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Background We sought to understand the impact of the COVID-19 pandemic on lipid-lowering therapy prescribing as a potential cause of the excess cardiovascular mortality seen post-pandemic in England. We examined temporal changes over 3 years in the prescribing of high-intensity and non-high-intensity statin therapy and ezetimibe. Sources of data We utilized data available via the National Health Service (NHS) Business Services Authority (NHSBSA) Information Services Data Warehouse, extracting 3 monthly data from October 2018 to December 2021 on high- and low-intensity statin and ezetimibe prescribing, (commencement, cessation or continuation) through each time period of study and those before, and after, the period of interest. Areas of agreement Optimizing lipid management is a key component of the NHS Long Term Plan ambition to reduce deaths from cardiovascular disease, stroke and dementia. Areas of controversy The COVID-19 pandemic and associated lockdown have seen a significant reduction in prescribing of lipid-lowering therapies. If cardiovascular risk is not to worsen in the forthcoming years, urgent action is needed to ensure that the impact of the pandemic upon optimization of cholesterol and the historical undertreatment of cholesterol is reversed and improved. Areas timely for developing research Prescription data available via NHSBSA can support our understanding of the implications of policy and behaviour and highlight the impact of guidelines in practise. Growing points Understanding the impact of the COVID-19 pandemic upon cholesterol management and the opportunities for newer lipid-lowering therapies delivered using a population health approach have the potential to enhance lipid-lowering and improve cardiovascular mortality and morbidity and reduce health inequalities.

Background Intravenous thrombolysis and intra-arterial thrombectomy are proven emergency treatments for acute ischaemic stroke, but they require rapid delivery to selected patients within specialist services. National audit data have shown that treatment provision is suboptimal. Objectives The aims were to (1) determine the content, clinical effectiveness and day 90 cost-effectiveness of an enhanced paramedic assessment designed to facilitate thrombolysis delivery in hospital and (2) model thrombectomy service configuration options with optimal activity and cost-effectiveness informed by expert and public views. Design A mixed-methods approach was employed between 2014 and 2019. Systematic reviews examined enhanced paramedic roles and thrombectomy effectiveness. Professional and service user groups developed a thrombolysis-focused Paramedic Acute Stroke Treatment Assessment, which was evaluated in a pragmatic multicentre cluster randomised controlled trial and parallel process evaluation. Clinicians, patients, carers and the public were surveyed regarding thrombectomy service configuration. A decision tree was constructed from published data to estimate thrombectomy eligibility of the UK stroke population. A matching discrete-event simulation predicted patient benefits and financial consequences from increasing the number of centres. Setting The paramedic assessment trial was hosted by three regional ambulance services (in north-east England, north-west England and Wales) serving 15 hospitals. Participants A total of 103 health-care representatives and 20 public representatives assisted in the development of the paramedic assessment. The trial enrolled 1214 stroke patients within 4 hours of symptom onset. Thrombectomy service provision was informed by a Delphi exercise with 64 stroke specialists and neuroradiologists, and surveys of 147 patients and 105 public respondents. Interventions The paramedic assessment comprised additional pre-hospital information collection, structured hospital handover, practical assistance up to 15 minutes post handover, a pre-departure care checklist and clinician feedback. Main outcome measures The primary outcome was the proportion of patients receiving thrombolysis. Secondary outcomes included day 90 health (poor status was a modified Rankin Scale score of > 2). Economic outputs reported the number of cases treated and cost-effectiveness using quality-adjusted life-years and Great British pounds. Data sources National registry data from the Sentinel Stroke National Audit Programme and the Scottish Stroke Care Audit were used. Review methods Systematic searches of electronic bibliographies were used to identify relevant literature. Study inclusion and data extraction processes were described using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results The paramedic assessment trial found a clinically important but statistically non-significant reduction in thrombolysis among intervention patients, compared with standard care patients [197/500 (39.4%) vs. 319/714 (44.7%), respectively] (adjusted odds ratio 0.81, 95% confidence interval 0.61 to 1.08; p = 0.15). The rate of poor health outcomes was not significantly different, but was lower in the intervention group than in the standard care group [313/489 (64.0%) vs. 461/690 (66.8%), respectively] (adjusted odds ratio 0.86, 95% confidence interval 0.60 to 1.2; p = 0.39). There was no difference in the quality-adjusted life-years gained between the groups (0.005, 95% confidence interval –0.004 to 0.015), but total costs were significantly lower for patients in the intervention group than for those in the standard care group (–£1086, 95% confidence interval –£2236 to –£13). It has been estimated that, in the UK, 10,140–11,530 patients per year (i.e. 12% of stroke admissions) are eligible for thrombectomy. Meta-analysis of published data confirmed that thrombectomy-treated patients were significantly more likely to be functionally independent than patients receiving standard care (odds ratio 2.39, 95% confidence interval 1.88 to 3.04; n = 1841). Expert consensus and most public survey respondents favoured selective secondary transfer for accessing thrombectomy at regional neuroscience centres. The discrete-event simulation model suggested that six new English centres might generate 190 quality-adjusted life-years (95% confidence interval –6 to 399 quality-adjusted life-years) and a saving of £1,864,000 per year (95% confidence interval –£1,204,000 to £5,017,000 saving per year). The total mean thrombectomy cost up to 72 hours was £12,440, mostly attributable to the consumables. There was no significant cost difference between direct admission and secondary transfer (mean difference –£368, 95% confidence interval –£1016 to £279; p = 0.26). Limitations Evidence for paramedic assessment fidelity was limited and group allocation could not be masked. Thrombectomy surveys represented respondent views only. Simulation models assumed that populations were consistent with published meta-analyses, included limited parameters reflecting underlying data sets and did not consider the capital costs of setting up new services. Conclusions Paramedic assessment did not increase the proportion of patients receiving thrombolysis, but outcomes were consistent with improved cost-effectiveness at day 90, possibly reflecting better informed treatment decisions and/or adherence to clinical guidelines. However, the health difference was non-significant, small and short term. Approximately 12% of stroke patients are suitable for thrombectomy and widespread provision is likely to generate health and resource gains. Clinician and public views support secondary transfer to access treatment. Future work Further evaluation of emergency care pathways will determine whether or not enhanced paramedic assessment improves hospital guideline compliance. Validation of the simulation model post reconfiguration will improve precision and describe wider resource implications. Trial registration This trial is registered as ISRCTN12418919 and the systematic review protocols are registered as PROSPERO CRD42014010785 and PROSPERO CRD42015016649. Funding The project was funded by the National Institute for Health and Care Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 10, No. 4. See the NIHR Journals Library website for further project information.

ObjectiveTo evaluate the effectiveness and cost-effectiveness of the National PReCePT Programme (NPP) in increasing use of magnesium sulfate (MgSO4) in preterm births.DesignBefore-and-after study.SettingMaternity units (N=137) within NHS England and the Academic Health Science Network (AHSN) in 2018.ParticipantsBabies born ≤30 weeks’ gestation admitted to neonatal units in England.InterventionsThe NPP was a quality improvement (QI) intervention including the PReCePT (Preventing Cerebral Palsy in Pre Term labour) QI toolkit and materials (preterm labour proforma, staff training presentations, parent leaflet, posters for the unit and learning log), regional AHSN-level support, and up to 90 hours funded backfill for a midwife ‘champion’ to lead implementation.Main outcome measuresMgSO4uptake post implementation was compared with pre-NPP implementation uptake. Implementation and lifetime costs were estimated.ResultsCompared with pre-implementation estimates, the average MgSO4uptake for babies born ≤30 weeks’ gestation, in 137 maternity units in England, increased by 6.3 percentage points (95% CI 2.6 to 10.0 percentage points) to 83.1% post implementation, accounting for unit size, maternal, baby and maternity unit factors, time trends, and AHSN. Further adjustment for early/late initiation of NPP activities increased the estimate to 9.5 percentage points (95% CI 4.3 to 14.7 percentage points). From a societal and lifetime perspective, the health gains and cost savings associated with the NPP effectiveness generated a net monetary benefit of £866 per preterm baby and the probability of the NPP being cost-effective was greater than 95%.ConclusionThis national QI programme was effective and cost-effective. National programmes delivered via coordinated regional clinical networks can accelerate uptake of evidence-based therapies in perinatal care.

