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Abstract Background It has long been noted that the chain from identification of need (research gap) to impact in the real world is both long and tortuous. This study aimed to contribute evidence about research ethics and governance arrangements and processes in the UK with a focus on: what works well; problems; impacts on delivery; and potential improvements. Methods Online questionnaire widely distributed 20th May 2021, with request to forward to other interested parties. The survey closed on 18th June 2021. Questionnaire included closed and open questions related to demographics, role, study objectives. Results Responses were received from 252 respondents, 68% based in universities 25% in the NHS. Research methods used by respondents included interviews/focus groups (64%); surveys/questionnaires (63%); and experimental/quasi experimental (57%). Respondents reported that participants in the research they conducted most commonly included: patients (91%); NHS staff (64%) and public (50%). Aspects of research ethics and governance reported to work well were: online centralised systems; confidence in rigorous, respected systems; and helpful staff. Problems with workload, frustration and delays were reported, related to overly bureaucratic, unclear, repetitive, inflexible and inconsistent processes. Disproportionality of requirements for low-risk studies was raised across all areas, with systems reported to be risk averse, defensive and taking little account of the risks associated with delaying or deterring research. Some requirements were reported to have unintended effects on inclusion and diversity, particularly impacting Patient and Public Involvement (PPI) and engagement processes. Existing processes and requirements were reported to cause stress and demoralisation, particularly as many researchers are employed on fixed term contracts. High negative impacts on research delivery were reported, in terms of timescales for completing studies, discouraging research particularly for clinicians and students, quality of outputs and costs. Suggested improvements related to system level changes / overall approach and specific refinements to existing processes. Conclusions Consultation with those involved in Health Services Research in the UK revealed a picture of overwhelming and increasing bureaucracy, delays, costs and demoralisation related to gaining the approvals necessary to conduct research in the NHS. Suggestions for improvement across all three areas focused on reducing duplication and unnecessary paperwork/form filling and reaching a better balance between risks of harm through research and harms which occur because research to inform practice is delayed or deterred.

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.

Abstract Background Pre-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. Methods A 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. Results 2887 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. Conclusions Pre-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.

Background: Loss of arm function is common after stroke. Robot-assisted training may improve arm outcomes. Objective: The 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. Design: This was a pragmatic, observer-blind, multicentre randomised controlled trial with embedded health economic and process evaluations. Setting: The trial was set in four NHS trial centres. Participants: Patients with moderate or severe upper limb functional limitation, between 1 week and 5 years following first stroke, were recruited. Interventions: Robot-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 measures: The 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. Results: A 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. Conclusions: Robot-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 work: Further 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. Limitations: Pragmatic 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 registration: Current Controlled Trials ISRCTN69371850. 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. 54. See the NIHR Journals Library website for further project information.

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: Dopamine is a key modulator of striatal function and learning, and may improve motor recovery after stroke. Seven small trials of dopamine agonists after stroke have provided equivocal evidence of the clinical effectiveness of dopamine agonists in improving motor recovery. Design: Dopamine Augmented Rehabilitation in Stroke was a multicentre, randomised, double-blind, placebo-controlled trial with stroke patients randomised to receive 6 weeks of co-careldopa (Sinemet®, Merck Sharp & Dohme Ltd) or placebo in combination with occupational and physical rehabilitation. Methods: The primary outcome measure was the proportion of patients walking independently at 8 weeks [Rivermead Mobility Index (RMI) score of ≥ 7 points and ‘yes’ to item 7 on the RMI]. Secondary outcome measures assessed physical functioning, pain, cognition, mood, fatigue and carer burden at 8 weeks, 6 months and 12 months. Results: Between May 2011 and March 2014, 593 patients (mean age 68.5 years) and 165 carers (mean age 59.7 years) were recruited from stroke rehabilitation units; 308 patients were randomised to co-careldopa and 285 to placebo at a median of 15 days following stroke onset. The study drug was to be taken 45–60 minutes before therapy, which included motor activities (mean 23.2 and 24.8 sessions in the co-careldopa and placebo groups, respectively). The mean number of investigational medicinal product doses taken was 20.6 in the co-careldopa group and 22.4 in the placebo group. Ability to walk independently was not improved at 8 weeks [40.6% (co-careldopa) vs. 44.6% (placebo); odds ratio 0.78, 95% confidence interval (CI) 0.53 to 1.15], 6 months [51.6% (co-careldopa) vs. 53.3% (placebo)] or 12 months [51.6% (co-careldopa) vs. 56.8% (placebo)]. There were no significant differences for Barthel Index, Nottingham Extended Activities of Daily Living, ABILHAND Manual Ability Measure or Modified Rankin Scale, pain or fatigue at any time point. Montreal Cognitive Assessment scores did not significantly differ; the majority of participants had cognitive impairment at baseline, which improved during 12 months’ follow-up. No difference was observed in General Health Questionnaire 12-item version scores between groups at 8 weeks and 12 months but, at 6 months, those in the co-careldopa group reported significantly better general health [mean difference (MD) –1.33, 95% CI –2.57 to –0.10]. Mortality at 12 months was not significantly different. Carers in the placebo group reported significantly greater burden at 6 months (MD 5.05, 95% CI 0.10 to 10.01) and 12 months (MD 7.52, 95% CI 1.87 to 13.18). Conclusion: Co-careldopa in addition to routine NHS occupational and physical therapy is not clinically effective or cost-effective in improving walking, physical functioning, mood or cognition following stroke. We recommend further research to develop imaging and clinical markers that would allow identification of promising drug therapies that would enhance motor therapy in improving walking ability and arm function. Further research is needed to compare strategies of giving drug therapy intermittently immediately prior to therapy sessions or as continuous background daily administration. Limitations: In total, 10.3% of patients were lost to follow-up at 8 weeks and

