Although we are making progress in overcoming infectious diseases and cancer, one of the major medical challenges of the mid-21st century will be the increasing prevalence of stroke. Occlusions in large vessels are especially debilitating, yet effective treatment-needed within hours to achieve best outcomes-remains limited because of geographic accessibility. One solution for improving timely access to mechanical thrombectomy in geographically diverse populations is the widespread deployment of robotic surgical systems. Artificial intelligence assistance may enable the safe and effective upskilling of operators in this emerging therapeutic delivery approach. Our aim was to establish consensus frameworks for developing and validating artificial intelligence-assisted robots for thrombectomy. Objectives included standardizing effectiveness metrics and defining reference testbeds across in silico, in vitro, ex vivo, and in vivo environments. To achieve this, we convened experts in neurointervention, robotics, data science, health economics, policy, statistics, and patient advocacy. Consensus was built through an incubator day, a Delphi process, and a final position statement. We identified that the 4 essential testbed environments each had distinct validation roles. Realism requirements vary: simpler testbeds should include realistic vessel anatomy compatible with guidewire and catheter use, whereas standard testbeds should incorporate deformable vessels. More advanced testbeds should include blood flow, pulsatility, and disease features, such as atheromatous plaques. There are 2 macroclasses of effectiveness metrics: one for in silico, in vitro, and ex vivo stages focusing on technical navigation (eg, path-following error), and another for in vivo stages, focused on clinical outcomes (eg, modified treatment in cerebral infarction scores). Patient safety is central, and not a barrier, to this technology's development. One requisite patient safety task needed now is to correlate in vitro measurements to in vivo complications.

BACKGROUND:Outcome from large vessel occlusion stroke can be significantly improved by time-critical thrombectomy but treatment is only available in regional comprehensive stroke centres (CSCs). Many patients are first admitted to a local primary stroke centre (PSC) and require transfer to a CSC, which delays treatment and decreases the chance of a good outcome. Access to thrombectomy might be improved if eligible patients could be identified in the prehospital setting and selectively redirected to a CSC. This study is evaluating a new specialist prehospital redirection pathway intended to facilitate access to thrombectomy. METHODS AND ANALYSIS:This study is a multicentre cluster randomised controlled trial with included health economic and process evaluations. Clusters are ambulance stations (or teams) which are work bases for ambulance practitioners. Intervention allocated ambulance practitioners use the Specialist PrE-hospital rEDirection for ischaemic stroke thrombectomY ('SPEEDY') pathway which comprises initiation according to specific criteria followed by contact with CSC staff who undertake a remote assessment to select patients for direct CSC admission. Control allocated ambulance practitioners continue to provide standard care which comprises admission to a local PSC and transfer to a CSC for thrombectomy if required. A co-primary outcome of thrombectomy treatment rate and time from stroke symptom onset to thrombectomy treatment will evaluate the impact of the pathway. Secondary outcomes include key aspects of emergency care including prehospital/hospital time intervals, receipt of other treatments including thrombolysis, and performance characteristics of the pathway. A broad population of all ambulance practitioner suspected and confirmed stroke patients across participating regions is being enrolled with a consent waiver. Data about SPEEDY pathway delivery are captured onto a study case record form, but all other data are obtained from routine healthcare records. Powered on a 'primary analysis population' (ischaemic stroke patients with pathway initiation criteria), 894 participants will detect an 8.4% difference in rate and data from 564 thrombectomy procedures will detect a 30 minute difference in time to treatment. The full study population is estimated to be approximately 80 000. Regression modelling will be used to examine primary and secondary outcomes in several analysis populations. The economic analyses will include cost-effectiveness and cost-utility analyses, and calculation of willingness to pay at a range of accepted threshold values. The process evaluation involves semi-structured interviews with professionals and patient/family members to explore views and experiences about the SPEEDY pathway. ETHICS AND DISSEMINATION:This study has ethical, Health Research Authority and participating NHS Trust approvals.Dissemination of study results will include presentations at national and international conferences and events, publication in peer-reviewed journals, and plain English summaries for patient/public engagement activities. TRIAL REGISTRATION NUMBER:ISRCTN77453332.

