Cost-effectiveness of tenecteplase versus alteplase for acute ischemic stroke.

INTRODUCTION: Alteplase is widely used as an intravenous thrombolytic drug in acute ischemic stroke (AIS). Recently however, tenecteplase, a modified form of tissue plasminogen activator, has been shown to increase early recanalization rate and has proven to be non-inferior with a similar safety profile compared to alteplase. This study aims to evaluate the cost-effectiveness of 0.25 mg/kg tenecteplase versus 0.9 mg/kg alteplase for intravenous thrombolysis in AIS patients from the Dutch healthcare payer perspective. METHODS: A Markov decision-analytic model was constructed to assess total costs, total quality-adjusted life year (QALY), an incremental cost-effectiveness ratio, and incremental net monetary benefit (INMB) of two treatments at willingness-to-pay (WTP) thresholds of €50,000/QALY and €80,000/QALY over a 10-year time horizon. One-way sensitivity analysis, probabilistic sensitivity analysis, and scenario analysis were conducted to test the robustness of results. Clinical data were obtained from large randomized controlled trials and real-world data. RESULTS: Treatment with tenecteplase saved €21 per patient while gaining 0.05 QALYs, resulting in INMB of €2381, clearly rendering tenecteplase cost-effective compared to alteplase. Importantly, tenecteplase remained the cost-effective alternative in all scenarios, including AIS patients due to large vessel occlusion (LVO). Probabilistic sensitivity analysis proved tenecteplase to be cost-effective with a 71.0% probability at a WTP threshold of €50,000/QALY. CONCLUSIONS: Tenecteplase treatment was cost-effective for all AIS patients (including AIS patients with LVO) compared to alteplase. The finding supports the broader use of tenecteplase in acute stroke care, as health outcomes improve at acceptable costs while having practical advantages, and a similar safety profile.

'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.

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

BACKGROUND 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.

Cost-effectiveness of improvement strategies for reperfusion treatments in acute ischemic stroke: a systematic review.

BACKGROUND: 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.

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.

Factors Influencing Procurement of Digital Healthcare: A Case Study in Dutch District Nursing.

BACKGROUND: Digital health is considered a promising solution in keeping health care accessible and affordable. However, implementation is often complex and sustainable funding schemes are lacking. Despite supporting policy, scaling up innovative forms of health care progresses much slower than intended in Dutch national framework agreements. The aim of this study is to identify factors that influence the procurement of digital health particular in district nursing. METHODS: A case study approach was used, in which multiple stakeholder perspectives are compared using thematic framework analysis. The case studied was the procurement of digital health in Dutch district nursing. Literature on implementation of digital health, public procurement and payment models was used to build the analytic framework. We analysed fourteen interviews (secondary data), two focus groups organised by the national task force procurement and eight governmental and third-party reports. RESULTS: Five themes emerged from the analysis: 1) rationale 2) provider-payer relationship, 3) resources, 4) evidence, and 5) the payment model. Per theme a number of factors were identified, mostly related to the design and functioning of the Dutch health system and to the implementation process at providers' side. CONCLUSION: This study identified factors influencing the procurement of digital health in Dutch district nursing. The findings, however, are not unique for digital health, district nursing or the Dutch health system. The results presented will support policy makers, and decision makers to improve procurement of digital health. Investing in better relationships between payer and care provider organisations and professionals is an important next step towards scaling digital health.

Post-discharge Telemonitoring of Physical Activity, Vital Signs, and Patient-Reported Symptoms in Older Patients Undergoing Cancer Surgery.