AIM:To investigate atrial flow patterns in the normal adult heart, to explore whether caval vein arrangement and patency of the foramen ovale (PFO) may be associated with flow pattern. MATERIALS AND METHODS:Time-resolved, three-dimensional velocity encoded magnetic resonance imaging (4D flow) was employed to assess atrial flow patterns in thirteen healthy subjects (6 male, 40 years, range 25-50) and thirteen subjects (6 male, 40 years, range 21-50) with cryptogenic stroke and patent foramen ovale (CS-PFO). Right atrial flow was defined as vortical, helico-vortical, helical and multiple vortices. Time-averaged and peak systolic and diastolic flows in the caval and pulmonary veins and their anatomical arrangement were compared. RESULTS:A spectrum of right atrial flow was observed across the four defined categories. The right atrial flow patterns were strongly associated with the relative position of the caval veins. Right atrial flow patterns other than vortical were more common (p = 0.015) and the separation between the superior and inferior vena cava greater (10±5mm versus 3±3mm, p = 0.002) in the CS-PFO group. In the left atrium all subjects except one had counter-clockwise vortical flow. Vortex size varied and was associated with left lower pulmonary vein flow (systolic r = 0.61, p = 0.001, diastolic r = 0.63 p = 0.002). A diastolic vortex was less common and time-averaged left atrial velocity was greater in the CS-PFO group (17±2cm/sec versus 15±1, p = 0.048). One CS-PFO subject demonstrated vortical retrograde flow in the descending aortic arch; all other subjects had laminar descending aortic flow. CONCLUSION:Right atrial flow patterns in the normal heart are heterogeneous and are associated with the relative position of the caval veins. Patterns, other than 'typical' vortical flow, are more prevalent in the right atrium of those with cryptogenic stroke in the context of PFO. Left atrial flow patterns are more homogenous in normal hearts and show a relationship with flow arising from the left pulmonary veins.

BACKGROUND:Stroke is associated with the development of cognitive impairment and dementia. We assessed the effect of intensive blood pressure (BP) and/or lipid lowering on cognitive outcomes in patients with recent stroke in a pilot trial. METHODS:In a multicentre, partial-factorial trial, patients with recent stroke, absence of dementia, and systolic BP (SBP) 125-170 mmHg were assigned randomly to at least 6 months of intensive (target SBP

