Safety of intravenous thrombolysis for acute ischemic stroke in patients receiving antiplatelet therapy at stroke onset

<p><b>Background and Purpose:</b> Antiplatelets (APs) may increase the risk of symptomatic intracerebral hemorrhage (ICH) following intravenous thrombolysis after ischemic stroke.</p> <p><b>Methods:</b> We assessed the safety of thrombolysis under APs in 11 865 patients compliant with the European license criteria and recorded between 2002 and 2007 in the Safe Implementation of Treatments in Stroke (SITS) International Stroke Thrombolysis Register (SITS-ISTR). Outcome measures of univariable and multivariable analyses included symptomatic ICH (SICH) per SITS Monitoring Study (SITS-MOST [deterioration in National Institutes of Health Stroke Scale >= 4 plus ICH type 2 within 24 hours]), per European Cooperative Acute Stroke Study II (ECASS II [deterioration in National Institutes of Health Stroke Scale >= 4 plus any ICH]), functional outcome at 3 months and mortality.</p> <p><b>Results:</b> A total of 3782 (31.9%) patients had received 1 or 2 AP drugs at baseline: 3016 (25.4%) acetylsalicylic acid (ASA), 243 (2.0%) clopidogrel, 175 (1.5%) ASA and dipyridamole, 151 (1.3%) ASA and clopidogrel, and 197 (1.7%) others. Patients receiving APs were 5 years older and had more risk factors than AP nave patients. Incidences of SICH per SITS-MOST (ECASS II respectively) were as follows: 1.1% (4.1%) AP naive, 2.5% (6.2%) any AP, 2.5% (5.9%) ASA, 1.7% (4.2%) clopidogrel, 2.3% (5.9%) ASA and dipyridamole, and 4.1% (13.4%) ASA and clopidogrel. In multivariable analyses, the combination of ASA and clopidogrel was associated with increased risk for SICH per ECASS II (odds ratio, 2.11; 95% CI, 1.29 to 3.45; P = 0.003). However, we found no significant increase in the risk for mortality or poor functional outcome, irrespective of the AP subgroup or SICH definition.</p> <p><b>Conclusion:</b> The absolute excess of SICH of 1.4% (2.1%) in the pooled AP group is small compared with the benefit of thrombolysis seen in randomized trials. Although caution is warranted in patients receiving the combination of ASA and clopidogrel, AP treatment should not be considered a contraindication to thrombolysis.</p&gt

Rationale and design for studying organisation of care for intra-arterial thrombectomy in the Netherlands:simulation modelling study

INTRODUCTION: The introduction of intra-arterial thrombectomy (IAT) challenges acute stroke care organisations to provide fast access to acute stroke therapies. Parameters of pathway performance include distances to primary and comprehensive stroke centres (CSCs), time to treatment and availability of ambulance services. Further expansion of IAT centres may increase treatment rates yet could affect efficient use of resources and quality of care due to lower treatment volume. The aim was to study the organisation of care and patient logistics of IAT for patients with ischaemic stroke in the Netherlands. METHODS AND ANALYSES: Using a simulation modelling approach, we will quantify performance of 16 primary and CSCs offering IAT in the Netherlands. Patient data concerning both prehospital and intrahospital pathway logistics will be collected and used as input for model validation. A previously validated simulation model for intravenous thrombolysis (IVT) patients will be expanded with data of the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry and trials performed in the Collaboration for New Treatments in Acute Stroke consortium to represent patient logistics, time delays and outcomes in IAT patients. Simulation experiments aim to assess effectiveness and efficiency of alternative network topologies, that is, IAT with or without IVT at the nearest primary stroke centre (PSC) versus centralised care at a CSC. Primary outcomes are IAT treatment rates and clinical outcome according to the modified Rankin Scale. Secondary outcomes include onset-to-treatment time and resource use. Mann-Whitney U and Fisher's exact tests will be used to estimate differences for continuous and categorical variables. Model and parameter uncertainty will be tested using sensitivity analyses. ETHICS AND DISSEMINATION: This will be the first study to examine the organisation of acute stroke care for IAT delivery on a national scale using discrete event simulation. There are no ethics or safety concerns regarding the dissemination of information, which includes publication in peer-reviewed journals and (inter)national conference presentations. TRIAL REGISTRATION NUMBER: ISRCTN99503308, ISRCTN76741621, ISRCTN19922220, ISRCTN80619088, NCT03608423; Pre-results

