Healthcare professional views about a prehospital redirection pathway for stroke thrombectomy: a multiphase deductive qualitative study.

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

The impact of large core and late treatment trials: An update on the modelled annual thrombectomy eligibility of UK stroke patients.

INTRODUCTION: To support decisions about thrombectomy provision, we have previously estimated the annual UK population eligible for treatment as ∼10% of stroke admissions. Since then, eight further randomised trials that could alter the eligibility rate have reported in 2021-23. We updated our estimates of the eligible population from these trials and other recent studies. PATIENTS AND METHODS: An updated decision tree describing the EVT eligible population for UK stroke admissions was produced. Decision criteria were derived from the highest level of evidence available. For nodes where no specific RCT data existed, evidence was obtained from the latest systematic review(s) or the highest quality observational data. RESULTS: We estimate that 15,420 (approximately 15%) of admitted UK stroke patients are now eligible for thrombectomy, or 14,930 if advanced brain imaging using MRI/CT perfusion or collateral assessment were used in all patients. This is a 54% increase in our previous estimate in 2021. Over 50% of LAO strokes are now potentially eligible for thrombectomy. The increase in eligibility is principally due to a much larger cohort of later presenting and/or larger ischaemic core patients. CONCLUSION: Most previously independent LAO stroke patients presenting within 24 h, even in the presence of a large ischaemic core on initial non-contrast CT, should be considered for thrombectomy with use of advanced brain imaging in those presenting beyond 12 h to identify salvageable penumbral brain tissue. Treatment in most patients remains critically time-dependent and our estimates should be interpreted with this in mind.

Prehospital transdermal glyceryl trinitrate for ultra-acute ischaemic stroke: data from the RIGHT-2 randomised sham-controlled ambulance trial.

BACKGROUND: The effect of transdermal glyceryl trinitrate (GTN, a nitrovasodilator) on clinical outcome when administered before hospital admission in suspected stroke patients is unclear. Here, we assess the safety and efficacy of GTN in the prespecified subgroup of patients who had an ischaemic stroke within the Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2 (RIGHT-2). METHODS: RIGHT-2 was an ambulance-based multicentre sham-controlled blinded-endpoint study with patients randomised within 4 hours of onset. The primary outcome was a shift in scores on the modified Rankin scale (mRS) at day 90. Secondary outcomes included death; a global analysis (Wei-Lachin test) containing Barthel Index, EuroQol-5D, mRS, telephone interview for cognitive status-modified and Zung depression scale; and neuroimaging-determined 'brain frailty' markers. Data were reported as n (%), mean (SD), median [IQR], adjusted common OR (acOR), mean difference or Mann-Whitney difference (MWD) with 95% CI. RESULTS: 597 of 1149 (52%) patients had a final diagnosis of ischaemic stroke; age 75 (12) years, premorbid mRS>2 107 (18%), Glasgow Coma Scale 14 (2) and time from onset to randomisation 67 [45, 108] min. Neuroimaging 'brain frailty' was common: median score 2 [2, 3] (range 0-3). At day 90, GTN did not influence the primary outcome (acOR for increased disability 1.15, 95% CI 0.85 to 1.54), death or global analysis (MWD 0.00, 95% CI -0.10 to 0.09). In subgroup analyses, there were non-significant interactions suggesting GTN may be associated with more death and dependency in participants randomised within 1 hour of symptom onset and in those with more severe stroke. CONCLUSIONS: In patients who had an ischaemic stroke, ultra-acute administration of transdermal GTN in the ambulance did not improve clinical outcomes in a population with more clinical and radiological frailty than seen in previous in-hospital trials.

A prospective study of MRI biomarkers in the brain and lower limb muscles for prediction of lower limb motor recovery following stroke.