Background: Intravenous thrombolysis for patients with acute ischaemic stroke is underused (only 80% of eligible patients receive it) and there is variation in its use across the UK. Previously, variation might have been explained by structural differences; however, continuing variation may reflect differences in clinical decision-making regarding the eligibility of patients for treatment. This variation in decision-making could lead to the underuse, or result in inappropriate use, of thrombolysis. Objectives: To identify the factors which contribute to variation in, and influence, clinicians’ decision-making about treating ischaemic stroke patients with intravenous thrombolysis. Methods: A discrete choice experiment (DCE) using hypothetical patient vignettes framed around areas of clinical uncertainty was conducted to better understand the influence of patient-related and clinician-related factors on clinical decision-making. An online DCE was developed following an iterative five-stage design process. UK-based clinicians involved in final decision-making about thrombolysis were invited to take part via national professional bodies of relevant medical specialties. Mixed-logit regression analyses were conducted. Results: A total of 138 clinicians responded and opted to offer thrombolysis in 31.4% of cases. Seven patient factors were individually predictive of the increased likelihood of offering thrombolysis (compared with reference levels in brackets): stroke onset time of 2 hours 30 minutes (50 minutes); pre-stroke dependency modified Rankin Scale score (mRS) of 3 (mRS4); systolic blood pressure (SBP) of 185 mmHg (140 mmHg); stroke severity scores of National Institutes of Health Stroke Scale (NIHSS) 5 without aphasia, NIHSS 14 and NIHSS 23 (NIHSS 2 without aphasia); age 85 years (65 years); and Afro-Caribbean (white). Factors predictive of not offering thrombolysis were age 95 years; stroke onset time of 4 hours 15 minutes; severe dementia (no memory problems); and SBP of 200 mmHg. Three clinician-related factors were predictive of an increased likelihood of offering thrombolysis (perceived robustness of the evidence for thrombolysis; thrombolysing more patients in the past 12 months; and high discomfort with uncertainty) and one factor was predictive of a decreased likelihood of offering treatment (clinicians’ being comfortable treating patients outside the licensing criteria). Limitations: We anticipated a sample size of 150–200. Nonetheless, the final sample of 138 is good considering that the total population of eligible UK clinicians is relatively small. Furthermore, data from the Royal College of Physicians suggest that our sample is representative of clinicians involved in decision-making about thrombolysis. Conclusions: There was considerable heterogeneity among respondents in thrombolysis decision-making, indicating that clinicians differ in their thresholds for treatment across a number of patient-related factors. Respondents were significantly more likely to treat 85-year-old patients than patients aged 68 years and this probably reflects acceptance of data from Third International Stroke Trial that report benefit for patients aged > 80 years. That respondents were more likely to offer thrombolysis to patients with severe stroke than to patients with mild stroke may indicate uncertainty/concern about the risk/benefit balance in treatment of minor stroke. Findings will be disseminated via peer-review publication and presentation at national/international conferences, and will be linked to training/continuing professional development (CPD) programmes. Future work: The nature of DCE design means that only a subset of potentially influential factors could be explored. Factors not explored in this study warrant future research. Training/CPD should address the impact of non-medical influences on decision-making using evidence-based strategies. Funding: The National Institute for Health Research Health Services and Delivery Research programme.

Introduction: The incidence of stroke is increasing in India. Prehospital stroke care is crucial for reducing stroke morbidity and mortality, but its implementation in India faces several challenges. Limited original research exists on prehospital stroke care in India, making it essential to identify the problems in implementing effective prehospital stroke care. Methods: A web-based survey was conducted among registered medical practitioners in India who treat acute stroke. The survey questionnaire was developed in English and included 26 questions divided into five parts: questions about the physician’s practice setup/hospital in India, perception of community awareness, existing prehospital care/systems, in-hospital stroke care availability, and specific issues faced. Results: Eighty-three doctors in India participated in the survey (43% response rate). Most of the respondents worked in private hospitals (68%) and urban areas (76%). While 89% of hospitals had ambulance services, over 33% reported that patients had to pay for ambulance transport. Among respondents, 12% reported a community stroke care network, with infrequent prehospital procedures such as random blood glucose measurement (22%), stroke identification (15.7%), “last seen normal” documentation (14.5%), and low prehospital notification to hospitals (5%). Delays in referral from peripheral centers were reported by 73% of respondents. Most hospitals had standard operating procedures (SOPs) (84%), computed tomography (CT) (94%), magnetic resonance imaging (MRI) (85%), and offered intravenous thrombolysis (IVT) (77%). However, 24 h availability of CT was reported only by 6%, MRI by 19% and IVT by 12%. Nearly half (45%) reported treatment with thrombolysis was not covered by insurance. Mechanical thrombectomy was available in 34% of hospitals and 63% of hospitals conducted in-hospital audits for stroke patients. Conclusions: The capabilities of stroke-catering hospitals in urban settings are encouraging, with many having SOPs, imaging capabilities, and thrombolysis and mechanical thrombectomy services. However, there is much room for improvement, in making the essential stroke care services financially accessible to all and available around the clock.

