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Evidence-based decisions on clinical and cost-effectiveness of interventions are ideally informed by meta-analyses of intervention trial data. However, when undertaken, such meta-analyses in ageing research have typically been conducted using standard methods whereby summary (aggregate) data are extracted from published trial reports. Although meta-analysis of aggregate data can provide useful insights into the average effect of interventions within a selected trial population, it has limitations regarding robust conclusions on which subgroups of people stand to gain the greatest benefit from an intervention or are at risk of experiencing harm. Future evidence synthesis using individual participant data from ageing research trials for meta-analysis could transform understanding of the effectiveness of interventions for older people, supporting evidence-based and sustainable commissioning. A major advantage of individual participant data meta-analysis (IPDMA) is that it enables examination of characteristics that predict treatment effects, such as frailty, disability, cognitive impairment, ethnicity, gender and other wider determinants of health. Key challenges of IPDMA relate to the complexity and resources needed for obtaining, managing and preparing datasets, requiring a meticulous approach involving experienced researchers, frequently with expertise in designing and analysing clinical trials. In anticipation of future IPDMA work in ageing research, we are establishing an international Ageing Research Trialists collective, to bring together trialists with a common focus on transforming care for older people as a shared ambition across nations.

Rationale: The evidence base for acute post-stroke rehabilitation is inadequate and global guideline recommendations vary. Aim: To define optimal early mobility intervention regimens for ischemic stroke patients of mild and moderate severity. Hypotheses: Compared with a prespecified reference arm, the optimal dose regimen(s) will result in more participants experiencing little or no disability (mRS 0–2) at 3 months post-stroke (primary), fewer deaths at 3 months, fewer and less severe complications during the intervention period, faster recovery of unassisted walking, and better quality of life at 3 months (secondary). We also hypothesize that these regimens will be more cost-effective. Sample size estimates: For the primary outcome, recruitment of 1300 mild and 1400 moderate participants will yield 80% power to detect a 10% risk difference. Methods and design: Multi-arm multi-stage covariate-adjusted response-adaptive randomized trial of mobility training commenced within 48 h of stroke in mild (NIHSS 2) and hemorrhagic stroke. With four arms per stratum (reference arm retained throughout), only the single treatment arm demonstrating the highest proportion of favorable outcomes at the first stage will proceed to the second stage in each stratum, resulting in a final comparison with the reference arm. Three prognostic covariates of age, geographic region and reperfusion interventions, as well as previously observed mRS 0–2 responses inform the adaptive randomization procedure. Participants randomized receive prespecified mobility training regimens (functional task-specific), provided by physiotherapists/nurses until discharge or 14 days. Interventions replace usual mobility training. Fifty hospitals in seven countries (Australia, Malaysia, United Kingdom, Ireland, India, Brazil, Singapore) are expected to participate. Summary: Our novel adaptive trial design will evaluate a wider variety of mobility regimes than a traditional two-arm design. The data-driven adaptions during the trial will enable a more efficient evaluation to determine the optimal early mobility intervention for patients with mild and moderate ischemic stroke.

Background Solitary Rectal Ulcer Syndrome (SRUS) is an important but often delayed diagnosis with a prevalence of 1:100,000 people per year. It is rare in children. Manifestations include rectal bleeding, pain, tenesmus and, occasionally, rectal prolapse. 26% are asymptomatic. Classically, sigmoidoscopy reveals ulceration within 10cm of the anus and histology demonstrates mucosal layer thickening with crypt distortion and lamina propria fibromuscular obliteration. It is, however, a misnomer as only 20% have a solitary ulcer with the remainder have lesions ranging from hyperemic mucosa through to broad based polypoid lesions. It’s not uncommon that patients are initially misdiagnosed as constipation or inflammatory bowel disease (IBD). The mainstay of treatment includes biofeedback though some patients require surgery for rectal prolapse. Whilst the aetiology of SRUS remains unclear hypothesised causes include ineffective straining and/or uncoordinated puborectalis contraction increasing intra-rectal pressure and causing ischaemic ulceration or local vascular trauma due to intussusception. Objectives To highlight awareness of SRUS and how it can mimic constipation and IBD. Methods A 9 year old female patient presented with apparent constipation, resistant to laxatives. Initial abdominal pain and passage of a type 2 stool weekly progressed to rectal bleeding and passage of mucus. A later more in depth history also identified straining and tenesmus. Over several months she was treated with escalating doses of Movicol, Sodium Picosulfate, Liquid Paraffin and Klean Prep. Treatment compliance was an issue initially. Ileocolonoscopy with rectal retroflexion detected a macroscopic solitary rectal ulcer and only isolated diffuse rectal inflammation on histology. Her faecal calprotectin was normal. A diagnosis of inflammatory bowel disease was questioned but treatment with Mesalazine foam enemas was unhelpful. She also developed dysfunctional voiding during the course of treatment with significant bladder retention. Non-compliance with intermittent catheterisation due to significant anxiety led to insertion of a suprapubic catheter. Further investigation with a colonic transit study was performed due to her ongoing requirement for high dose laxatives and found markers pooled in the rectum. A diagnosis of rectal dyssynergia/dysfunctional elimination was reached. She responded to suppositories which later weaned following successful use of Botulinum toxin despite her anorectal manometry not showing high resting pressures. Results SRUS is an important comorbidity in children presenting with constipation on a background of rectal dyssynergia/dysfunctional elimination. Our patient’s significant anxiety has contributed to her dysfunctional elimination and she has ongoing CAMHS involvement so that biofeedback can be initiated. The absence of conclusive histology perhaps delayed a diagnosis being reached and her initial non-compliance with treatment was likely to be a significant contributing factor too. The key to diagnosis here was reviewing her histology in the context of her initial presenting features including passage of blood and mucus alongside straining and tenesmus. Conclusions Whilst SRUS is a relatively uncommon diagnosis seen in the paediatric population, good history taking and consideration of clinical features is key to its diagnosis, even if histology is not confirmatory.