The aim of this prospective observational longitudinal study was to explore and decipher the predictive value of prospective MRI biomarkers in the brain and lower limb muscles for 3-month lower limb motor recovery following stroke. In the brain, we measured the integrity of the corticospinal tract (fractional anisotropy/"FA"). In the muscles, we measured volume, fatty replacement (fat fraction analysis and proton spectroscopy) and oedema. Measurements were taken at two time points: (1) within 4 weeks of stroke (baseline measurement, clinical and imaging) and (2) 3 months following stroke (follow up measurement, clinical only). Clinical measurements consisted of assessments of functional ability and strength (Fugl-Meyer score, motor NIHSS, Functional Ambulation Category/"FAC", and muscle dynamometry). Twenty-three patients completed imaging and clinical assessments at baseline and follow-up; five patients had partial imaging assessment. The results provided some evidence that damage to the corticospinal tract would result in less motor recovery: recovery of the Fugl-Meyer score and dynamometric ankle plantarflexion, ankle dorsiflexion, and knee extension correlated positively and significantly with fractional anisotropy (0.406-0.457; p = 0.034-p = 0.016). However, fractional anisotropy demonstrated a negative correlation with recovery of the Functional Ambulation Category (-0.359, p = 0.046). For the muscle imaging, significant inverse correlation was observed between vastus lateralis fat fraction vs. NIHSS recovery (-0.401, p = 0.04), and a strong positive correlation was observed between ratio of intra- to extra-myocellular lipid concentrations and the recovery of knee flexion (0.709, p = 0.007). This study supports previous literature indicating a positive correlation between the integrity of the corticospinal tract and motor recovery post-stroke, expanding the limited available literature describing this relationship specifically for the lower limb. However, recovery of functional ambulation behaved differently to other clinical recovery markers by demonstrating an inverse relationship with corticospinal tract integrity. The study also introduces some muscle imaging biomarkers as potentially valuable in the prediction of 3-month lower limb motor recovery following stroke.

Prehospital transdermal glyceryl trinitrate in patients with ultra-acute presumed stroke (RIGHT-2): effects on outcomes at day 365 in a randomised, sham-controlled, blinded, phase III, superiority ambulance-based trial.

Background: The Rapid Intervention with Glyceryl Trinitrate in Hypertensive Stroke Trial-2 (RIGHT-2) reported no overall treatment difference between glyceryl trinitrate (GTN) and sham at day 90. Here we assess participants' outcomes 1 year after randomisation. Methods: RIGHT-2 was an ambulance-based prospective randomised controlled trial where patients with presumed stroke and systolic blood pressure (BP) of >120 mm Hg received either GTN (5 mg/day) or sham patch. Centralised blinded telephone follow-up was performed at days 90 (primary endpoint) and 365 (secondary endpoint). The lead outcome was dependency assessed with the modified Rankin Scale (mRS). Results: 1149 patients were recruited to RIGHT-2 between October 2015 and May 2018, and 1097 (95.5%) had outcome data recorded at day 365. At baseline, the patients were; female (48%), had a mean age of 73 (15) years, BP of 162 (25)/92 (18) mm Hg, onset to randomisation of 70 (45-115) min, diagnosis of ischaemic stroke (52%), intracerebral haemorrhage (ICH) (13%), transient ischaemic attack (TIA) (9%) and mimics (26%). There was no effect of GTN on mRS score at day 365 in participants with confirmed stroke/TIA (adjusted common odds ratio (acOR) 1.10, 95% CI 0.86 to 1.42) or in all patients. In patients randomised to GTN, mRS at day 365 tended to be worse in those with ICH (acOR 1.65, 95% CI 0.84 to 3.25) and better in those with a mimic diagnosis (acOR 0.53, 95% CI 0.33 to 0.84). Conclusion: At 1 year post randomisation, dependency did not differ between GTN and sham treatment in either the target population or overall. In prespecified subgroup analyses, GTN was associated with reduced dependency in participants with a final diagnosis of mimic and a non-significant worse outcome in participants with ICH. Trial registration number: ISRCTN26986053.