Abstract Background Comprehensive stroke centres across England have developed investment proposals, showing the estimated increases in mechanical thrombectomy (MT) treatment volume that would justify extending the standard hours to a 24/7 service provision. These investment proposals have been developed taking a financial accounting perspective, that is by considering the financial revenues from tariff income. However, given the pressure put on local health authorities to provide value for money services, an affordability question emerges. That is, at what additional MT treatment volume the additional treatment costs are offset by the additional health economic benefits, that is quality-adjusted life years (QALYs) and societal cost savings, generated by administering MT compared to standard care. Methods A break-even analysis was conducted to identify the additional MT treatment volume required. The incremental hospital-related costs associated with the 24/7 MT extension were estimated using information and parameters from four relevant business cases. The additional societal cost savings and health benefits were estimated by adapting a previously developed Markov chain-based model. Results The additional hospital-related annual costs for extending MT to a 24/7 service were estimated at a mean of £3,756,818 (range £1,847,387 to £5,092,788). On average, 750 (range 246 to 1,571) additional eligible stroke patients are required to be treated with MT yearly for the proposed 24/7 service extension to be affordable from a health economic perspective. Overall, the additional facility and equipment costs associated with the 24/7 extension would affect this estimate by 20%. Conclusions These findings support the ongoing debate regarding the optimal levels of MT treatment required for a 24/7 extension and respective changes in hospital organisational activities. They also highlight a need for a regional-level coordination between local authorities and hospital administrations to ensure equity provision in that stroke patients can benefit from MT and that the optimal MT treatment volume is reached. Future studies should contemplate reproducing the presented analysis for different health service provision settings and decision making contexts.

Background: Rapid access to emergency stroke care can reduce death and disability by enabling immediate provision of interventions such as thrombolysis, physiological monitoring and stabilisation. One of the ways that access to services can be facilitated is through emergency medical service (EMS) dispatchers. The sensitivity of EMS dispatchers for identifying stroke is

OBJECTIVE:In February 2009, the Department of Health in England launched the Face, Arm, Speech, and Time (FAST) mass media campaign, to raise public awareness of stroke symptoms and the need for an emergency response. We aimed to evaluate the impact of three consecutive phases of FAST using population-level measures of behaviour in England. METHODS:Interrupted time series (May 2007 to February 2011) assessed the impact of the campaign on: access to a national stroke charity's information resources (Stroke Association [SA]); emergency hospital admissions with a primary diagnosis of stroke (Hospital Episode Statistics for England); and thrombolysis activity from centres in England contributing data to the Safe Implementation of Thrombolysis in Stroke UK database. RESULTS:Before the campaign, emergency admissions (and patients admitted via accident and emergency [A&E]) and thrombolysis activity was increasing significantly over time, whereas emergency admissions via general practitioners (GPs) were decreasing significantly. SA webpage views, calls to their helpline and information materials dispatched increased significantly after phase one. Website hits/views, and information materials dispatched decreased after phase one; these outcomes increased significantly during phases two and three. After phase one there were significant increases in overall emergency admissions (505, 95% CI = 75 to 935) and patients admitted via A&E (451, 95% CI = 26 to 875). Significantly fewer monthly emergency admissions via GPs were reported after phase three (-19, 95% CI = -29 to -9). Thrombolysis activity per month significantly increased after phases one (3, 95% CI = 1 to 6), and three (3, 95% CI = 1 to 4). CONCLUSIONS:Phase one had a statistically significant impact on information seeking behaviour and emergency admissions, with additional impact that may be attributable to subsequent phases on information seeking behaviour, emergency admissions via GPs, and thrombolysis activity. Future campaigns should be accompanied by evaluation of impact on clinical outcomes such as reduced stroke-related morbidity and mortality.