Background: Prehospital care including recognition of stroke symptoms by the public and professionals combined with an efficient and effective emergency medical service (EMS) is essential to increase access to effective acute stroke care. We undertook a survey to document the status of stroke prehospital care globally. Methods: A survey was distributed via email to the World Stroke Organisation (WSO) members. Information was sought on the current status of stroke prehospital delay globally including 1) ambulance availability and whether payment for use is required, 2) ambulance response times and the proportion of patients arriving at hospital by ambulance, 3) the proportion of patients arriving within 3 hours and more than 24 hours after symptom, 4) whether stroke care training of paramedics, call handlers and primary care staff, 5) availability of specialist centers, and 6) the proportion of patients taken to specialist centers. Respondents were also asked to identify the top three changes in prehospital care that would benefit their population. Data were analysed descriptively at both country and continent level. Results: Responses were received from 116 individuals in 43 countries, with a response rate of 4.7%. Most respondents (90%) reported access to ambulances but 40% of respondents reported payment was required by the patient. Where an ambulance service was available (105 respondents) 37% of respondents reported that less than 50% of patients used an ambulance and 12% less than 20% of patients used an ambulance. Large variations in ambulance response times were reported both within and between countries. Most of the participating High-Income Countries (HIC) offered a service used by patients, but this was rarely the case for the Low and Middle Income Countries (LMIC). Time to admission was often much longer in LMIC and there was less access to stroke training for EMS and primary care staff. Conclusions: Significant deficiencies in stroke prehospital care exist globally especially in LMIC. In all countries there are opportunities to improve the quality of the service in ways that would likely result in improved outcomes after acute stroke.

ObjectiveTo evaluate the effectiveness and cost-effectiveness of the National PreCePT Programme (NPP) in increasing magnesium sulphate (MgSO4) in pre-term births.DesignA quasi-experimental before-and-after designSettingMaternity units within NHS England and the AHSN network in 2018.ParticipantsMaternity units in England (n=137) who participated in the NPP.InterventionsNPP support which included the PReCePT QI toolkit and materials (pre-term labour proforma, staff training presentations, parent leaflet, posters for the unit, learning log), regional AHSN level support, and up to 90 hours funded backfill for a midwife ‘champion’ to lead implementation.Main outcome measuresMgSO4 post-implementation uptake compared to pre-implementation uptake. Implementation and lifetime costs were estimated.ResultsCompared to pre-implementation estimates, the average MgSO4 uptake in 137 maternity units in England increased by 6.3 percentage points (95% CI 2.6 to 10.0 percentage points) to 83.1% post-implementation, accounting for unit size, maternal, baby, and maternity unit factors, time trends, and AHSN. Further adjustment for early or late initiation of NPP activities increased the estimate to 9.5 percentage points (95% CI 4.3 to 14.7 percentage points). From a societal and lifetime perspective, the health gains and cost-savings associated with the NPP effectiveness generated a net monetary benefit of £866 per preterm baby and the probability of the NPP being cost-effective was greater than 95%.ConclusionThis national QI programme was effective and cost-effective. National programmes delivered via coordinated regional clinical networks can accelerate uptake of evidence-based therapies in perinatal care.WHAT IS ALREADY KNOWN ON THIS TOPICSince 2015 the UK National Institute for Health and Care Excellence (NICE) has recommended administration of Magnesium Sulphate (MgSO4) for fetal neuroprotection in very preterm deliveries as a core part of maternity care. By 2017, only two-thirds of all eligible women in England were being given MgSO4, with wide regional variation. The PReCePT pilot study showed an increase in uptake from 21% (2012-2013) to 88% after the introduction of the tool in2015 in 5 units. The National PReCePT Programme (NPP) was rolled out in 2018 by the national network of Academic Health Science Networks with a target to increase MgSO4 administration in England to 85% by 2020.WHAT THIS STUDY ADDSThe study has shown that the nationwide implementation of the NPP, which provided a Quality Improvement (QI) toolkit and materials, cross unit AHSN regional level support, and funded backfill for a unit midwife ‘champion’ through local regional support was effective and cost-effective. Scaling-up of network supported QI programmes at national level can accelerate uptake of new therapies and promote improvements in perinatal care delivery.

BackgroundLoss of arm function is common after stroke. Robot-assisted training may improve arm outcomes.ObjectiveThe objectives were to determine the clinical effectiveness and cost-effectiveness of robot-assisted training, compared with an enhanced upper limb therapy programme and with usual care.DesignThis was a pragmatic, observer-blind, multicentre randomised controlled trial with embedded health economic and process evaluations.SettingThe trial was set in four NHS trial centres.ParticipantsPatients with moderate or severe upper limb functional limitation, between 1 week and 5 years following first stroke, were recruited.InterventionsRobot-assisted training using the Massachusetts Institute of Technology-Manus robotic gym system (InMotion commercial version, Interactive Motion Technologies, Inc., Watertown, MA, USA), an enhanced upper limb therapy programme comprising repetitive functional task practice, and usual care.Main outcome measuresThe primary outcome was upper limb functional recovery ‘success’ (assessed using the Action Research Arm Test) at 3 months. Secondary outcomes at 3 and 6 months were the Action Research Arm Test results, upper limb impairment (measured using the Fugl-Meyer Assessment), activities of daily living (measured using the Barthel Activities of Daily Living Index), quality of life (measured using the Stroke Impact Scale), resource use costs and quality-adjusted life-years.ResultsA total of 770 participants were randomised (robot-assisted training,n = 257; enhanced upper limb therapy,n = 259; usual care,n = 254). Upper limb functional recovery ‘success’ was achieved in the robot-assisted training [103/232 (44%)], enhanced upper limb therapy [118/234 (50%)] and usual care groups [85/203 (42%)]. These differences were not statistically significant; the adjusted odds ratios were as follows: robot-assisted training versus usual care, 1.2 (98.33% confidence interval 0.7 to 2.0); enhanced upper limb therapy versus usual care, 1.5 (98.33% confidence interval 0.9 to 2.5); and robot-assisted training versus enhanced upper limb therapy, 0.8 (98.33% confidence interval 0.5 to 1.3). The robot-assisted training group had less upper limb impairment (as measured by the Fugl-Meyer Assessment motor subscale) than the usual care group at 3 and 6 months. The enhanced upper limb therapy group had less upper limb impairment (as measured by the Fugl-Meyer Assessment motor subscale), better mobility (as measured by the Stroke Impact Scale mobility domain) and better performance in activities of daily living (as measured by the Stroke Impact Scale activities of daily living domain) than the usual care group, at 3 months. The robot-assisted training group performed less well in activities of daily living (as measured by the Stroke Impact Scale activities of daily living domain) than the enhanced upper limb therapy group at 3 months. No other differences were clinically important and statistically significant. Participants found the robot-assisted training and the enhanced upper limb therapy group programmes acceptable. Neither intervention, as provided in this trial, was cost-effective at current National Institute for Health and Care Excellence willingness-to-pay thresholds for a quality-adjusted life-year.ConclusionsRobot-assisted training did not improve upper limb function compared with usual care. Although robot-assisted training improved upper limb impairment, this did not translate into improvements in other outcomes. Enhanced upper limb therapy resulted in potentially important improvements on upper limb impairment, in performance of activities of daily living, and in mobility. Neither intervention was cost-effective.Future workFurther research is needed to find ways to translate the improvements in upper limb impairment seen with robot-assisted training into improvements in upper limb function and activities of daily living. Innovations to make rehabilitation programmes more cost-effective are required.LimitationsPragmatic inclusion criteria led to the recruitment of some participants with little prospect of recovery. The attrition rate was higher in the usual care group than in the robot-assisted training or enhanced upper limb therapy groups, and differential attrition is a potential source of bias. Obtaining accurate information about the usual care that participants were receiving was a challenge.Trial registrationCurrent Controlled Trials ISRCTN69371850.FundingThis project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 24, No. 54. See the NIHR Journals Library website for further project information.

