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Thrombolysis, the only Optimally Rapid Reperfusion Treatment

Published on: 23rd June, 2017

OCLC Number/Unique Identifier: 7286427398

Thrombolysis with tissue plasminogen activator (tPA) has been plagued by inadequate efficacy and a high risk of intracranial hemorrhage (ICH), which led to its replacement by procedures like percutaneous coronary intervention (PCI) whenever possible. Since this requires hospitalization, it is time-consuming, and compromising salvage of brain tissue and myocardium. Thrombolysis is the only first-line treatment that can provide sufficiently timely treatment for optimal recovery of organ function. However, for this potential to be realized, its efficacy and safety must be significantly improved over the current method. By adopting the sequential, synergistic fibrinolytic paradigm of the endogenous system, already verified by a clinical trial, this becomes possible. The endogenous system’s function is evidenced by the fibrinolytic product D-dimer that is invariably present in blood, and which increases >20-fold in the presence of thromboembolism. This system uses tPA to initiate lysis, which is then completed by the other fibrin-specific activator prourokinase (proUK). Since tPA and proUK in combination are synergistic in fibrinolysis, it helps explain their efficacy at their low endogenous concentrations.
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Fibrinolytic therapy with tPA failed because it was based on a flawed concept

Published on: 16th June, 2020

OCLC Number/Unique Identifier: 8628672035

Fibrinolytic therapy has become synonymous with tissue plasminogen activator (tPA) based on the belief that tPA alone was responsible for natural fibrinolysis. Although this assumption was belied from the outset by disappointing clinical results, it persisted, eventually causing fibrinolysis to be discredited and replaced by an endovascular procedure. Since time to reperfusion is the critical determinant of outcome, which in acute myocardial infarction (AMI) means within two hours, a time-consuming hospital procedure is ill-suited as first line treatment. For this purpose, fibrinolysis is more fitting. The assumption that tPA is responsible for fibrinolysis is contradicted by published findings. Instead, tPA ‘s function is limited to the initiation of fibrinolysis, which is continued by urokinase plasminogen activator (uPA) and that has the dominant effect. tPA and uPA gene deletion and clot lysis studies showed the activators have complementary functions, requiring both for a full effect at fibrin-specific doses. They are also synergistic in combination thereby requiring lower doses for efficacy. A clinical proof of concept study in 101 AMI patients who were treated with a 5 mg bolus of tPA followed by a 90 minute infusion of prouPA, the native form of uPA. A near doubling of the 24 h TIMI-3 infarct artery patency rate was obtained compared to that in the best of the tPA trials (GUSTO). In further contrast to tPA, there were no reocclusions and the mortality was only 1% [1]. A sequential combination of both activators, mimicking natural fibrinolysis, holds promise to significantly improve the efficacy and safety of therapeutic fibrinolysis.
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Connected Health Apps and Devices: Implications for Healthcare Delivery

Published on: 25th June, 2019

OCLC Number/Unique Identifier: 8172451194

Healthcare is realizing the importance of health information technology - its applications and devices in play today. Advancing healthcare best practices will rely on up to date data and analysis to provide the most effective forms of therapy. Healthcare is becoming more reliant on patients who are engaging in their own healthcare. With this we are seeing an increase in available health related apps for these devices. This summary reviews various connected health strategies using proven apps and devices to improving the quality of care, promoting patient engagement, and improving outcomes. Here we discuss several trends and the healthcare delivery implications.
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