This opinion piece discusses the challenges of managing a person with sight-threatening papilloedema due to idiopathic intracranial hypertension (IIH). With no available randomised controlled trials, clinicians often choose locally available surgical intervention. An increasing number of studies have advocated using dural venous sinus stenting in IIH. Big data studies show that shunts have been the mainstay of surgical treatment for IIH, and recent evidence shows improved outcomes and fewer revision surgeries. There remains genuine equipoise in the choice of intervention between shunting and dural venous stenting in IIH. The IIH Intervention Trial funded by the National Institute of Health Research is underway in the UK, the first randomised control trial to evaluate both of these surgical interventions in people with sight-threatening IIH.

BACKGROUND:The endovascular clip system (eCLIPs), a unique extra-saccular device for treatment of wide necked bifurcation aneurysms (WNBAs), was evaluated in the French eCLIPs efficacy and safety study (EESIS-FR). This paper summarizes the patient demographics, procedural characteristics, and 30 day adverse event (AE) data. METHODS:The EESIS-FR trial was a prospective study from 18 centers, enrolling 123 adults with WNBAs at the carotid (CT) and basilar (BT) termini. The study protocol was approved by a central ethics committee, had independent adjudication of AEs by a Clinical Events Committee, and had independent core laboratory adjudication of effectiveness outcomes. RESULTS:Mean age was 55.0±1.2 years (19-78 years); 73% were women. 43% and 57% of the aneurysms were located at BT and CT, respectively. Mean neck length was 4.8 mm, neck depth 4.2 mm, dome height 5.4 mm, and dome width 6.3 mm. Successful implantation was achieved in 115 cases (93%). Implant time averaged 36 min. Three primary safety events (2.4%) occurred within the first 30 days, all at the index procedure: subarachnoid hemorrhage (SAH) due to a distal guidewire perforation, death from SAH due to rupture of the aneurysm, and spinal cord infarction caused by an occlusive access catheter. Five minor strokes (4.1%) and three transient ischemic attacks (2.4%) occurred, all of which were procedurals. None of these patients had a modified Rankin Scale score of >2 at 30 days. No patient had further ischemic or hemorrhagic events beyond the periprocedural period to 30 days. CONCLUSION:eCLIPs treated WNBAs at BT and CT, with procedural safety and technical success similar to those with intrasaccular devices.

INTRODUCTION:The role of CT angiography (CTA) and CT perfusion (CTP) in patient selection for thrombolysis <4.5 h after onset is unclear. Additional imaging may improve specificity of diagnosis by excluding stroke mimics or those without salvageable tissue, but may delay treatment. PATIENTS AND METHODS:In a multicentre prospective randomised trial, thrombolysis-eligible patients <4.5 h from symptom onset were randomised 1:1 to non-contrast CT (NCCT) or multimodal CT (NCCT + CTA + CTP). The primary endpoint was the proportion receiving thrombolysis. Secondary end-points were times to decision-making and treatment delivery, early neurological recovery, functional recovery at 3 months and incidence of symptomatic intracerebral haemorrhage (SICH). RESULTS:Between March 2015 and May 2018, 271 patients were randomised, 134 to multimodal CT and 137 to NCCT. After initial NCCT, 114 had no contraindication to thrombolysis in the multimodal CT group and 108 in the NCCT group. Mean age was 67.5 years and median NIHSS score was 6 (interquartile range 3-12). Fewer patients assigned multimodal CT received thrombolysis (56/114, 49.1%) compared to NCCT (73/108, 67.6%, adjusted odds ratio (aOR) 0.46 (95% CI: 0.25-0.83), p = 0.0102). Times to treatment decision or thrombolytic administration, early neurological recovery and day 90 functional outcome did not differ significantly. SICH occurred in two patients, both assigned NCCT. Mortality was 6/114 (5.3%) in the multimodal CT group compared to 11/108 (10.2%; aOR 0.46 (95% CI: 0.16, 1.31), p = 0.147) in the NCCT group. DISCUSSION:Despite fewer patients receiving thrombolysis after multimodal imaging, treatment decision times and clinical outcomes did not differ significantly. Multimodal CT may identify patients who do not require thrombolysis such as stroke mimics and non-disabling strokes. CONCLUSION:Among acute stroke patients imaged <4.5 h from symptom onset, multimodal CT reduced use of thrombolysis. Treatment decision times and clinical outcomes did not differ between groups.

