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Jeffrey L. Saver - One of the best experts on this subject based on the ideXlab platform.
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subject retention in prehospital Stroke research using a telephone based physician investigator driven enrollment method
Cerebrovascular Diseases Extra, 2019Co-Authors: Bryant J Rosell, Jeffrey L. Saver, Robin Conwit, Marc Eckstein, Sidney Starkman, Kristina Shkirkova, Latisha Sharma, David S Liebeskind, May Kimtenser, Scott HamiltonAbstract:Author(s): Rosell, Bryant J; Shkirkova, Kristina; Saver, Jeffrey L; Liebeskind, David S; Starkman, Sidney; Kim-Tenser, May; Eckstein, Marc; Sharma, Latisha; Conwit, Robin; Hamilton, Scott; Sanossian, Nerses | Abstract: BACKGROUND AND PURPOSE:Subject retention into clinical trials is vital, and prehospital enrollment may be associated with higher rates of subject withdrawal than more traditional methods of enrollment. We describe rates of subject retention in a prehospital trial of acute Stroke Therapy. METHODS:All subjects were enrolled into the NIH Field Administration of Stroke Therapy-Magnesium (FAST-MAG) phase 3 clinical trial. Paramedics screened eligible subjects and contacted the physician-investigator using a dedicated in-ambulance cellular phone. Physician-investigators obtained explicit informed consent from the subject or on-scene legally authorized representative (LAR) who reviewed and signed a consent form. Exception from informed consent (EFIC) was utilized in later stages of the study. RESULTS:There were 1,700 subjects enrolled; 1,017 provided consent (60%), 662 were enrolled via LAR (39%), and 21 were enrolled via EFIC (1%). Of the 1,700 patients, 1,413 (83%) completed the 90-day visit, 265 (16%) died prior to the 90-day visit, and 22 (1.3%) withdrew from the study before completion. There were no differences in rates of withdrawal by method of study enrolment, i.e., self-consent (n = 14), 1.4%; LAR (n = 8), 1.2%; EFIC (n = 0) 0%. CONCLUSION:There was a high rate of retention when subjects were enrolled into prehospital Stroke research using a phone-based method to obtain explicit consent.
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balancing autonomy and beneficence in acute Stroke Therapy neurologist attitudes toward delaying thrombolysis in order to obtain informed consent p7 332
Neurology, 2015Co-Authors: Brett D Kaplan, Jessica Cranston, Jeffrey L. SaverAbstract:OBJECTIVE: To determine how U.S. Stroke physicians are currently balancing patient autonomy and beneficence. BACKGROUND: In clinical practice, when no consent provider is immediately available to authorize start of thrombolytic Stroke Therapy, acute Stroke physicians face a fundamental conflict between the ethical principles of autonomy (respect for persons) and beneficence (maximizing benefit). Delaying Therapy to reach a consent provider maximizes autonomy but reduces benefit. Physician attitudes toward resolving this conflict have not previously been delineated. DESIGN/METHODS: A 6 item internet-based survey was administered to US academic Stroke neurologists. Respondents were asked to indicate how much time (minutes), patients (number who fail to benefit due to delay), and brain (neurons lost due to delay) they would spend trying to reach consent provider for an aphasic acute Stroke patient before proceeding with treatment under the doctrine of presumed consent. RESULTS: Survey responses were received from 103 of 332 academic Stroke neurologists. In the time tradeoff framework, respondents indicated they would spend a median of 1.75 minutes trying to contact a consent provider before proceeding with thrombolysis. In the patient tradeoff framework, they would accept a median of 0 per 1000 treated patients failing to benefit from Therapy before proceeding. In the brain tradeoff scenario, they would accept a median of 0 neurons lost before proceeding. Converting all choices to time, respondents indicated they would trade off shorter times in the patient framework (0 minutes) and the neuron framework (0 minutes) than in the time framework (1.75 minutes). CONCLUSIONS: Vascular neurologists indicate they emphasize beneficence over autonomy in deciding when to forego further attempts to reach consent providers to proceed with thrombolytic Therapy under the doctrine of presumed consent. Their preference for rapid intervention is magnified when decisions are framed in person failure to benefit and neuron loss, compared with simple chronologic time. Disclosure: Dr. Kaplan has nothing to disclose. Dr. Cranston has nothing to disclose. Dr. Saver has received personal compensation for activities with the University of California, BrainsGate, CoAxia, eV3, Talecris Biotherapeutics Inc., and PhotoThera, Inc.