Auditory rhythmical cueing to improve gait in community-dwelling stroke survivors (ACTIVATE): a pilot randomised controlled trial.

BACKGROUND: Gait impairment limiting mobility and restricting activities is common after stroke. Auditory rhythmical cueing (ARC) uses a metronome beat delivered during exercise to train stepping and early work reports gait improvements. This study aimed to establish the feasibility of a full scale multicentre randomised controlled trial to evaluate an ARC gait and balance training programme for use by stroke survivors in the home and outdoors. METHODS: A parallel-group observer-blind pilot randomised controlled trial was conducted. Adults within 2 years of stroke with a gait-related mobility impairment were recruited from four NHS stroke services and randomised to an ARC gait and balance training programme (intervention) or the training programme without ARC (control). Both programmes consisted of 3x30 min sessions per week for 6 weeks undertaken at home/nearby outdoor community. One session per week was supervised and the remainder self-managed. Gait and balance performance assessments were undertaken at baseline, 6 and 10 weeks. Key trial outcomes included recruitment and retention rates, programme adherence, assessment data completeness and safety. RESULTS: Between November 2018 and February 2020, 59 participants were randomised (intervention n=30, control n=29), mean recruitment rate 4/month. At baseline, 6 weeks and 10 weeks, research assessments were conducted for 59/59 (100%), 47/59 (80%) and 42/59 (71%) participants, respectively. Missing assessments were largely due to discontinuation of data collection from mid-March 2020 because of the UK COVID-19 pandemic lockdown. The proportion of participants with complete data for each individual performance assessment ranged from 100% at baseline to 68% at 10 weeks. In the intervention group, 433/540 (80%) total programme exercise sessions were undertaken, in the control group, 390/522 (75%). Falls were reported by five participants in the intervention group, six in the control group. Three serious adverse events occurred, all unrelated to the study. CONCLUSION: We believe that a definitive multicentre RCT to evaluate the ARC gait and balance training programme is feasible. Recruitment, programme adherence and safety were all acceptable. Although we consider that the retention rate and assessment data completeness were not sufficient for a future trial, this was largely due to the UK COVID-19 pandemic lockdown. TRIAL REGISTRATION: ISRCTN, ISRCTN10874601 , Registered on 05/03/2018.

Feasibility, acceptability, and fidelity of Physical Activity Routines After Stroke (PARAS): a multifaceted behaviour change intervention targeting free-living physical activity and sedentary behaviour in community-dwelling adult stroke survivors.

BACKGROUND: Low levels of habitual physical activity and high levels of sedentary behaviour are commonly observed post-stroke. We aimed to assess the feasibility, acceptability and fidelity of a multifaceted, theory- and evidence-informed supported self-management intervention targeting physical activity and sedentary behaviour after stroke: Physical Activity Routines After Stroke (PARAS). METHODS: Adult stroke survivors and healthcare professionals were recruited from North East England stroke services. Stroke survivor physical activity and sedentary behaviour were targeted by a self-management behavioural intervention supported by healthcare professionals trained in intervention delivery. The main outcomes were protocol and intervention acceptability and feasibility and fidelity of intervention delivery. RESULTS: Eleven healthcare professionals (9 physiotherapists; 2 occupational therapists) participated in the study. Stroke survivor recruitment was lower than anticipated (19 versus target of up to 35). The healthcare professional training programme was feasible, with fidelity assessment of delivery supporting this finding. Data completeness was acceptable according to a priori criteria (>60%), except for stroke survivor questionnaire return rate (59%) and interview uptake (52%). No serious adverse events occurred. Healthcare professionals and stroke survivors perceived intervention delivery to be feasible and acceptable with minor modifications highlighted including the potential for earlier delivery in the stroke pathway. CONCLUSIONS: The study protocol and intervention delivery were feasible and acceptable to stroke survivors and healthcare professionals with modifications required before large-scale evaluation. TRIAL REGISTRATION: ISRCTN35516780 . Registered on October 24, 2018.