Made available in DSpace on 2019-10-04T12:41:37Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-07-02 National Health and Medical Research Council of Australia Background-The uptake of proven stroke treatments varies widely. We aimed to determine the association of evidence-based processes of care for acute ischemic stroke (AIS) and clinical outcome of patients who participated in the HEADPOST (Head Positioning in Acute Stroke Trial), a multicenter cluster crossover trial of lying flat versus sitting up, head positioning in acute stroke. Methods and Results-Use of 8 AIS processes of care were considered: reperfusion therapy in eligible patients; acute stroke unit care; antihypertensive, antiplatelet, statin, and anticoagulation for atrial fibrillation; dysphagia assessment; and physiotherapist review. Hierarchical, mixed, logistic regression models were performed to determine associations with good outcome (modified Rankin Scale scores 0-2) at 90 days, adjusted for patient and hospital variables. Among 9485 patients with AIS, implementation of all processes of care in eligible patients, or defect-free care, was associated with improved outcome (odds ratio, 1.40; 95% CI, 1.18-1.65) and better survival (odds ratio, 2.23; 95% CI, 1.62-3.09). Defect-free stroke care was also significantly associated with excellent outcome (modified Rankin Scale score 0-1) (odds ratio, 1.22; 95% CI, 1.04-1.43). No hospital characteristic was independently predictive of outcome. Only 1445 (15%) of eligible patients with AIS received all processes of care, with significant regional variations in overall and individual rates. Conclusions-Use of evidence-based care is associated with improved clinical outcome in AIS. Strategies are required to address regional variation in the use of proven AIS treatments. Univ New South Wales, Fac Med, George Inst Global Hlth, Sydney, NSW, Australia Ctr Estudios Clin, Inst Ciencias & Innovac Med, Santiago, Chile Clin Alemana Univ Desarrollo, Fac Med, Serv Neurol, Dept Neurol & Psiquiatria, Santiago, Chile Peking Univ, Hlth Sci Ctr, George Inst Global Hlth, Beijing, Peoples R China Australian Catholic Univ, Nursing Res Inst, St Vincents Hlth Australia Sydney, Sydney, NSW, Australia Univ Cent Lancashire, Fac Hlth & Wellbeing, Preston, Lancs, England Univ Chile, Fac Med, Dept Ciencias Neurol, Santiago, Chile Univ Sao Paulo, Ribeirao Preto Med Sch, Stroke Serv Neurol Div, Ribeirao Preto, Brazil Fukuoka Univ, Fac Med, Dept Prevent Med & Publ Hlth, Fukuoka, Fukuoka, Japan Univ Leicester, Dept Cardiovasc Sci, Leicester Biomed Res Ctr, Leicester, Leics, England Univ Leicester, Natl Inst Hlth Res, Leicester Biomed Res Ctr, Leicester, Leics, England Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh, Midlothian, Scotland George Inst Global Hlth, Sydney, NSW, Australia Univ Desarrollo, Serv Neurol, Dept Neurol & Psiquiatria Clin Alemana Santiago, Santiago, Chile St Vincents Hlth Australia Sydney, Sydney, NSW, Australia Australian Catholic Univ, Sydney, NSW, Australia Univ Cent Lancashire, Stroke Practice Res Unit, Sch Hlth, Lancashire Clin Trials Unit, Preston, Lancs, England Univ Leicester, Dept Cardiovasc Sci, Cardiovasc Res Ctr, British Heart Fdn, Leicester, Leics, England Univ Kelaniya, Dept Pharmacol, Fac Med, Colombo, Sri Lanka Christian Med Coll & Hosp, Dept Neurol, Ludhiana, India Kaohsiung Med Univ & Hosp, Dept Neurol, Kaohsiung, Taiwan Linkou Chang Gung Mem Hosp, Dept Neurol, Taipei, Taiwan Peking Union Med Coll Hosp, Beijing, Peoples R China Univ Sao Paulo, Ribeirao Preto Sch Med, Ribeirao Preto, Brazil Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic, Australia Univ Cent Lancashire, Sch Hlth Sci, Coll Hlth & Wellbeing, Preston, Lancs, England Univ Desarrollo, Santiago, Chile Univ New South Wales, Neurosci Res Australia, Sydney, NSW, Australia Natl Univ Singapore, Dept Pharmacol, Singapore, Singapore Bradford Royal Infirm, Bradford Inst Hlth Res, Leeds, W Yorkshire, England Christian Med College, Ludhiana, Punjab, India RemediumOne Pvt Ltd, Kandy, Sri Lanka Kaohsiung Med Univ, Chung Ho Mem Hosp, Kaohsiung, Taiwan Calvary Publ Hosp Bruce, Bruce, Australia Royal North Shore Hosp, St Leonards, NSW, Australia Royal Prince Alfred Hosp, Camperdown, NSW, Australia Concord Repatriat Gen Hosp, Camperdown, NSW, Australia Fiona Stanley Hosp, Camperdown, NSW, Australia Macquarie Base Hosp, Melbourne, Vic, Australia Univ Sao Paulo, Fac Med Ribeirao Preto, Hosp Clin, Sao Paulo, Brazil Hosp Governador Celso Ramos, Florianopolis, SC, Brazil Sao Paulo State Univ, Hosp Fac Med Botucatu, UNESP, Sao Paulo, Brazil Yangquan Coalmine Grp Gen Hosp, Yangquan, Peoples R China Nanjing Med Univ, Nanjing Hosp 1, Nanjing, Jiangsu, Peoples R China 85 Hosp Peoples Liberat Army, Beijing, Peoples R China Chifeng Univ, Affiliated Hosp, Chifeng, Peoples R China Beijing Pinggu Hosp, Beijing, Peoples R China Wenzhou Med Univ, Affiliated Hosp 1, Wenzhou, Peoples R China Soochow Univ, Affiliated Hosp 2, Suzhou, Peoples R China Hebei Med Univ, Hosp 3, Shijiazhuang, Hebei, Peoples R China Capital Med Univ, Xuanwu Hosp, Beijing, Peoples R China Jining Med Univ, Affiliated Hosp, Jining, Peoples R China Third Peoples Hosp Huizhou, Huizhou, Peoples R China Second Cangzhou Cent Hosp, Cangzhou, Peoples R China Shanghai Jiao Tong Univ, Hosp Affiliated, Sch Med, Shanghai, Peoples R China Baogang Hosp, Baotou, Peoples R China Harbin Med Univ, Affiliated Hosp 1, Harbin, Heilongjiang, Peoples R China Shanghai Jiao Tong Univ Sch, Tong Ren Hosp, Peoples Hosp Hejian City, Shanghai, Peoples R China Peking Univ, Shougang Hosp, Beijing, Peoples R China Guangzhou Med Univ, Affiliated Hosp 3, Guangzhou, Guangdong, Peoples R China Second Hosp Nanchang, Nanchang, Jiangxi, Peoples R China Bethune Int Peace Hosp, Beijing, Peoples R China Hua Henan Prov Peoples Hosp, Beijing, Peoples R China Hua Henan Prov Peoples Hosp, Zhengzhou, Henan, Peoples R China Shanghai Jiao Tong Univ, Sch Med, Shanghai Ninth Peoples Hosp, Shanghai, Peoples R China Shijiazhuang Cent Hosp, Shijiazhuang, Hebei, Peoples R China Hosp Base San Jos de Osorno, Osorno, Chile Christian Med Coll & Hosp, Ludhiana, Punjab, India Unit Narayana Hrudayalaya Ltd, Mazumdar Shaw Med Ctr, Bangalore, Karnataka, India Dr Ramesh Cardiac & Multispecial Hosp Pvt Ltd, Guntur, India Post Grad Inst Med Educ & Res, Chandigarh, India Baby Mem Hosp Ltd, Calicut, Kerala, India Sree Chitra Tirunal Inst Med Sci & Technol, Thiruvananthapuram, Kerala, India Sri Jayawardenepura Gen Hosp, Sri Jayawardenepura Kott, Sri Lanka Colombo North Teaching Hosp, Colombo, Sri Lanka Colombo South Coching Hosp, Colombo, Sri Lanka Linkou Chang Gung Mem Hosp, Taoyuan, Taiwan Taipei Med Univ, Shuang Ho Hosp, Taipei, Taiwan En Chu Kong Hosp, New Taipei, Taiwan Natl Cheng Kung Univ Hosp, Tainan, Taiwan Queen Alexandra Hosp, Portsmouth, Hants, England Portsmouth Hosp NHS Natl Hlth Serv iTrust, Portsmouth, Hants, England Univ Coll London Hosp NHS Fdn Trust, London, England Univ Hosp Birmingham NHS Fdn Trust, Queen Elizabeth Hosp Birmingham, Birmingham, W Midlands, England Southend Univ Hosp NHS Fdn Trust, Southend On Sea, England Kings Coll Hosp London, London, England York Teaching Hosp NHS Fdn Trust, York, N Yorkshire, England Nottingham Univ Hosp NHS Trust, Nottingham, England Blackpool Teaching Hosp NHS Fdn Trust, Blackpool, England Gloucestershire Hosp NHS Fdn Trust, Gloucestershire Royal Hosp, Gloucester, England Teaching Hospi NHS Fdn Trust, London, England Royal Cornwall Hosp NHS Trust, Truro, England Royal London Hosp, Barts Hlth NHS Trust, London, England Sheffield Teaching Hosp NHS Fdn Trust, Sheffield, S Yorkshire, England Cambridge Univ Hosp NHS Fdn Trust, Addenbrookes Hosp, Cambridge, England Royal Victoria Hosp, Belfast Hlth & Social Care Trust, London, England Pinderfields Gen Hosp, Mid Yorkshire Hosp NHS Trust, Wakefield, England Royal Devon & Exeter NHS Fdn Trust, London, England Bradford Teaching Hosp NHS Fdn Trust, Bradford, W Yorkshire, England Great Western Hosp NHS Fdn Trust, Swindon, Wilts, England Watford Dist Gen Hosp, Watford, England Imperial Coll Healthcare NHS Trust, London, England Medway NHS Fdn Trust, Gillingham, England Royal Liverpool & Broadgreen Univ NHS Trust, Liverpool, Merseyside, England Calderdale & Huddersfield NHS Fdn Trust, Huddersfield, W Yorkshire, England Hywel Dda Univ Hlth Board, Haverfordwest, Wales Chesterfield Royal Hosp NHS Fdn Trust, Calow, England Luton & Dunstable Univ Hosp NHS Fdn Trust, Luton, Beds, England Countess Chester Hosp NHS Fdn Trust, Chester, Cheshire, England Peterborough City Hosp, Peterborough, Cambs, England Univ Hosp Leicester NHS Trust, Leicester Royal Infirm, Leicester, Leics, England Dist Hosp NHS Fdn Trust, London, England Barnsley Hosp NHS Fdn Trust, Barnsley, England Dorset Cty Hosp NHS Fdn Trust, Dorchester, England Royal Bournemouth & Christchurch Hosp NHS Fdn Tru, Royal Bournemouth Hosp, Bournemouth, Dorset, England Southern Hlth & Social Care Trust, Craigavon Area Hosp, Portadown, England United Lincolnshire Hosp NHS Trust, Pilgrim Hosp, Lincoln, England Bedford Hosp NHS Trust, Bedford, England Sao Paulo State Univ, Hosp Fac Med Botucatu, UNESP, Sao Paulo, Brazil National Health and Medical Research Council of Australia: 1066966