Summary: Background: Deprescribing of antihypertensive medications is recommended for some older patients with low blood pressure and frailty. The OPTiMISE trial showed that this deprescribing can be achieved with no differences in blood pressure control at 3 months compared with usual care. We aimed to examine effects of deprescribing on longer-term hospitalisation and mortality. Methods: This randomised controlled trial enrolled participants from 69 general practices across central and southern England. Participants aged 80 years or older, with systolic blood pressure less than 150 mm Hg and who were receiving two or more antihypertensive medications, were randomly assigned (1:1) to antihypertensive medication reduction (removal of one antihypertensive) or usual care. General practitioners and participants were aware of the treatment allocation following randomisation but individuals responsible for analysing the data were masked to the treatment allocation throughout the study. Participants were followed up via their primary and secondary care electronic health records at least 3 years after randomisation. The primary outcome was time to all-cause hospitalisation or mortality. Intention-to-treat analyses were done using Cox regression modelling. A per-protocol analysis of the primary outcome was also done, excluding participants from the intervention group who did not reduce treatment or who had medication reinstated during the initial trial 12-week follow-up period. This study is registered with the European Union Drug Regulating Authorities Clinical Trials Database (EudraCT2016-004236-38) and the ISRCTN Registry (ISRCTN97503221). Findings: Between March 20, 2017, and Sept 30, 2018, a total of 569 participants were randomly assigned. Of these, 564 (99%; intervention=280; control=284) were followed up for a median of 4·0 years (IQR 3·7–4·3). Participants had a mean age of 84·8 years (SD 3·4) at baseline and 273 (48%) were women. Medication reduction was sustained in 109 participants at follow-up (51% of the 213 participants alive in the intervention group). Participants in the intervention group had a larger reduction in antihypertensives than the control group (adjusted mean difference –0·35 drugs [95% CI –0·52 to –0·18]). Overall, 202 (72%) participants in the intervention group and 218 (77%) participants in the control group experienced hospitalisation or mortality during follow-up (adjusted hazard ratio [aHR] 0·93 [95% CI 0·76 to 1·12]). There was some evidence that the proportion of participants experiencing the primary outcome in the per-protocol population was lower in the intervention group (aHR 0·80 [0·64 to 1·00]). Interpretation: Half of participants sustained medication reduction with no evidence of an increase in all-cause hospitalisation or mortality. These findings suggest that an antihypertensive deprescribing intervention might be safe for people aged 80 years or older with controlled blood pressure taking two or more antihypertensives. Funding: British Heart Foundation and National Institute for Health and Care Research.

OBJECTIVE:Effective provision of urgent stroke care relies upon admission to hospital by emergency ambulance and may involve pre-hospital redirection. The proportion and characteristics of patients who do not arrive by emergency ambulance and their impact on service efficiency is unclear. To assist in the planning of regional stroke services we examined the volume, characteristics and prognosis of patients according to the mode of presentation to local services. STUDY DESIGN AND SETTING:A prospective regional database of consecutive acute stroke admissions was conducted in North East, England between 01/09/10-30/09/11. Case ascertainment and transport mode were checked against hospital coding and ambulance dispatch databases. RESULTS:Twelve acute stroke units contributed data for a mean of 10.7 months. 2792/3131 (89%) patients received a diagnosis of stroke within 24 hours of admission: 2002 arrivals by emergency ambulance; 538 by private transport or non-emergency ambulance; 252 unknown mode. Emergency ambulance patients were older (76 vs 69 years), more likely to be from institutional care (10% vs 1%) and experiencing total anterior circulation symptoms (27% vs 6%). Thrombolysis treatment was commoner following emergency admission (11% vs 4%). However patients attending without emergency ambulance had lower inpatient mortality (2% vs 18%), a lower rate of institutionalisation (1% vs 6%) and less need for daily carers (7% vs 16%). 149/155 (96%) of highly dependent patients were admitted by emergency ambulance, but none received thrombolysis. CONCLUSION:Presentations of new stroke without emergency ambulance involvement were not unusual but were associated with a better outcome due to younger age, milder neurological impairment and lower levels of pre-stroke dependency. Most patients with a high level of pre-stroke dependency arrived by emergency ambulance but did not receive thrombolysis. It is important to be aware of easily identifiable demographic groups that differ in their potential to gain from different service configurations.