How do interventions to improve the efficiency of acute stroke care affect prehospital times? A systematic review and narrative synthesis.

BACKGROUND: Emergency medical services (EMS) are the first point of contact for most acute stroke patients. EMS call to hospital times have increased in recent years for stroke patients in the UK which is undesirable due to the relationship between time and effectiveness of reperfusion treatment. This review aimed to identify and describe interventions devised to improve the efficiency of acute stroke care which reported an impact on ground-based EMS call to hospital times. METHODS: A systematic review of published literature identified from five databases (Medline, EMBASE, CINAHL, the Cochrane library and the Database of Research in Stroke (DORIS)) from January 2000 to December 2020 with narrative synthesis was conducted. Inclusion criteria were primary studies of ground-based EMS, focused on stroke and aiming to improve EMS times. Papers published before 2000, focussing on mobile stroke units or in languages other than English were excluded. Two reviewers independently screened prospective titles. Cochrane ROB2 and ROBINS-I tools were used to assess for risk of bias. This review was funded by a Stroke Association fellowship. RESULTS: From 3767 initial records, 11 studies were included in the review. Included studies were categorised into three groups: studies targeting EMS dispatch and EMS clinicians (n = 4); studies targeting EMS clinicians only (n = 4); and studies targeting whole system change (n = 3). Suspected stroke patients were the primary population studied and most (n = 10) interventions involved clinician education. Only one study (9%) reported a significant decrease in call to hospital time in one subgroup whereas two studies (18%) reported a significant increase in call to hospital time and all other studies (73%) reported no significant change. CONCLUSIONS: Based on the included studies, interventions intended to improve the efficiency of the acute stroke pathway rarely improved EMS call to hospital times. Included studies were heterogenous and rarely focussed on the review topic which limits the usability of the findings. Further research is needed to explore the trade-off between changes to EMS stroke care and call to hospital times and subsequent impacts on in-hospital care and patient outcomes.

Using intervention mapping to develop and facilitate implementation of a multifaceted behavioural intervention targeting physical activity and sedentary behaviour in stroke survivors: Physical Activity Routines After Stroke (PARAS): intervention development study.

Objectives: The benefits of increased physical activity for stroke survivors include improved function and mental health and wellbeing. However, less than 30% achieve recommended physical activity levels, and high levels of sedentary behaviour are reported. We developed a multifaceted behavioural intervention (and accompanying implementation plan) targeting physical activity and sedentary behaviour of stroke survivors. Design: Intervention Mapping facilitated intervention development. Step 1 involved a systematic review, focus group discussions and a review of care pathways. Step 2 identified social cognitive determinants of behavioural change and behavioural outcomes. Step 3 linked determinants of behavioural outcomes with specific behaviour change techniques (BCTs) to target behaviours of interest. Step 4 involved intervention development informed by steps 1-3. Subsequently, an implementation plan was developed (Step 5) followed by an evaluation plan (Step 6). Setting: Community and secondary care settings, North East England. Participants: Stroke survivors and healthcare professionals (HCPs) working in stroke services. Results: Systematic review findings informed selection of nine 'promising' BCTs (e.g. problem-solving). Focus groups with stroke survivors (n = 18) and HCPs (n = 24) identified the need for an intervention delivered throughout the rehabilitation pathway, tailored to individual needs with training for HCPs delivering the intervention. Intervention delivery was considered feasible within local stroke services. The target behaviours for the intervention were levels of physical activity and sedentary behaviour in adult stroke survivors. Assessment of acceptability and usability with 11 HCPs and 21 stroke survivors/relatives identified issues with self-monitoring tools and the need for a physical activity repository of local services' and training for HCPs with feedback on intervention delivery. A feasibility study protocol was designed to evaluate the intervention. Conclusions: A systematic development process using intervention mapping resulted in a multi-faceted evidence- and theory-informed intervention (Physical Activity Routines After Stroke - PARAS) for delivery by community stroke rehabilitation teams.