Our prespecified dose-response analyses of A Very Early Rehabilitation Trial (AVERT) aim to provide practical guidance for clinicians on the timing, frequency, and amount of mobilization following acute stroke.Eligible patients were aged ≥18 years, had confirmed first (or recurrent) stroke, and were admitted to a stroke unit within 24 hours of stroke onset. Patients were randomized to receive very early and frequent mobilization, commencing within 24 hours, or usual care. We used regression analyses and Classification and Regression Trees (CART) to investigate the effect of timing and dose of mobilization on efficacy and safety outcomes, irrespective of assigned treatment group.A total of 2,104 patients were enrolled, of whom 2,083 (99.0%) were followed up at 3 months. We found a consistent pattern of improved odds of favorable outcome in efficacy and safety outcomes with increased daily frequency of out-of-bed sessions (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.09 to 1.18, p0.001), keeping time to first mobilization and mobilization amount constant. Increased amount (minutes per day) of mobilization reduced the odds of a good outcome (OR 0.94, 95% CI 0.91 to 0.97, p0.001). Session frequency was the most important variable in the CART analysis, after prognostic variables age and baseline stroke severity.These data suggest that shorter, more frequent mobilization early after acute stroke is associated with greater odds of favorable outcome at 3 months when controlling for age and stroke severity.This study provides Class III evidence that shorter, more frequent early mobilization improves the chance of regaining independence after stroke.