BACKGROUND: Postoperative home monitoring could potentially detect complications early, but evidence in oncogeriatric surgery is scarce. Therefore, we evaluated whether post-discharge physical activity, vital signs, and patient-reported symptoms are related to post-discharge complications and hospital readmissions in older patients undergoing cancer surgery. METHODS: In this observational cohort study, we monitored older patients (≥65 years of age) undergoing cancer surgery, for 2 weeks post-discharge using tablet-based applications and connected devices. Outcome measures were post-discharge complications and readmissions; physical activity and patient-reported symptoms over time; and threshold violations for physical activity (step count <1000 steps/day), vital signs (temperature <36°C or >38°C; blood pressure <100/60 mmHg or >150/100 mmHg; heart rate <50 bpm or >100 bpm; weight -5% or +5% of weight at discharge); and patient-reported symptoms (pain score greater than the previous day; presence of dyspnea, vomiting, dizziness, fever). RESULTS: Of 58 patients (mean age 72 years), 24 developed a post-discharge complication and 13 were readmitted. Measured parameters indicated 392 threshold violations out of 5379 measurements (7.3%) in 40 patients, mostly because of physical inactivity. Patients with readmissions had lower physical activity at discharge and at day 9 after discharge and violated a physical activity threshold more often. Patients with post-discharge complications had a higher median pain score compared with patients without these adverse events. No differences in threshold violations of other parameters were observed between patients with and without post-discharge complications and readmissions. CONCLUSION: Our results show the potential of telemonitoring older patients after cancer surgery but confirm that detecting post-discharge complications is complex and multifactorial.

Remote Home Monitoring of Older Surgical Cancer Patients: Perspective on Study Implementation and Feasibility.

BACKGROUND: Remote home monitoring might fill the perceived surveillance gap after hospital discharge. However, it is unclear whether older oncologic patients will be able to use the required new digital technologies. The study aimed to assess the feasibility of postoperative remote home monitoring for this population. METHODS: This observational cohort study recruited patients aged 65 years or older scheduled for oncologic surgery. The study patients used a mobile application and activity tracker preoperatively until 3 months postoperatively. A subset of the patients used additional devices (thermometer, blood pressure monitor, weight scale) and completed electronic health questionnaires 2 weeks after hospital discharge. Feasibility was assessed by the study completion rate, compliance in using components of the information technology system, acceptability [Net Promotor Score (NPS)] and usability [System Usability Scale (SUS)]. The NPS score varied from - 100 to + 100. An SUS higher than 68 was considered above average. RESULTS: Of 47 participants (mean age, 72 years; range, 65-85 years), 37 completed a follow-up assessment, yielding a completion rate of 79%. Compliance in using the activity tracker (n = 41) occurred a median of 81 days [interquartile range (IQR), 70-90 days] out of 90 post-discharge days. Compliance in measuring vital signs and completing health questionnaires varied from a median of 10.5 days (IQR, 4.5-14.0 days) to 12 days (IQR, 5-14 days) out of 14 days. The NPS was + 29.7%, and the mean SUS was 74.4 ± 19.3. CONCLUSION: Older oncologic patients in the study considered postoperative home monitoring acceptable and usable. Once they consented to participate, the patients were compliant, and the completion rate was high.

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.

Perioperative telemonitoring of older adults with cancer: Can we connect them all?

OBJECTIVES: Although the increasing cancer incidence in older patients is widely recognised, older patients remain underrepresented in clinical cancer trials and eHealth studies. The aim of this research is to identify technological and patient-related barriers to inclusion of this population in a clinical eHealth study. MATERIAL AND METHODS: This is a retrospective analysis of a prospective cohort study with older patients (≥ 65 years) undergoing cancer-related surgery, who were identified for a perioperative telemonitoring study. Reasons for ineligibility and refusal had been prospectively registered. Characteristics and postoperative outcomes were compared between participants and non-participants. RESULTS: Between May 2018 and March 2020, 151 patients were assessed for eligibility, resulting in 65 participants and 86 non-participants. The main reason for ineligibility was lack of internet access at home (n = 16), while main reasons for refusal were perceived high mental burden (n = 46) and insufficient digital skills (n = 12). Compared with participants, non-participants were significantly older (mean age 75 vs. 73, p = 0.01); more often female (64% vs. 35%, p = 0.00), unmarried (42% vs. 8%, p = 0.01) living alone (38% vs. 19%, p = 0.02); had a higher ASA classification (43% vs. 19%, p = 0.00); often had polypharmacy (67% vs. 43%, p = 0.00); and were more often discharged to skilled nursing facilities (0% vs. 15%, p = 0.00). CONCLUSION: Our results confirm the underrepresentation of older female patients with little support from a partner and higher comorbidity. We should be aware of technological and patient-related barriers to including older adults with cancer, in order to avoid further dividing patients with low and high digital health literacy.

Integrated Care for Older Adults: A Struggle for Sustained Implementation in Northern Netherlands.

