Summary Background Cerebral microbleeds are a neuroimaging biomarker of stroke risk. A crucial clinical question is whether cerebral microbleeds indicate patients with recent ischaemic stroke or transient ischaemic attack in whom the rate of future intracranial haemorrhage is likely to exceed that of recurrent ischaemic stroke when treated with antithrombotic drugs. We therefore aimed to establish whether a large burden of cerebral microbleeds or particular anatomical patterns of cerebral microbleeds can identify ischaemic stroke or transient ischaemic attack patients at higher absolute risk of intracranial haemorrhage than ischaemic stroke. Methods We did a pooled analysis of individual patient data from cohort studies in adults with recent ischaemic stroke or transient ischaemic attack. Cohorts were eligible for inclusion if they prospectively recruited adult participants with ischaemic stroke or transient ischaemic attack; included at least 50 participants; collected data on stroke events over at least 3 months follow-up; used an appropriate MRI sequence that is sensitive to magnetic susceptibility; and documented the number and anatomical distribution of cerebral microbleeds reliably using consensus criteria and validated scales. Our prespecified primary outcomes were a composite of any symptomatic intracranial haemorrhage or ischaemic stroke, symptomatic intracranial haemorrhage, and symptomatic ischaemic stroke. We registered this study with the PROSPERO international prospective register of systematic reviews, number CRD42016036602. Findings Between Jan 1, 1996, and Dec 1, 2018, we identified 344 studies. After exclusions for ineligibility or declined requests for inclusion, 20 322 patients from 38 cohorts (over 35 225 patient-years of follow-up; median 1·34 years [IQR 0·19–2·44]) were included in our analyses. The adjusted hazard ratio [aHR] comparing patients with cerebral microbleeds to those without was 1·35 (95% CI 1·20–1·50) for the composite outcome of intracranial haemorrhage and ischaemic stroke; 2·45 (1·82–3·29) for intracranial haemorrhage and 1·23 (1·08–1·40) for ischaemic stroke. The aHR increased with increasing cerebral microbleed burden for intracranial haemorrhage but this effect was less marked for ischaemic stroke (for five or more cerebral microbleeds, aHR 4·55 [95% CI 3·08–6·72] for intracranial haemorrhage vs 1·47 [1·19–1·80] for ischaemic stroke; for ten or more cerebral microbleeds, aHR 5·52 [3·36–9·05] vs 1·43 [1·07–1·91]; and for ≥20 cerebral microbleeds, aHR 8·61 [4·69–15·81] vs 1·86 [1·23–2·82]). However, irrespective of cerebral microbleed anatomical distribution or burden, the rate of ischaemic stroke exceeded that of intracranial haemorrhage (for ten or more cerebral microbleeds, 64 ischaemic strokes [95% CI 48–84] per 1000 patient-years vs 27 intracranial haemorrhages [17–41] per 10...

The presence of CMB on MRI and the dichotomized cutoff of ≥5 CMBs might identify subgroups of ischemic stroke patients with AF with high ICH risk and after further validation could help in risk stratification, in anticoagulation decisions, and in guiding randomized trials and ongoing large observational studies.

Studies investigating the effect of physical activity on risk for developing osteoarthritis at weight-bearing joints have reported conflicting results. We examine evidence to suggest that this may be due to the existence of subgroups of individuals who differ in their response to physical activity, as well as methodological issues associated with the assessment of knee joint structure and physical activity. Recommendations for future studies of physical activity and the development of knee osteoarthritis are discussed. IntroductionIt is widely accepted that participation in physical activity is associated with physical, psychological and social benefits [1]. Physical activity not only reduces the risk for cardiovascular disease [2] (a major cause of mortality in developed countries) but is also recommended for the management of obesity and the treatment of mental illness [3]. Globally, a vast number of large-scale public health campaigns is aimed at promoting physical activity. Exercise is also widely recommended by health care professionals in the prevention and management of chronic health conditions such as osteoarthritis (OA). However, our knowledge of the effect of physical activity on risk for developing OA is limited.OA is the most common joint disorder affecting the elderly. In particular, radiographic knee OA affects at least 30% of people aged over 60 years [4] and is a major cause of functional disability [5]. With our population ageing, the prevalence of OA in the developed world is expected to increase and it is anticipated that OA will become the fourth leading cause of disability in the coming decades [6]. A population-wide initiative, such as promotion of physical activity, has the potential to contribute inadvertently to the growing burden of this disease.Epidemiological studies that have investigated the effect of physical activity on the knee joint have reported conflicting findings. Although some studies have reported that physical activity is associated with risk for knee OA [7][8][9], other studies have shown that physical activity may have no effect [10,11] or may even protect the knee joint from degenerative changes [12,13]. These conflicting findings may be a result of individual variation in response to exercise and/or different methodology employed by studies to measure knee structure and physical activity.We propose that there may be subgroups of individuals who differ in their response to physical activity within our community. Although some individuals may have specific characteristics that enable them to exercise without increasing their risk for knee OA, others may require these individual factors and/or their exercise programme to be modified before they can commence or continue to exercise safely. In this review, we examine the roles played by a number of parameters that may mediate the relationship between physical activity and knee OA. We focus on the role of physical activity in the risk for developing OA, and do not consider its effect on those individuals with estab...

Research in context panel: 445Identifying people at highest risk of ICH may facilitate timely and accurate prognostication to allow mitigation of reversible risk factors for bleeding (e.g. intensive blood pressure control), and selection of participants for clinical trials. While more complex combinations of clinical, biochemical, and radiological markers might further improve stroke risk prediction, balancing accuracy with simplicity will remain important.

Background and purposeCerebral microbleeds (CMBs), cortical superficial siderosis, white matter lesions (WML), and cerebral atrophy may signify greater bleeding risk particularly in patients in whom anticoagulation is to be considered. We investigated their prevalence and associations with stroke type in patients with stroke and atrial fibrillation (AF).Materials and MethodsCross-sectional sample, Monash Medical Centre (Melbourne, Australia) between 2010 and 2013, with brain MRI. MRI abnormalities were rated using standardized methods. Logistic regression was used to study associations adjusting for age and sex.ResultsThere were 170 patients, mean age 78 years (SD 9.8), 154 (90.6%) with ischemic stroke. Prevalence of MRI markers were any microbleed 49%, multiple (≥2) microbleeds 30%, confluent WMLs 18.8%, siderosis 8.9%, severe cerebral atrophy 37.7%. Combinations of the severe manifestations of these markers were much less prevalent (2.9–12.4%). Compared with ischemic stroke, those with hemorrhagic stroke were more likely to have ≥10 microbleeds (OR 5.50 95% CI 1.46–20.77, p = 0.012) and siderosis (OR 6.24, 95% CI 1.74–22.40, p = 0.005). Siderosis was associated with multiple microbleeds (OR 8.14, 95% CI 2.38–27.86, p = 0.001). Patients admitted with hemorrhagic stroke and multiple microbleeds were more frequently anticoagulated prior to stroke (6/7, 85.7%) than in those with single (1/2, 50%) or no microbleeds (4/7, 57%).ConclusionMultiple CMBs, severe WML, and severe cerebral atrophy were common individually in hospitalized patients with stroke and AF, but less so in combination. A higher burden of CMBs may be associated with intracerebral hemorrhage in stroke patients with AF.