Objective: To report the fidelity of the enhanced upper limb therapy programme within the Robot-Assisted Training for the Upper Limb after stroke (RATULS) randomized controlled trial, the types of goals selected and the proportion of goals achieved. Design: Descriptive analysis of data on fidelity, goal selection and achievement from an intervention group within a randomized controlled trial. Setting: Out-patient stroke rehabilitation within four UK NHS centres. Subjects: 259 participants with moderate-severe upper limb activity limitation (Action Research Arm Test 0–39) between one week and five years post first stroke. Intervention: The enhanced upper limb therapy programme aimed to provide 36 one-hour sessions, including 45 minutes of face-to-face therapy focusing on personal goals, over 12 weeks. Results: 7877/9324 (84%) sessions were attended; a median of 34 [IQR 29–36] per participant. A median of 127 [IQR 70–190] repetitions were achieved per participant per session attended. Based upon the Canadian Occupational Performance Measure, goal categories were: self-care 1449/2664 (54%); productivity 374/2664 (14%); leisure 180/2664 (7%) and ‘other’ 661/2664 (25%). For the 2051/2664 goals for which data were available, 1287 (51%) were achieved, ranging between 27% by participants more than 12 months post stroke with baseline Action Research Arm Test scores 0–7, and 88% by those less than three months after stroke with scores 8–19. Conclusions: Intervention fidelity was high. Goals relating to self-care were most commonly selected. The proportion of goals achieved varied, depending on time post stroke and baseline arm activity limitation.

Background Study was a PROBE design phase II randomized controlled trial (RCT). We assessed trial feasibility and technical efficacy and safety of two novel thrombectomy devices – ERIC (a retriever device) and SOFIA (a distal access catheter) – used alone or in combination depending on operator preference. Methods Four UK neuroscience centers enrolled adults with proximal large artery occlusion (LAO) stroke on imaging where arterial puncture was achievable within 5.5 hours (8.5 hours for posterior circulation) of symptom onset; National Institutes of Health Stroke Scale (NIHSS) ≥6 with limited ischemic change on CT imaging. Randomization was 2:1 into intervention arm (ERIC and/or SOFIA). Patients and core lab were blinded to allocation. Primary outcome was independent core lab adjudication of reperfusion (modified Thrombolysis in Cerebral Infarction (mTICI) scale). Secondary outcomes were modified Rankin score (mRS) at 90 and 365 days (independence and shift analysis), 30-day mortality, symptomatic intracranial hemorrhage (sICH), procedural complications and NIHSS change. Results Sixty-six patients were enrolled. TICI 2B/3 reperfusion was achieved in 72% in intervention compared with 90% in control arm on intention to treat (ITT) analysis (P=0.2) and 78% compared with 86% on per protocol analysis (P=0.7). Functional independence at 90 days was 40% (intervention) compared with 43% (control) on ITT analysis (P=1.0). sICH rates were low at 0% and 5%, respectively (P=0.3). The 30-day mortality was 9% intervention compared with 14% control (P=0.7). Conclusions Study indicated feasibility of a phase II RCT trial approach for assessing new thrombectomy devices. In a broad LAO stroke population ERIC and SOFIA were not statistically different from control devices. Larger trials are needed.

Introduction Approaches to economic evaluations of stroke therapies are varied and inconsistently described. An objective of the European Stroke Organisation (ESO) Health Economics Working Group is to standardise and improve the economic evaluations of interventions for stroke. Methods The ESO Health Economics Working Group and additional experts were contacted to develop a protocol and a guidance document for data collection for economic evaluations of stroke therapies. A modified Delphi approach, including a survey and consensus processes, was used to agree on content. We also asked the participants about resources that could be shared to improve economic evaluations of interventions for stroke. Results Of 28 experts invited, 16 (57%) completed the initial survey, with representation from universities, government, and industry. More than half of the survey respondents endorsed 13 specific items to include in a standard resource use questionnaire. Preferred functional/quality of life outcome measures to use for economic evaluations were the modified Rankin Scale (14 respondents, 88%) and the EQ-5D instrument (11 respondents, 69%). Of the 12 respondents who had access to data used in economic evaluations, 10 (83%) indicated a willingness to share data. A protocol template and a guidance document for data collection were developed and are presented in this article. Conclusion The protocol template and guidance document for data collection will support a more standardised and transparent approach for economic evaluations of stroke care.

Supplemental Digital Content is available in the text., Background and Purpose— There is limited evidence to guide rehabilitation to meet the longer term needs of stroke survivors. The clinical effectiveness and cost-effectiveness of an extended stroke rehabilitation service (EXTRAS) provided following early supported discharge were determined. Methods— EXTRAS was a pragmatic parallel-group observer-blind randomized controlled trial involving 19 UK centers. Patients with stroke were individually randomized to receive EXTRAS or usual care at discharge from early supported discharge. Five EXTRAS reviews were provided by an early supported discharge team member between one and 18 months, usually by telephone. Reviews consisted of a semi-structured interview assessing progress, rehabilitation needs, and service provision, with goal setting and action planning. The primary outcome was performance in extended activities of daily living (Nottingham EADL Scale) at 24 months post-randomization. The Nottingham EADL Scale is scored 0 to 66, with higher scores indicating better performance in these activities. Cost-effectiveness was estimated using resource utilization costs and Quality Adjusted Life Years. Analyses were intention to treat. Results— Between January 9, 2013 and October 26, 2015, 573 participants were randomized (EXTRAS, n=285; usual care, n=288). Mean 24 month Nottingham EADL Scale scores were EXTRAS (n=219) 40.0 (SD 18.1) and usual care (n=231) 37.2 (SD 18.5) giving an adjusted mean difference of 1.8 (95% CI, –0.7 to 4.2). 1155/1338 (86%) of expected EXTRAS reviews were undertaken. Over 24 months, the mean cost of resource utilization was lower in the intervention group: –£311 (–$450 [95% CI, −£3292 to £2787; −$4764 to $4033]). EXTRAS provided more Quality Adjusted Life Years (0.07 [95% CI, 0.01 to 0.12]). At current conventional thresholds of willingness to pay (£20 000 [$28 940] per Quality Adjusted Life Years), there was a 90% chance that EXTRAS could be considered cost-effective. Conclusions— EXTRAS did not significantly improve stroke survivors’ performance in extended activities of daily living. However, given the impact on costs and Quality Adjusted Life Years, EXTRAS may be an affordable addition to improve stroke care. Clinical Trial Registration— URL: www.isrctn.com. Unique identifier: ISRCTN45203373.

Background We have previously modelled that the optimal number of comprehensive stroke centres (CSC) providing endovascular thrombectomy (EVT) in England would be 30 (net 6 new centres). We now estimate the relative effectiveness and cost-effectiveness of increasing the number of centres from 24 to 30. Methods We constructed a discrete event simulation (DES) to estimate the effectiveness and lifetime cost-effectiveness (from a payer perspective) using 1 year’s incidence of stroke in England. 2000 iterations of the simulation were performed comparing baseline 24 centres to 30. Results Of 80,800 patients admitted to hospital with acute stroke/year, 21,740 would be affected by the service reconfiguration. The median time to treatment for eligible early presenters ( Conclusion Changes in acute stroke service configuration will produce clinical and cost benefits when the time taken for patients to receive treatment is reduced. Benefits are highly likely to be cost saving over 5 years before any capital investment above £8 million is required.