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abstract w p294 balancing autonomy and beneficence in acute Stroke Therapy neurologist attitudes toward delaying thrombolysis in order to obtain informed consent
Stroke, 2015Co-Authors: Brett D Kaplan, Jessica Cranston, Jeffrey L. SaverAbstract:Background: In clinical practice, when no consent provider is immediately available to authorize start of thrombolytic Stroke Therapy, acute Stroke physicians face a fundamental conflict between the ethical principles of autonomy (respect for persons) and beneficence (maximizing benefit). Delaying Therapy to reach a consent provider maximizes autonomy but reduces benefit. Physician attitudes toward resolving this conflict have not previously been delineated. Methods: A 6 item internet-based survey was administered to US academic Stroke neurologists. Respondents were asked to indicate how much time (minutes), patients (number who fail to benefit due to delay), and brain (neurons lost due to delay) they would spend trying to reach consent provider for an aphasic acute Stroke patient before proceeding with treatment under the doctrine of presumed consent. Results: Survey responses were received from 103 of 332 academic Stroke neurologists. All respondents were engaged in Stroke clinical care, with cerebrovascular disease accounting for more than half of practice time in over 70%. Career duration was substantial, with over 72% having been in practice for more than 5 years. In the time tradeoff framework, respondents indicated they would spend a median of 1.75 minutes (interquartile range, IQR, 0 - 10.0 minutes) trying to contact a consent provider before proceeding with thrombolysis. In the patient tradeoff framework, they would accept a median of 0 (IQR 0-0) per 1000 treated patients failing to benefit from Therapy before proceeding. In the brain tradeoff scenario, they would accept a median of 0 (IQR 0-1) neurons lost before proceeding. Converting all choices to time, respondents indicated they would trade off shorter times in the patient framework (0 minutes) and the neuron framework (0 minutes) than in the time framework (1.75 minutes). Conclusion: Vascular neurologists indicate they emphasize beneficence over autonomy in deciding when to forego further attempts to reach consent providers to proceed with thrombolytic Therapy under the doctrine of presumed consent. Their preference for rapid intervention is magnified when decisions are framed in person failure to benefit and neuron loss, compared with simple chronologic time.
Gary K Steinberg - One of the best experts on this subject based on the ideXlab platform.
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potential of adult neural stem cells in Stroke Therapy
Regenerative Medicine, 2008Co-Authors: Robert H Andres, Raymond Choi, Gary K Steinberg, Raphael GuzmanAbstract:Despite state-of-the-art Therapy, clinical outcome after Stroke remains poor, with many patients left permanently disabled and dependent on care. Stem cell Therapy has evolved as a promising new therapeutic avenue for the treatment of Stroke in experimental studies, and recent clinical trials have proven its feasibility and safety in patients. Replacement of damaged cells and restoration of function can be accomplished by transplantation of different cell types, such as embryonic, fetal or adult stem cells, human fetal tissue and genetically engineered cell lines. Adult neural stem cells offer the advantage of avoiding the ethical problems associated with embryonic or fetal stem cells and can be harvested as autologous grafts from the individual patients. Furthermore, stimulation of endogenous adult stem cell-mediated repair mechanisms in the brain might offer new avenues for Stroke Therapy without the necessity of transplantation. However, important scientific issues need to be addressed to advance our u...
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interrupting reperfusion as a Stroke Therapy ischemic postconditioning reduces infarct size after focal ischemia in rats
Journal of Cerebral Blood Flow and Metabolism, 2006Co-Authors: Heng Zhao, Robert M Sapolsky, Gary K SteinbergAbstract:Cerebral ischemic preconditioning protects against Stroke, but is clinically feasible only when the occurrence of Stroke is predictable. Reperfusion plays a critical role in cerebral injury after Stroke; we tested the hypothesis that interrupting reperfusion lessens ischemic injury. We found for the first time that such postconditioning with a series of mechanical interruptions of reperfusion significantly reduces ischemic damage. Focal ischemia was generated by permanent distal middle cerebral artery (MCA) occlusion plus transient bilateral common carotid artery (CCA) occlusion. After 30 secs of CCA reperfusion, ischemic postconditioning was performed by occluding CCAs for 10 secs, and then allowing for another two cycles of 30 secs of reperfusion and 10 secs of CCA occlusion. Infarct size was measured 2 days later. Cerebral blood flow (CBF) was measured in animals subjected to permanent MCA occlusion plus 15mins of bilateral CCA occlusion, which demonstrates that postconditioning disturbed the early hyp...