BACKGROUND:Physical activity and sedentary behaviour are key moderators of cardiovascular disease risk and metabolic control. Despite the importance of a physically active lifestyle, little is known about the effects of stroke on physical activity. We assessed physical activity and sedentary behaviour at three time points following stroke compared to a healthy control group. METHODS:Physical activity and sedentary behaviour were objectively measured using a portable multi-sensor array in 31 stroke participants (73±9 years, National Institute of Health Stroke Scale 2±2, mobile 10 metres with/without aid) within seven days and at three and six months. Stroke data were compared with an age, sex and body mass index matched healthy control group (n = 31). RESULTS:Within seven days of stroke, total energy expenditure and physical activity were significantly lower and sedentary time higher in the stroke group compared to controls (total energy expenditure 1840±354 vs. 2220±489 kcal, physical activity 28±32 vs. 79±46 min/day, steps 3111±2290 vs. 7996±2649, sedentary time 1383±42 vs. 1339±44 min/day, p

Abstract Background and aims Uncertainty persists over the effects of blood pressure (BP) lowering in acute stroke. The INTEnsive ambulance-delivered blood pressure Reduction in hyper-Acute stroke Trial (INTERACT4) aims to determine efficacy and safety of hyperacute intensive BP lowering in patients with suspected acute stroke. Given concerns over the safety of this treatment in the pre-hospital setting, particularly in relation to patients with intracerebral hemorrhage, we provide an update on progress of the study and profile of participants to date. Methods INTERACT4 is an ongoing multicentre, ambulance-delivered, randomized, open-label, blinded endpoint trial of pre-hospital BP lowering in patients with suspected acute stroke and elevated BP in China. Patients are randomized via a mobile phone digital system to intensive (target systolic BP [SBP]

ObjectivesTo identify the reasons why individuals contact, or delay contacting, emergency medical services in response to stroke symptoms.DesignQualitative interview study with a purposive sample of stroke patients and witnesses, selected according to method of accessing medical care and the time taken to do so. Data were analysed using the Framework approach.SettingArea covered by three acute stroke units in the north east of England.ParticipantsNineteen stroke patients and 26 witnesses who had called for help following the onset of stroke symptoms.ResultsFactors influencing who called emergency medical services and when they called included stroke severity, how people made sense of symptoms and their level of motivation to seek help. Fear of the consequences of stroke, including future dependence or disruption to family life, previous negative experience of hospitals, or involving a friend or relations in the decision to access medical services, all resulted in delayed admission. Lack of knowledge of stroke symptoms was also an important determinant. Perceptions of the remit of medical services were a major cause of delays in admission, with many people believing the most appropriate action was to telephone their GP. Variations in the response of primary care teams to acute stroke symptoms were also evident.ConclusionsThe factors influencing help-seeking decisions are complex. There remains a need to improve recognition by patients, witnesses and health care staff of the need to treat stroke as a medical emergency by calling emergency medical services, as well as increasing knowledge of symptoms of stroke among patients and potential witnesses. Fear, denial and reticence to impose on others hinders the process of seeking help and will need addressing specifically with appropriate interventions. Variability in how primary care services respond to stroke needs further investigation to inform interventions to promote best practice.Trial registrationUK Clinical Research Network UKCRN 6590.

BackgroundDelay in calling emergency medical services following stroke limits access to early treatment that can reduce disability. Emergency medical services contact is mostly initiated by stroke witnesses (often relatives), rather than stroke patients. This study explored appraisal and behavioural factors that are potentially important in influencing witness behaviour in response to stroke.Methods and findingsSemi-structured interviews with 26 stroke witnesses were transcribed and theory-guided content analysed was undertaken based on the Common Sense Self-Regulation Model (appraisal processes) and Theory Domains Framework (behavioural determinants). Response behaviours were often influenced by heuristics-guided appraisal (i.e. mental rules of thumb). Some witnesses described their responses to the situation as 'automatic' and 'instinctive', rather than products of deliberation. Potential behavioural influences included: environmental context and resources (e.g. time of day), social influence (e.g. prompts from patients) and beliefs about consequences (e.g. 999 accesses rapid help). Findings are based on retrospective accounts and need further verification in prospective studies.ConclusionsWitnesses play a key role in patient access to emergency medical services. Factors that potentially influence witnesses' responses to stroke were identified and could inform behavioural interventions and future research. Interventions might benefit from linking automatic/instinctive threat perceptions with deliberate appraisal of stroke symptoms, prompting action to call emergency medical services.