Background and Objectives:Diffusion tensor imaging (DTI) networks integrate damage from a variety of pathological processes in cerebral small vessel disease (SVD) and may be a sensitive marker to detect treatment effects. We determined whether brain network analysis could detect treatment effects in the PRESERVE trial dataset, in which intensive versus standard blood pressure (BP) lowering was compared. The primary endpoint of DTI had not shown treatment differences.Methods:Subjects with lacunar stroke were randomised to standard (systolic 130-140 mmHg), or intensive (systolic Results:Data were available in 82 subjects; standard n=40 (mean age 66.3±1.5), intensive n=42 (69.6±1.0). Mean (SD) systolic blood pressure was reduced by 13(14) and 23(23) mmHg in the standard and intensive groups respectively (PDiscussion:Brain network analysis may be a sensitive surrogate marker in trials in small vessel disease. This work suggests that measures of brain network efficiency may be more sensitive to the effects of blood pressure control treatment than conventional DTI metrics.Trial Registration Information:The trial is registered with the ISRCTN Registry (ISRCTN37694103; //doi.org/10.1186/ISRCTN37694103) and the NIHR Clinical Research Network (CRN 10962; //public-odp.nihr.ac.uk/QvAJAXZfc/opendoc.htm?document=crncc_users%5Cfind%20a%20clinical%20research%20study.qvw&lang=en-US&host=QVS%40crn-prod-odp-pu&anonymous=true)Classification of Evidence:This study provides Class II evidence that intensive BP lowering in patients with small vessel disease results in improved brain network function when assessed by DTI based brain network metrics.

Introduction: Endovascular thrombectomy (EVT) is a highly effective treatment for acute ischaemic stroke due to large arterial occlusion (LAO). To support decisions about service provision, we previously estimated the annual UK population eligible for EVT as ∼10% of stroke admissions. Since then, several trials have produced evidence that could alter these figures. We update our estimates considering information from studies and trials reporting 2018–2021 on incidence, presentation time and stroke severity and consider the possible impact of predicted demographic changes in the next 10–20 years.\ud Patients and Methods: We produce an updated decision tree describing the EVT eligible population for UK stroke admissions. One-way sensitivity analyses (using upper and lower confidence intervals for estimates at each branch of our decision tree) were used to identify where further research evidence is necessary to increase certainty around estimates for numbers of EVT eligible patients.\ud Results: The updated estimate for the number of UK stroke patients eligible for EVT annually was between 10,020 (no advanced imaging in early presenting patients) and 9,580 (advanced imaging in all early presenting patients), which compared with our estimates in 2017 is a minimal reduction. One-way sensitivity analyses established that enhanced evidence about eligibility for milder strokes, ASPECTS scores and pre-stroke disability are offset by evidence regarding a lower incidence of LAO. Importantly, predicted increases in life expectancy by 2040 may increase thrombectomy need by 40%.\ud Discussion: Information from additional randomised trials published during 2018–2020 with updated estimates of LAO prevalence had a minimal impact on overall estimates of stroke patients eligible for EVT in the UK. Ongoing research into the benefits of EVT for patients with mild stroke or European Stroke Journal For Peer Review lower ASPECTS scores has the potential to increase the estimates of the eligible population; future need for EVT will increase with the ageing population.\ud Conclusion: Our updated analyses show overall numbers eligible little changed, but evidence from ongoing trials and demographic changes have the potential to increase the need for EVT significantly.\ud Patients and Methods: We produce an updated decision-tree describing the EVT eligible population for UK stroke admissions. One-way sensitivity analyses (using upper and lower confidence intervals for estimates at each branch of our decision tree) were used to identify where further research evidence is necessary to increase certainty around estimates for numbers of EVT eligible patients.\ud \ud Results: The updated estimate for the number of UK stroke patients eligible for EVT annually was between 10,020 (no advanced imaging in early presenting patients) and 9,580 (advanced imaging in all early presenting patients), which compared with our estimates in 2017 is a minimal reduction. One-way sensitivity analyses established that enhanced evidence about eligibility for milder strokes, ASPECTS scores and pre-stroke disability are offset by evidence regarding a lower incidence of LAO. Importantly, predicted increases in life expectancy by 2040 may increase thrombectomy need by 40%.\ud \ud Discussion: Information from additional randomised trials published 2018-2020 with updated estimates of LAO prevalence had a minimal impact on overall estimates of stroke patients eligible for EVT in the UK. Ongoing research into the benefits of EVT for patients with mild stroke or lower ASPECTS scores has the potential to increase the estimates of the eligible population; future need for EVT will increase with the ageing population.\ud \ud Conclusion: Our updated analyses show overall numbers eligible little changed but evidence from ongoing trials and demographic changes have the potential to increase the need for EVT significantly.

Background Early pre-hospital initiation of blood pressure (BP) lowering could improve outcomes for patients with acute stroke, by reducing hematoma expansion in intracerebral hemorrhage (ICH), and time to reperfusion treatment and risk of intracranial hemorrhage in ischemic stroke (IS). We present the design of the fourth INTEnsive ambulance-delivered blood pressure Reduction in hyper-ACute stroke Trial (INTERACT4). Methods A multi-center, ambulance-delivered, prospective, randomized, open-label, blinded endpoint (PROBE) assessed trial of pre-hospital BP lowering in 3116 hypertensive patients with suspected acute stroke at 50+ sites in China. Patients are randomized through a mobile phone digital system to intensive BP lowering to a target systolic BP of α = 0.05) to detect a 22% reduction in the odds of a worse functional outcome using ordinal logistic regression. Discussion INTERACT4 is a pragmatic clinical trial to provide reliable evidence on the effectiveness and safety of ambulance-delivered hyperacute BP lowering in patients with suspected acute stroke. Trial registration ClinicalTrials.gov NCT03790800. Registered on 2 January 2019; Chinese Trial Registry ChiCTR1900020534. Registered on 7 January 2019. All items can be found in this protocol paper.

Background Rapid treatment of stroke improves outcomes, but accurate early recognition can be challenging. Between 20 and 40% of patients suspected to have stroke by ambulance and emergency department staff later receive a non-stroke ‘mimic’ diagnosis after stroke specialist investigation. This early diagnostic uncertainty results in displacement of mimic patients from more appropriate services, inappropriate demands on stroke specialist resources and delayed access to specialist therapies for stroke patients. Blood purine concentrations rise rapidly during hypoxic tissue injury, which is a key mechanism of damage during acute stroke but is not typical in mimic conditions. A portable point of care fingerprick test has been developed to measure blood purine concentration which could be used to triage patients experiencing suspected stroke symptoms into those likely to have a non-stroke mimic condition and those likely to have true stroke. This study is evaluating test performance for identification of stroke mimic conditions. Methods Design: prospective observational cohort study Setting: regional UK ambulance and acute stroke services Participants: a convenience series of two populations will be tested: adults with a label of suspected stroke assigned (and tested) by attending ambulance personnel and adults with a label of suspected stroke assigned at hospital (who have not been tested by ambulance staff). Index test: SMARTChip Purine assay Reference standard tests: expert clinician opinion informed by brain imaging and/or other investigations will assign the following diagnoses which constitute the suspected stroke population: ischaemic stroke, haemorrhagic stroke, TIA and stroke mimic conditions. Sample size: ambulance population (powered for mimic sensitivity) 935 participants; hospital population (powered for mimic specificity) 377 participants. Analyses: area under the receiver operating curve (ROC) and optimal sensitivity, specificity, and negative and positive predictive values for identification of mimic conditions. Optimal threshold for the ambulance population will maximise sensitivity, minimum 80%, and aim to keep specificity above 70%. Optimal threshold for the hospital population will maximise specificity, minimum 80%, and aim to keep sensitivity above 70%. Discussion The results from this study will determine how accurately the SMARTChip purine assay test can identify stroke mimic conditions within the suspected stroke population. If acceptable performance is confirmed, deployment of the test in ambulances or emergency departments could enable more appropriate direction of patients to stroke or non-stroke services. Trial registration Registered with ISRCTN (identifier: ISRCTN22323981) on 13/02/2019 http://www.isrctn.com/ISRCTN22323981

