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  • 1
    Online-Ressource
    Online-Ressource
    Rationale and design for studying organisation of care for intra-arterial thrombectomy in the Netherlands: simulation modelling study
    BMJ ; 2020
    In:  BMJ Open Vol. 10, No. 1 ( 2020-01), p. e032754-
    Details
    In: BMJ Open, BMJ, Vol. 10, No. 1 ( 2020-01), p. e032754-
    Kurzfassung: 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.
    Materialart: Online-Ressource
    ISSN: 2044-6055 , 2044-6055
    URL: Article
    DOI: 10.1136/bmjopen-2019-032754
    Sprache: Englisch
    Verlag: BMJ
    Publikationsdatum: 2020
    ZDB Id: 2599832-8
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    Online-Ressource
    Online-Ressource
    Expediting workflow in the acute stroke pathway for endovascular thrombectomy in the northern Netherlands: a simulation model
    BMJ ; 2022
    In:  BMJ Open Vol. 12, No. 4 ( 2022-04), p. e056415-
    Details
    In: BMJ Open, BMJ, Vol. 12, No. 4 ( 2022-04), p. e056415-
    Kurzfassung: 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.
    Materialart: Online-Ressource
    ISSN: 2044-6055 , 2044-6055
    URL: Article
    DOI: 10.1136/bmjopen-2021-056415
    Sprache: Englisch
    Verlag: BMJ
    Publikationsdatum: 2022
    ZDB Id: 2599832-8
    Standort Signatur Einschränkungen Verfügbarkeit
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    Online-Ressource
  • 3
    Online-Ressource
    Online-Ressource
    Pathway Design for Acute Stroke Care in the Era of Endovascular Thrombectomy : A Critical Overview of Optimization Efforts
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Stroke Vol. 51, No. 11 ( 2020-11), p. 3452-3460
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 51, No. 11 ( 2020-11), p. 3452-3460
    Kurzfassung: 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.
    Materialart: Online-Ressource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.120.030392
    RVK:
    XA 10000
    Sprache: Englisch
    Verlag: Ovid Technologies (Wolters Kluwer Health)
    Publikationsdatum: 2020
    ZDB Id: 1467823-8
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
    Online-Ressource
    Online-Ressource
    A novel FcγRIIa Q27W gene variant is associated with common variable immune deficiency through defective FcγRIIa downstream signaling
    Elsevier BV ; 2014
    In:  Clinical Immunology Vol. 155, No. 1 ( 2014-11), p. 108-117
    Details
    In: Clinical Immunology, Elsevier BV, Vol. 155, No. 1 ( 2014-11), p. 108-117
    Materialart: Online-Ressource
    ISSN: 1521-6616
    URL: Article
    DOI: 10.1016/j.clim.2014.09.006
    RVK:
    XA 36852
    Sprache: Englisch
    Verlag: Elsevier BV
    Publikationsdatum: 2014
    ZDB Id: 1462862-4
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 5
    Online-Ressource
    Online-Ressource
    Variations in Modeling for Treating All Patients With Stroke With Suspected Large Vessel Occlusion
    American Medical Association (AMA) ; 2019
    In:  JAMA Neurology Vol. 76, No. 5 ( 2019-05-01), p. 624-
    Details
    In: JAMA Neurology, American Medical Association (AMA), Vol. 76, No. 5 ( 2019-05-01), p. 624-
    Materialart: Online-Ressource
    ISSN: 2168-6149
    DOI: 10.1001/jamaneurol.2019.0348
    Sprache: Englisch
    Verlag: American Medical Association (AMA)
    Publikationsdatum: 2019
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 6
    Online-Ressource
    Online-Ressource
    ‘Drive the doctor’ for endovascular thrombectomy in a rural area: a simulation study
    Springer Science and Business Media LLC ; 2023
    In:  BMC Health Services Research Vol. 23, No. 1 ( 2023-07-20)
    Details
    In: BMC Health Services Research, Springer Science and Business Media LLC, Vol. 23, No. 1 ( 2023-07-20)
    Kurzfassung: 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.
    Materialart: Online-Ressource
    ISSN: 1472-6963
    URL: Article
    DOI: 10.1186/s12913-023-09672-5
    Sprache: Englisch
    Verlag: Springer Science and Business Media LLC
    Publikationsdatum: 2023
    ZDB Id: 2050434-2
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 7
    Online-Ressource
    Online-Ressource
    Cost-effectiveness of improvement strategies for reperfusion treatments in acute ischemic stroke: a systematic review
    Springer Science and Business Media LLC ; 2023
    In:  BMC Health Services Research Vol. 23, No. 1 ( 2023-03-30)
    Details
    In: BMC Health Services Research, Springer Science and Business Media LLC, Vol. 23, No. 1 ( 2023-03-30)
    Kurzfassung: Reducing delays along the acute stroke pathway significantly improves clinical outcomes for acute ischemic stroke patients eligible for reperfusion treatments. The economic impact of different strategies reducing onset to treatment (OTT) is crucial information for stakeholders in acute stroke management. This systematic review aimed to provide an overview on the cost-effectiveness of several strategies to reduce OTT. Methods A comprehensive literature search was conducted in EMBASE, PubMed, and Web of Science until January 2022. Studies were included if they reported 1/ stroke patients treated with intravenous thrombolysis and/or endovascular thrombectomy, 2/ full economic evaluation, and 3/ strategies to reduce OTT. The Consolidated Health Economic Evaluation Reporting Standards statement was applied to assess the reporting quality. Results Twenty studies met the inclusion criteria, of which thirteen were based on cost-utility analysis with the incremental cost-effectiveness ratio per quality-adjusted life year gained as the primary outcome. Studies were performed in twelve countries focusing on four main strategies: educational interventions, organizational models, healthcare delivery infrastructure, and workflow improvements. Sixteen studies showed that the strategies concerning educational interventions, telemedicine between hospitals, mobile stroke units, and workflow improvements, were cost-effective in different settings. The healthcare perspective was predominantly used, and the most common types of models were decision trees, Markov models and simulation models. Overall, fourteen studies were rated as having high reporting quality (79%-94%). Conclusions A wide range of strategies aimed at reducing OTT is cost-effective in acute stroke care treatment. Existing pathways and local characteristics need to be taken along in assessing proposed improvements.
