Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Rehabilitation using virtual gaming for Hospital and hOMe-Based training for the Upper limb post Stroke (RHOMBUS II): protocol of a feasibility randomised controlled trial

Introduction Upper limb (UL) rehabilitation is most effective early after stroke, with higher doses leading to improved outcomes. For the stroke survivor, the repetition may be monotonous. For clinicians, providing a clinically meaningful level of input can be challenging. As such, time spent engaged in UL activity among subacute stroke survivors remains inadequate. Opportunities for the stroke survivor to engage with UL rehabilitation in a safe, accessible and engaging way are essential to improving UL outcomes following stroke. The NeuroBall is a non-immersive virtual reality (VR) digital system designed for stroke rehabilitation, specifically for the arm and hand. The aim of the Rehabilitation using virtual gaming for Hospital and hOMe-Based training for the Upper limb post Stroke study is to determine the safety, feasibility and acceptability of the NeuroBall as a rehabilitation intervention for the UL in subacute stroke. Methods and analysis A feasibility randomised controlled trial (RCT) will compare the NeuroBall plus usual care with usual care only, in supporting UL rehabilitation over 7 weeks. Twenty-four participants in the subacute poststroke phase will be recruited while on the inpatient or early supported discharge (ESD) stroke pathway. Sixteen participants will be randomised to the intervention group and eight to the control group. Outcomes assessed at baseline and 7 weeks include gross level of disability, arm function, spasticity, pain, fatigue and quality of life (QoL). Safety will be assessed by recording adverse events and using pain, spasticity and fatigue scores. A parallel process evaluation will assess feasibility and acceptability of the intervention. Feasibility will also be determined by assessing fidelity to the intervention. Postintervention, semistructured interviews will be used to explore acceptability with 12 participants from the intervention group, four from the usual care group and with up to nine staff involved in delivering the intervention. Ethics and dissemination This trial has ethical approval from Brunel University London’s Research Ethics Committee 25257-NHS-Oct/2020-28121-2 and the Wales Research Ethics Committee 5 Bangor (Health and Care Research Wales) REC ref: 20/WA/0347. The study is sponsored by Brunel University London. Contact: Dr Derek Healy, Chair, University Research Ethics committee ([email protected]). Trial results will be submitted for publication in peer-reviewed journals, presented at national and international conferences and distributed to people with stroke. Trial registration number ISRCTN11440079; Pre-results

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Global, regional, and national burden of traumatic brain injury and spinal cord injury, 1990–2016: A systematic analysis for the Global Burden of Disease Study 2016

© 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Background: Traumatic brain injury (TBI) and spinal cord injury (SCI) are increasingly recognised as global health priorities in view of the preventability of most injuries and the complex and expensive medical care they necessitate. We aimed to measure the incidence, prevalence, and years of life lived with disability (YLDs) for TBI and SCI from all causes of injury in every country, to describe how these measures have changed between 1990 and 2016, and to estimate the proportion of TBI and SCI cases caused by different types of injury. Methods: We used results from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2016 to measure the global, regional, and national burden of TBI and SCI by age and sex. We measured the incidence and prevalence of all causes of injury requiring medical care in inpatient and outpatient records, literature studies, and survey data. By use of clinical record data, we estimated the proportion of each cause of injury that required medical care that would result in TBI or SCI being considered as the nature of injury. We used literature studies to establish standardised mortality ratios and applied differential equations to convert incidence to prevalence of long-term disability. Finally, we applied GBD disability weights to calculate YLDs. We used a Bayesian meta-regression tool for epidemiological modelling, used cause-specific mortality rates for non-fatal estimation, and adjusted our results for disability experienced with comorbid conditions. We also analysed results on the basis of the Socio-demographic Index, a compound measure of income per capita, education, and fertility. Findings: In 2016, there were 27·08 million (95% uncertainty interval [UI] 24·30–30·30 million) new cases of TBI and 0·93 million (0·78–1·16 million) new cases of SCI, with age-standardised incidence rates of 369 (331–412) per 100 000 population for TBI and 13 (11–16) per 100 000 for SCI. In 2016, the number of prevalent cases of TBI was 55·50 million (53·40–57·62 million) and of SCI was 27·04 million (24·98–30·15 million). From 1990 to 2016, the age-standardised prevalence of TBI increased by 8·4% (95% UI 7·7 to 9·2), whereas that of SCI did not change significantly (−0·2% [–2·1 to 2·7]). Age-standardised incidence rates increased by 3·6% (1·8 to 5·5) for TBI, but did not change significantly for SCI (−3·6% [–7·4 to 4·0]). TBI caused 8·1 million (95% UI 6·0–10·4 million) YLDs and SCI caused 9·5 million (6·7–12·4 million) YLDs in 2016, corresponding to age-standardised rates of 111 (82–141) per 100 000 for TBI and 130 (90–170) per 100 000 for SCI. Falls and road injuries were the leading causes of new cases of TBI and SCI in most regions. Interpretation: TBI and SCI constitute a considerable portion of the global injury burden and are caused primarily by falls and road injuries. The increase in incidence of TBI over time might continue in view of increases in population density, population ageing, and increasing use of motor vehicles, motorcycles, and bicycles. The number of individuals living with SCI is expected to increase in view of population growth, which is concerning because of the specialised care that people with SCI can require. Our study was limited by data sparsity in some regions, and it will be important to invest greater resources in collection of data for TBI and SCI to improve the accuracy of future assessments. Funding: Bill & Melinda Gates Foundation