Objectives To guide policy when planning thrombolysis (IVT) and thrombectomy (MT) services for acute stroke in England, focussing on the choice between ‘mothership’ (direct conveyance to an MT centre) and ‘drip-and-ship’ (secondary transfer) provision and the impact of bypassing local acute stroke centres. Design Outcome-based modelling study. Setting 107 acute stroke centres in England, 24 of which provide IVT and MT (IVT/MT centres) and 83 provide only IVT (IVT-only units). Participants 242,874 emergency admissions with acute stroke over 3 years (2015–2017). Intervention Reperfusion delivered by drip-and-ship, mothership or ‘hybrid’ models; impact of additional travel time to directly access an IVT/MT centre by bypassing a more local IVT-only unit; effect of pre-hospital selection for large artery occlusion (LAO). Main outcome measures Population benefit from reperfusion, time to IVT and MT, admission numbers to IVT-only units and IVT/MT centres. Results Without pre-hospital selection for LAO, 94% of the population of England live in areas where the greatest clinical benefit, assuming unknown patient status, accrues from direct conveyance to an IVT/MT centre. However, this policy produces unsustainable admission numbers at these centres, with 78 out of 83 IVT-only units receiving fewer than 300 admissions per year (compared to 3 with drip-and-ship). Implementing a maximum permitted additional travel time to bypass an IVT-only unit, using a pre-hospital test for LAO, and selecting patients based on stroke onset time, all help to mitigate the destabilising effect but there is still some significant disruption to admission numbers, and improved selection of patients suitable for MT selectively reduces the number of patients who would receive IVT at IVT-only centres, challenging the sustainability of IVT expertise in IVT-only centres. Conclusions Implementation of reperfusion for acute stroke based solely on achieving the maximum population benefit potentially leads to destabilisation of the emergency stroke care system. Careful planning is required to create a sustainable system, and modelling may be used to help planners maximise benefit from reperfusion while creating a sustainable emergency stroke care system.

ObjectiveTo determine whether robot-assisted training is cost-effective compared with an enhanced upper limb therapy (EULT) programme or usual care.DesignEconomic evaluation within a randomised controlled trial.SettingFour National Health Service (NHS) centres in the UK: Queen’s Hospital, Barking, Havering and Redbridge University Hospitals NHS Trust; Northwick Park Hospital, London Northwest Healthcare NHS Trust; Queen Elizabeth University Hospital, NHS Greater Glasgow and Clyde; and North Tyneside General Hospital, Northumbria Healthcare NHS Foundation Trust.Participants770 participants aged 18 years or older with moderate or severe upper limb functional limitation from first-ever stroke.InterventionsParticipants randomised to one of three programmes provided over a 12-week period: robot-assisted training plus usual care; the EULT programme plus usual care or usual care.Main economic outcome measuresMean healthcare resource use; costs to the NHS and personal social services in 2018 pounds; utility scores based on EQ-5D-5L responses and quality-adjusted life years (QALYs). Cost-effectiveness reported as incremental cost per QALY and cost-effectiveness acceptability curves.ResultsAt 6 months, on average usual care was the least costly option (£3785) followed by EULT (£4451) with robot-assisted training being the most costly (£5387). The mean difference in total costs between the usual care and robot-assisted training groups (£1601) was statistically significant (pConclusionsThe cost-effectiveness analysis suggested that neither robot-assisted training nor EULT, as delivered in this trial, were likely to be cost-effective at any of the cost per QALY thresholds considered.Trial registration numberISRCTN69371850.

Objectives: To guide policy when planning reperfusion thrombolysis (IVT) and thrombectomy (MT) services for acute stroke in England, focussing on the choice between ‘mothership’ (direct conveyance to an MT centre) and ‘drip-and-ship' (secondary transfer for MT after local IVT) provision and the impact of bypassing local acute stroke centres.Methods: Computer modelling was used to estimate the likely outcomes from reperfusion therapies, along with admission numbers to units, based on expected times to IVT and MT.Results: Without pre-hospital selection for LAO, 94% of the population of England live in areas where the greatest clinical benefit accrues from direct conveyance to an IVT/MT centre. If this model was followed then net benefit from reperfusion is predicted to be increased from 31 to 34 additional disability-free outcomes / 1,000 admissions. However, this policy produces unsustainable admission numbers at these centres, and depletes all but 19 IVT-only units of all stroke admissions. Implementing a maximum permitted additional travel time to bypass an IVT-only unit, or using a pre-hospital test for LAO, both increase net benefit over the current drip-and-ship model, but produce a similar destabilising effect on acute systems of care. Use of IVT-only units manage admission numbers to IVT/MT centres.Conclusions: The mothership model reduces time to MT at the cost of increased time to IVT, but the benefit of faster MT is predicted to lead to a modest improvement in overall outcomes. Providing a sustainable national system of acute stroke care requires a hybrid of mothership and drip-and-ship provision.

Summary Background Loss of arm function is a common problem after stroke. Robot-assisted training might improve arm function and activities of daily living. We compared the clinical effectiveness of robot-assisted training using the MIT-Manus robotic gym with an enhanced upper limb therapy (EULT) programme based on repetitive functional task practice and with usual care. Methods RATULS was a pragmatic, multicentre, randomised controlled trial done at four UK centres. Stroke patients aged at least 18 years with moderate or severe upper limb functional limitation, between 1 week and 5 years after their first stroke, were randomly assigned (1:1:1) to receive robot-assisted training, EULT, or usual care. Robot-assisted training and EULT were provided for 45 min, three times per week for 12 weeks. Randomisation was internet-based using permuted block sequences. Treatment allocation was masked from outcome assessors but not from participants or therapists. The primary outcome was upper limb function success (defined using the Action Research Arm Test [ARAT]) at 3 months. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN69371850. Findings Between April 14, 2014, and April 30, 2018, 770 participants were enrolled and randomly assigned to either robot-assisted training (n=257), EULT (n=259), or usual care (n=254). The primary outcome of ARAT success was achieved by 103 (44%) of 232 patients in the robot-assisted training group, 118 (50%) of 234 in the EULT group, and 85 (42%) of 203 in the usual care group. Compared with usual care, robot-assisted training (adjusted odds ratio [aOR] 1·17 [98·3% CI 0·70–1·96]) and EULT (aOR 1·51 [0·90–2·51]) did not improve upper limb function; the effects of robot-assisted training did not differ from EULT (aOR 0·78 [0·48–1·27]). More participants in the robot-assisted training group (39 [15%] of 257) and EULT group (33 [13%] of 259) had serious adverse events than in the usual care group (20 [8%] of 254), but none were attributable to the intervention. Interpretation Robot-assisted training and EULT did not improve upper limb function after stroke compared with usual care for patients with moderate or severe upper limb functional limitation. These results do not support the use of robot-assisted training as provided in this trial in routine clinical practice. Funding National Institute for Health Research Health Technology Assessment Programme.