Item does not contain fulltext OBJECTIVES: To investigate the effects of intensive blood pressure (BP) lowering according to baseline BP levels and optimal achieved BP levels in patients with acute intracerebral hemorrhage (ICH). METHODS: INTERACT2 was an open, blinded endpoint, randomized controlled trial in 2,839 patients with ICH within 6 hours of onset and elevated systolic BP (SBP) (150-220 mm Hg) who were allocated to receive intensive (target SBP /=190 mm Hg (p homogeneity = 0.790). Analyses of achieved BP showed linear increases in the risk of physical dysfunction for achieved SBP above 130 mm Hg for both hyperacute (1-24 hours) and acute (2-7 days) phases while modest increases were also observed for achieved SBP below 130 mm Hg. CONCLUSIONS: Intensive BP lowering appears beneficial across a wide range of baseline SBP levels, and target SBP level of 130-139 mm Hg is likely to provide maximum benefit in acute ICH. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that the effect of intensive BP lowering on physical function is not influenced by baseline BP.

The biblical accounts of seeing (and hearing) God are mixed in kind, but the clear assumption of most traditions is that no one can, in fact, see God. There was consistency in this respect with the results of a recent survey of Winchester churchgoers’ perceptions of God, which also produced one or two surprises. Seeing (and hearing) God is a matter of interpretation, and has much in common with signs and analogies.

Contains fulltext : 167926.PDF (Publisher’s version ) (Open Access) BACKGROUND: Rates of acute intracerebral hemorrhage (ICH) increase in winter months but the magnitude of risk is unknown. We aimed to quantify the association of ambient temperature with the risk of ICH in the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT2) participants on an hourly timescale. METHODS: INTERACT2 was an international, open, blinded endpoint, randomized controlled trial of patients with spontaneous ICH (

Item does not contain fulltext OBJECTIVES: To determine the association of hyponatremia at presentation with clinical and imaging outcomes in patients with acute intracerebral hemorrhage. DESIGN: Retrospective pooled analysis of prospectively collected data from 3,243 participants of the pilot and main phases of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trials 1 and 2 (international, multicenter, open, blinded endpoint, randomized controlled trials designed to assess the effects of early intensive blood pressure lowering in patients with acute intracerebral hemorrhage). SETTING: Clinical hospital sites in 21 countries. PATIENTS: Patients with predominantly mild-moderate severity of spontaneous intracerebral hemorrhage within 6 hours of onset and elevated systolic blood pressure (150-220 mm Hg) were included in the study. INTERVENTIONS: Patients were assigned to receive intensive (target systolic blood pressure, < 140 mm Hg within 1 hr) or guideline-recommended (target systolic blood pressure, < 180 mm Hg) blood pressure-lowering therapy. MEASUREMENTS AND MAIN RESULTS: Presentation hyponatremia was defined as serum sodium less than 135 mEq/L. The primary outcome was death at 90 days. Multivariable logistic regression was used to assess the association of hyponatremia with important clinical events. Of 3,002 patients with available data, 349 (12%) had hyponatremia. Hyponatremia was associated with death (18% vs 11%; multivariable-adjusted odds ratio, 1.81; 95% CI, 1.28-2.57; p < 0.001) and larger baseline intracerebral hemorrhage volume (multivariable adjusted, p = 0.046) but not with baseline perihematomal edema volume nor with growth of intracerebral hemorrhage or perihematomal edema during the initial 24 hours. CONCLUSIONS: Hyponatremia at presentation is associated with increased mortality in patients with predominantly deep and modest volume intracerebral hemorrhage through mechanisms that seem independent of growth in intracerebral hemorrhage or perihematomal edema.

Objective: To investigate whether the location and extent of the CT hyperdense artery sign (HAS) at presentation affects response to IV alteplase in the randomized controlled Third International Stroke Trial (IST-3). Methods: All prerandomization and follow-up (24–48 hours) CT brain scans in IST-3 were assessed for HAS presence, location, and extent by masked raters. We assessed whether HAS grew, persisted, shrank, or disappeared at follow-up, the association with 6-month functional outcome, and effect of alteplase. IST-3 is registered (ISRCTN25765518). Results: HAS presence (vs absence) independently predicted poor 6-month outcome (increased Oxford Handicap Scale [OHS]) on adjusted ordinal regression analysis (odds ratio [OR] 0.66, p < 0.001). Outcome was worse in patients with more (vs less) extensive HAS (OR 0.61, p = 0.027) but not in proximal (vs distal) HAS (p = 0.420). Increasing age was associated with more HAS growth at follow-up (OR 1.01, p = 0.013). Treatment with alteplase increased HAS shrinkage/disappearance at follow-up (OR 0.77, p = 0.006). There was no significant difference in HAS shrinkage with alteplase in proximal (vs distal) or more (vs less) extensive HAS (p = 0.516 and p = 0.580, respectively). There was no interaction between presence vs absence of HAS and benefit of alteplase on 6-month OHS (p = 0.167). Conclusions: IV alteplase promotes measurable reduction in HAS regardless of HAS location or extent. Alteplase increased independence at 6 months in patients with and without HAS. Classification of evidence: This study provides Class I evidence that for patients within 6 hours of ischemic stroke with a CT hyperdense artery sign, IV alteplase reduced intra-arterial hyperdense thrombus.

Background: This study aimed at identifying the determinants and prognostic significance of a sedimentation level (fluid-blood level) in the hematoma among patients with acute intracerebral hemorrhage (ICH) who participated in the main Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2). Methods: Post-hoc analysis of the INTERACT2 dataset, a randomized controlled trial of patients with acute ICH with elevated systolic blood pressure (SBP), randomly assigned to intensive (target SBP Results: Of 2,065 participants, 19 (1%) had sedimentation level on baseline CT, which was independently associated with warfarin use (p = 0.006) and lobar ICH (p = 0.025). Sedimentation level was also associated with death or major disability at 90-day in both crude (84 vs. 53%; p = 0.014) and multivariable analyses adjusted for age, gender, Chinese region, warfarin use, baseline National Institutes of Health Stroke Scale score, onset to CT time, volume and location of ICH, intraventricular extension, and randomized intensive BP lowering (OR 3.94, 95% CI 1.01-15.37; p = 0.049). Conclusions: The presence of hematoma sedimentation level on baseline CT is associated with warfarin use and lobar location of ICH, and predicts a worse outcome. Although uncommon, sedimentation level is an easily detectable prognostic factor in acute ICH.

