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

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

Optimising acute stroke care organisation: a simulation study to assess the potential to increase intravenous thrombolysis rates and patient gains

Objectives: To assess potential increases in intravenous thrombolysis (IVT) rates given particular interventions in the stroke care pathway. Design: Simulation modelling was used to compare the performance of the current pathway, best practices based on literature review and an optimised model. Setting: Four hospitals located in the North of the Netherlands, as part of a centralised organisational model. Participants: Ischaemic stroke patients prospectively ascertained from February to August 2010. Intervention: The interventions investigated included efforts aimed at patient response and mode of referral, prehospital triage and intrahospital delays. Primary and secondary outcome measures: The primary outcome measure was thrombolysis utilisation. Secondary measures were onset-treatment time (OTT) and the proportion of patients with excellent functional outcome (modified Rankin scale (mRS) 0–1) at 90 days. Results: Of 280 patients with ischaemic stroke, 125 (44.6%) arrived at the hospital within 4.5 hours, and 61 (21.8%) received IVT. The largest improvements in IVT treatment rates, OTT and the proportion of patients with mRS scores of 0–1 can be expected when patient response is limited to 15 min (IVT rate +5.8%; OTT −6 min; excellent mRS scores +0.2%), door-to- needle time to 20 min (IVT rate +4.8%; OTT −28 min; excellent mRS scores+3.2%) and 911 calls are increased to 60% (IVT rate +2.9%; OTT −2 min; excellent mRS scores+0.2%). The combined implementation of all potential best practices could increase IVT rates by 19.7% and reduce OTT by 56 min. Conclusions: Improving IVT rates to well above 30% appears possible if all known best practices are implemented

Pathway Design for Acute Stroke Care in the Era of Endovascular Thrombectomy:A Critical Overview of Optimization Efforts

The efficacy of intravenous thrombolysis and endovascular thrombectomy (EVT) for acute ischemic stroke is highly time dependent. Optimal organization of acute stroke care is therefore important to reduce treatment delays but has become more complex after the introduction of EVT as regular treatment for large vessel occlusions. There is no singular optimal organizational model that can be generalized to different geographic regions worldwide. Current dominant organizational models for EVT include the drip-and-ship- and mothership model. Guidelines recommend routing of suspected patients with stroke to the nearest intravenous thrombolysis capable facility; however, the choice of routing to a certain model should depend on regional stroke service organization and individual patient characteristics. In general, design approaches for organizing stroke care are required, in which 2 key strategies could be considered. The first entails the identification of interventions within existing organizational models for optimizing timely delivery of intravenous thrombolysis and/or EVT. This includes adaptive patient routing toward a comprehensive stroke center, which focuses particularly on prehospital triage tools; bringing intravenous thrombolysis or EVT to the location of the patient; and expediting services and processes along the stroke pathway. The second strategy is to develop analytical or simulation model-based approaches enabling the design and evaluation of organizational models before their implementation. Organizational models for acute stroke care need to take regional and patient characteristics into account and can most efficiently be assessed and optimized through the application of model-based approaches

Assessment of the local SAR Distortion by Major Anatomical Structures in a Cylindrical Neck Phantom

The objective of this work is to gain insight in the distortions on the local SAR distribution by various major anatomical structures in the neck. High resolution 3D FDTD calculations based on a variable grid are made for a semi-3D generic phantom based on average dimensions obtained from CT-derived human data and in which simplified structures representing trachea, cartilage, spine and spinal cord are inserted. In addition, phantoms with dimensions equal to maximum and minimum values within the CT-derived data are also studied. In all cases, the phantoms are exposed to a circular coherent array of eight dipoles within a water bolus and driven at 433 MHz. Comparisons of the SAR distributions due to individual structures or a combination of structures are made relative to a cylindrical phantom with muscle properties. The calculations predict a centrally located region of high SAR within all neck phantoms. This focal region, expressed as contours at either 50% or 75% of the peak SAR, changes from a circular cross-section in the case of the muscle phantom to a doughnut shaped region when the anatomical structures are present. The presence of the spine causes the greatest change in the SAR distribution, followed closely by the trachea. Global changes in the mean SAR relative to the uniform phantom are <11%, whilst local changes are as high as 2.7-fold. There is little difference in the focal dimensions between the average and smallest phantoms, but a decrease in the focal region is seen in the case of the largest phantom. This study presents a first step towards understanding of the complex influences of the various parameters on the SAR pattern which will facilitate the design of a site-specific head and neck hyperthermia applicator