Introduction Idiopathic intracranial hypertension (IIH) is characterised by raised intracranial pressure (ICP) and typically affects young women with obesity. Patients are at risk of permanent visual loss due to papilloedema. Some require emergency intervention to rapidly reduce papilloedema and preserve vision. The international standard of care for patients with sight-threatening IIH is cerebrospinal fluid (CSF) shunting. However, dural venous sinus stenting (DVSS) is an emerging procedure that is offered at many neuroscience centres internationally as the primary intervention. Currently, there are no randomised controlled trial data supporting the efficacy of any interventional approach for preserving vision in sight-threatening IIH. Methods and analysis IIH Intervention is a UK-based two-arm, open-label, multicentre, randomised controlled phase IIb clinical trial with integrated health economic evaluation to compare CSF shunting with DVSS in patients who have confirmed IIH and are at risk of permanent visual loss due to severe papilloedema. The primary outcome is the global thickness of the peripapillary retinal nerve fibre layer (RNFL), an indicator of papilloedema, measured by optical coherence tomography (OCT) over a 6-month period. Secondary outcomes are global thickness of the RNFL over 12 and 24 months, as well as macular ganglion cell layer volume, perimetric mean deviation, headache outcomes, intervention reporting measures (including complications and revisions) and patient-reported outcomes over 6, 12 and 24 months. Ethics and dissemination The protocol was approved initially on 12 December 2022 by West Midlands-South Birmingham Research Ethics Committee (ref: 22/WM/0230). Participants will be required to provide written informed consent. The results of this trial will be disseminated through national and international presentations and peer-reviewed publications. Trial registration number ISRCTN57142415 .

Objective To explore multiprofessional views about system-wide factors influencing (impeding or facilitating) the delivery of stroke mechanical thrombectomy (MT) services and/or improvements to this pathway in England.Design A pragmatic exploratory qualitative study using online focus groups and semi-structured interviews with National Health Service (NHS) professionals and those working in a stroke strategic/policy lead role. We thematically analysed the data using the Framework Approach to understand participants’ views on the challenges to improving current and future MT implementation.Setting NHS trusts and other key stroke strategic/policy organisations covering 10 geographical regions in England and a national perspective.Participants A total of 29 professionals, working in an NHS clinical and managerial position and/or a stroke strategic national/regional clinical/policy lead role, participated in five focus groups and six individual semi-structured interviews between April and June 2024.Results We identified five themes relating to MT implementation progress and challenges (1) workforce, (2) clinical care pathways, (3) service/system, (4) cross-cutting theme: communications and (5) cross-cutting theme: culture. Our analysis emphasised the increasing complexity and inter-related factors shaping the emergency stroke pathway for MT provision and a need to acknowledge key people-related, organisational and sociocultural factors during service planning.Conclusions Despite the challenges and complexity, professionals were optimistic that further progress would be made with MT delivery in England. However, ongoing improvement strategies are required, which also acknowledge wider cultural factors and system-wide relationships and are not just focused on care pathways and resources.