‘Drive the doctor’ for endovascular thrombectomy in a rural area:a simulation study

Background: Patients who present in a primary stroke center (PSC) with ischemic stroke are usually transferred to a comprehensive stroke center (CSC) in case of a large vessel occlusion (LVO) for endovascular thrombectomy (EVT) treatment, the so-called ‘drip-and-ship’ (DS) model. The ‘drive-the-doctor’ (DD) model modifies the DS model by allowing mobile interventionalists (MIs) to transfer to an upgraded PSC acting as a thrombectomy capable stroke center (TSC), instead of transferring patients to a CSC. Using simulation we estimated time savings and impact on clinical outcome of DD in a rural region.Methods: Data from EVT patients in northern Netherlands was prospectively collected in the MR CLEAN Registry between July 2014 - November 2017. A Monte Carlo simulation model of DS patients served as baseline model. Scenarios included regional spread of TSCs, pre-hospital patient routing to ‘the nearest PSC’ or ‘nearest TSC’, MI’s notification after LVO confirmation or earlier prehospital, and MI’s transport modalities. Primary outcomes are onset to groin puncture (OTG) and predicted probability of favorable outcome (PPFO) (mRS 0–2).Results: Combining all scenarios OTG would be reduced by 28–58 min and PPFO would be increased by 3.4-7.1%. Best performing and acceptable scenario was a combination of 3 TSCs, prehospital patient routing based on the RACE scale, MI notification after LVO confirmation and MI’s transfer by ambulance. OTG would reduce by 48 min and PPFO would increase by 5.9%.Conclusions: A DD model is a feasible scenario to optimize acute stroke services for EVT eligible patients in rural regions. Key design decisions in implementing the DD model for a specific region are regional spread of TSCs, patient routing strategy, and MI’s notification moment and transport modality

Simulation modelling to study the impact of adding comprehensive stroke centres. Can we deliver endovascular thrombectomy sooner?

OBJECTIVES: Regional accessibility and distribution of endovascular thrombectomy (EVT) capable facilities, that is, comprehensive stroke centres (CSCs), may significantly influence time to treatment. We analysed the impact of adding CSCs in the north of the Netherlands, a region with roughly 1.7 million inhabitants currently served by one CSC and eight primary stroke centres (PSCs).DESIGN: Monte Carlo simulation modelling was used to establish new CSCs in our region by hypothetically upgrading existing PSCs to CSCs and ensuing adjustments in health services set-up.SETTING: One CSC and eight PSCs in the north of the Netherlands.PARTICIPANTS: 165 patients with acute stroke treated with EVT and underwent interhospital transfer between PSC and CSC (drip and ship patients).PRIMARY AND SECONDARY OUTCOMES: Time from onset to groin (OTG) puncture and predicted probability of favourable outcome (modified Rankin Scale 0-2) after 90 days. Sensitivity analyses were performed to assess uncertainty in workflow efficiency of CSCs.RESULTS: Adding one or two CSCs would reduce the OTG time up to approximately 17 min and increases the predicted probability of favourable outcome by approximately 2%. Sensitivity analyses revealed that 'slow-acting' CSCs may reduce OTG by 3-5 min compared with 24-32 min for 'fast-acting' CSCs.CONCLUSIONS: This study suggests that adding one or two CSCs in the north of the Netherlands would have modest impact. Improving workflow efficiencies seems to be more potent when aiming to improve existing acute stroke care systems.</p