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interrupting reperfusion as a Stroke Therapy ischemic postconditioning reduces infarct size after focal ischemia in rats
Journal of Cerebral Blood Flow and Metabolism, 2006Co-Authors: Heng Zhao, Robert M Sapolsky, Gary K SteinbergAbstract:Cerebral ischemic preconditioning protects against Stroke, but is clinically feasible only when the occurrence of Stroke is predictable. Reperfusion plays a critical role in cerebral injury after Stroke; we tested the hypothesis that interrupting reperfusion lessens ischemic injury. We found for the first time that such postconditioning with a series of mechanical interruptions of reperfusion significantly reduces ischemic damage. Focal ischemia was generated by permanent distal middle cerebral artery (MCA) occlusion plus transient bilateral common carotid artery (CCA) occlusion. After 30 secs of CCA reperfusion, ischemic postconditioning was performed by occluding CCAs for 10 secs, and then allowing for another two cycles of 30 secs of reperfusion and 10 secs of CCA occlusion. Infarct size was measured 2 days later. Cerebral blood flow (CBF) was measured in animals subjected to permanent MCA occlusion plus 15 mins of bilateral CCA occlusion, which demonstrates that postconditioning disturbed the early hyperemia immediately after reperfusion. Postconditioning dose dependently reduced infarct size in animals subjected to permanent MCA occlusion combined with 15, 30, and 60 mins of bilateral CCA occlusion, by reducing infarct size approximately 80%, 51%, and 17%, respectively. In addition, postconditioning blocked terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling-positive staining, a marker of apoptosis, in the penumbra 2 days after Stroke. Furthermore, in situ superoxide detection using hydroethidine suggested that postconditioning attenuated superoxide products during early reperfusion after Stroke. In conclusion, postconditioning reduced infarct size, most plausibly by blocking apoptosis and free radical generation. With further study it may eventually be clinically applicable for Stroke treatment.
Nikolaus J Sucher - One of the best experts on this subject based on the ideXlab platform.
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Stroke Therapy in traditional chinese medicine tcm prospects for drug discovery and development
Phytomedicine, 2002Co-Authors: Xiandi Gong, Nikolaus J SucherAbstract:Brain injuries resulting from Stroke are a major and increasing public health problem in both developed and developing countries worldwide. China's extensive experience in the use of traditional Chinese medicines (TCMs) in Stroke Therapy indicates that TCM preparations are effective, with few or no side-effects. There are more than 100 traditional medicines in use for Stroke Therapy in China. Some of their therapeutic effects in Stroke have been confirmed by recent clinical studies. A large number of compounds have been isolated from TCMs and most of these resources have not yet been characterized for pharmacological purposes. Here, this article explains how TCM provides an extensive and knowledge-rich foundation for implementing a strategically focused pharmacological research program aimed at the development of new drugs.
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Stroke Therapy in traditional chinese medicine tcm prospects for drug discovery and development
Trends in Pharmacological Sciences, 1999Co-Authors: Xiandi Gong, Nikolaus J SucherAbstract:Brain injuries resulting from Stroke are a major and increasing public health problem in both developed and developing countries worldwide. China's extensive experience in the use of traditional Chinese medicines (TCMs) in Stroke Therapy indicates that TCM preparations are effective, with few or no side-effects. There are more than 100 traditional medicines in use for Stroke Therapy in China. Some of their therapeutic effects in Stroke have been confirmed by recent clinical studies. A large number of compounds have been isolated from TCMs and most of these resources have not yet been characterized for pharmacological purposes. Here, this article explains how TCM provides an extensive and knowledge-rich foundation for implementing a strategically focused pharmacological research programme aimed at the development of new drugs.
David S Liebeskind - One of the best experts on this subject based on the ideXlab platform.
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histological Stroke clot analysis after thrombectomy technical aspects and recommendations
International Journal of Stroke, 2020Co-Authors: Senna Staessens, Werner Hacke, David S Liebeskind, Sean Fitzgerald, Tommy Andersson, Frederic Clarencon, Frederik Denorme, Matthew J Gounis, Istvan SzikoraAbstract:The recent advent of endovascular procedures has created the unique opportunity to collect and analyze thrombi removed from cerebral arteries, instigating a novel subfield in Stroke research. Insights into thrombus characteristics and composition could play an important role in ongoing efforts to improve acute ischemic Stroke Therapy. An increasing number of centers are collecting Stroke thrombi. This paper aims at providing guiding information on thrombus handling, procedures, and analysis in order to facilitate and standardize this emerging research field.