Background: We investigate whether the NIHSS at 24 hours could serve as an alternative primary outcome measure in acute ischemic stroke trials, and whether combining 90-day modified Rankin Score (mRS) and 24-hour NIHSS in a hierarchical outcome could enhance detection of treatment effect, using EVT as an exemplary study intervention. Methods: Post-hoc analysis from the HERMES collaboration that pooled data from 7 randomized controlled EVT trials. Validity of 24-hour NIHSS as a surrogate outcome for 90-day mRS was assessed in a causal mediation model (Figure 1). A 7-point ordinal NIHSS score was generated by grouping 24-hour NIHSS, including death as a separate category (“ordinal” NIHSS). EVT effect sizes and sample sizes required for detecting EVT benefit with 80% power were compared when using granular 24-hour NIHSS, ordinal 24-hour NIHSS, 90-day mRS, and hierarchical outcome (win-ratio) that combines 90-day mRS and 24-hour NIHSS. Subgroup analyses were performed in patients with baseline NIHSS<10 and ≥25. Results: A total of 1720 patients were included. Median 90-day mRS in the EVT/control arms was 3.0(IQR:1.0-4.0)/4.0(IQR:2.0-5.0) and median 24-hour NIHSS was 9.0(IQR:3.0-17.0)/14.0(IQR:7.5-19.0), see Figure 2. 24-hour NIHSS mediated the association between EVT and 90-day mRS and met the criteria for a surrogate outcome. Effect sizes were highest and sample sizes required to detect EVT benefit smallest for the win ratio approach (228), followed by 90-day mRS(240) and ordinal 24-hour NIHSS(242), see Table 1. In subgroup analyses of patients with baseline NIHSS<10 and≥25, ordinal 24-hour NIHSS resulted in the highest effect size/ smallest sample size. Conclusion: 24-hour NIHSS may be a valid surrogate outcome for 90-day mRS in acute ischemic stroke patients undergoing EVT, with a similar EVT effect size compared to 90-day mRS. It could potentially enhance detection of EVT benefit in patient subgroups with very low or very high baseline NIHSS. Combining 90-day mRS and 24-hour NIHSS in an ordered hierarchical could improve detection of EVT treatment effect compared to 90-day mRS.

Commissioning of innovations in healthcare is a complex socio-technical process, ideally informed by high quality evidence. However, evidence is not always prepared and presented in a format usable for commissioning decisions. Agile methodology, combined with qualitative co-design, were used to develop a digital web application incorporating machine learning models of stroke outcomes to inform commissioning decisions for the implementation of Mobile Stroke Units (MSUs) in England, followed by usability testing using Think Aloud methodology. Sixteen stakeholders involved in developing consensus on model parameters and pathways participated with data thematically analysed. Required improvements to the web application were identified and novel insights into the complexity of context-specific commissioning decisions were generated, which also informed participants’ views on the viability of MSUs. This study provides empirical evidence in support of developing innovative and accessible digital dissemination methods to engage with commissioning processes and prospectively understand commissioning challenges.

Intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) are well-established emergency reperfusion treatments for stroke caused by clots. Both reduce disability but effectiveness is highly time-dependent, declining in the first few hours after stroke onset. Mobile stroke units (MSUs) have been proposed as a way of improving outcomes after stroke. MSUs enable on-scene brain imaging and delivery of IVT, and can allow for better choice of destination hospital. The primary objective of the study was to model the likely effect of MSUs on clinical outcomes (the ability to live independently, modified Rankin Scale 0–2) across all of England assuming no resource restrictions during deployment. We used modelling of times to treatment and outcomes. Modelling was performed for Lower Super Output Areas (LSOAs) in England. Admission numbers were based on Hospital Episode Statistics and travel times estimated from data from Open Street Map. Outcomes were predicted based on times to IVT and MT; we report outcomes as utility or the proportion of patients able to live independently at 3-6 months after stroke. We assumed MSUs and stroke units all had the same propensity to use IVT. For every 100 patients suitable for IVT or MT, there will likely be 1–3 more people who can live independently following MSU care. The benefit comes from both earlier IVT and the direct transfer of patients likely to benefit from MT to their closest MT-centre by avoiding inter-hospital transfers that would be used in usual care. If, as is likely, about 1 in 5 stroke patients are suitable candidates for IVT or MT, an MSU would need to attend approximately 250 stroke patients for every one extra independent-living outcome. If about half of the patients to whom an MSU is dispatched are actual strokes (the others being stroke mimics), an MSU would need to attend approximately 500 patients for every one extra independent-living outcome. Some areas, furthest from where MSUs are based, will receive no benefit from MSU care, whereas other areas may have up to 4 additional independent-living outcomes for every 100 patients suitable for IVT or MT. Quick MSU dispatch and fast on-scene treatment are crucial to achieving the benefit of MSUs, otherwise use of MSUs may have no overall benefit, or worse outcomes, than usual care. The above benefits do not include any other possible benefits unrelated to earlier IVT or MT. This study suggests that the overall benefit of MSU care if deployed across all of England is likely to be modest. Selective use of MSUs in specific areas is likely to be more effective than widespread implementation. Rapid dispatch, fast on-scene treatment of patients, and careful selection of which patients to dispatch the MSU to (by location and confidence in that person being a confirmed stroke patient), are all critical for maximising benefits from MSU care. MSUs should not be seen as an alternative to optimising day-to-day emergency stroke systems.