INTRODUCTION: Integrated care has been suggested as a promising solution to the disparities in access and sustained high quality long-term care emerging in Europe's ageing population. We aim to gain a better understanding of context-specific barriers to and facilitators of implementation of integrated care by doing a retrospective assessment of seven years of Embrace. This Dutch integrated person-centred health service for older adults was based on two evidence-based models (the Chronic Care Model and the Kaiser Permanente Triangle). Despite successful deployment the programme ended in 2018. In this case study we assess the impact of the programme based on past evaluations, reflect on why it ended, lessons learned and ideas to take forward. DISCUSSION: The majority of health outcomes were positive and the perceived quality of care improved, albeit no clear-cut savings were observed, and the costs were not balanced across stakeholders. The Embrace payment model did not support the integration of health services, despite reforms in long-term care in 2015. KEY LESSONS: Enabling policy and funding are crucial to the sustained implementation of integrated person-centred health services. The payment model should incentivize the integration of care before the necessary changes can be made at organizational and clinical levels towards providing proactive and preventive health services.

Feasibility of Perioperative eHealth Interventions for Older Surgical Patients: A Systematic Review.

OBJECTIVES: EHealth interventions are increasingly being applied in perioperative care but have not been adequately studied for older surgical patients who could potentially benefit from them. Therefore, we evaluated the feasibility of perioperative eHealth interventions for this population. DESIGN: A systematic review of prospective observational and interventional studies was conducted. Three electronic databases (PubMed, EMBASE, CINAHL) were searched between January 1999 and July 2019. Study quality was assessed by Methodological Index for Non-Randomized Studies (MINORS) with and without control group. SETTING AND PARTICIPANTS: Studies of surgical patients with an average age ≥65 years undergoing any perioperative eHealth intervention with active patient participation (with the exception of telerehabilitation following orthopedic surgery) were included. MEASURES: The main outcome measure was feasibility, defined as a patient's perceptions of usability, satisfaction, and/or acceptability of the intervention. Other outcomes included compliance and study completion rate. RESULTS: Screening of 1569 titles and abstracts yielded 7 single-center prospective studies with 223 patients (range n = 9-69 per study, average age 66-74 years) undergoing oncological, cardiovascular, or orthopedic surgery. The median MINORS scores were 13.5 of 16 for 6 studies without control group, and 14 of 24 for 1 study with a control group. Telemonitoring interventions were rated as "easy to use" by 89% to 95% of participants in 3 studies. Patients in 3 studies were satisfied with the eHealth intervention and would recommend it to others. Acceptability (derived from consent rate) ranged from 71% to 89%, compliance from 53% to 86%, and completion of study follow-up from 54% to 95%. CONCLUSIONS AND IMPLICATIONS: Results of 7 studies involving perioperative eHealth interventions suggest their feasibility and encourage further development of technologies for older surgical patients. Future feasibility studies require clear definitions of appropriate feasibility outcome measures and a comprehensive description of patient characteristics such as functional performance, level of education, and socioeconomic status.

Postoperative recovery of accelerometer-based physical activity in older cancer patients.

INTRODUCTION: Recovery of physical activity is an important functional outcome measure after cancer surgery. However, objective data on physical activity for older cancer patients is scarce. The aims of this study were to quantify perioperative physical activity levels, assess recovery of physical activity three months after surgery, and characterise patients who achieved recovery. MATERIALS AND METHODS: This observational cohort study analysed physical activity data collected from patients aged >65 who were scheduled for cancer surgery between May 2018 and July 2019. Perioperative daily step count was measured using a Fitbit device. The primary outcome measure was the percentage of patients who returned to (≥90% of) their preoperative (baseline) physical activity levels three months after surgery. RESULTS: Fifty patients (mean age 73) were recruited, and available Fitbit data was analysed. Median daily step counts at baseline (n = 40), before hospital discharge (n = 40), and three months postoperative (n = 37) were 5,974 (IQR 4,250-7,922), 1,619 (IQR 920-2,839), and 4,674 (IQR 3,047-7,592), respectively. The 15/37 (41%) patients who had reached baseline levels three months after surgery seemed to have more preoperative self-reported physical activity, better anaesthesiologists' physical status classification, and fewer in-hospital complications compared to patients who had not, although the differences were statistically non-significant. CONCLUSION: Perioperative physical activity was quantified for older cancer patients, and 41% returned to baseline levels within three months. Accelerometer-based physical activity provided a valuable outcome measure for postoperative physical recovery. Future studies using objective physical activity measures are needed to evaluate effects of interventional studies aimed at improving physical activity.

