Background The aim of this study was to determine the cost-effectiveness of tPA treatment in the 3 to 4.5 hour time-window after ischemic stroke. Methods Decision-analytic and Markov state-transition models were created to determine the cost-effectiveness of treatment of ischemic stroke patients with intravenous tPA administered in the 3 to 4.5 hour time-window compared with medical therapy without tPA. Health benefits were measured in quality-adjusted life-years (QALYs). The economic outcome measure of the model was the difference in estimated healthcare costs between the two treatment alternatives. The incremental cost-effectiveness ratio (ICER) was calculated by dividing the cost difference by the difference in QALYs. One-way sensitivity and probabilistic analyses were performed to test the robustness of the model. Results The administration of tPA over standard medical therapy resulted in a lifetime gain of 0.28 QALYs for an additional cost of $6,050, yielding an ICER of $21,978 per QALY. One-way sensitivity analyses demonstrated that the ICER was most sensitive to the cost of hospitalization for patients who received tPA. Based on probabilistic analysis there is 88% probability that tPA is the preferred treatment at a willingness to pay threshold of $50,000 per QALY. Conclusion The balance of costs and benefits favors treatment with intravenous tPA in the 3 to 4.5 hour time-window. This supports, from a societal perspective, the use of tPA therapy in this treatment time-window for acute ischemic stroke.

Overexpression of Angiopoietin (Ang) 1 in the brain results in increased vascularization and altered neuronal dendrite configuration. We hypothesized that Ang1 acts directly on neurons inducing neurite outgrowth. We stimulated PC12 cells with Ang1 and observed outgrowth levels comparable to nerve growth factor (NGF). Western blotting and RT-PCR demonstrated the absence of the Ang1 receptor, Tie2 and the presence of β1-integrin. Downstream of β1-integrin, Ang1 stimulation led to a ~2.6 fold increase in focal adhesion kinase (FAK) phosphorylation and no change in activation of mitogen-activated protein kinase (MAPK) nor c-Jun N-terminal kinase (JNK). Conversely, NGF stimulation had no effect on FAK phosphorylation but lead to a ~3.1 and ~2 fold increase in phosphorylation of MAPK and JNK. Ang1, but not NGF-mediated outgrowth was attenuated following functional inhibition of β1-integrin and FAK, and Wortmannin inhibited neurite outgrowth mediated by both. Our results suggest that Ang1 induces neurite outgrowth in PC12 cells in a Tie2-independent, β1-integrin-FAK-PI3K-Akt dependent manner and that NGF and Ang1 mediate neurite outgrowth via two independent signaling mechanisms. KeywordsNeurovascular; neurite outgrowth; nerve growth factor; angiopoietin; integrin; signaling The nervous and vascular systems contain many common organizational features and develop similarly in terms of anatomical patterning. These similarities in patterning and proximity may reflect coordinated development based on responsiveness to similar growth factors and their receptors, including VEGF/VEGFR2, netrins/Unc5, Ephs/ephrins; and semaphorins/ neuropilin Li, 2007, Zacchigna et al., 2008). Angiopoietins represent another family of growth factors that may mediate effects in both vascular and nervous systems (Ward and LaManna, 2004 Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Ang1 is a growth factor that binds to its endothelial cell specific receptor Tie2, recruiting pericytes to developing vessels and stabilizing the vasculature (Eklund and Olsen, 2006, Morisada et al., 2006). Ex vivo work done by others (Kosacka et al., 2005, Kosacka et al., 2006 has suggested that Ang1 can elicit neurite outgrowth of explanted dorsal root ganglion (DRG) cells in a Tie2 dependent manner. Moreover, previous work done by our lab suggests that Ang1 overexpression in the mouse nervous system leads to increases in vascularization and altered neuronal dendrite patterning . The mechanisms underlying the dendritic effects remain unknown as we failed to find Tie2 expression on neurons in these studies. Based on...

Background: It is important to evaluate patients with transient ischemic attack (TIA) or stroke for atrial fibrillation (AF) because the detection of AF changes the recommended anti-thrombotic regimen from treatment with an antiplatelet agent to oral anticoagulation. This study describes the diagnostic yield of a patch-based, single-use, and water-resistant 14-day continuous cardiac rhythm monitor (ZIO Patch) in patients with stroke or TIA.Methods: We obtained data from the manufacturer and servicer of the ZIO Patch (iRhythm Technologies). Patients who were monitored between January 2012 and June 2013 and whose indication for monitoring was TIA or stroke were included. The duration of monitoring, the number and type of arrhythmias, and the time to first arrhythmia were documented.Results: One thousand one hundred seventy-one monitoring reports were analyzed. The mean monitor wear time was 10.9 days and the median wear time was 13.0 days (interquartile range 7.2–14.0). The median analyzable time relative to the total wear time was 98.7% (IQR 96.0–99.5%). AF was present in 5.0% of all reports. The mean duration before the first episode of paroxysmal AF (PAF) was 1.5 days and the median duration was 0.4 days. 14.3% of first PAF episodes occurred after 48 h. The mean PAF burden was 12.7% of the total monitoring duration.Conclusion: Excellent quality of the recordings and very good patient compliance coupled with a substantial proportion of AF detection beyond the first 48 h of monitoring suggest that the cardiac patch is superior to conventional 48-h Holter monitors for AF detection in patients with stroke or TIA.

TIA triage in the ED using a protocol with neurological consultation and acute MRI is feasible and safe. The majority of patients were discharged without hospitalization and rates of recurrent stroke were not higher than predicted.