Background Lowering of LDL cholesterol reduces major vascular events, but whether more intensive therapy safely produces extra benefits is uncertain. We aimed to establish efficacy and safety of more intensive statin treatment in patients at high cardiovascular risk. Methods We undertook a double-blind randomised trial in 12 064 men and women aged 18–80 years with a history of myocardial infarction. Participants were either currently on or had clear indication for statin therapy, and had a total cholesterol concentration of at least 3·5 mmol/L if already on a statin or 4·5 mmol/L if not. Randomisation to either 80 mg or 20 mg simvastatin daily was done centrally using a minimisation algorithm. Participants were assessed at 2, 4, 8, and 12 months after randomisation and then every 6 months until final follow-up. The primary endpoint was major vascular events, defined as coronary death, myocardial infarction, stroke, or arterial revascularisation. Analysis was by intention to treat. This study is registered, number ISRCTN74348595. Findings 6031 participants were allocated 80 mg simvastatin daily, and 6033 allocated 20 mg simvastatin daily. During a mean follow-up of 6·7 (SD 1·5) years, allocation to 80 mg simvastatin produced an average 0·35 (SE 0·01) mmol/L greater reduction in LDL cholesterol compared with allocation to 20 mg. Major vascular events occurred in 1477 (24·5%) participants allocated 80 mg simvastatin versus 1553 (25·7%) of those allocated 20 mg, corresponding to a 6% proportional reduction (risk ratio 0·94, 95% CI 0·88–1·01; p=0·10). There were no apparent differences in numbers of haemorrhagic strokes (24 [0·4%] vs 25 [0·4%]) or deaths attributed to vascular (565 [9·4%] vs 572 [9·5%]) or non-vascular (399 [6·6%] vs 398 [6·6%]) causes. Compared with two (0·03%) cases of myopathy in patients taking 20 mg simvastatin daily, there were 53 (0·9%) cases in the 80 mg group. Interpretation The 6% (SE 3·5%) reduction in major vascular events with a further 0·35 mmol/L reduction in LDL cholesterol in our trial is consistent with previous trials. Myopathy was increased with 80 mg simvastatin daily, but intensive lowering of LDL cholesterol can be achieved safely with other regimens. Funding Merck; The Clinical Trial Service Unit also receives funding from the UK Medical Research Council and the British Heart Foundation.

Background and Purpose— The Oxfordshire Community Stroke Project (OCSP) clinical stroke syndrome classification correlates well with the stroke lesion in established ischemic stroke, but there are few data in patients with hyperacute stroke. We wished to assess whether the OCSP correlated with the site and size of the ischemic lesion and location of cerebral vessel lesion on computed tomography (CT) in hyperacute stroke. Methods— Prospective study of ischemic stroke patients presenting within 6 hours of onset in the Third International Stroke Trial (IST-3), a randomized, controlled trial of rt-PA. OCSP syndrome was assigned by a computer-based algorithm. The CT assessment was made by a neuroradiologist blinded to clinical details. Results— We assessed baseline data and CT findings for the first 510 patients; early tissue ischemic changes were present in 329/510 (65%) total anterior circulation syndrome (TACS) - 79%; partial anterior circulation syndrome (PACS) - 57%, lacunar syndrome (LACS) - 40%; posterior circulation syndrome (POCS) - 33%. The site and size of ischemic change on CT was compatible with the clinical syndrome in 79%, 37%, 2%, and 14%, respectively. Assuming that all patients with a normal CT scan will develop an incompatible lesion these numbers reflected the “worst possible scenario.” For the “best possible scenario” we presumed that those with a normal CT will develop concordant ischemic change and the proportions were 100%, 80%, 62% and 81%, respectively. The hyperattenuated artery sign was seen in 206/510 (40%); (TACS 54%; PACS 35%, LACS 5%, and POCS 19%). Conclusions— Within 6 hours of stroke, in patients with a nonlacunar syndrome, the OCSP syndrome correlated well with the pattern of ischemic change on CT. For clinicians who wish to restrict the use of thrombolytic therapy to large-artery ischemic stroke, concordance of clinical and CT appearances may give greater confidence in making therapeutic decisions in hyperacute stroke. In centers where immediate access to MR is limited, use of the classification may help focus use of MR on patients with suspected LACS and POCS. The utility of the classification may further increase if IST-3 establishes that the OCSP syndrome significantly modifies response to thrombolytic therapy.

Background The heterogeneity of the pathology of stroke has been a major difficulty in assessing new treatments for acute stroke, and contributes to the complexity of stroke medicine. Some underlying mechanisms are poorly understood, such as small vessel (lacunar) disease. New technology such as advanced brain imaging has transformed our knowledge of large vessel disease and we suggest that other new technology such as detailed analysis of retinal vessels may provide new insights into the pathology of small vessel (lacunar) stroke disease. We hypothesise that retinal microvascular signs differ by pathological stroke subtype, and we plan to test this hypothesis in over 1000 acute stroke patients. Summary Eligible patients undergo a standardised neurological assessment followed by digital retinal photography. At a consensus meeting, an anatomical and aetiological classification is determined. Retinal photographs will be assessed qualitatively (e.g. retinal emboli, arteriovenous nicking) and quantitatively (arteriolar/venule ratio). Six-month vascular event rates together with disability and vital status are collected. Conclusion Retinal vessel appearances may provide a ‘window’ to the brain and help determine the important underlying pathophysiological mechanisms of small vessel disease stroke.

The need for stroke rehabilitation will lessen if stroke incidence declines and acute stroke medical and surgical treatment improves. The burden of stroke will also lessen as effective rehabilitation services (stroke rehabilitation units) and interventions are widely implemented. Despite the considerable amount of evidence available, implementation has been slow. Improvement in stroke rehabilitation will require continued professional advocacy, supported by local and national audit and future focused research.

