Development and Testing of Thrombolytics in Stroke.
Ontology highlight
ABSTRACT:
SUBMITTER: Nikitin D
PROVIDER: S-EPMC7900387 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:For many decades, intravenous (IV) thrombolytics have been delivered to treat acute thrombosis. Although these medications were originally effective for coronary thrombosis, their mechanisms have proven beneficial for many other disease processes, including ischemic stroke. Treatment paradigms for acute ischemic stroke have largely followed those of cardiology. Specifically, the aim has been to recanalize the occluded artery and to restore perfusion to the brain that remains salvageable. To that end, rapid clot lysis was sought using thrombolytic medicines already proven effective in the coronary arteries. IV-thrombolysis for ischemic stroke began its widespread adoption in the late 1990s after the publication of the National Institute of Neurological Disorders and Stroke study. Since that time, other promising IV-thrombolytics have been developed and tested in human trials, but as of yet, none have been proven better than a placebo. Adjunctive treatments are also being evaluated. The challenge remains balancing reperfusion and salvaging brain tissue with the potential risks of brain hemorrhage.
| S-EPMC3250277 | biostudies-literature
Project description:Purpose of reviewTo review the current evidence and ongoing clinical trials evaluating the efficacy and safety of tenecteplase (TNK), an alternative tissue plasminogen activator (tPA), in the acute management of arterial ischemic stroke (AIS). To date, alteplase is the only tPA approved by the United States FDA for use in AIS.Recent findingsThere have been multiple phase two and three trials investigating the safety and efficacy of TNK in AIS. In patients with AIS due to large vessel occlusion, one randomized controlled trial demonstrated superiority of TNK for vessel recanalization rates and long-term functional outcomes when compared to alteplase. A meta-analysis of all phase two and three trials evaluating TNK in AIS concluded that TNK has a comparable safety and efficacy profile to alteplase. The results of these trials prompted new recommendations in the Acute Stroke Guideline published by the AHA suggesting it may be reasonable to use as an alternative to alteplase. Furthermore, recent real-world data has also reported decreased door-to-needle time with TNK utilization.SummaryIn patients with AIS, use of a thrombolytic agent is standard of care and has been shown to reduce neurological disability and improve functional outcome. Randomized controlled trials have demonstrated that TNK is non-inferior to alteplase from a clinical outcome and safety standpoint. The existing data evaluating the efficacy of TNK compared to alteplase in acute AIS within 4.5 h from symptom onset showed no significant difference between these two agents with regard to functional outcome at 90 days but improved median time to treatment and large vessel recanalization in TNK-treated patients. The results from ongoing TNK trials in larger patient cohorts and in wake-up stroke populations will be instrumental to the wide-scale utilization of TNK in acute AIS management.
| S-EPMC9807245 | biostudies-literature
Project description: Not available
| S-EPMC6538464 | biostudies-literature
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.
| S-EPMC8258073 | biostudies-literature
Project description:Myocardial infarction and ischemic stroke are the most frequent causes of death or disability worldwide. Due to their ability to dissolve blood clots, the thrombolytics are frequently used for their treatment. Improving the effectiveness of thrombolytics for clinical uses is of great interest. The knowledge of the multiple roles of the endogenous thrombolytics and the fibrinolytic system grows continuously. The effects of thrombolytics on the alteration of the nervous system and the regulation of the cell migration offer promising novel uses for treating neurodegenerative disorders or targeting cancer metastasis. However, secondary activities of thrombolytics may lead to life-threatening side-effects such as intracranial bleeding and neurotoxicity. Here we provide a structural biology perspective on various thrombolytic enzymes and their key properties: (i) effectiveness of clot lysis, (ii) affinity and specificity towards fibrin, (iii) biological half-life, (iv) mechanisms of activation/inhibition, and (v) risks of side effects. This information needs to be carefully considered while establishing protein engineering strategies aiming at the development of novel thrombolytics. Current trends and perspectives are discussed, including the screening for novel enzymes and small molecules, the enhancement of fibrin specificity by protein engineering, the suppression of interactions with native receptors, liposomal encapsulation and targeted release, the application of adjuvants, and the development of improved production systems.
| S-EPMC6637190 | biostudies-literature
Project description:ImportanceFew tools are available to assess bimanual deficits after stroke.ObjectiveTo develop the Bimanual Assessment Measure (BAM), which assesses a person's hand coordination in both preferred and prestroke roles (i.e., stabilizer or manipulator).DesignDevelopment and psychometric testing of the BAM.SettingResearch laboratory.ParticipantsPeople with chronic stroke (n = 24), age-matched controls (n = 23), and occupational therapists (n = 40).Outcomes and measuresWe assessed the BAM's internal consistency, reliability, and face and known-groups validity.ResultsItems were selected as meaningful tasks that represented a range of bimanual coordination requirements (e.g., symmetrical forces and timing, asymmetrical forces and timing, time-limited reactive movement). Focus groups of people with stroke and occupational therapists provided input into BAM development. The BAM was found to have excellent reliability and internal consistency and face and known-groups validity.Conclusions and relevanceThe BAM is a valid, reliable measure for people with chronic stroke that identifies bimanual coordination deficits beyond unimanual impairments and the potential capacity for people to return to prestroke hand roles (i.e., as a manipulator). What This Article Adds: This article introduces the BAM as a new assessment measure of bimanual functioning with the potential capacity to restore prestroke hand roles as either a manipulator or a stabilizer among people with chronic stroke.