Surface electroencephalography (EEG) during the acute phase of stroke to assist with diagnosis and prediction of prognosis: a scoping review.

BACKGROUND: Stroke is a common medical emergency responsible for significant mortality and disability. Early identification improves outcomes by promoting access to time-critical treatments such as thrombectomy for large vessel occlusion (LVO), whilst accurate prognosis could inform many acute management decisions. Surface electroencephalography (EEG) shows promise for stroke identification and outcome prediction, but evaluations have varied in technology, setting, population and purpose. This scoping review aimed to summarise published literature addressing the following questions: 1. Can EEG during acute clinical assessment identify: a) Stroke versus non-stroke mimic conditions. b) Ischaemic versus haemorrhagic stroke. c) Ischaemic stroke due to LVO. 2. Can these states be identified if EEG is applied < 6 h since onset. 3. Does EEG during acute assessment predict clinical recovery following confirmed stroke. METHODS: We performed a systematic search of five bibliographic databases ending 19/10/2020. Two reviewers assessed eligibility of articles describing diagnostic and/or prognostic EEG application < 72 h since suspected or confirmed stroke. RESULTS: From 5892 abstracts, 210 full text articles were screened and 39 retained. Studies were small and heterogeneous. Amongst 21 reports of diagnostic data, consistent associations were reported between stroke, greater delta power, reduced alpha/beta power, corresponding ratios and greater brain asymmetry. When reported, the area under the curve (AUC) was at least good (0.81-1.00). Only one study combined clinical and EEG data (AUC 0.88). There was little data found describing whether EEG could identify ischaemic versus haemorrhagic stroke. Radiological changes suggestive of LVO were also associated with increased slow and decreased fast waves. The only study with angiographic proof of LVO reported AUC 0.86 for detection < 24 h since onset. Amongst 26 reports of prognostic data, increased slow and reduced fast wave EEG changes were associated with future dependency, neurological impairment, mortality and poor cognition, but there was little evidence that EEG enhanced outcome prediction relative to clinical and/or radiological variables. Only one study focussed solely on patients < 6 h since onset for predicting neurological prognosis post-thrombolysis, with more favourable outcomes associated with greater hemispheric symmetry and a greater ratio of fast to slow waves. CONCLUSIONS: Although studies report important associations with EEG biomarkers, further technological development and adequately powered real-world studies are required before recommendations can be made regarding application during acute stroke assessment.

Acceptability and deliverability of an auditory rhythmical cueing (ARC) training programme for use at home and outdoors to improve gait and physical activity post-stroke.

BACKGROUND: Although laboratory studies demonstrate that training programmes using auditory rhythmical cueing (ARC) may improve gait post-stroke, few studies have evaluated this intervention in the home and outdoors where deployment may be more appropriate. This manuscript reports stakeholder refinement of an ARC gait and balance training programme for use at home and outdoors, and a study which assessed acceptability and deliverability of this programme. METHODS: Programme design and content were refined during stakeholder workshops involving physiotherapists and stroke survivors. A two-group acceptability and deliverability study was then undertaken. Twelve patients post-stroke with a gait related mobility impairment received either the ARC gait and balance training programme or the gait and balance training programme without ARC. Programme provider written notes, participant exercise and fall diaries, adverse event monitoring and feedback questionnaires captured data about deliverability, safety and acceptability of the programmes. RESULTS: The training programme consisted of 18 sessions (six supervised, 12 self-managed) of exercises and ARC delivered by a low-cost commercially available metronome. All 12 participants completed the six supervised sessions and 10/12 completed the 12 self-managed sessions. Provider and participant session written records and feedback questionnaires confirmed programme deliverability and acceptability. CONCLUSION: An ARC gait and balance training programme refined by key stakeholders was feasible to deliver and acceptable to participants and providers. TRIAL REGISTRATION: ISCTRN 12/03/2018.