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subject retention in prehospital Stroke research using a telephone based physician investigator driven enrollment method
Cerebrovascular Diseases Extra, 2019Co-Authors: Bryant J Rosell, Jeffrey L. Saver, Robin Conwit, Marc Eckstein, Sidney Starkman, Kristina Shkirkova, Latisha Sharma, David S Liebeskind, May Kimtenser, Scott HamiltonAbstract:Author(s): Rosell, Bryant J; Shkirkova, Kristina; Saver, Jeffrey L; Liebeskind, David S; Starkman, Sidney; Kim-Tenser, May; Eckstein, Marc; Sharma, Latisha; Conwit, Robin; Hamilton, Scott; Sanossian, Nerses | Abstract: BACKGROUND AND PURPOSE:Subject retention into clinical trials is vital, and prehospital enrollment may be associated with higher rates of subject withdrawal than more traditional methods of enrollment. We describe rates of subject retention in a prehospital trial of acute Stroke Therapy. METHODS:All subjects were enrolled into the NIH Field Administration of Stroke Therapy-Magnesium (FAST-MAG) phase 3 clinical trial. Paramedics screened eligible subjects and contacted the physician-investigator using a dedicated in-ambulance cellular phone. Physician-investigators obtained explicit informed consent from the subject or on-scene legally authorized representative (LAR) who reviewed and signed a consent form. Exception from informed consent (EFIC) was utilized in later stages of the study. RESULTS:There were 1,700 subjects enrolled; 1,017 provided consent (60%), 662 were enrolled via LAR (39%), and 21 were enrolled via EFIC (1%). Of the 1,700 patients, 1,413 (83%) completed the 90-day visit, 265 (16%) died prior to the 90-day visit, and 22 (1.3%) withdrew from the study before completion. There were no differences in rates of withdrawal by method of study enrolment, i.e., self-consent (n = 14), 1.4%; LAR (n = 8), 1.2%; EFIC (n = 0) 0%. CONCLUSION:There was a high rate of retention when subjects were enrolled into prehospital Stroke research using a phone-based method to obtain explicit consent.
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paramedic initiation of neuroprotective agent infusions successful achievement of target blood levels and attained level effect on clinical outcomes in the fast mag pivotal trial field administration of Stroke Therapy magnesium
Stroke, 2017Co-Authors: Kristina Shkirkova, Nerses Sanossian, Scott Hamilton, Robin Conwit, Marc Eckstein, Samuel J Stratton, Sidney Starkman, Frank Pratt, Latisha Sharma, David S LiebeskindAbstract:Background and Purpose— Paramedic use of fixed-size lumen, gravity-controlled tubing to initiate intravenous infusions in the field may allow rapid start of neuroprotective Therapy for acute Stroke. In a large, multicenter trial, we evaluated its efficacy in attaining target serum levels of candidate neuroprotective agent magnesium sulfate and the relation of achieved magnesium levels to outcome. Methods— The FAST-MAG phase 3 trial (Field Administration of Stroke Therapy – Magnesium) randomized 1700 patients within 2 hours of onset to paramedic-initiated, a 15-minute loading intravenous infusion of magnesium or placebo followed by a 24-hour maintenance dose. The drug delivery strategy included fixed-size lumen, gravity-controlled tubing for field drug administration, and a shrink-wrapped ambulance kit containing both the randomized field loading and hospital maintenance doses for seamless continuation. Results— Among patient randomized to active treatment, magnesium levels in the first 72 hours were assessed 987 times in 572 patients. Mean patient age was 70 years (SD±14 years), and 45% were women. During the 24-hour period of active infusion, mean achieved serum level was 3.91 (±0.8), consistent with trial target. Mg levels were increased by older age, female sex, lower weight, height, body mass index, and estimated glomerular filtration rate, and higher blood urea nitrogen, hemoglobin, and higher hematocrit. Adjusted odds for clinical outcomes did not differ by achieved Mg level, including disability at 90 days, symptomatic hemorrhage, or death. Conclusions— Paramedic infusion initiation using gravity-controlled tubing permits rapid achievement of target serum levels of potential neuroprotective agents. The absence of association of clinical outcomes with achieved magnesium levels provides further evidence that magnesium is not biologically neuroprotective in acute Stroke.
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abstract wp29 clot size speaking the same language in endovascular Stroke Therapy across the globe
Stroke, 2016Co-Authors: David S Liebeskind, Nerses Sanossian, Rishi Gupta, Tudor G Jovin, Gregory W Albers, Fabien Scalzo, Bin Xiang, Helmi L Lutsep, Wade S Smith, Monika KilleroberpfalzerAbstract:Background: Clot size in acute ischemic Stroke has been ascribed to time from onset, used in imaging selection with varying techniques or definitions, and cited as a factor in both revascularizatio...