Aims The association of frailty with coronary plaque phenotype among older patients with non-ST-elevation acute coronary syndrome (NSTEACS) is not known. The aim of this study was to evaluate the association of frailty with coronary plaque phenotype among older patients with NSTEACS. Methods and results Older patients with NSTEACS who underwent invasive angiography were recruited. Frailty was measured using the Fried frailty score. Following angiography, patients underwent greyscale and virtual histology intravascular ultrasound (VH-IVUS) imaging. Of the 90 patients, 26 (28.9%) were robust, 49 (54.4%) patients were pre-frail, and 15 (16.7%) were frail. Mean age was 80.9±3.8 years; 59 (65.6%) were male. Compared to robust patients, the pre-frail group had a significantly greater presence of high-risk lesions including VH thin-cap fibroatheroma (TCFA, p=0.011), minimum lumen area (MLA) ≤4 mm2 (p=0.016), TCFA+MLA ≤4 mm2 (p=0.005), TCFA+plaque burden (PB) ≥70% (p=0.005) and TCFA+PB ≥70%+MLA ≤4 mm2 (p=0.003). By age- and sex-adjusted logistic regression analysis, frailty was found to be strongly and independently associated with the presence of TCFA (odds ratio [OR] 2.81, 95% confidence interval [CI]:1.06-7.48, p=0.039). Conclusions This is the first study to report the relationship between frailty phenotype and coronary plaque morphology among frail older NSTEACS patients. ClinicalTrials.gov Identifier: NCT01933581.

Background and Purpose— Hyperglycemia is a negative prognostic factor after acute ischemic stroke but is not known whether glucose is associated with the effects of endovascular thrombectomy (EVT) in patients with large-vessel stroke. In a pooled-data meta-analysis, we analyzed whether serum glucose is a treatment modifier of the efficacy of EVT in acute stroke. Methods— Seven randomized trials compared EVT with standard care between 2010 and 2017 (HERMES Collaboration [highly effective reperfusion using multiple endovascular devices]). One thousand seven hundred and sixty-four patients with large-vessel stroke were allocated to EVT (n=871) or standard care (n=893). Measurements included blood glucose on admission and functional outcome (modified Rankin Scale range, 0–6; lower scores indicating less disability) at 3 months. The primary analysis evaluated whether glucose modified the effect of EVT over standard care on functional outcome, using ordinal logistic regression to test the interaction between treatment and glucose level. Results— Median (interquartile range) serum glucose on admission was 120 (104–140) mg/dL (6.6 mmol/L [5.7–7.7] mmol/L). EVT was better than standard care in the overall pooled-data analysis adjusted common odds ratio (acOR), 2.00 (95% CI, 1.69–2.38); however, lower glucose levels were associated with greater effects of EVT over standard care. The interaction was nonlinear such that significant interactions were found in subgroups of patients split at glucose < or >90 mg/dL (5.0 mmol/L; P =0.019 for interaction; acOR, 3.81; 95% CI, 1.73–8.41 for patients < 90 mg/dL versus 1.83; 95% CI, 1.53–2.19 for patients >90 mg/dL), and glucose < or >100 mg/dL (5.5 mmol/L; P =0.004 for interaction; acOR, 3.17; 95% CI, 2.04–4.93 versus acOR, 1.72; 95% CI, 1.42–2.08) but not between subgroups above these levels of glucose. Conclusions— EVT improved stroke outcomes compared with standard treatment regardless of glucose levels, but the treatment effects were larger at lower glucose levels, with significant interaction effects persisting up to 90 to 100 mg/dL (5.0–5.5 mmol/L). Whether tight control of glucose improves the efficacy of EVT after large-vessel stroke warrants appropriate testing.

Background The Paramedic Acute Stroke Treatment Assessment (PASTA) trial evaluated an enhanced emergency care pathway which aimed to facilitate thrombolysis in hospital. A pre-planned health economic evaluation was included. The main results showed no statistical evidence of a difference in either thrombolysis volume (primary outcome) or 90-day dependency. However, counter-intuitive findings were observed with the intervention group showing fewer thrombolysis treatments but less dependency. Aims Cost-effectiveness of the PASTA intervention was examined relative to standard care. Methods A within trial cost-utility analysis estimated mean costs and quality-adjusted life years over 90 days’ time horizon. Costs were derived from resource utilization data for individual trial participants. Quality-adjusted life years were calculated by mapping modified Rankin scale scores to EQ-5D-3L utility tariffs. A post-hoc subgroup analysis examined cost-effectiveness when trial hospitals were divided into compliant and non-compliant with recommendations for a stroke specialist thrombolysis rota. Results The trial enrolled 1214 patients: 500 PASTA and 714 standard care. There was no evidence of a quality-adjusted life year difference between groups [0·007 (95% CI: −0·003 to 0·018)] but costs were lower in the PASTA group [−£1473 (95% CI: −£2736 to −£219)]. There was over 97.5% chance that the PASTA pathway would be considered cost-effective. There was no evidence of a difference in costs at seven thrombolysis rota compliant hospitals but costs at eight non-complaint hospitals costs were lower in PASTA with more dominant cost-effectiveness. Conclusions Analyses indicate that the PASTA pathway may be considered cost-effective, particularly if deployed in areas where stroke specialist availability is limited. Trial Registration: ISRCTN12418919 www.isrctn.com/ISRCTN12418919

BackgroundMechanical thrombectomy (MT) is a time-sensitive emergency procedure for patients who had ischaemic stroke leading to improved health outcomes. Health systems need to ensure that MT is delivered to as many patients as quickly as possible. Using decision modelling, we aimed to evaluate the cost-effectiveness of secondary transfer by helicopter emergency medical services (HEMS) compared with ground emergency medical services (GEMS) of rural patients eligible for MT in England.MethodsThe model consisted of (1) a short-run decision tree with two branches, representing secondary transfer transportation strategies and (2) a long-run Markov model for a theoretical population of rural patients with a confirmed ischaemic stroke. Strategies were compared by lifetime costs: quality-adjusted life years (QALYs), incremental cost per QALY gained and net monetary benefit. Sensitivity and scenario analyses explored uncertainty around parameter values.ResultsWe used the base case of early-presenting (6 hours to arterial puncture), ground transportation is the dominant strategy.ConclusionOur model indicates that using HEMS to transfer patients who had stroke eligible for MT from remote hospitals in England may be cost-effective when: travel time is reduced by at least 60 min compared with GEMS, and a £30 000/QALY threshold is used for decision-making. However, several other logistic considerations may impact on the use of air transportation.

BackgroundMultimorbidity presents an increasing challenge in the global ageing population. Predicting its development is necessary to help design and deliver effective healthcare.ObjectiveThis scoping review aimed to collate and present the body of published evidence on biomarkers and multimorbidity, identifying what work has been done and what gaps remain.MethodsWe searched the electronic databases MEDLINE, Register of Controlled Trials (Cochrane CENTRAL), CINAHL, PsycINFO, EMBASE, Scopus, Web of Science and TRIP database up until 11 August 2020 and hand-searched the reference lists of included articles.ResultsWe found 34 relevant studies including 12 reporting prospective data and 22 reporting cross-sectional data. These encompassed 14 studies on serum biomarkers, 2 on molecular biomarkers, 7 on physiological biomarkers, 8 on body size biomarkers and 3 on brain function biomarkers. Most studies were undertaken in European or North American populations. There was a broadly consistent finding that obesity was associated with increased multimorbidity. Other results were more varied, reflecting the diverse range of biomarkers investigated, and lack of standardisation of multimorbidity outcome definitions.Longitudinal studies have been set up that are maturing and further evidence can be expected over time.ConclusionThere has been limited research on biomarkers to predict the development of multimorbidity, with minimal investigation of putative biomarkers identified in basic research. High quality research studies in this area are needed to progress the development of targeted interventions to prevent or delay the onset of multimorbidity.