Commissioning of innovations in healthcare is a complex socio-technical process, ideally informed by high quality evidence. However, evidence is not always prepared and presented in a format usable for commissioning decisions. Agile methodology, combined with qualitative co-design, were used to develop a digital web application incorporating machine learning models of stroke outcomes to inform commissioning decisions for the implementation of mobile stroke units (MSUs) in England, followed by usability testing using think aloud methodology. Sixteen stakeholders involved in developing consensus on model parameters and pathways participated with data thematically analysed. Required improvements to the web application were identified and novel insights into the complexity of context-specific commissioning decisions were generated, which also informed participants’ views on the viability of MSUs. This study provides empirical evidence in support of developing innovative and accessible digital dissemination methods to engage with commissioning processes and prospectively understand commissioning challenges.

Mobile stroke units (MSUs) are specialist ambulances equipped with scanning and point of care testing that can identify patients eligible for intravenous thrombolysis – medication to dissolve a clot used in ischaemic strokes – and provide this on location. While benefits of MSUs have been demonstrated, this is context dependent. Routine use of MSUs across the English and Welsh National Health Service (NHS) has not yet been considered, and as such no pathway for their operation exists. This study aimed to co-design a viable pathway, detailing dispatch, staffing and treatment decisions, for MSUs within the NHS context. The study used interdisciplinary co-design alongside Nominal Group Technique (NGT) to generate consensus. Participants were recruited using a combination of purposive, opportunistic and snowball sampling. Data collection took place in online workshops, across three rounds, with supplemental interviews conducted where required. Data were analysed as an ongoing process, with participants checking interpretations after each round, and then further analysed deductively to identify key uncertainties following all the rounds. Consensus threshold for the NGT was set a priori at ≥ 80

Objectives: We aimed to address the following research questions: (1) Which geographic and socio-economic inequalities have been included when evaluating access to acute stroke treatment (including reperfusion therapies)? (2) How have the identified measures been considered/assessed/calculated? (3) Report any methodological approaches that have been proposed that might further improve the way in which acute stroke care interventions are analysed, specified relating to inequalities. Methods: PubMed and Scopus electronic databases were searched for studies that included participants who underwent acute stroke treatment and included quantitative measures of geographic and/or socioeconomic inequalities or inequities in accessing/receiving treatment. Results: Overall, 66 studies were included in the review. Fifty-nine included at least one measure of geographic inequalities or inequities while thirty-six included at least one measure of socioeconomic inequalities or inequities. Twenty-eight of these studies included both a geographic and socioeconomic measure of inequalities or inequities. There were no commonalities in the methods of defining, categorising and measuring the inequalities or inequities. No study provided their definition of inequality or inequity or stated any normative judgements they have made. Conclusions: It is vital that the evaluation of programmes like acute stroke care consider impacts on inequality and inequity. Researchers and policy makers should work together to determine relevant measures of inequality/inequity and the most appropriate methods of measuring and categorising them. In addition, researchers should make it clear within their work how they are defining inequality and inequity and what (if any) normative judgements have been made.