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reversing Stroke in the 2010s lessons from desmoteplase in acute ischemic Stroke 2 dias 2
Stroke, 2009Co-Authors: David S LiebeskindAbstract:Marc Fisher MD Kennedy Lees MD Section Editors: Only months from now, another decade will dawn on Stroke research with a dearth of therapeutic innovations developed to reverse the devastating effects of acute ischemic Stroke. Despite generations of academic research investigators and associated industry collaborations, our clinical trials have marked each decade by successive eras of failed treatments with only a few exceptions. The recent publication of results from the Desmoteplase In Acute ischemic Stroke (DIAS)-2 trial provides important lessons that may hold the clues to reversing Stroke in the 2010s.1 DIAS-2 was undoubtedly a landmark study, incorporating sophisticated trial design with the latest innovations in CT and MRI techniques to confirm benefit of a novel fibrinolytic agent to treat acute ischemic Stroke up to 9 hours after symptom onset. The potential for another Stroke Therapy in clinical practice was replaced by collective introspection on the determinants of yet another negative trial after earlier positive results.2 Once again, an article starts by underscoring the limited treatment options for Stroke, details the saga of an elaborate yet negative clinical trial, and ends by noting that the “criteria to optimize the selection and treatment outcomes” remain elusive. The perpetual motion of academia echoes the familiar chorus that further studies are indicated, but perhaps this philosophical juncture provides an opportunity to heed important lessons learned. An endless list of reasons can be cited for failure, like in the litany of articles on neuroprotective trials or the thoughtful considerations of Stroke Therapy Academic Industry Roundtable (STAIR),3,4 yet most are difficult to prove or easily remedy without a comprehensive overhaul. Overall, DIAS-2 teaches us that the traditional approaches to Stroke Therapy may require revision of our currently engrained textbook approach to key variables such as time, imaging of the penumbra, ischemic pathophysiology, …
Brianfred Fitzsimmons - One of the best experts on this subject based on the ideXlab platform.
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the penumbra system for mechanical thrombectomy in endovascular acute ischemic Stroke Therapy
Neurology, 2012Co-Authors: Syed I Hussain, Osama O Zaidat, Brianfred FitzsimmonsAbstract:Background: Efficacy of IV systemic thrombolysis is limited in patients with severe acute ischemic Stroke and large-vessel occlusion. Mechanical thrombectomy has been the mainstay Therapy in large-vessel occlusion. This review focuses on the Penumbra aspiration device. Method: Literature review. Results: The Penumbra prospective studies were reviewed and results are presented. The pivotal single-arm prospective trial that led to its approval by the US Food and Drug Administration enrolled 125 patients within 8 hours of symptom onset and demonstrated an 82% recanalization rate, to Thrombolysis in Myocardial Ischemia (TIMI) scores of 2 and 3. The risk of symptomatic intracranial hemorrhage was 10%, and modified Rankin Scale (mRS) score of ≤2 was 25%. In the postmarketing registry, 157 vessels were treated, with 87% achieving TIMI 2 and 3 recanalization and 41% having an mRS score of ≤2. Conclusion: The Penumbra aspiration system is an effective tool to safely revascularize large-vessel occlusions in patients within 8 hours of onset of acute ischemic Stroke who are either refractory to or excluded from IV thrombolytic Therapy. Further prospective, randomized controlled trials will be needed to address whether this ability translates into neurologic improvement and better functional outcomes for our patients.
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interventional acute ischemic Stroke Therapy with intracranial self expanding stent
Stroke, 2008Co-Authors: Osama O Zaidat, Thomas Wolfe, Syed I Hussain, John R Lynch, Rishi Gupta, Joanna Delap, Michel T Torbey, Brianfred FitzsimmonsAbstract:Background and Purpose— Rapid and safe recanalization of occluded intracranial arteries in acute ischemic Stroke (AIS) is challenging. Newly available self-expanding intracranial atherosclerotic stents (SEIS), which can be deployed rapidly and safely, make acute stenting an option for treating AIS. We present the feasibility of this technique. Methods— A retrospective analysis evaluated procedural protocols and clinical response to treatment in patients with AIS treated with SEIS. Descriptive statistics are presented with initial and follow-up National Institutes of Health Stroke Scale and modified Rankin Score. Results— Nine patients with AIS underwent acute SEIS placement. There was successful deployment of the Neuroform (n=4) and Wingspan (n=4/5) stents in the M1/M2 (n=5) and M3 (n=1) middle cerebral artery segments, intracranial internal carotid artery (one of 2), and intracranial vertebrobasilar junction (one). Mean time of SEIS deployment from AIS onset was 5.1 hours. Complete (Thrombolysis in Cereb...