Cost-effectiveness of Direct Transfer to Angiography Suite of Patients With Suspected Large Vessel Occlusion

Cost-effectiveness; Angiography; Large vessel occlusionCost-efectivitat; Angiografia; Oclusió de grans vasosCosto-efectividad; Angiografía; Oclusión de grandes vasosBackground and Objectives Patients with acute ischemic stroke due to large vessel occlusion (LVO) deemed eligible for endovascular thrombectomy (EVT) are transferred from the emergency room to the angiography suite to undergo the procedure. Recently, the strategy of direct transfer of patients with suspected LVO to the angiography suite (DTAS) has been shown to improve functional outcomes. This study aims to evaluate the cost-effectiveness of the DTAS strategy vs initial transfer of patients with suspected LVO (Rapid Arterial Occlusion Evaluation score >4 and NIH Stroke Scale >10) to the emergency room (ITER). Methods A decision-analytic Markov model was developed to estimate the cost-effectiveness of the DTAS strategy vs the ITER strategy from a Dutch health care perspective with a 10-year time horizon. The primary outcome was the incremental cost-effectiveness ratio (ICER) using Dutch thresholds of $59,135 (€50,000) and$94,616 (€80,000) per quality-adjusted life year (QALY). Uncertainty of input parameters was assessed using 1-way sensitivity analysis, scenario analysis, and probabilistic sensitivity analysis. Results The DTAS strategy yielded 0.65 additional QALYs at an additional $16,089, resulting in an ICER of$24,925/QALY compared with the ITER strategy. The ICER varied from $27,169 to$38,325/QALY across different scenarios. The probabilistic sensitivity analysis showed that the DTAS strategy had a 91.8% and 97.0% likelihood of being cost-effective at a decision threshold of $59,135/QALY and$94,616/QALY, respectively. Discussion The cost-effectiveness of the DTAS strategy over ITER is robust for patients with suspected LVO. Together with recently published clinical results, this means that implementation of the DTAS strategy may be considered to improve the workflow and outcome of EVT.The CONTRAST consortium is supported by Netherlands Cardiovascular Research Initiative, an initiative of the Dutch Heart Foundation (CVON2015-01: CONTRAST) and by the Brain Foundation Netherlands (HA2015.01.06) and powered by Health∼Holland, Top Sector Life Sciences and receives unrestricted funding from Medtronic and Cerenovus. The collaboration project is additionally financed by the Ministry of Economic Affairs by means of the PPP Allowance made available by the Top Sector Life Sciences & Health to stimulate public-private partnerships (LSHM17016). This work was funded in part through unrestricted funding by Stryker, Medtronic and Cerenovus

Fragmentation and depolymerization of microplastics in the earthworm gut: a potential for microplastic bioremediation?

The accumulation of microplastics poses potential risks to soil health. Here, we did a preliminary exploration on the potential of Lumbricus terrestris (Oligochaeta) to reduce low-density polyethylene (LDPE), polylactic acid (PLA), and polybutylene adipate terephthalate (PBAT) microplastic (20–648 µm) contamination in soils. The ingestion of microplastics-contaminated soil (1% of microplastics, dw/dw) in a mesocosm system and the ingestion of pure microplastics in the Petri Dish by earthworms were studied. Results show that earthworms survived in the microplastics-contaminated soil (0% mortality in 35 days) but barely when exposed solely to microplastics (30–80% mortality in 4 days). Size-dependent ingestion of microplastics was not observed. The fragmentation of LDPE microplastics in the gizzard facilitated by soil was confirmed by the significantly increased ratio of small-sized (20–113 µm) microplastics from the bulk soil to the gut (from 8.4% to 18.8%). PLA and PBAT microplastics were fragmented by gizzard without the facilitation of soil, the ratios of small-sized (20–113 µm) PLA and PBAT microplastics in the gut were 55.5% and 108.2% higher than in respective pristine distributions. Substantial depolymerization of PLA (weight-average molar mass reduced by 17.7% with shift in molecular weight distribution) and suspected depolymerization of PBAT were observed in the worm gut, while no change in the molar mass was observed for PLA and PBAT microplastics buried in the soil for 49 days. Our results suggest that ingested microplastics could undergo fragmentation and depolymerization (for certain polymers) in the earthworm gut. Further research is needed to reveal the mechanisms of polymer depolymerization in the earthworm gut and to evaluate the feasibility of microplastic bioremediation with earthworms