BACKGROUND: Oral anticoagulants are better than aspirin for secondary prevention after myocardial infarction and after cerebral ischaemia in combination with non-rheumatic atrial fibrillation. The European/Australasian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT) aimed to determine whether oral anticoagulation with medium intensity is more effective than aspirin in preventing future vascular events in patients with transient ischaemic attack or minor stroke of presumed arterial origin.METHODS: In this international, multicentre trial, patients were randomly assigned within 6 months after a transient ischaemic attack or minor stroke of presumed arterial origin either anticoagulants (target INR range 2.0-3.0; n=536) or aspirin (30-325 mg daily; n=532). The primary outcome was the composite of death from all vascular causes, non-fatal stroke, non-fatal myocardial infarction, or major bleeding complication, whichever occurred first. In a post hoc analysis anticoagulants were compared with the combination of aspirin and dipyridamole (200 mg twice daily). Treatment was open, but auditing of outcome events was blinded. Primary analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial (number ISRCTN73824458) and with ClinicalTrials.gov (NCT00161070).FINDINGS: The anticoagulants versus aspirin comparison of ESPRIT was prematurely ended because ESPRIT reported previously that the combination of aspirin and dipyridamole was more effective than aspirin alone. Mean follow-up was 4.6 years (SD 2.2). The mean achieved INR was 2.57 (SD 0.86). A primary outcome event occurred in 99 (19%) patients on anticoagulants and in 98 (18%) patients on aspirin (hazard ratio [HR] 1.02, 95% CI 0.77-1.35). The HR for ischaemic events was 0.73 (0.52-1.01) and for major bleeding complications 2.56 (1.48-4.43). The HR for the primary outcome event comparing anticoagulants with the combination treatment of aspirin and dipyridamole was 1.31 (0.98-1.75).INTERPRETATION: Oral anticoagulants (target INR range 2.0-3.0) are not more effective than aspirin for secondary prevention after transient ischaemic attack or minor stroke of arterial origin. A possible protective effect against ischaemic events is offset by increased bleeding complications.

ObjectiveTo assess whether the x-ray attenuation of intra-arterial obstruction measured on non-contrast CT in ischemic stroke can predict response to thrombolysis and subsequent functional outcome.MethodsThe Third International Stroke Trial (IST-3) was a multicenter randomized-controlled trial of intravenous thrombolysis (rt-PA) given within six hours of ischemic stroke. Ethical approval and informed consent were obtained. In a subgroup of 109 IST-3 patients (38 men, median age 82 years), a single reader, masked to all clinical and other imaging data, manually measured x-ray attenuation (Hounsfield Units, HU) on non-contrast CT at the location of angiographically-proven intra-arterial obstructions, pre-randomization and at 24–48 hour follow-up. We calculated change in attenuation between scans. We assessed the impact of pre-randomization arterial obstruction attenuation on six-month functional outcome.ResultsMost arterial obstructions (64/109, 59%) were hyperattenuating (mean 51.0 HU). Compared with control, treatment with rt-PA was associated with a greater, but non-significant, reduction in obstruction attenuation at follow-up (-8.0 HU versus -1.4 HU in patients allocated control, p = 0.117). In multivariable ordinal regression analysis controlled for patient age, stroke severity, location and extent of obstruction, time from stroke onset to baseline scan and rt-PA treatment allocation, the attenuation of pre-randomization arterial obstruction was not independently associated with six-month outcome (odds ratio = 0.99, 95% confidence interval = 0.94–1.03, p = 0.516).ConclusionsIn ischemic stroke, the x-ray attenuation of the arterial obstruction may decline more rapidly from baseline to 24–48 hours following treatment with thrombolysis but we found no evidence that baseline arterial obstruction attenuation predicts six-month outcome.

Introduction: Very early rehabilitation may be an important component of effective stroke unit care, but this requires testing. AVERT is an international clinical trial which can enroll eligible patients treated with rtPA if the physician allows. Patients randomized to intervention, commence training within 24hrs of stroke onset. Hypothesis: AVERT tests whether very early and frequent out of bed activity post stroke reduces 90 day death and disability. Due to the 24 hour time window, we hypothesized that around 20% of patients in the trial would be treated with rtPA. Methods: Inclusion criteria: adults over 18 yrs admitted within 24 hrs of stroke, whose physiological parameters fall within set limits. Exclusions: patients with severe premorbid disability, severe comorbidities or requiring palliative care. The intervention is delivered by a nurse/physiotherapy team and starts within 24 hours, for a maximum of 14 days. Control group patients receive standard care. A blinded assessor evaluates 3 and 12 month outcomes. Primary outcome: 3 month modified Rankin Scale. Secondary outcomes include complication rates, quality of life, time to walking (days) and cost effectiveness. Sample size is 2104 patients (n=1052 per group) with recruitment from 5 countries (Australia, New Zealand, Malaysia, Singapore, UK). Patients are followed for 12 months with primary endpoint (mRS) at 90 days. Results: Current recruitment sits at 2017 patients and is expected to close in early October 2014. Recruited patients: mean(SD) age: 70.6(12.9) years; male: 61.0%; first stroke: 81.5%; infarct 87.8%; mean(SD) NIHSS: 8.7(6.3); rtPA: 24.0%. Data completion rates are excellent: primary and secondary outcome over 90%, cognitive function and mood over 80%. rtPA patients have been recruited from Australia (250 patients), UK (189), New Zealand (30), Singapore and Malaysia (6 each). Conclusions: The trial data quality is high. The Data Monitoring Committee has met 14 times and no safety issues have been identified. By the conclusion of the trial we expect to have recruited 500 patients treated with rtPA.

Background: Conflicting data exist of an association between off-hour (weekend, holiday, or night-time) hospital admission and adverse outcome in intracerebral hemorrhage (ICH). We determined the association between off-hour admissions and poor clinical outcome, and of any differential effect of early intensive blood pressure (BP) lowering treatment between off- and on-hour admissions, among participants of the Intensive BP Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2). Methods: Subsidiary analysis of INTERACT2, a multinational, multicenter, clinical trial of patients with spontaneous ICH with elevated systolic BP, randomly assigned to intensive (target systolic BP Results: Of 2,794 patients with information on the primary outcome, 1,770 (63%) were admitted to study centers during off-hours. Off-hour admission was not associated with risk of poor outcome at 90 days (53% off-hour vs. 55% on-hour; p = 0.49), even after adjustment for comorbid risk factors (odds ratio 0.92; 95% CI 0.76-1.12). Consistency exists in the effects of intensive BP lowering between off- and on-hour admission (p = 0.85 for homogeneity). Conclusions: Off-hour admission was not associated with increased risks of death or major disability among trial protocol participants with acute ICH. Intensive BP lowering can provide similar treatment effect irrespective of admission hours.