Centralising acute stroke care within clinical practice in the Netherlands: lower bounds of the causal impact.

BACKGROUND: Authors in previous studies demonstrated that centralising acute stroke care is associated with an increased chance of timely Intra-Venous Thrombolysis (IVT) and lower costs compared to care at community hospitals. In this study we estimated the lower bound of the causal impact of centralising IVT on health and cost outcomes within clinical practice in the Northern Netherlands. METHODS: We used observational data from 267 and 780 patients in a centralised and decentralised system, respectively. The original dataset was linked to the hospital information systems. Literature on healthcare costs and Quality of Life (QoL) values up to 3 months post-stroke was searched to complete the input. We used Synthetic Control Methods (SCM) to counter selection bias. Differences in SCM outcomes included 95% Confidence Intervals (CI). To deal with unobserved heterogeneity we focused on recently developed methods to obtain the lower bounds of the causal impact. RESULTS: Using SCM to assess centralising acute stroke 3 months post-stroke revealed healthcare savings of $US 1735 (CI, 505 to 2966) while gaining 0.03 (CI, - 0.01 to 0.73) QoL per patient. The corresponding lower bounds of the causal impact are $US 1581 and 0.01. The dominant effect remained stable in the deterministic sensitivity analyses with $US 1360 (CI, 476 to 2244) as the most conservative estimate. CONCLUSIONS: In this study we showed that a centralised system for acute stroke care appeared both cost-saving and yielded better health outcomes. The results are highly relevant for policy makers, as this is the first study to address the issues of selection and unobserved heterogeneity in the evaluation of centralising acute stroke care, hence presenting causal estimates for budget decisions.

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.

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.

Evaluation of integrated care services in Catalonia: population-based and service-based real-life deployment protocols.

BACKGROUND: Comprehensive assessment of integrated care deployment constitutes a major challenge to ensure quality, sustainability and transferability of both healthcare policies and services in the transition toward a coordinated service delivery scenario. To this end, the manuscript articulates four different protocols aiming at assessing large-scale implementation of integrated care, which are being developed within the umbrella of the regional project Nextcare (2016-2019), undertaken to foster innovation in technologically-supported services for chronic multimorbid patients in Catalonia (ES) (7.5 M inhabitants). Whereas one of the assessment protocols is designed to evaluate population-based deployment of care coordination at regional level during the period 2011-2017, the other three are service-based protocols addressing: i) Home hospitalization; ii) Prehabilitation for major surgery; and, iii) Community-based interventions for frail elderly chronic patients. All three services have demonstrated efficacy and potential for health value generation. They reflect different implementation maturity levels. While full coverage of the entire urban health district of Barcelona-Esquerra (520 k inhabitants) is the main aim of home hospitalization, demonstration of sustainability at Hospital Clinic of Barcelona constitutes the core goal of the prehabilitation service. Likewise, full coverage of integrated care services addressed to frail chronic patients is aimed at the city of Badalona (216 k inhabitants). METHODS: The population-based analysis, as well as the three service-based protocols, follow observational and experimental study designs using a non-randomized intervention group (integrated care) compared with a control group (usual care) with a propensity score matching method. Evaluation of cost-effectiveness of the interventions using a Quadruple aim approach is a central outcome in all protocols. Moreover, multi-criteria decision analysis is explored as an innovative method for health delivery assessment. The following additional dimensions will also be addressed: i) Determinants of sustainability and scalability of the services; ii) Assessment of the technological support; iii) Enhanced health risk assessment; and, iv) Factors modulating service transferability. DISCUSSION: The current study offers a unique opportunity to undertake a comprehensive assessment of integrated care fostering deployment of services at regional level. The study outcomes will contribute refining service workflows, improving health risk assessment and generating recommendations for service selection. TRIALS REGISTRATION: NCT03130283 (date released 04/06/2018), NCT03768050 (date released 12/05/2018), NCT03767387 (date released 12/05/2018).