scholarly journals PRIMED2 Preclinical Evidence Scoring Tool to Assess Readiness for Translation of Neuroprotection Therapies

2021 ◽  
Author(s):  
Mersedeh Bahr-Hosseini ◽  
Marom Bikson ◽  
Marco Iacoboni ◽  
David S. Liebeskind ◽  
Jason D. Hinman ◽  
...  
Keyword(s):  
Acute Stroke ◽  
Assessment Tool ◽  
Time Windows ◽  
Preclinical Model ◽  
Model Studies ◽  
Content Domain ◽  
Stroke Models ◽  
Scoring Tool ◽  
Pharmacologic Agents ◽  
Acute Stroke Therapy

AbstractMany neuroprotective and other therapies for treatment of acute ischemic stroke have failed in translation to human studies, indicating a need for more rigorous, multidimensional quality assessment of the totality of preclinical evidence supporting a therapy prior to conducting human trials. A consensus panel of stroke preclinical model and human clinical trial experts assessed candidate items for the translational readiness scale, compiled from prior instruments (STAIR, ARRIVE, CAMARADES, RoB 2) based on importance, reliability, and feasibility. Once constructed, the tool was applied by two independent raters to four current candidate acute stroke therapies, including two pharmacologic agents [nerinetide and trans-sodium crocetinate] and two device interventions [cathodal transcranial direct current stimulation and fastigial nucleus stimulation]. The Preclinical evidence of Readiness In stroke Models Evaluating Drugs and Devices (PRIMED2) assessment tool rates the totality of evidence available from all reported preclinical animal stroke model studies in 11 domains related to diversity of tested animals, time windows, feasibility of agent route of delivery, and robustness of effect magnitude. Within each content domain, clearly operationalized rules assign strength of evidence ratings of 0–2. When applied to the four assessed candidate agents, inter-rater reliability was high (kappa = 0.88), and each agent showed a unique profile of evidentiary strengths and weaknesses. The PRIMED2 assessment tool provides a multidimensional assessment of the cumulative preclinical evidence for a candidate acute stroke therapy on factors judged important for successful basic-to-clinical translation. Further evaluation and refinement of this tool is desirable to improve successful translation of therapies for acute stroke.

Abstract WP310: PRIMED Preclinical Evidence Scoring Tool to Assess Readiness for Translation of Neuroprotection Therapies

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Mersedeh Bahr Hosseini ◽  
Marom Bikosn ◽  
Marco Iacoboni ◽  
Stanley Thomas Carmichael ◽  
Jeffrey L Saver
Keyword(s):  
Animal Studies ◽  
Assessment Tool ◽  
Summary Score ◽  
Current Development ◽  
Readiness Assessment ◽  
Stroke Models ◽  
Detailed Assessment ◽  
Scoring Tool ◽  
Pharmacologic Agents ◽  
Neuroprotective Therapies

Introduction: Multiple neuroprotective therapies (NPT’s) for treatment of acute ischemic stroke have failed in translation to human studies, indicating a need for more rigorous quality assessment of all the cumulative preclinical evidence supporting an NPT prior to conducting human trials. There is a need for an updated translational readiness assessment tool to assess candidate therapies that combines desirable elements of existing instruments (STAIR 2.0, CAMARADES, RoB2) and include additional important elements. Methods: Candidate items for the intervention translational readiness scale, based on prior instruments, were rated by importance, reliability, and feasibility. For illustrative purposes, the assessment tool was applied to four NPT in current development, including two pharmacologic agents [uric acid (UA) and trans sodium crocetinate (TSC)] and two neuromodulatory device interventions [cathodal direct current stimulation (C-DCS) of ischemic hemisphere and fastigial nucleus stimulation (FSN)]. Results: The final Preclinical evidence of Readiness In stroke Models Evaluating Drugs/Devices (PRIMED) assessment tool rates evidence available from all reported animal studies in 10 domains (Fig1). Among the four assessed candidate NPT’s, the scores for two pharmacologic NPT’s indicated high translational readiness (UA and TSC 17) and the two neuromodulatory NPT’s had intermediate readiness-for-translation (C-DCS 12, FNS 8). Conclusion: The PRIMED assessment tool is an updated, multidimensional tool that provides a detailed assessment of multiple important readiness features across all preclinical experiments testing an NPT to assess readiness for translation, applicable to both pharmocologic and device therapies for acute stroke, providing both qualitative profiling of agent strengths and weaknesses and a quantitative summary score. Based on this tool, translational readiness is high for UA and TSC and intermediate for C-DCS and FNS.