Stroke is a common disease. Every year, stroke kills about 5 5 million people around the world (1). Almost 5 billion years of healthy life are lost as a result of yearly strokes (1). In the United Kingdom, it is the single most expensive condition looked after by the National Health Service, costing 2 8 billion pounds (5 2 billion US dollars) in direct care costs alone (2). In Europe, Australia and the United States, about 80% of strokes are ischaemic (3). Unfortunately, ischaemic stroke has few effective treatments. Coordinated stroke unit care reduces the number of patients left dead or dependent due to stroke by 56 per 1000 patients treated (3). Once established, stroke units can care for most patients with stroke, so that their effect on improving outcome is larger than any other treatment. Treatment with aspirin soon after ischaemic stroke reduces the chance of death or disability by about 12 patients per 1000 treated, probably by reducing the chance of stroke recurrence (4). Although the treatment effect is small, aspirin is cheap and widely applicable so it too has a large effect on reducing the overall burden of disability from stroke. Thrombolysis for stroke with recombinant tissue plasminogen activator (rtPA) is effective, though expensive and difficult to deliver, and currently applicable to only a small group of patients. Consequently, the impact of thrombolysis on reducing stroke-related disability in the population from stroke is currently relatively small (5). Only stroke units and aspirin are in widespread use for the treatment of acute ischaemic stroke.

When the row between Government and the Today programme erupted, Lindley felt again that moment of nervousness that was familiar to him and most of his contemporaries at Panorama, the BBC current affairs flagship that is celebrating its fiftieth anniversary. The fact that they were often paranoid did not always mean that somebody wasn't out to get them, he recalls - "We might have felt pleased and proud to have got a story on air but we knew there would be repercussions, and sometimes we could not tell how far our colleagues and our bosses in the BBC would support us. Occasionally, facing hostile reaction, we might wish we'd told the story just slightly differently."

It all began with a new bit of lawn. For the last two years my index and middle fingers had became numb for an hour or two after using the grass trimmer. I attributed this to vibration. However, earlier last year I trimmed all the lawn edges in one go, and by the end of the job the middle and index finger of my right hand were completely numb. On this occasion it didn’t resolve and I confirmed that vibration was indeed a recognised trigger for carpal tunnel syndrome.1 I hoped it would get better during the following few weeks’ holiday on Lord Howe Island, an idyllic spot for walking and snorkelling. In fact the island was memorable for the very strenuous guided walk I had done some years previously. On that occasion I had been severely embarrassed to be the last up (and last down) Mount Gower. At the end of that day I had reached a point of complete exhaustion, not even being able to climb out of the bath. But then I have never been known for my athletic prowess! I had reached a point of complete exhaustion, not even being able to climb out of the bath. But then I have never been known for my athletic prowess! On my return from the island …

The aim of this study was to identify seminal Australasian Journal on Ageing papers published over 30 years through a Delphi consensus process.The main data collection was a three-round Delphi consensus study with 38 past and current members of the Australasian Journal on Ageing Editorial Board, Editorial Team and Management Committee.Three papers were agreed as top-ranking. One of the top-ranking articles was also highly cited. One article was published in the 1990 s, two in 2001.While it is difficult to judge how well the top-ranking papers represent seminal papers arising over 30 years, these papers do represent three different research strengths in Australasia, they do span three different disciplines, and they do reflect some of the diversity that characterises ageing research in Australasia over 30 years.

Item does not contain fulltext Cerebral small vessel disease (SVD) is a common accompaniment of ageing. Features seen on neuroimaging include recent small subcortical infarcts, lacunes, white matter hyperintensities, perivascular spaces, microbleeds, and brain atrophy. SVD can present as a stroke or cognitive decline, or can have few or no symptoms. SVD frequently coexists with neurodegenerative disease, and can exacerbate cognitive deficits, physical disabilities, and other symptoms of neurodegeneration. Terminology and definitions for imaging the features of SVD vary widely, which is also true for protocols for image acquisition and image analysis. This lack of consistency hampers progress in identifying the contribution of SVD to the pathophysiology and clinical features of common neurodegenerative diseases. We are an international working group from the Centres of Excellence in Neurodegeneration. We completed a structured process to develop definitions and imaging standards for markers and consequences of SVD. We aimed to achieve the following: first, to provide a common advisory about terms and definitions for features visible on MRI; second, to suggest minimum standards for image acquisition and analysis; third, to agree on standards for scientific reporting of changes related to SVD on neuroimaging; and fourth, to review emerging imaging methods for detection and quantification of preclinical manifestations of SVD. Our findings and recommendations apply to research studies, and can be used in the clinical setting to standardise image interpretation, acquisition, and reporting. This Position Paper summarises the main outcomes of this international effort to provide the STandards for ReportIng Vascular changes on nEuroimaging (STRIVE).

International audience; BACKGROUND: Whether rapid lowering of elevated blood pressure would improve the outcome in patients with intracerebral hemorrhage is not known. METHODS: We randomly assigned 2839 patients who had had a spontaneous intracerebral hemorrhage within the previous 6 hours and who had elevated systolic blood pressure to receive intensive treatment to lower their blood pressure (with a target systolic level of

The Statistical analysis plan (SAP) for the second INTEnsive blood pressure Reduction in Acute Cerebral hemorrhage Trial (INTERACT2).

