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Objective: To test the hypothesis that imaging signs of 'brain frailty' and acute ischaemia predict clinical outcomes and symptomatic intracranial haemorrhage (sICH) after thrombolysis for acute ischaemic stroke (AIS) in the alteplase dose arm of ENhanced Control of Hypertension ANd Thrombolysis strokE stuDy (ENCHANTED).Methods: Blinded assessors coded baseline images for acute ischaemic signs (presence, extent, swelling and attenuation of acute lesions; and hyperattenuated arteries) and pre-existing changes (atrophy, leucoaraiosis and old ischaemic lesions). Logistic regression models assessed associations between imaging features and death at 7 and 90 days; good recovery (modified Rankin Scale scores 0-2 at 90 days) and sICH. Data are reported with adjusted ORs and 95% CIs.Results: 2916 patients (67±13 years, National Institutes of Health Stroke Scale 8 (5-14)) were included. Visible ischaemic lesions, severe hypoattenuation, large ischaemic lesion, swelling and hyperattenuated arteries were associated with 7-day death (OR (95% CI): 1.52 (1.06 to 2.18); 1.51 (1.01 to 2.18); 2.67 (1.52 to 4.71); 1.49 (1.03 to 2.14) and 2.17 (1.48 to 3.18)) and inversely with good outcome. Severe atrophy was inversely associated with 7-day death (0.52 (0.29 to 0.96)). Atrophy (1.52 (1.08 to 2.15)) and severe leucoaraiosis (1.74 (1.20 to 2.54)) were associated with 90-day death. Hyperattenuated arteries were associated with sICH (1.71 (1.01 to 2.89)). No imaging features modified the effect of alteplase dose.Conclusions: Non-expert-defined brain imaging signs of brain frailty and acute ischaemia contribute to the prognosis of thrombolysis-treated AIS patients for sICH and mortality. However, these imaging features showed no interaction with alteplase dose. [ABSTRACT FROM AUTHOR]

Objective: We performed a systematic review and meta-analysis to determine the association of fluid-attenuated inversion recovery (FLAIR) hyperintense arteries (FLAIR-HAs) on brain MRI and prognosis after acute ischaemic stroke (AIS).Methods: We searched Medline, Embase and Cochrane Central Register of Controlled Trials for studies reporting clinical or imaging outcomes with presence of FLAIR-HAs after AIS. Two researchers independently assessed eligibility of retrieved studies and extracted data, including from the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). Outcomes were unfavourable functional outcome (primary, modified Rankin scale scores 3-6 or 2-6), death, intermediate clinical and imaging outcomes. We performed subgroup analyses by treatment or types of FLAIR-HAs defined by location (at proximal/distal middle cerebral artery (MCA), within/beyond diffusion-weighted imaging (DWI) lesion) or extent.Results: We included 36 cohort studies (33 prospectively collected) involving 3577 patients. FLAIR-HAs were not associated with functional outcome overall (pooled risk ratio 0.87, 95% CI 0.71 to 1.06), but were significantly associated with better outcome in those receiving endovascular therapy (0.56, 95% CI 0.41 to 0.75). Contrary to FLAIR-HAs at proximal MCA or within DWI lesions, FLAIR-HAs beyond DWI lesions were associated with better outcome (0.67, 95% CI 0.57 to 0.79). FLAIR-HAs favoured recanalisation (1.21, 95% CI 1.06 to 1.38) with increased risk of intracerebral haemorrhage (2.07, 95% CI 1.37 to 3.13) and early neurological deterioration (1.93, 95% CI 1.30 to 2.85).Conclusions: FLAIR-HAs were not associated with functional outcome overall but were associated with outcome after endovascular therapy for AIS. FLAIR-HAs were also associated with early recanalisation or haemorrhagic complications, and early neurologic deterioration.Prospero Registration Number: CRD42019131168. [ABSTRACT FROM AUTHOR]