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

BACKGROUND: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. METHODS: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). FINDINGS: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29-146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0- 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25-1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39-1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65-1·60]; p=0·92). INTERPRETATION: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention. FUNDING: British Heart Foundation

124 The Use of Simulation in Improving Stroke Recognition, Assessment and Management

Stroke remains the second leading cause of death worldwide and an important diagnosis requiring early recognition and action for optimal clinical outcomes which are time dependent The aim of the course was to inform about the local stroke pathways, ensure juniors are comfortable with recognition of stroke and to develop the non-technical skills required in stroke management, thus enabling skill acquisition in a safe environment.An innovative course was created using SimMan 3G with a focus on ensuring high fidelity to overcome the limitations associated with the practical aspect of stroke assessment in a mannequin. Five scenarios were created to last 15 minutes: three of which involved acute stroke diagnosis and two about stroke ‘mimics’. These scenarios included the involvement of a junior doctor, an acting nurse and acting members of the multi-disciplinary team as required. The debrief following each scenario would cover the technical aspects of management and self and group reflections. To add to the fidelity when assessing a mannequin for neurological conditions, we ensured that slurred speech could be mimicked, weakness in the limbs was showcased and facial asymmetry represented with innovative techniques using the mannequin.Two sessions have been delivered involving nine junior doctors and this has been implemented as a regular course for junior doctors and nurses. All attendees felt more confident with stroke recognition, awareness of stroke mimics and of the local pathways when managing patients with acute stroke.The positive feedback received and the outcome that all attendees felt more confident following the course suggest that stroke recognition and management can be learnt using simulation with a focus on the human factors required to optimize patient care. We hope to continue delivering this course to junior doctors rotating through the hospital and hope to open it up to the wider multi-disciplinary team including nursing staff, healthcare assistants and therapists with a focus on recognition and escalation. Dissemination of learning on local pathways and management using simulation is effective and can impact patient care.</jats:p

Rehabilitation using virtual gaming for Hospital and hOMe-Based training for the Upper limb post Stroke (RHOMBUS II): protocol of a feasibility randomised controlled trial

IntroductionUpper limb (UL) rehabilitation is most effective early after stroke, with higher doses leading to improved outcomes. For the stroke survivor, the repetition may be monotonous. For clinicians, providing a clinically meaningful level of input can be challenging. As such, time spent engaged in UL activity among subacute stroke survivors remains inadequate. Opportunities for the stroke survivor to engage with UL rehabilitation in a safe, accessible and engaging way are essential to improving UL outcomes following stroke. The NeuroBall is a non-immersive virtual reality (VR) digital system designed for stroke rehabilitation, specifically for the arm and hand. The aim of the Rehabilitation using virtual gaming for Hospital and hOMe-Based training for the Upper limb post Stroke study is to determine the safety, feasibility and acceptability of the NeuroBall as a rehabilitation intervention for the UL in subacute stroke.Methods and analysisA feasibility randomised controlled trial (RCT) will compare the NeuroBall plus usual care with usual care only, in supporting UL rehabilitation over 7 weeks. Twenty-four participants in the subacute poststroke phase will be recruited while on the inpatient or early supported discharge (ESD) stroke pathway. Sixteen participants will be randomised to the intervention group and eight to the control group. Outcomes assessed at baseline and 7 weeks include gross level of disability, arm function, spasticity, pain, fatigue and quality of life (QoL). Safety will be assessed by recording adverse events and using pain, spasticity and fatigue scores. A parallel process evaluation will assess feasibility and acceptability of the intervention. Feasibility will also be determined by assessing fidelity to the intervention. Postintervention, semistructured interviews will be used to explore acceptability with 12 participants from the intervention group, four from the usual care group and with up to nine staff involved in delivering the intervention.Ethics and disseminationThis trial has ethical approval from Brunel University London’s Research Ethics Committee 25257-NHS-Oct/2020-28121-2 and the Wales Research Ethics Committee 5 Bangor (Health and Care Research Wales) REC ref: 20/WA/0347. The study is sponsored by Brunel University London. Contact: Dr Derek Healy, Chair, University Research Ethics committee ([email protected]). Trial results will be submitted for publication in peer-reviewed journals, presented at national and international conferences and distributed to people with stroke.Trial registration numberISRCTN11440079; Pre-results.</jats:sec

Rapid automated quantification of cerebral leukoaraiosis on CT images:A Multicenter Validation Study

Purpose - To validate a fully-automated, machine-learning method (random forest) for segmenting cerebral white matter lesions (WML) on computerized tomography (CT). Materials and Methods – A retrospective sample of 1082 acute ischemic stroke cases was obtained, comprising unselected patients: 1) treated with thrombolysis; or 2) undergoing contemporaneous MR imaging and CT; and 3) a subset of IST-3 trial participants. Automated (‘Auto’) WML images were validated relative to experts’ manual tracings on CT, and co-registered FLAIR-MRI; and ratings using two conventional ordinal scales. Analyses included correlations between CT and MR imaging volumes, and agreements between Auto and expert ratings. Results - Auto WML volumes correlated strongly with expert-delineated WML volumes on MR imaging and on CT (r2=0.85, 0.71 respectively; p0.05). Auto preprocessing failure rate was 4%; rating errors occurred in a further 4%. Total Auto processing time averaged 109s (range: 79 - 140 s). Conclusion - An automated method for quantifying CT cerebral white matter lesions achieves a similar accuracy to experts in unselected and multicenter cohorts