    Materialart: Online-Ressource
    ISSN: 1472-6963
    URL: Article
    DOI: 10.1186/s12913-023-09310-0
    Sprache: Englisch
    Verlag: Springer Science and Business Media LLC
    Publikationsdatum: 2023
    ZDB Id: 2050434-2
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 8
    Online-Ressource
    Online-Ressource
    Simulation modelling to study the impact of adding comprehensive stroke centres. Can we deliver endovascular thrombectomy sooner?
    BMJ ; 2023
    In:  BMJ Open Vol. 13, No. 7 ( 2023-07), p. e068749-
    Details
    In: BMJ Open, BMJ, Vol. 13, No. 7 ( 2023-07), p. e068749-
    Kurzfassung: 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.
    Materialart: Online-Ressource
    ISSN: 2044-6055 , 2044-6055
    URL: Article
    URL: Article
    DOI: 10.1136/bmjopen-2022-068749
    DOI: 10.1136/bmjopen-2022-068749.supp1
    Sprache: Englisch
    Verlag: BMJ
    Publikationsdatum: 2023
    ZDB Id: 2599832-8
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 9
    Online-Ressource
    Online-Ressource
    B and T Lymphocyte Attenuator Mediates Inhibition of Tumor-Reactive CD8+ T Cells in Patients After Allogeneic Stem Cell Transplantation
    The American Association of Immunologists ; 2012
    In:  The Journal of Immunology Vol. 189, No. 1 ( 2012-07-01), p. 39-49
    Details
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 189, No. 1 ( 2012-07-01), p. 39-49
    Kurzfassung: Allogeneic stem cell transplantation (allo-SCT) can cure hematological malignancies by inducing alloreactive T cell responses targeting minor histocompatibility antigens (MiHA) expressed on malignant cells. Despite induction of robust MiHA-specific T cell responses and long-term persistence of alloreactive memory T cells specific for the tumor, often these T cells fail to respond efficiently to tumor relapse. Previously, we demonstrated the involvement of the coinhibitory receptor programmed death-1 (PD-1) in suppressing MiHA-specific CD8+ T cell immunity. In this study, we investigated whether B and T lymphocyte attenuator (BTLA) plays a similar role in functional impairment of MiHA-specific T cells after allo-SCT. In addition to PD-1, we observed higher BTLA expression on MiHA-specific CD8+ T cells compared with that of the total population of CD8+ effector-memory T cells. In addition, BTLA’s ligand, herpes virus entry mediator (HVEM), was found constitutively expressed by myeloid leukemia, B cell lymphoma, and multiple myeloma cells. Interference with the BTLA–HVEM pathway, using a BTLA blocking Ab, augmented proliferation of BTLA+PD-1+ MiHA-specific CD8+ T cells by HVEM-expressing dendritic cells. Notably, we demonstrated that blocking of BTLA or PD-1 enhanced ex vivo proliferation of MiHA-specific CD8+ T cells in respectively 7 and 9 of 11 allo-SCT patients. Notably, in 3 of 11 patients, the effect of BTLA blockade was more prominent than that of PD-1 blockade. Furthermore, these expanded MiHA-specific CD8+ T cells competently produced effector cytokines and degranulated upon Ag reencounter. Together, these results demonstrate that BTLA–HVEM interactions impair MiHA-specific T cell functionality, providing a rationale for interfering with BTLA signaling in post-stem cell transplantation therapies.
    Materialart: Online-Ressource
    ISSN: 0022-1767 , 1550-6606
    URL: Article
    DOI: 10.4049/jimmunol.1102807
    RVK:
    XA 54100
    RVK:
    XA 10000
    Sprache: Englisch
    Verlag: The American Association of Immunologists
    Publikationsdatum: 2012
    ZDB Id: 1475085-5
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 10
    Online-Ressource
    Online-Ressource
    A Q Fever Outbreak in the Netherlands: Consequences for Tissue Banking
    S. Karger AG ; 2011
    In:  Transfusion Medicine and Hemotherapy Vol. 38, No. 6 ( 2011), p. 357-364
    Details
    In: Transfusion Medicine and Hemotherapy, S. Karger AG, Vol. 38, No. 6 ( 2011), p. 357-364
    Materialart: Online-Ressource
    ISSN: 1660-3818 , 1660-3796
    URL: Article
    DOI: 10.1159/000334599
    Sprache: Englisch
    Verlag: S. Karger AG
    Publikationsdatum: 2011
    ZDB Id: 2100533-3
    Standort Signatur Einschränkungen Verfügbarkeit
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