemorrhage using data taken from the Virtual International Stroke Trials Archive Plus, and incorporated into the tool.ResultsFocus group participants recommended making numeric prognostic information optional due to possible emotional distress. Pie charts were generally favored by participants for graphical presentation of prognostic information, though a horizontal stacked bar chart was also added due to its prevalence in stroke literature. Plain language descriptions of the modified Rankin Scale were created to accompany the prognostic information. A values clarification exercise was developed consisting of a list of 13 situations that may make an individual consider comfort measures only. The final version of the web based tool (which can be viewed on tablets) included the following sections: general introduction to stroke, outcomes (prognostic information and recovery), in-hospital and life-sustaining treatments, decision making and values clarification, post-hospital care, tips for talking to the health care team, and a summary report. Preliminary usability testing received generally favorable feedback.ConclusionWe developed Understanding Stroke, a tailored decision support tool for surrogate decision makers of stroke patients. The tool was well received and will be formally pilot tested in a group of stroke surrogate decision makers.Trial registrationClinicalTrials.gov ( NCT03427645 ).

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Development and Testing of Thrombolytics in Stroke.

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Development and Testing of Thrombolytics in Stroke.

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