Background: There are a lot of advances that may affect the way treatment is delivered prehospital, including mobile stroke units and point-of-care diagnostics. These have the potential to affect populations differently and therefore affect the distribution of health outcomes. Objectives: We aimed to address the following research questions: (1) Which geographic and socioeconomic inequalities have been included when evaluating access to acute stroke treatment (including reperfusion therapies)? (2) How have the identified measures been considered/assessed/calculated? (3) We also report any methodological approaches that have been proposed that might further improve the way in which acute stroke care interventions are analysed, specified relating to inequalities. Methods: PubMed and Scopus electronic databases were searched for studies that included participants who underwent acute stroke treatment and included quantitative measures of geographic and/or socioeconomic inequalities or inequities in accessing/receiving treatment. Results: Overall, sixty-six studies were included in the review. Fifty-nine included at least one measure of geographic inequalities or inequities while thirty-six included at least one measure of socioeconomic inequalities or inequities. Twenty-eight of these studies included both a geographic and socioeconomic measure of inequalities or inequities. There were no commonalities in the methods of defining, categorising and measuring the inequalities or inequities. No study provided their definition of inequality or inequity or stated any normative judgements they had made. Conclusions: It is vital that the evaluation of programmes like acute stroke care consider impacts on inequality and inequity. Researchers and policy makers should work together to determine relevant measures of inequality/inequity and the most appropriate methods of measuring and categorising them. In addition, researchers should make it clear within their work how they are defining inequality and inequity and what (if any) normative judgements have been made.

Background Evidence for Mobile Stroke Units (MSUs) demonstrates that onset to treatment times for intravenous thrombolysis can be reduced and access to mechanical thrombectomy might be improved. Despite growing use of MSUs internationally, to date there have been no studies in NHS England and NHS Wales exploring the acceptability of MSUs to clinicians, patient and public representatives and other key stakeholders, which are important when considering potential feasibility and implementation. Methods This study used a mixed methods design with a cross-sectional survey and qualitative workshops and interviews between October 2023 to May 2024. Survey data were collected from clinicians involved in emergency stroke care. Qualitative data involved clinical and non-clinical professionals involved in stroke care alongside patient and public representatives with experience of stroke. Survey data were descriptively analysed while content analysis was used on open-ended questions. Qualitative data were thematically analysed, prior to triangulation using a convergent coding matrix. Results The study results, drawn from 25 respondents to the survey and 21 participants in qualitative workshops, found that almost all participants had positive affective attitudes to the concept of MSUs. However, several key areas of concern were identified that need to be addressed prior to implementing MSUs. These concerns included how MSUs would be staffed; whether and how telemedicine could contribute; the types of economic impacts; extent to which triage systems could accurately identify stroke patients for MSUs to attend; where the base location and geographic coverage of MSUs should be, the impact of MSUs on equitable access to stroke care, and how to improve public awareness of MSUs. Conclusion Whilst MSUs are mostly acceptable to key stakeholders, numerous areas of concern need to be addressed prior to MSU implementation. We recommend further research to address these issues prior to implementation in the NHS.

Background Robust collateral circulation has been linked with better reperfusion and clinical outcomes. It remains unclear how individual assessments of collateral circulation may be translated into clinical practice. Methods The pooled Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials (HERMES) angiography dataset was analyzed by a centralized, independent imaging core blinded to other clinical data. Conventional angiography was acquired immediately prior to endovascular therapy. Collaterals were graded with the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN) system and associated with baseline patient characteristics, reperfusion, and day 90 modified Rankin Score (mRS). Both 90-day all-cause mortality and day 90 mRS were modeled via multivariable logistic regression. Results Angiography was available in 376/605 (62%) patients. Baseline ASPECTS (Alberta Stroke Program Early CT Score) (p=0.043), history of diabetes mellitus (p=0.048), site of occlusion (p<0.001), and degree of subsequent Thrombolysis in Cerebral Infarction (TICI) reperfusion (p<0.001) were associated with collateral grades. ASITN collateral grade was strongly associated with ordinal mRS from baseline to 90 days in an unadjusted analysis (p<0.001). Multivariable regression demonstrated that collateral status is a strong determinant of mRS outcome in the presence of other predictors (OR=1.37 per grade, 95% CI [1.05 to 1.74], p=0.018). By comparing ORs, 1 unit of ASITN was determined to be approximately equivalent to 4.5 points of NIHSS, 11 years of age, 1.5 points of ASPECTS, or 100 min less delay from onset to puncture, in terms of impact on mRS. Conclusions Individual collateral physiology may contribute significantly to reperfusion success and clinical outcomes after acute ischemic stroke. Building a consensus for the role of angiographic collateral assessment in the allocation of adjuvant reperfusion therapies may help galvanize a precision medicine approach in stroke.