Abstract 96: CTP-Mismatch Maps Improve Interobserver Agreement

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Waimei A Tai ◽  
Archana Purushotham ◽  
Matus Straka ◽  
Rebecca M Sugg ◽  
Naveed Akhtar ◽  
...  
Keyword(s):  
Acute Stroke ◽  
Ct Perfusion ◽  
Interobserver Reliability ◽  
Observer Agreement ◽  
Absolute Difference ◽  
Stroke Therapy ◽  
Adequate Quality ◽  
Ischemic Core ◽  
Observer Disagreement ◽  
Acute Stroke Therapy

Introduction: The use of mismatch between the ischemic core and penumbra to select patients who are likely to benefit from acute stroke therapy has gained popularity. Interpretation of the ischemic core and penumbra on standard CT-perfusion (CTP) maps is subjective. This may lead to variability among physicians in the decision if a patient is a good candidate for acute stroke therapy. A CTP-Mismatch map with outlines of the ischemic core and penumbra could limit this variability. The goal of this study was to determine if inter-observer agreement regarding a patient’s suitability for acute stroke therapy improves with the use of a CTP-Mismatch map. The figure shows a typical CTP-Mismatch map. Methods: Ninety-six consecutive patients evaluated with CTP prior to intra-arterial therapy at St. Lukes Hospital in 2008-09 were included. 79 patients had adequate quality CTP for this analysis. Standard CTP maps (CBV, CBF, MTT, and Tmax) and a CTP-Mismatch map were generated with a fully automated program for processing of CTP source images (RAPID). RAPID assessed the ischemic core using a CBF threshold <30% of the contralateral hemisphere (rCBF<30%). The ischemic penumbra was defined by a Tmax threshold of >6 sec (Tmax>6s). The standard CTP maps and the CTP-Mismatch map were independently analyzed by two vascular neurologists in a blinded fashion. The raters assessed a patient's suitability for intra-arterial therapy based on the following mismatch criteria: (1) a ratio between (Tmax>6s) and (rCBF<30%) volumes >1.8 and (2) an absolute difference between (Tmax>6s) and (CBF<30%) volumes >15ml. Interobserver reliability was assessed with Cohen’s kappa. Results: When assessment of suitability for intra-arterial therapy was based on interpretation of standard CTP maps, the two raters agreed in 58 of 79 patients (kappa=0.46; 95% CI=0.24-0.60). The agreement between observers improved when suitability was determined using CTP-Mismatch maps (agreement in 76 of 79 cases; kappa=0.92; 95% CI=0.75-0.92; p<0.001 for difference between kappa values). The 3 cases with inter-observer disagreement had artifact on the CTP-Mismatch map. Following concensus adjudication of these 3 cases, 40 of the 79 patients (51%) were deemed suitable candidates for acute stroke therapy. Conclusion: CTP-Mismatch maps with estimates of ischemic core and penumbra volumes markedly improve inter-observer agreement regarding assessment of suitability for acute stroke therapy. Such maps, which can be generated automatically, may help standardize decision making algorithms for evaluation of potential intra-arterial therapy candidates.

A qualitative study using the Theoretical Domains Framework to investigate why patients were or were not assessed for rehabilitation after stroke

2016 ◽  
Vol 31 (7) ◽  
pp. 966-977 ◽  
Author(s):  
Elizabeth A Lynch ◽  
Julie A Luker ◽  
Dominique A Cadilhac ◽  
Caroline E Fryer ◽  
Susan L Hillier
Keyword(s):  
Qualitative Study ◽  
Acute Stroke ◽  
Health Professionals ◽  
Assessment Tool ◽  
Theoretical Domains Framework ◽  
Assessment Practices ◽  
Stroke Units ◽  
Changing Practice ◽  
Referral Practices ◽  
Rehabilitation Assessment