Stroke is a leading cause of disability. Early treatment of acute ischaemic stroke with rtPA reduces the risk of longer term dependency but carries an increased risk of causing immediate bleeding complications. To understand the challenges of knowledge translation and decision making about treatment with rtPA in hyperacute stroke and hence to inform development of appropriate decision support we interviewed patients, their family and health professionals. The emergency setting and the symptomatic effects of hyper-acute stroke shaped the form, content and manner of knowledge translation to support decision making. Decision making about rtPA in hyperacute stroke presented three conundrums for patients, family and clinicians. 1) How to allow time for reflection in a severely time-limited setting. 2) How to facilitate knowledge translation regarding important treatment risks and benefits when patient and family capacity is blunted by the effects and shock of stroke. 3) How to ensure patient and family views are taken into account when the situation produces reliance on the expertise of clinicians. Strategies adopted to meet these conundrums were fourfold: face to face communication; shaping decisions; incremental provision of information; and communication tailored to the individual patient. Relational forms of interaction were understood to engender trust and allay anxiety. Shaping decisions with patients was understood as an expression of confidence by clinicians that helped alleviate anxiety and offered hope and reassurance to patients and their family experiencing the shock of the stroke event. Neutral presentations of information and treatment options promoted uncertainty and contributed to anxiety. 'Drip feeding' information created moments for reflection: clinicians literally made time. Tailoring information to the particular patient and family situation allowed clinicians to account for social and emotional contexts. The principal responses to the challenges of decision making about rtPA in hyperacute stroke were relational decision support and situationally-sensitive knowledge translation.

IntroductionIn a drip-and-ship model for endovascular thrombectomy (EVT), early identification of large vessel occlusion (LVO) and timely referral to a comprehensive center (CSC) are crucial when patients are admitted to an acute stroke center (ASC). Several artificial intelligence (AI) decision-aid tools are increasingly being used to facilitate the rapid identification of LVO. This retrospective cohort study aimed to evaluate the impact of deploying e-Stroke AI decision support software in the hyperacute stroke pathway on process metrics and patient outcomes at an ASC in the United Kingdom.MethodsExcept for the deployment of e-Stroke on 01 March 2020, there were no significant changes made to the stroke pathway at the ASC. The data were obtained from a prospective stroke registry between 01 January 2019 and 31 March 2021. The outcomes were compared between the 14 months before and 12 months after the deployment of AI (pre-e-Stroke cohort vs. post-e-Stroke cohort) on 01 March 2020. Time window analyses were performed using Welch’s t-test. Cochran–Mantel–Haenszel test was used to compare changes in disability at 3 months assessed by modified Rankin Score (mRS) ordinal shift analysis, and Fisher’s exact test was used for dichotomised mRS analysis.ResultsIn the pre-e-Stroke cohort, 19 of 22 patients referred received EVT. In the post-e-Stroke cohort, 21 of the 25 patients referred were treated. The mean door-in-door-out (DIDO) and door-to-referral times in pre-e-Stroke vs. post-e-Stroke cohorts were 141 vs. 79 min (difference 62 min, 95% CI 96.9–26.8 min, p

Background. Nitric oxide (NO) donors are a candidate treatment for acute stroke and two trials have suggested that they might improve outcome if administered within 4–6 hours of stroke onset. We assessed the safety and efficacy of NO donors using individual patient data (IPD) from completed trials. Methods. Randomised controlled trials of NO donors in patients with acute or subacute stroke were identified and IPD sought from the trialists. The effect of NO donor versus control on functional outcome was assessed using the modified Rankin scale (mRS) and death, by time to randomisation. Secondary outcomes included measures of disability, mood, and quality of life. Results. Five trials (4,197 participants) were identified, all involving glyceryl trinitrate (GTN). Compared with control, GTN lowered blood pressure by 7.4/3.3 mmHg. At day 90, GTN did not alter any clinical measures. However, in 312 patients randomised within 6 hours of stroke onset, GTN was associated with beneficial shifts in the mRS (odds ratio (OR) 0.52, 95% confidence interval (CI) 0.34–0.78) and reduced death (OR 0.32, 95% CI 0.14–0.78). Conclusions. NO donors do not alter outcome in patients with recent stroke. However, when administered within 6 hours, NO donors might improve outcomes in both ischaemic and haemorrhagic stroke.