Background and Purpose: Limited data exist on health-related quality of life (HRQoL) after intracerebral haemorrhage (ICH). We aimed to determine baseline factors associated with HRQoL among participants of the pilot and main phases of the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trials (INTERACT 1 and 2).Methods: The INTERACT studies were randomised controlled trials of early intensive blood pressure (BP) lowering in patients with ICH (<6 hours) and elevated systolic BP (150-220 mm Hg). HRQoL was determined using the European Quality of Life Scale (EQ-5D) at 90 days, completed by patients or proxy responders. Binary logistic regression analyses were performed to identify factors associated with poor overall HRQoL.Results: 2756 patients were included. Demographic, clinical and radiological factors associated with lower EQ-5D utility score were age, randomisation outside of China, antithrombotic use, high baseline National Institutes of Health Stroke Scale (NIHSS) score, larger ICH, presence of intraventricular extension and use of proxy responders. High (≥14) NIHSS score, larger ICH and proxy responders were associated with low scores in all five dimensions of the EQ-5D. The NIHSS score had a strong association with poor HRQoL (p<0.001). Female gender and antithrombotic use were associated with decreased scores in dimensions of pain/discomfort and usual activity, respectively.Conclusions: Poor HRQoL was associated with age, comorbidities, proxy source of assessment, clinical severity and ICH characteristics. The strongest association was with initial clinical severity defined by high NIHSS score.Trial Registration Numbers: NCT00226096 and NCT00716079; Post-results. [ABSTRACT FROM AUTHOR]

Background and Purpose: Intraventricular extension of intracerebral haemorrhage (ICH) predicts poor outcome, but the significance of delayed intraventricular haemorrhage (dIVH) is less well defined. We determined the prognostic significance of dIVH in the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trials (INTERACT 1 and 2).Methods: Pooled analyses of the INTERACT CT substudies-international, multicentre, prospective, open, blinded end point, randomised controlled trials of patients with acute spontaneous ICH and elevated systolic blood pressure (SBP)-randomly assigned to intensive (<140 mm Hg) or guideline-based (<180 mm Hg) SBP management. Participants had blinded central analyses of baseline and 24 h CTs, with dIVH defined as new intraventricular haemorrhage (IVH) on the latter scan. Outcomes of death and major disability were defined by modified Rankin Scale scores at 90 days.Results: There were 349 (27%) of 1310 patients with baseline IVH, and 107 (11%) of 961 initially IVH-free patients who developed dIVH. Significant associations of dIVH were prior warfarin anticoagulation, high (≥15) baseline National Institutes of Health Stroke Scale score, larger (≥15 mL) ICH volume, greater ICH growth and higher achieved SBP over 24 h. Compared with those who were IVH-free, dIVH had greater odds of 90-day death or major disability versus initial IVH (adjusted ORs 2.84 (95% CI 1.52 to 5.28) and 1.87 (1.36 to 2.56), respectively (p trend <0.0001)).Conclusions: Although linked to factors determining greater ICH growth including poor SBP control, dIVH is independently associated with poor outcome in acute small to moderate-size ICH.Trial Registration Numbers: NCT00226096 and NCT00716079. [ABSTRACT FROM AUTHOR]

Objective: Antithrombotic agents increase risks of intracerebral haemorrhage (ICH) and associated adverse outcomes. We determined differential effects of early blood pressure (BP) lowering in patients with/without antithrombotic-associated ICH in the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trials (INTERACT1 and 2).Design: Post hoc pooled analyses of the INTERACT studies-international, multicentre, prospective, open, blinded end point trials of patients with ICH (<6 h) and elevated systolic BP (SBP 150-180 mm Hg) randomly assigned to intensive (target SBP <140 mm Hg) or guideline-based (SBP <180 mm Hg) BP management. Associations of antithrombotic use and (1) death or dependency (modified Rankin scale scores 3-6) were analysed using logistic regression, and (2) of increased haematoma+intraventricular haemorrhage volume (IVH) with/without intraventricular haemorrhage (IVH) over 24 h were estimated in analyses of covariance.Results: In all, 3184 patients were included in these analyses. Antithrombotic-associated ICH (364 patients, 11%) was not associated with a significantly increased risk of death or dependency (OR 1.38, 95% CI 0.93 to 2.04). There was no heterogeneity in the BP-lowering treatment effect on death or dependency. Among 1309 patients who underwent follow-up CT after 24 h, absolute increase in haematoma±IVH volume was larger (5.2/5.0 mL) in those with compared to those without prior antithrombotics (2.2/0.9 mL; p=0.022/0.031). Intensive BP lowering reduced haematoma±IVH growth by 4.7/7.1 mL in patients on antithrombotics versus 1.3/1.4 mL in those without, although these differences did not reach statistical significance (p homogeneity=0.104/0.059).Conclusions: In patients with ICH, prior antithrombotic therapy is associated with greater haematoma growth, which may be reduced by early intensive BP-lowering treatment.Trial Registration Number: NCT00226096, NCT00716079. [ABSTRACT FROM AUTHOR]