© 2020 The Authors. Journal of the American Geriatrics Society published by Wiley Periodicals LLC on behalf of The American Geriatrics Society. BACKGROUND/OBJECTIVES: Randomized controlled trials are used to inform clinical guidelines on the management of hypertension in older adults, but it is unclear to what extent these trials represent the general population attending routine clinical practice. This study aimed to define the proportion and characteristics of patients eligible for hypertension trials conducted in older people. DESIGN: Cross-sectional study. SETTING: A total of 24 general practices in England. PARTICIPANTS: Anonymized electronic health record data from all individuals aged 80 and older. MEASUREMENTS: Descriptive statistics were used to define the proportion and characteristics of patients eligible for two previous medication intensification trials (HYVET, SPRINT) and one medication reduction trial (OPTiMISE). A logistic regression model was constructed to estimate predictors of eligibility for each trial. RESULTS: Of 15,376 patients identified, 268 (1.7%; 95% confidence interval [CI] = 1.5–2.0%), 5,290 (34.4%; 95%CI = 33.7–35.2%), and 3,940 (25.6%; 95%CI = 24.9–26.3%) were eligible for the HYVET, SPRINT, and OPTiMISE trials, respectively. Between 5.6% and 30.7% of exclusions from each trial were due to eligibility criteria excluding those with high or uncontrolled blood pressure. Frailty (odds ratio [OR] =.44; 95%CI =.36–.54 [OPTiMISE]), cardiovascular polypharmacy (OR =.61; 95%CI =.55–.68 [SPRINT]) and multimorbidity (OR =.72; 95%CI =.64–.82 [SPRINT]) were associated with a lower likelihood of being eligible for one or more of the trials. CONCLUSION: A possible unintended consequence of blood pressure criteria used by trials attempting to answer different primary questions is that for many older patients, no trial evidence exists to inform treatment decisions in routine practice. Caution should be exercised when applying results from existing trials to patients with frailty or multimorbidity.

Background Recent clinical trials have demonstrated the efficacy of mechanical thrombectomy in acute ischemic stroke. Aims To determine the cost-effectiveness, value of future research, and value of implementation of mechanical thrombectomy. Methods Using UK clinical and cost data from the Pragmatic Ischemic Stroke Thrombectomy Evaluation (PISTE) trial, we estimated the cost-effectiveness of mechanical thrombectomy over time horizons of 90-days and lifetime, based on a decision-analytic model, using all existing evidence. We performed a meta-analysis of seven clinical trials to estimate treatment effects. We used sensitivity analysis to address uncertainty. Value of implementation analysis was used to estimate the potential value of additional implementation activities to support routine delivery of mechanical thrombectomy. Results Over the trial period (90 days), compared with best medical care alone, mechanical thrombectomy incurred an incremental cost of £5207 and 0.025 gain in QALY (incremental cost-effectiveness ratio (ICER) £205,279), which would not be considered cost-effective. However, mechanical thrombectomy was shown to be cost-effective over a lifetime horizon, with an ICER of £3466 per QALY gained. The expected value of perfect information per patient eligible for mechanical thrombectomy in the UK is estimated at £3178. The expected value of full implementation of mechanical thrombectomy is estimated at £1.3 billion over five years. Conclusion Mechanical thrombectomy was cost-effective compared with best medical care alone over a patient’s lifetime. On the assumption of 30% implementation being achieved throughout the UK healthcare system, we estimate that the population health benefits obtained from this treatment are greater than the cost of implementation. Trial registration NCT01745692.

As clinical researchers in stroke we applaud the rapid mobilisation of research into covid-19 in response to this new global threat.1 Nearly 100 urgent research studies in covid-19 have been approved over the past few weeks, many of them complex trials that would have taken months or years to start before the pandemic.2 This has been made possible, in part, by streamlined and proportionate regulation and approvals. But …

Background There is limited evidence about the effectiveness of rehabilitation in meeting the longer-term needs of stroke patients and their carers. Objective To determine the clinical effectiveness and cost-effectiveness of an extended stroke rehabilitation service (EXTRAS). Design A pragmatic, observer-blind, parallel-group, multicentre randomised controlled trial with embedded health economic and process evaluations. Participants were randomised (1 : 1) to receive EXTRAS or usual care. Setting Nineteen NHS study centres. Participants Patients with a new stroke who received early supported discharge and their informal carers. Interventions Five EXTRAS reviews provided by an early supported discharge team member between 1 and 18 months post early supported discharge, usually over the telephone. Reviewers assessed rehabilitation needs, with goal-setting and action-planning. Control treatment was usual care post early supported discharge. Main outcome measures The primary outcome was performance in extended activities of daily living (Nottingham Extended Activities of Daily Living Scale) at 24 months post randomisation. Secondary outcomes at 12 and 24 months included patient mood (Hospital Anxiety and Depression Scale), health status (Oxford Handicap Scale), experience of services and adverse events. For carers, secondary outcomes included carers’ strain (Caregiver Strain Index) and experience of services. Cost-effectiveness was estimated using resource utilisation costs (adaptation of the Client Service Receipt Inventory) and quality-adjusted life-years. Results A total of 573 patients (EXTRAS, n = 285; usual care, n = 288) with 194 carers (EXTRAS, n = 103; usual care, n = 91) were randomised. Mean 24-month Nottingham Extended Activities of Daily Living Scale scores were 40.0 (standard deviation 18.1) for EXTRAS (n = 219) and 37.2 (standard deviation 18.5) for usual care (n = 231), giving an adjusted mean difference of 1.8 (95% confidence interval –0.7 to 4.2). The mean intervention group Hospital Anxiety and Depression Scale scores were not significantly different at 12 and 24 months. The intervention did not improve patient health status or carer strain. EXTRAS patients and carers reported greater satisfaction with some aspects of care. The mean cost of resource utilisation was lower in the intervention group: –£311 (95% confidence interval –£3292 to £2787), with a 68% chance of EXTRAS being cost-saving. EXTRAS was associated with 0.07 (95% confidence interval 0.01 to 0.12) additional quality-adjusted life-years. At current conventional thresholds of willingness to pay for a quality-adjusted life-year, there is a 90% chance that EXTRAS is cost-effective. Conclusions EXTRAS did not improve stroke survivors’ performance in extended activities of daily living but did improve their overall satisfaction with services. Given the impact on costs and quality-adjusted life-years, there is a high chance that EXTRAS could be considered cost-effective. Future work Further research is required to identify whether or not community-based interventions can improve performance of extended activities of daily living, and to understand the improvements in health-related quality of life and costs seen by provision of intermittent longer-term specialist review. Trial registration Current Controlled Trials ISRCTN45203373. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 24. See the NIHR Journals Library website for further project information.

Background Outcomes for acute ischaemic stroke patients with large artery occlusion are significantly improved with endovascular thrombectomy (EVT). We aimed to identify preferences of stroke survivors, their relatives/carers and the public in England on: (i) EVT service organisation (localised versus centralised expert-delivered EVT services) and (ii) modelled outcomes for EVT effectiveness, equity of access and costs of EVT provision (based on increasing the number of comprehensive stroke centres across England that provide EVT from 24 to 30).Methods Stroke survivors, their relatives/carers and the public were engaged in an iterative co-design process to develop an accessible survey incorporating two Best-Worst Scaling (BWS) tasks: EVT service organisation (4 attributes each with 2 levels) and modelled outcomes (3 attributes each with 2 levels). On-line pilot testing was undertaken with 10 stroke survivors/carers. BWS data were transformed into standardised scores with corresponding 95% confidence intervals (CIs).Results 105 respondents completed the survey (stroke survivors [18%]; relative/carer of stroke survivor [32%]; member of public [50%]). Centralised (local) EVT provision by experienced and specialised medical teams was associated with the strongest positive preference (0.76, 95% CIs = 0.69, 0.82), followed by secondary inter-hospital transfer for EVT; associated with positive preferences whether required (0.15, 95% CIs = 0.07, 0.22) or not (0.30, 95% CIs = 0.22, 0.38). Travel times by emergency ambulance > 45 min (-0.29, 95% CIs=-0.37, -0.22) were associated with stronger negative preferences than length of stay