Objective: To explore the factors perceived to affect rehabilitation assessment and referral practices for patients with stroke. Design: Qualitative study using data from focus groups analysed thematically and then mapped to the Theoretical Domains Framework. Setting: Eight acute stroke units in two states of Australia. Subjects: Health professionals working in acute stroke units. Interventions: Health professionals at all sites had participated in interventions to improve rehabilitation assessment and referral practices, which included provision of copies of an evidence-based decision-making rehabilitation Assessment Tool and pathway. Results: Eight focus groups were conducted (32 total participants). Reported rehabilitation assessment and referral practices varied markedly between units. Continence and mood were not routinely assessed (4 units), and people with stroke symptoms were not consistently referred to rehabilitation (4 units). Key factors influencing practice were identified and included whether health professionals perceived that use of the Assessment Tool would improve rehabilitation assessment practices (theoretical domain ‘social and professional role’); beliefs about outcomes from changing practice such as increased equity for patients or conversely that changing rehabilitation referral patterns would not affect access to rehabilitation (‘belief about consequences’); the influence of the unit’s relationships with other groups including rehabilitation teams (‘social influences’ domain) and understanding within the acute stroke unit team of the purpose of changing assessment practices (‘knowledge’ domain). Conclusion: This study has identified that health professionals’ perceived roles, beliefs about consequences from changing practice and relationships with rehabilitation service providers were perceived to influence rehabilitation assessment and referral practices on Australian acute stroke units.

scholarly journals Interpreting CT perfusion in stroke

2018 ◽  
Vol 19 (2) ◽  
pp. 136-142 ◽  
Author(s):  
Stevan Christopher Wing ◽  
Hugh S Markus
Keyword(s):  
Acute Stroke ◽  
Perfusion Imaging ◽  
Treatment Time ◽  
Ct Perfusion ◽  
Time Windows ◽  
Onset Time ◽  
Brain Perfusion ◽  
Reperfusion Therapy ◽  
Imaging Protocol ◽  
Stroke Imaging

CT perfusion images can be rapidly obtained on all modern CT scanners and easily incorporated into an acute stroke imaging protocol. Here we discuss the technique of CT perfusion imaging, how to interpret the data and how it can contribute to the diagnosis of acute stroke and selection of patients for treatment. Many patients with acute stroke are excluded from reperfusion therapy if the onset time is not known or if they present outside of traditional treatment time windows. There is a growing body of evidence supporting the use of perfusion imaging in these patients to identify patterns of brain perfusion that are favourable for recanalisation therapy.

Temporal Validation of an Assessment Tool that Predicts a Possibility of Home Discharge for Patients with Acute Stroke

2022 ◽  
Vol 31 (1) ◽  
pp. 106188
Author(s):  
Takahiro Itaya ◽  
Yusuke Murakami ◽  
Akiko Ota ◽  
Ryo Shimomura ◽  
Tomoko Fukushima ◽  
...  
Keyword(s):  
Acute Stroke ◽  
Assessment Tool ◽  
Home Discharge ◽  
Temporal Validation

Abstract WP121: Incorporating CT-Perfusion Imaging in Acute Stroke Therapy Workflow Does Not Delay Door to Needle Time for Intravenous t-PA

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Bahareh Sianati ◽  
Russel Cerejo ◽  
David Wright ◽  
Ashish Tayal ◽  
Patty Noah ◽  
...  
Keyword(s):  
Acute Stroke ◽  
Perfusion Imaging ◽  
Ct Perfusion ◽  
Brain Perfusion ◽  
Stroke Therapy ◽  
Brain Perfusion Imaging ◽  
Group 2 ◽  
Acute Stroke Therapy ◽  
Iv Tpa ◽  
Group 1

Introduction: Brain perfusion imaging has become an integral part of acute stroke therapy, especially for the extended time window. A streamlined workflow is essential to reduce delays in acute stroke therapy. Incorporating standard and advanced imaging together may reduce time to endovascular therapy but may delay administration of intravenous (IV) tPA. Method: A retrospective analysis of all acute stroke therapy cases between August 2017 and March of 2018 was performed at a single stroke center. Brain perfusion imaging was instituted into the workflow in December of 2017. We included patients who received IV tPA before and after implementation of CT perfusion (CT-P). Demographics, clinical presentation, stroke treatment times and imaging characteristics were collected. Results: During the eight-month period, we identified 117 patients who met inclusion criteria. We divided the cohort into two groups, pre CT-P implementation (Group 1) and post CT-P implementation (Group 2). We identified 66 patients in Group 1 and 51 patients in Group 2. In Group 1, 29 (44%) were females with median age of 63 years. In Group 2, 33 (65%) were females, with median age of 72 years. There was no difference in median times for door to needle in Group 1 (57 minutes, interquartile range [IQR] 42 – 76) compared to Group 2 (53 minutes, [IQR] 40 – 68) ( P = 0.20). Conclusion: Incorporating CT-P in the imaging workflow did not delay door to needle time for IV tPA in acute stroke therapy.

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