Cost-effectiveness of an enhanced Paramedic Acute Stroke Treatment Assessment (PASTA) during emergency stroke care: Economic results from a pragmatic cluster randomized trial.

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.

Colchicine for prevention of vascular inflammation in Non-CardioEmbolic stroke (CONVINCE) - study protocol for a randomised controlled trial.

BACKGROUND: Inflammation contributes to unstable atherosclerotic plaque and stroke. In randomised trials in patients with coronary disease, canukinumab (an interleukin-1B antagonist) and colchicine (a tubulin inhibitor with pleiotropic anti-inflammatory effects) reduced recurrent vascular events.Hypothesis: Anti-inflammatory therapy with low-dose colchicine plus usual care will reduce recurrent vascular events in patients with non-severe, non-cardioembolic stroke and TIA compared with usual care alone. DESIGN: CONVINCE is a multi-centre international (in 17 countries) Prospective, Randomised Open-label, Blinded-Endpoint assessment (PROBE) controlled Phase 3 clinical trial in 3154 participants. The intervention is colchicine 0.5 mg/day and usual care versus usual care alone (antiplatelet, lipid-lowering, antihypertensive treatment, lifestyle advice). Included patients are at least 40 years, with non-severe ischaemic stroke (modified Rankin score ≤3) or high-risk TIA (ABCD2 > 3, or positive DWI, or cranio-cervical artery stenosis) within 72 hours-28 days of randomisation, with qualifying stroke/TIA most likely caused by large artery stenosis, lacunar disease, or cryptogenic embolism. Exclusions are stroke/TIA caused by cardio-embolism or other defined cause (e.g. dissection), contra-indication to colchicine (including potential drug interactions), or incapacity for participation in a clinical trial. The anticipated median follow-up will be 36 months. The primary analysis will be by intention-to-treat. OUTCOME: The primary outcome is time to first recurrent ischaemic stroke, myocardial infarction, cardiac arrest, or hospitalisation with unstable angina (non-fatal or fatal). SUMMARY: CONVINCE will provide high-quality randomised data on the efficacy and safety of anti-inflammatory therapy with colchicine for secondary prevention after stroke. SCHEDULE: First-patient first-visit was December 2016. Recruitment to complete in 2021, follow-up to complete in 2023.

A Novel Combination of Blood Biomarkers and Clinical Stroke Scales Facilitates Detection of Large Vessel Occlusion Ischemic Strokes.

Acute ischemic stroke caused by large vessel occlusions (LVOs) is a major contributor to stroke deaths and disabilities; however, identification for emergency treatment is challenging. We recruited two separate cohorts of suspected stroke patients and screened a panel of blood-derived protein biomarkers for LVO detection. Diagnostic performance was estimated by using blood biomarkers in combination with NIHSS-derived stroke severity scales. Multivariable analysis demonstrated that D-dimer (OR 16, 95% CI 5-60; p-value < 0.001) and GFAP (OR 0.002, 95% CI 0-0.68; p-value < 0.05) comprised the optimal panel for LVO detection. Combinations of D-dimer and GFAP with a number of stroke severity scales increased the number of true positives, while reducing false positives due to hemorrhage, as compared to stroke scales alone (p-value < 0.001). A combination of the biomarkers with FAST-ED resulted in the highest accuracy at 95% (95% CI: 87-99%), with sensitivity of 91% (95% CI: 72-99%), and specificity of 96% (95% CI: 90-99%). Diagnostic accuracy was confirmed in an independent cohort, in which accuracy was again shown to be 95% (95% CI: 87-99%), with a sensitivity of 82% (95% CI: 57-96%), and specificity of 98% (95% CI: 92-100%). Accordingly, the combination of D-dimer and GFAP with stroke scales may provide a simple and highly accurate tool for identifying LVO patients, with a potential impact on time to treatment.