Introduction The clinical efficacy and cost-effectiveness of mechanical thrombectomy (MT) for the treatment of large vessel occlusion stroke is well established, but uncertainty remains around the true cost of delivering this treatment within the NHS. The aim of this study was to establish the cost of providing MT within the hyperacute phase of care and to explore differences in resources used and costs across different neuroscience centres in the UK. Method This was a multicentre retrospective study using micro-costing methods to enable a precise assessment of the costs of MT from an NHS perspective. Data on resources used and their costs were collected from five UK neuroscience centres between 2015 and 2018. Results Data were collected on 310 patients with acute ischaemic stroke treated with MT. The mean total cost of providing MT and inpatient care within 24 hours was £10,846 (95% confidence interval (CI) 10,527–11,165) per patient. The main driver of cost was MT procedure costs, accounting for 73% (£7,943; 95% CI 7,649–8,237) of the total 24-hour cost. Costs were higher for patients treated under general anaesthesia (£11,048; standard deviation (SD) 2,654) than for local anaesthesia (£9,978; SD 2,654), mean difference £1,070 (95% CI 381–1,759; p=0.003); admission to an intensive care unit (ICU; £12,212; SD 3,028) against for admission elsewhere (£10,179; SD 2,415), mean difference £2,032 (95% CI 1,345–2,719; p The mean cost within 72 hours was £12,440 (95% CI 10,628–14,252). The total costs for the duration of inpatient care before discharge from a thrombectomy centre was £14,362 (95% CI 13,603–15,122). Conclusions Major factors contributing to costs of MT for stroke include consumables and staff for intervention, use of general anaesthesia and ICU admissions. These findings can inform the reimbursement, provision and strategic planning of stroke services and aid future economic evaluations.

[Background] The prevalence of ex vivo ‘high on-treatment platelet reactivity (HTPR)’ and its relationship with recurrent vascular events/outcomes in patients with ischaemic cerebrovascular disease (CVD) is unclear., [Methods] A systematic review and meta-analysis was performed in accordance with the PRISMA statement. MEDLINE, EMBASE and Cochrane Library were searched for completed manuscripts until May 2019 on TIA/ischaemic stroke patients, ≥ 18 years, treated with commonly-prescribed antiplatelet therapy, who had platelet function/reactivity testing and prospective follow-up data on recurrent stroke/TIA, myocardial infarction, vascular death or other cerebrovascular outcomes. Data were pooled using random-effects meta-analysis. Primary outcome was the composite risk of recurrent stroke/TIA, myocardial infarction or vascular death. Secondary outcomes were recurrent stroke/TIA, severe stroke (NIHSS > 16) or disability/impairment (modified Rankin scale ≥ 3) during follow-up., [Results] Antiplatelet–HTPR prevalence was 3–65% with aspirin, 8–56% with clopidogrel and 1.8–35% with aspirin–clopidogrel therapy. Twenty studies (4989 patients) were included in our meta-analysis. There was a higher risk of the composite primary outcome (OR 2.93, 95% CI 1.90–4.51) and recurrent ischaemic stroke/TIA (OR 2.43, 95% CI 1.51–3.91) in patients with vs. those without ‘antiplatelet–HTPR’ on any antiplatelet regimen. These risks were also more than twofold higher in patients with vs. those without ‘aspirin–HTPR’ and ‘dual antiplatelet–HTPR’, respectively. Clopidogrel–HTPR status did not significantly predict outcomes, but the number of eligible studies was small. The risk of severe stroke was higher in those with vs. without antiplatelet–HTPR (OR 2.65, 95% CI 1.00–7.01)., [Discussion] Antiplatelet–HTPR may predict risks of recurrent vascular events/outcomes in CVD patients. Given the heterogeneity between studies, further prospective, multi-centre studies are warranted., Dr. Lim’s research was funded by The Meath Foundation, The Irish Institute of Clinical Neuroscience/Novartis Ireland Fellowship Grant, The Vascular Neurology Research Foundation Ireland, the Irish Heart Foundation Stroke Prevention Bursary programme, and by an unrestricted educational grant from Biogen Idec, Ireland. Dr. Murphy’s research was funded by the Trinity College Dublin Innovation Bursary, The Meath Foundation, Joint Irish Institute of Clinical Neuroscience/Merck Serono Fellowship in Neuroscience Grant, The Vascular Neurology Research Foundation Ireland, and by an unrestricted educational grant from Bayer HealthCare, Ireland and Verum Diagnostica, GmbH. Dr Offiah’s Research is funded by The Meath Foundation and The Vascular Neurology Research Foundation Ireland and by an unrestricted educational grant from SINNOWA Medical Science & Technology Co., China. Prof Thijs’ research is supported by The Florey Institute of Neuroscience and Mental Health, which acknowledges support from the Victorian Government and funding from an Operational Infrastructure Support Grant. Prof Prodan’s research is supported by a United States Department of Veterans Affairs Merit Award (1I01CX000340). Prof Kelly is supported by grants from the Health Research Board Ireland. Prof Barber is supported by grants from the Canadian Institute of Health Research and the Heart and Stroke Foundation of Canada. Prof Werring receives research support from the Stroke Association and the British Heart Foundation. Prof Thijs has received personal fees for lectures and consulting fees from Bayer, Boehringer Ingelheim, BMS/Pfizer and Amgen. Prof. Bath is a Stroke Association Professor of Stroke Medicine and NIHR Senior Investigator, a non-executive Director of ‘Platelet Solutions Ltd.®, and owns 3 shares; he has received personal fees for consulting from DiaMedica, Moleac, Nestle, Sanofi and Phagenesis. Prof Werring has received honoraria for consulting and lectures from Bayer and Portola, and for consulting from Alnylam.

BackgroundPre-hospital identification of key subgroups within the suspected stroke population could reduce delays to emergency treatment. We aimed to identify and describe technology with existing proof of concept for diagnosis or stratification of patients in the pre-hospital setting.MethodsA systematic electronic search of published literature (from 01/01/2000 to 06/06/2019) was conducted in five bibliographic databases. Two reviewers independently assessed eligibility of studies or study protocols describing diagnostic/stratification tests (portable imaging/biomarkers) or technology facilitating diagnosis/stratification (telemedicine) used by ambulance personnel during the assessment of suspected stroke. Eligible descriptions required use of tests or technology during the actual assessment of suspected stroke to provide information directly to ambulance personnel in the pre-hospital setting. Due to study, intervention and setting heterogeneity there was no attempt at meta-analysis.Results2887 articles were screened for eligibility, 19 of which were retained. Blood biomarker studies (n = 2) were protocols of prospective diagnostic accuracy studies, one examining purines and the other a panel of known and novel biomarkers for identifying stroke sub-types (versus mimic). No data were yet available on diagnostic accuracy or patient health outcomes. Portable imaging studies (n = 2) reported that an infrared screening device for detecting haemorrhages yielded moderate sensitivity and poor specificity in a small study, whilst a dry-EEG study to detect large vessel occlusion in ischaemic stroke has not yet reported results. Fifteen evaluations of pre-hospital telemedicine were identified (12 observational and 3 controlled comparisons) which all involved transmission of stroke assessment data from the pre-hospital setting to the hospital. Diagnosis was generally comparable with hospital diagnosis and most telemedicine systems reduced time-to-treatment; however, it is unknown whether this time saving translated into more favourable clinical outcomes. Telemedicine systems were deemed acceptable by clinicians.ConclusionsPre-hospital technologies to identify clinically important subgroups amongst the suspected stroke population are in development but insufficient evidence precludes recommendations about routine use in the pre-hospital setting. Multi-centre diagnostic accuracy studies and clinical utility trials combining promising technologies are warranted.