Expediting workflow in the acute stroke pathway for endovascular thrombectomy in the northern Netherlands:a simulation model

OBJECTIVE: The objective of this study is to identify barriers for the timely delivery of endovascular thrombectomy (EVT) and to investigate the effects of potential workflow improvements in the acute stroke pathway. DESIGN: Hospital data prospectively collected in the MR CLEAN Registry were linked to emergency medical services data for each EVT patient and used to build two Monte Carlo simulation models. The 'mothership (MS) model', reflecting patients who arrived directly at the comprehensive stroke centre (CSC); and the 'drip and ship' (DS) model, reflecting patients who were transferred to the CSC from primary stroke centres (PSCs). SETTING: Northern region of the Netherlands. One CSC provides EVT, and its catchment area includes eight PSCs. PARTICIPANTS: 248 patients who were treated with EVT between July 2014 and November 2017. OUTCOME MEASURES: The main outcome measures were total delay from stroke onset until groin puncture, functional independence at 90 days (modified Rankin Scale 0-2) and mortality. RESULTS: Barriers identified included fast-track emergency department routing, prealert for transfer to the CSC, reduced handover time between PSC and ambulance, direct transfer from CSC arrival to angiography suite entry, and reducing time to groin puncture. Taken together, all workflow improvements could potentially reduce the time from onset to groin puncture by 59 min for the MS model and 61 min for the DS model. These improvements could thus result in more patients-3.7% MS and 7.4% DS-regaining functional independence after 90 days, in addition to decreasing mortality by 3.0% and 5.0%, respectively. CONCLUSIONS: In our region, the proposed workflow improvements might reduce time to treatment by about 1 hour and increase the number of patients regaining functional independence by 6%. Simulation modelling is useful for assessing the potential effects of interventions aimed at reducing time from onset to EVT

Study protocol of validating a numerical model to assess the blood flow in the circle of Willis

Introduction We developed a zero-dimensional (0D) model to assess the patient-specific haemodynamics in the circle of Willis (CoW). Similar numerical models for simulating the cerebral blood flow (CBF) had only been validated qualitatively in healthy volunteers by magnetic resonance (MR) angiography and transcranial Doppler (TCD). This study aims to validate whether a numerical model can simulate patient-specific blood flow in the CoW under pathological conditions. Methods and analysis This study is a diagnostic accuracy study. We aim to collect data from a previously performed prospective study that involved patients with aneurysmal subarachnoid haemorrhage (aSAH) receiving both TCD and brain Computerd Tomography angiography (CTA) at the same day. The cerebral flow velocities are calculated by the 0D model, based on the vessel diameters measured on the CTA of each patient. In this study, TCD is considered the gold standard for measuring flow velocity in the CoW. The agreement will be analysed using Pearson correlation coefficients. Ethics and dissemination This study protocol has been approved by the Medical Ethics Review Board of the University Medical Center Groningen: METc2019/103. The results will be submitted to an international scientific journal for peer-reviewed publication. Trial registration number NL8114

Patient-Specific Cerebral Blood Flow Simulation Based on Commonly Available Clinical Datasets

Cerebral hemodynamics play an important role in the development of cerebrovascular diseases. In this work, we propose a numerical framework for modeling patient-specific cerebral blood flow, using commonly available clinical datasets. Our hemodynamic model was developed using Simscape Fluids library in Simulink, based on a block diagram language. Medical imaging data obtained from computerized tomography angiography (CTA) in 59 patients with aneurysmal subarachnoid hemorrhage was used to extract arterial geometry parameters. Flow information obtained from transcranial Doppler (TCD) measurement was employed to calibrate input parameters of the hemodynamic model. The results show that the proposed numerical model can reproduce blood flow in the circle of Willis (CoW) per patient per measurement set. The resistance at the distal end of each terminal branch was the predominant parameter for the flow distribution in the CoW. The proposed model may be a promising tool for assessing cerebral hemodynamics in patients with cerebrovascular disease