Purines for Rapid Identification of Stroke Mimics (PRISM): study protocol for a diagnostic accuracy study.

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.

Predictors of recognition of out of hospital cardiac arrest by emergency medical services call handlers in England: a mixed methods diagnostic accuracy study.

BACKGROUND: The aim of this study was to identify key indicator symptoms and patient factors associated with correct out of hospital cardiac arrest (OHCA) dispatch allocation. In previous studies, from 3% to 62% of OHCAs are not recognised by Emergency Medical Service call handlers, resulting in delayed arrival at scene. METHODS: Retrospective, mixed methods study including all suspected or confirmed OHCA patients transferred to one acute hospital from its associated regional Emergency Medical Service in England from 1/7/2013 to 30/6/2014. Emergency Medical Service and hospital data, including voice recordings of EMS calls, were analysed to identify predictors of recognition of OHCA by call handlers. Logistic regression was used to explore the role of the most frequently occurring (key) indicator symptoms and characteristics in predicting a correct dispatch for patients with OHCA. RESULTS: A total of 39,136 dispatches were made which resulted in transfer to the hospital within the study period, including 184 patients with OHCA. The use of the term 'Unconscious' plus one or more of symptoms 'Not breathing/Ineffective breathing/Noisy breathing' occurred in 79.8% of all OHCAs, but only 72.8% of OHCAs were correctly dispatched as such. 'Not breathing' was associated with recognition of OHCA by call handlers (Odds Ratio (OR) 3.76). The presence of key indicator symptoms 'Breathing' (OR 0.29), 'Reduced or fluctuating level of consciousness' (OR 0.24), abnormal pulse/heart rate (OR 0.26) and the characteristic 'Female patient' (OR 0.40) were associated with lack of recognition of OHCA by call handlers (p-values < 0.05). CONCLUSIONS: There is a small proportion of calls in which cardiac arrest indicators are described but the call is not dispatched as such. Stricter adherence to dispatch protocols may improve call handlers' OHCA recognition. The existing dispatch protocol would not be improved by the addition of further terms as this would be at the expense of dispatch specificity.

Updating estimates of the number of UK stroke patients eligible for endovascular thrombectomy: incorporating recent evidence to facilitate service planning.

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. 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. 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%. 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. 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.

Evaluation of the enhanced upper limb therapy programme within the Robot-Assisted Training for the Upper Limb after Stroke trial: descriptive analysis of intervention fidelity, goal selection and goal achievement.

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.

Glucagon-like peptide-1 receptor agonists as neuroprotective agents for ischemic stroke: a systematic scoping review.

Stroke mortality and morbidity is expected to rise. Despite considerable recent advances within acute ischemic stroke treatment, scope remains for development of widely applicable neuroprotective agents. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), originally licensed for the management of Type 2 Diabetes Mellitus, have demonstrated pre-clinical neuroprotective efficacy in a range of neurodegenerative conditions. This systematic scoping review reports the pre-clinical basis of GLP-1RAs as neuroprotective agents in acute ischemic stroke and their translation into clinical trials. We included 35 pre-clinical studies, 11 retrospective database studies, 7 cardiovascular outcome trials and 4 prospective clinical studies. Pre-clinical neuroprotection was demonstrated in normoglycemic models when administration was delayed by up to 24 h following stroke induction. Outcomes included reduced infarct volume, apoptosis, oxidative stress and inflammation alongside increased neurogenesis, angiogenesis and cerebral blood flow. Improved neurological function and a trend towards increased survival were also reported. Cardiovascular outcomes trials reported a significant reduction in stroke incidence with semaglutide and dulaglutide. Retrospective database studies show a trend towards neuroprotection. Prospective interventional clinical trials are on-going, but initial indicators of safety and tolerability are favourable. Ultimately, we propose that repurposing GLP-1RAs is potentially advantageous but appropriately designed trials are needed to determine clinical efficacy and cost-effectiveness.