BACKGROUND: Thrombolysis is of net benefit in patients with acute ischaemic stroke, who are younger than 80 years of age and are treated within 4·5 h of onset. The third International Stroke Trial (IST-3) sought to determine whether a wider range of patients might benefit up to 6 h from stroke onset. METHODS: In this international, multicentre, randomised, open-treatment trial, patients were allocated to 0·9 mg/kg intravenous recombinant tissue plasminogen activator (rt-PA) or to control. The primary analysis was of the proportion of patients alive and independent, as defined by an Oxford Handicap Score (OHS) of 0-2 at 6 months. The study is registered, ISRCTN25765518. FINDINGS: 3035 patients were enrolled by 156 hospitals in 12 countries. All of these patients were included in the analyses (1515 in the rt-PA group vs 1520 in the control group), of whom 1617 (53%) were older than 80 years of age. At 6 months, 554 (37%) patients in the rt-PA group versus 534 (35%) in the control group were alive and independent (OHS 0-2; adjusted odds ratio [OR] 1·13, 95% CI 0·95-1·35, p=0·181; a non-significant absolute increase of 14/1000, 95% CI -20 to 48). An ordinal analysis showed a significant shift in OHS scores; common OR 1·27 (95% CI 1·10-1·47, p=0·001). Fatal or non-fatal symptomatic intracranial haemorrhage within 7 days occurred in 104 (7%) patients in the rt-PA group versus 16 (1%) in the control group (adjusted OR 6·94, 95% CI 4·07-11·8; absolute excess 58/1000, 95% CI 44-72). More deaths occurred within 7 days in the rt-PA group (163 [11%]) than in the control group (107 [7%], adjusted OR 1·60, 95% CI 1·22-2·08, p=0·001; absolute increase 37/1000, 95% CI 17-57), but between 7 days and 6 months there were fewer deaths in the rt-PA group than in the control group, so that by 6 months, similar numbers, in total, had died (408 [27%] in the rt-PA group vs 407 [27%] in the control group). INTERPRETATION: For the types of patient recruited in IST-3, despite the early hazards, thrombolysis within 6 h improved functional outcome. Benefit did not seem to be diminished in elderly patients. FUNDING: UK Medical Research Council, Health Foundation UK, Stroke Association UK, Research Council of Norway, Arbetsmarknadens Partners Forsakringsbolag (AFA) Insurances Sweden, Swedish Heart Lung Fund, The Foundation of Marianne and Marcus Wallenberg, Polish Ministry of Science and Education, the Australian Heart Foundation, Australian National Health and Medical Research Council (NHMRC), Swiss National Research Foundation, Swiss Heart Foundation, Assessorato alla Sanita, Regione dell'Umbria, Italy, and Danube University.

Background: Each year approximately 12,000 Australians of working age survive a stroke. An ability to participate in paid employment has been identified by younger stroke survivors as having important psychological and economic consequences. Methods: The POISE study (Psychosocial Outcome In StrokE 1 ) is the largest cohort of young ( Results: Among 441 participants, 218 were in paid full-time and 53 in paid part-time work immediately before their stroke, of whom 202 returned to paid part- or full-time work within 12 months of their stroke. Being free of depression at 28-days was the only independent predictor of return to work (OR 2.6, 95% CI 1.1 to 6.5) following adjustment for age, sex, and history of depression before stroke (C statistic 0.73). Conclusion: Three quarters of previously employed participants returned to paid employment within 12 months of stroke, with those not depressed most likely to return. Depression is potentially modifiable and early management of depressive symptoms may increase the proportion of those able to return to paid employment. 1 Hackett M, Glozier N, Jan S, Lindley R. Psychosocial Outcomes In StrokE: the POISE observational stroke study protocol. BMC Neurology 2009, 9:24

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 leave 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, and should be considered by trial investigators when planning research and estimating budgets. However, the celebration of new life became a highlight of the annual AVERT collaborators’ 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.

BACKGROUND: Deep vein thrombosis (DVT) is an important complication of stroke, but the evidence to support commonly used prophylactic strategies is conflicting. OBJECTIVES: To describe the incidence, extent, associated clinical features and evolution of DVT after stroke. PATIENTS/METHODS: The CLOTS trials 1 and 2 together randomized 5632 immobile stroke patients in 135 hospitals in nine countries. We screened patients for asymptomatic DVT with compression duplex ultrasound (CDU) at about 7-10 days and again at about 25-30 days after enrollment. RESULTS: Six hundred and forty-one (11.4%) of 5632 patients had DVT detected on the first CDU scan at a median of 8 days (interquartile range [IQR] 7-10 days) after enrollment, and an additional 176 (3.1%) had a DVT on the second CDU scan at a median of 28 days (IQR 26-30 days). Of the 817 with DVTs, 289 (35%) were symptomatic and 39 (5%) had pulmonary embolism (PE) confirmed by imaging. Six hundred and seventy-six (83%) were unilateral, 141 (17%) were bilateral, 322 (39%) were limited to calf veins, 172 (21%) were popliteal, and 323 (40%) were femoral. Among the 542 patients with DVT and a weak leg, the DVT affected the weaker leg in 396 (73%), the stronger leg in 59 (11%), and was bilateral in 87 (16%). Among the 318 patients with a DVT detected on the first CDU scan who had a second scan, the DVT regressed in 148 (47%), stayed the same in 140 (44%), and progressed in only 30 (9%). CONCLUSIONS: Although most DVTs develop within the first week, some develop later, and some early DVTs progress. Any prophylaxis needs to be started early but ideally continued for at least 4 weeks.

Recombinant tissue plasminogen activator (rt-PA, alteplase) for acute ischaemic stroke was provisionally granted in Europe in 2002 and the granted license excluded many patient groups from treatment. Uncertainties about the balance of risk and benefit in several categories of patients still remain. The aim of the Third International Stroke Trial (IST-3) is to determine whether more patients can benefit from treatment. We present the rationale for the study and compare the characteristics of patients recruited to the study in Poland with those recruited in other countries.Patients recruited to IST-3 from May 5th 2000 to April 9th 2008 (in Poland from November 2nd 2003). We compared the baseline characteristics for patients recruited in Poland and other countries.1118 patients were recruited, 179 from centres in Poland and 939 from other countries. There was no significant difference between Poland and other countries in mean age (73.0 vs. 74.7 years), or distribution of gender (53.2% and 49.2% males), but the mean delay from onset to randomization was significantly longer (4.30 vs. 3.94 hours, p0.001), and baseline stroke severity was less (mean NIHSS 9.6 vs. 12.8, p0.001), respectively. The proportion of patients with a total anterior circulation clinical syndrome was lower, and lacunar and posterior circulation syndromes were more common among Polish patients.Polish patients are somewhat different from those recruited in other countries, reflecting clinician's differing areas of uncertainty. These differences will be taken into account in the final trial analysis plan. The trial is still ongoing and more centres are welcome to join.

Frail older people have been systematically excluded from randomised controlled trials (RCT). We aim to recruit older, frail hospitalised patients in an RCT and evaluate the frailty index (FI) as a measure to describe the types of people included in the study. We recruited 315 hospitalised patients aged 65 years; age ranged from 60 to 102 years. Baseline assessment scores ranged as follow: Mini-Mental Status Examination from 7 to 30, Barthel index from 5 to 100 and FI from 2 to 24. Total deaths were 20 (6%). We demonstrated that it is feasible to recruit frail older people into RCTs. The FI does not show any 'floor' or 'ceiling' effects. We can measure frailty in an RCT cohort, and we believe that clinical trials should include more frail older people and that the use of an FI can facilitate such trials and generate reliable data to guide future medical practice in a rapidly ageing society.