The risk of a first-ever epileptic seizure from CCM is low. Four of 5 patients who experience a first unprovoked epileptic seizure develop a recurrent seizure within 10 years, justifying diagnosis of CRE after a first unprovoked epileptic seizure due to CCM. Most of the patients with CRE achieve 2-year/5-year seizure freedom within 10 years. These long-term findings can inform patients and guide clinical practice.

Background We investigate whether the National Institutes of Health Stroke Scale (NIHSS) at 24 hours could serve as a primary outcome in acute ischemic stroke trials, and whether combining 90‐day modified Rankin Scale (mRS) and 24‐hour NIHSS in a hierarchical outcome could enhance detection of treatment effect, using endovascular treatment (EVT) as an exemplary study intervention. Methods This was a post hoc analysis of pooled data from 7 randomized EVT trials. Twenty‐four‐hour NIHSS as a surrogate outcome for 90‐day mRS was assessed in a causal mediation model. A 7‐point ordinal NIHSS score was generated by grouping 24‐hour NIHSS, including death as a separate category (“ordinal” NIHSS). EVT effect sizes and sample sizes required for detecting EVT benefit with 80% power were compared when using granular 24‐hour NIHSS, ordinal 24‐hour NIHSS, 90‐day mRS, and a hierarchical outcome (win ratio) that combines 90‐day mRS and 24‐hour NIHSS. Results A total of 1720 patients were included. Twenty‐four‐hour NIHSS mediated the association between EVT and 90‐day mRS and met criteria for a useful surrogate outcome. Effect sizes were highest and sample sizes required to detect EVT benefit smallest for the win ratio approach (228), followed by 90‐day mRS (240) and ordinal 24‐hour NIHSS (242). In patients with baseline NIHSS <10 and ≥25, ordinal 24‐hour NIHSS resulted in the highest effect size. Conclusions Twenty‐four‐hour NIHSS is a useful surrogate outcome for 90‐day mRS in patients with acute ischemic stroke undergoing EVT, with a similar EVT effect size compared with 90‐day mRS. It could potentially enhance detection of EVT benefit in patients with very low or high baseline NIHSS. An ordered hierarchical outcome could improve detection of EVT treatment effect.

BACKGROUND:Mechanical thrombectomy for stroke is highly effective but time-critical. Delays are common because many patients require transfer between local hospitals and regional centres. A two-stage prehospital redirection pathway consisting of a simple ambulance screen followed by regional centre assessment to select patients for direct admission could optimise access. However, implementation might be challenged by the limited number of thrombectomy providers, a lack of prehospital diagnostic tests for selecting patients and whether finite resources can accommodate longer ambulance journeys plus greater central admissions. We undertook a three-phase, multiregional, qualitative study to obtain health professional views on the acceptability and feasibility of a new pathway. METHODS:Online focus groups/semistructured interviews were undertaken designed to capture important contextual influences. We purposively sampled NHS staff in four regions of England. Anonymised interview transcripts underwent deductive thematic analysis guided by the NASSS (Non-adoption, Abandonment and Challenges to Scale-up, Spread and Sustainability, Implementation) Implementation Science framework. RESULTS:Twenty-eight staff participated in 4 focus groups, 2 group interviews and 18 individual interviews across 4 Ambulance Trusts, 5 Hospital Trusts and 3 Integrated Stroke Delivery Networks (ISDNs). Five deductive themes were identified: (1) (suspected) stroke as a condition, (2) the pathway change, (3) the value participants placed on the proposed pathway, (4) the possible impact on NHS organisations/adopter systems and (5) the wider healthcare context. Participants perceived suspected stroke as a complex scenario. Most viewed the proposed new thrombectomy pathway as beneficial but potentially challenging to implement. Organisational concerns included staff shortages, increased workflow and bed capacity. Participants also reported wider socioeconomic issues impacting on their services contributing to concerns around the future implementation. CONCLUSIONS:Positive views from health professionals were expressed about the concept of a proposed pathway while raising key content and implementation challenges and useful 'real-world' issues for consideration.