| S-EPMC9638932 | biostudies-literature
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 ).
| S-EPMC7370629 | biostudies-literature
Project description:Thrombolytic therapy might reduce venous thromboembolism-related mortality and morbidity, but it could also increase the risk of major bleeding. We systematically reviewed the literature to evaluate the effectiveness and safety of thrombolytics in patients with pulmonary embolism (PE) and/or deep venous thrombosis (DVT). We searched Medline, Embase, and Cochrane databases for relevant randomized controlled trials up to February 2019. Multiple investigators independently screened and collected data. We included 45 studies (4740 participants). Pooled estimates of PE studies indicate probable reduction in mortality with thrombolysis (risk ratio [RR], 0.61; 95% confidence interval [CI], 0.40-0.94) (moderate certainty) and possible reduction in nonfatal PE recurrence (RR, 0.56; 95% CI, 0.35-0.89) (low certainty). Pooled estimates of DVT studies indicate the possible absence of effects on mortality (RR, 0.77; 95% CI, 0.26-2.28) (low certainty) and recurrent DVT (RR, 0.99; 95% CI, 0.56-1.76) (low certainty), but possible reduction in postthrombotic syndrome (PTS) with thrombolytics (RR, 0.70; 95% CI, 0.59-0.83) (low certainty). Pooled estimates of the complete body of evidence indicate increases in major bleeding (RR, 1.89; 95% CI, 1.46-2.46) (high certainty) and a probable increase in intracranial bleeding (RR, 3.17; 95% CI 1.19-8.41) (moderate certainty) with thrombolytics. Our findings indicate that thrombolytics probably reduce mortality in patients with submassive- or intermediate-risk PE and may reduce PTS in patients with proximal DVT at the expense of a significant increase in major bleeding. Because the balance between benefits and harms is profoundly influenced by the baseline risks of critical outcomes, stakeholders involved in decision making would need to weigh these effects to define which clinical scenarios merit the use of thrombolytics.
| S-EPMC7160254 | biostudies-literature
Project description:ObjectiveWe investigated the association between the presence of major vessel occlusion (MVO) and the intensity of the International Normalized Ratio (INR) in cardioembolic high-risk patients taking warfarin. We also evaluated whether the presence of MVO could predict the subtherapeutic range of INR ?1.7 ensuring safe administration of intravenous thrombolytics.MethodsThe medical records of 177 cardioembolic stroke patients who were taking warfarin between April, 2008 and March, 2015 were retrospectively analyzed. Logistic regression analysis was performed to calculate the odds ratios (ORs) and 95% confidence intervals (95% CIs) for the association between vessel occlusion and intensity of INR. To predict INR ?1.7, decision tree analysis was performed.ResultsINR was inversely associated with MVO in an unadjusted model (OR, 0.36; 95% CI, 0.17-0.76), and in a model adjusted for initial NIHSS score and time from symptom onset to arrival (OR, 0.28; 95% CI, 0.11-0.73). Fifty-two of 58 (89.7%) patients with MVO had an INR ?1.7, compared with 83 of 119 (69.7%) patients without MVO. Indication for anticoagulation agent use was dichotomized into NVAF and others, and applied to the subgroup of patients with MVO. All patients with NVAF (31/31, 100%) had INR ?1.7, while 21 of 27 of the other patients (77.8%) had INR ?1.7.ConclusionsLow INR at presentation in cardioembolic stroke patients during anticoagulation treatment was associated with occurrence of major vessel occlusive stroke. Presence of MVO and indications for anticoagulation may be utilized to ensure the feasibility of administration of intravenous thrombolytics.
| S-EPMC5291417 | biostudies-literature
Project description:Dengue fever is a tropical endemic disease; however, because of climate change, it may become a problem in South Korea in the near future. Research on vaccines for dengue fever and outbreak preparedness are currently insufficient. In addition, because there are no appropriate animal models, controversial results from vaccine efficacy assessments and clinical trials have been reported. Therefore, to study the mechanism of dengue fever and test the immunogenicity of vaccines, an appropriate animal model is urgently needed. In addition to mouse models, more suitable models using animals that can be humanized will need to be constructed. In this report, we look at the current status of model animal construction and discuss which models require further development.
| S-EPMC5540958 | biostudies-other