Introduction: People with mobility limitations can benefit from rehabilitation programmes that provide a high dose of exercise. However, since providing a high dose of exercise is logistically challenging and resourceintensive, people in rehabilitation spend most of the day inactive. This trial aims to evaluate the effect of the addition of affordable technology to usual care on physical activity and mobility in people with mobility limitations admitted to inpatient aged and neurological rehabilitation units compared to usual care alone. Methods and analysis: A pragmatic, assessor blinded, parallel-group randomised trial recruiting 300 consenting rehabilitation patients with reduced mobility will be conducted. Participants will be individually randomised to intervention or control groups. The intervention group will receive technology-based exercise to target mobility and physical activity problems for 6 months. The technology will include the use of video and computer games/exercises and tablet applications as well as activity monitors. The control group will not receive any additional intervention and both groups will receive usual inpatient and outpatient rehabilitation care over the 6-month study period. The coprimary outcomes will be objectively assessed physical activity (proportion of the day spent upright) and mobility (Short Physical Performance Battery) at 6 months after randomisation. Secondary outcomes will include: self-reported and objectively assessed physical activity, mobility, cognition, activity performance and participation, utility-based quality of life, balance confidence, technology self-efficacy, falls and service utilisation. Linear models will assess the effect of group allocation for each continuously scored outcome measure with baseline scores entered as a covariate. Fall rates between groups will be compared using negative binomial regression. Primary analyses will be preplanned, conducted while masked to group allocation and use an intention-to-treat approach. Ethics and dissemination: The protocol has been approved by the relevant Human Research Ethics Committees and the results will be disseminated widely through peer-reviewed publication and conference presentations. [ABSTRACT FROM AUTHOR]

Introduction: Prevention of falls and promotion of physical activity are essential for maximising well-being in older age. However, there is evidence that promoting physical activity among older people without providing fall prevention advice may increase fall rates. This trial aims to establish the impact of a physical activity and fall prevention programme compared with a healthy eating programme on physical activity and falls among people aged 60+ years. Methods and analysis: This cluster randomised controlled trial will involve 60 groups of community-dwelling people aged 60+ years. Participating groups will be randomised to: (1) a physical activity and fall prevention intervention (30 groups), involving written information, fall risk assessment and prevention advice, a pedometer-based physical activity tracker and telephone-based health coaching; or (2) a healthy eating intervention (30 groups) involving written information and telephone-based dietary coaching. Primary outcomes will be objectively measured physical activity at 12 months post-randomisation and self-reported falls throughout the 12-month trial period. Secondary outcomes include: the proportion of fallers, the proportion of people meeting the Australian physical activity guidelines, body mass index, eating habits, mobility goal attainment, mobility-related confidence, quality of life, fear of falling, risk-taking behaviour, mood, well-being, self-reported physical activity, disability, and health and community service use. The between-group difference in the number of falls per person-year will be analysed using negative binomial regression models. For the continuously scored primary and secondary outcome measures, linear regression adjusted for corresponding baseline scores will assess the effect of group allocation. Analyses will be preplanned, conducted while masked to group allocation, will take into account cluster randomisation, and will use an intention-to-treat approach. Ethics and dissemination: Protocol has been approved by the Human Research Ethics Committee at The University of Sydney, Australia (number 2015/517). Results will be disseminated via peer-reviewed journal articles, international conference presentations and participants' newsletters. Trial registration number: ACTRN12615001190594. [ABSTRACT FROM AUTHOR]

Introduction: In low-income and middle-income countries, people with spinal cord injury (SCI) are vulnerable to life-threatening complications after they are discharged from hospital. The aim of this trial is to determine the effectiveness and cost-effectiveness of an inexpensive and sustainable model of community-based care designed to prevent and manage complications in people with SCI in Bangladesh. Methods and analysis: A pragmatic randomised controlled trial will be undertaken. 410 wheelchairdependent people with recent SCI will be randomised to Intervention and Control groups shortly after discharge from hospital. Participants in the Intervention group will receive regular telephonebased care and three home visits from a health professional over the 2 years after discharge. Participants in the Control group will receive standard care, which does not involve regular contact with health professionals. The primary outcome is allcause mortality at 2 years. Recruitment started on 12 July 2015 and the trial is expected to take 5 years to complete. Ethics and dissemination: Ethical approval was obtained from the Institutional Ethics Committee at the site in Bangladesh and from the University of Sydney, Australia. The study will be conducted in compliance with all stipulations of its protocol, the conditions of ethics committee approval, the NHMRC National Statement on Ethical Conduct in Human Research (2007), the Note for Guidance on Good Clinical Practice (CPMP/ICH-135/95) and the Bangladesh Guidance on Clinical Trial Inspection (2011). The results of the trial will be disseminated through publications in peer-reviewed scientific journals and presentations at scientific conferences. [ABSTRACT FROM AUTHOR]

Background and Purpose: Controversy exists over the prognostic significance of the affected hemisphere in stroke. We aimed to determine the relationship between laterality of acute intracerebral haemorrhage (ICH) and poor clinical outcomes.Methods: A subsidiary analysis of the INTERACT Pilot and INTERACT2 studies--randomised controlled trials of patients with spontaneous acute ICH with elevated systolic blood pressure (BP), randomly assigned to intensive (target systolic BP <140 mm Hg) or guideline-based (<180 mm Hg) BP management. Outcomes were the combined and separate end points of death and major disability (modified Rankin scale (mRS) scores of 3-6, 6 and 3-5, respectively) at 90 days.Results: A total of 2708 patients had supratentorial/hemispheric ICH and information on mRS at 90 days. Patients with right hemispheric ICH (1327, 49%) had a higher risk of death at 90 days compared to those with left hemispheric ICH after adjustment for potential confounding variables (OR, 1.77 (95% CI 1.33 to 2.37)). There were no differences between patients with right and left hemispheric ICH regarding the combined end point of death or major disability or major disability in the multivariable-adjusted models (1.07 (0.89 to 1.29) and 0.85 (0.72 to 1.01), respectively).Conclusions: Right hemispheric lesion was associated with increased risk of death in patients with acute ICH. The laterality of the ICH does not appear to affect the level of disability in survivors.Trial Registration Number: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00226096 and NCT00716079. [ABSTRACT FROM AUTHOR]

Presents several correspondence related to medicine. Access to heart surgery for smokers; Guidelines for medical education; Services for elderly people with psychiatric disorder.

Presents correspondence about the National Health Service (NHS) in Great Britain. Implications on performance of circumcision in the NHS; Treatment of the fats in the cell carcinoma; Identification of the malignant melanoma.

Abstract Objectives To determine whether consumer involvement would help to solve some of the ethical problems associated with research into thrombolysis for acute ischaemic stroke, with its inherent risk of fatal intracranial haemorrhage. Design: Quantitative and qualitative research. Setting and participants: Consultation phase: three meetings were held to discuss the planned research, and participants completed a questionnaire. Qualitative work: focus group meetings explored the issues raised during the consultation phase. Design of information leaflets for patients and relatives: trial materials were drafted during the consultation phase and revised in the light of feedback from the focus group meetings and review by patients and carers on a stroke rehabilitation unit. Results: 54 people attended the consultation meetings. Four (9%) participants considered the risks of thrombolysis too great, but most (89%) were prepared to accept the treatment in a clinical trial. Nearly all would accept treatment if it was shown to be effective. Most (85%) would give their consent to enter the planned trial. The focus group meetings and feedback from patients and carers led to significant changes in the information leaflets. The revised trial materials were considered ethical by a national multicentre research ethics committee. Contusions: Consumers generally supported a planned trial, and their involvement helped to refine trial consent procedures and led to an ethically acceptable trial design. [ABSTRACT FROM AUTHOR]

Focuses on the ethical aspect of informed consent in thrombolytic treatment for acute ischemic stroke. Ethical requirements for trials of thrombolytic treatments; Encouraging participation in randomized controlled trials; Conclusions. INSETS: Summary points;Criteria needed to justify trials of thrombolytic treatment...;Information needed for informed consent for a thrombolytic trial.

Objective To report the number of participants needed to recruit per baby born to trial staff during AVERT, a large international trial on acute stroke, and to describe trial management consequences. Design Retrospective observational analysis. Setting 56 acute stroke hospitals in eight countries. Participants 1074 trial physiotherapists, nurses, and other clinicians. Outcome measures Number of babies born during trial recruitment per trial participant recruited. Results With 198 site recruitment years and 2104 patients recruited during AVERT, 120 babies were born to trial staff. Births led to an estimated 10% loss in time to achieve recruitment. Parental eave was linked to six trial site closures. The number of participants needed to recruit per baby born was 17.5 (95% confidence interval 14.7 to 21.0); additional trial costs associated with each birth were estimated at 5736 Australian dollars on average. Conclusion The staff absences registered in AVERT owing to parental leave led to delayed trial recruitment and increased costs. However, the celebration of new life became a highlight of the annual AVERT meetings and helped maintain a cohesive collaborative group. Trial registration Australian New Zealand Clinical Trials Registry no 12606000185561. Disclaimer Participation in a rehabilitation trial does not guarantee successful reproductive activity. [ABSTRACT FROM AUTHOR]

A review is presented of the article "Time to Treatment With Intravenous Alteplase and Outcome in Stroke: An Updated Pooled Analysis of ECASS, ATLANTIS, NINDS, and EPITHET Trials" by K. R. Lees et al., which appeared in a 2010 issue of "The Lancet".

Two letters to the editor are presented in response to the article "Thrombolysis in Very Elderly People: Controlled Comparison of SITS International Stroke Thrombolysis Registry and Virtual International Stroke Trials Archive," by N. K. Mishra and colleagues, published in the 2010 issue.

Objective: We performed a systematic review and meta-analysis to determine the association of fluid-attenuated inversion recovery (FLAIR) hyperintense arteries (FLAIR-HAs) on brain MRI and prognosis after acute ischaemic stroke (AIS)., Methods: We searched Medline, Embase and Cochrane Central Register of Controlled Trials for studies reporting clinical or imaging outcomes with presence of FLAIR-HAs after AIS. Two researchers independently assessed eligibility of retrieved studies and extracted data, including from the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). Outcomes were unfavourable functional outcome (primary, modified Rankin scale scores 3-6 or 2-6), death, intermediate clinical and imaging outcomes. We performed subgroup analyses by treatment or types of FLAIR-HAs defined by location (at proximal/distal middle cerebral artery (MCA), within/beyond diffusion-weighted imaging (DWI) lesion) or extent., Results: We included 36 cohort studies (33 prospectively collected) involving 3577 patients. FLAIR-HAs were not associated with functional outcome overall (pooled risk ratio 0.87, 95% CI 0.71 to 1.06), but were significantly associated with better outcome in those receiving endovascular therapy (0.56, 95% CI 0.41 to 0.75). Contrary to FLAIR-HAs at proximal MCA or within DWI lesions, FLAIR-HAs beyond DWI lesions were associated with better outcome (0.67, 95% CI 0.57 to 0.79). FLAIR-HAs favoured recanalisation (1.21, 95% CI 1.06 to 1.38) with increased risk of intracerebral haemorrhage (2.07, 95% CI 1.37 to 3.13) and early neurological deterioration (1.93, 95% CI 1.30 to 2.85)., Conclusions: FLAIR-HAs were not associated with functional outcome overall but were associated with outcome after endovascular therapy for AIS. FLAIR-HAs were also associated with early recanalisation or haemorrhagic complications, and early neurologic deterioration., Prospero Registration Number: CRD42019131168., Competing Interests: Competing interests: GM reports grants from The Stroke Association. AMD reports personal fees from Medtronic and Daiichi Sankyo (outside the work). JMW reports grants from The Stroke Association and UK Medical Research Council. CSA reports honorarium from Takeda, Boehringer Ingelheim and Amgen., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: Controversy exists over the prognostic significance of the affected hemisphere in stroke. We aimed to determine the relationship between laterality of acute intracerebral haemorrhage (ICH) and poor clinical outcomes., Methods: A subsidiary analysis of the INTERACT Pilot and INTERACT2 studies--randomised controlled trials of patients with spontaneous acute ICH with elevated systolic blood pressure (BP), randomly assigned to intensive (target systolic BP <140 mm Hg) or guideline-based (<180 mm Hg) BP management. Outcomes were the combined and separate end points of death and major disability (modified Rankin scale (mRS) scores of 3-6, 6 and 3-5, respectively) at 90 days., Results: A total of 2708 patients had supratentorial/hemispheric ICH and information on mRS at 90 days. Patients with right hemispheric ICH (1327, 49%) had a higher risk of death at 90 days compared to those with left hemispheric ICH after adjustment for potential confounding variables (OR, 1.77 (95% CI 1.33 to 2.37)). There were no differences between patients with right and left hemispheric ICH regarding the combined end point of death or major disability or major disability in the multivariable-adjusted models (1.07 (0.89 to 1.29) and 0.85 (0.72 to 1.01), respectively)., Conclusions: Right hemispheric lesion was associated with increased risk of death in patients with acute ICH. The laterality of the ICH does not appear to affect the level of disability in survivors., Trial Registration Number: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00226096 and NCT00716079., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)