Rustam Al-Shahi Salman
University of Edinburgh
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Featured researches published by Rustam Al-Shahi Salman.
Lancet Neurology | 2009
Steven M. Greenberg; Meike W. Vernooij; Charlotte Cordonnier; Anand Viswanathan; Rustam Al-Shahi Salman; Steven Warach; Lenore J. Launer; Mark A. van Buchem; Monique M.B. Breteler
Cerebral microbleeds (CMBs) are increasingly recognised neuroimaging findings in individuals with cerebrovascular disease and dementia, and in normal ageing. There has been substantial progress in the understanding of CMBs in recent years, particularly in the development of newer MRI methods for the detection of CMBs and the application of these techniques to population-based samples of elderly people. In this Review, we focus on these recent developments and their effects on two main questions: how CMBs are detected, and how CMBs should be interpreted. The number of CMBs detected depends on MRI characteristics, such as pulse sequence, sequence parameters, spatial resolution, magnetic field strength, and image post-processing, emphasising the importance of taking into account MRI technique in the interpretation of study results. Recent investigations with sensitive MRI techniques have indicated a high prevalence of CMBs in community-dwelling elderly people. We propose a procedural guide for identification of CMBs and suggest possible future approaches for elucidating the role of these common lesions as markers for, and contributors to, small-vessel brain disease.
The Lancet | 2014
J. P. Mohr; Michael K. Parides; Christian Stapf; Ellen Moquete; Claudia S. Moy; Jessica R. Overbey; Rustam Al-Shahi Salman; Eric Vicaut; William L. Young; E. Houdart; Charlotte Cordonnier; Marco Antonio Stefani; Andreas Hartmann; Rüdiger von Kummer; Alessandra Biondi; Joachim Berkefeld; Catharina J.M. Klijn; Kirsty Harkness; Richard Libman; Xavier Barreau; Alan J. Moskowitz
BACKGROUND The clinical benefit of preventive eradication of unruptured brain arteriovenous malformations remains uncertain. A Randomised trial of Unruptured Brain Arteriovenous malformations (ARUBA) aims to compare the risk of death and symptomatic stroke in patients with an unruptured brain arteriovenous malformation who are allocated to either medical management alone or medical management with interventional therapy. METHODS Adult patients (≥18 years) with an unruptured brain arteriovenous malformation were enrolled into this trial at 39 clinical sites in nine countries. Patients were randomised (by web-based system, in a 1:1 ratio, with random permuted block design [block size 2, 4, or 6], stratified by clinical site) to medical management with interventional therapy (ie, neurosurgery, embolisation, or stereotactic radiotherapy, alone or in combination) or medical management alone (ie, pharmacological therapy for neurological symptoms as needed). Patients, clinicians, and investigators are aware of treatment assignment. The primary outcome is time to the composite endpoint of death or symptomatic stroke; the primary analysis is by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00389181. FINDINGS Randomisation was started on April 4, 2007, and was stopped on April 15, 2013, when a data and safety monitoring board appointed by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health recommended halting randomisation because of superiority of the medical management group (log-rank Z statistic of 4·10, exceeding the prespecified stopping boundary value of 2·87). At this point, outcome data were available for 223 patients (mean follow-up 33·3 months [SD 19·7]), 114 assigned to interventional therapy and 109 to medical management. The primary endpoint had been reached by 11 (10·1%) patients in the medical management group compared with 35 (30·7%) in the interventional therapy group. The risk of death or stroke was significantly lower in the medical management group than in the interventional therapy group (hazard ratio 0·27, 95% CI 0·14-0·54). No harms were identified, other than a higher number of strokes (45 vs 12, p<0·0001) and neurological deficits unrelated to stroke (14 vs 1, p=0·0008) in patients allocated to interventional therapy compared with medical management. INTERPRETATION The ARUBA trial showed that medical management alone is superior to medical management with interventional therapy for the prevention of death or stroke in patients with unruptured brain arteriovenous malformations followed up for 33 months. The trial is continuing its observational phase to establish whether the disparities will persist over an additional 5 years of follow-up. FUNDING National Institutes of Health, National Institute of Neurological Disorders and Stroke.
BMJ | 2009
Zoe Morris; William Whiteley; W. T. Longstreth; Frank Weber; Yi-Chung Lee; Yoshito Tsushima; Hannah H. Alphs; Susanne C. Ladd; Charles Warlow; Joanna M. Wardlaw; Rustam Al-Shahi Salman
Objective To quantify the prevalence of incidental findings on magnetic resonance imaging (MRI) of the brain. Design Systematic review and meta-analysis of observational studies. Data sources Ovid Medline (1950 to May 2008), Embase (1980 to May 2008), and bibliographies of relevant articles. Review methods Two reviewers sought and assessed studies of people without neurological symptoms who underwent MRI of the brain with or without intravenous contrast for research purposes or for occupational, clinical, or commercial screening. Main outcome measures Overall disease specific and age specific prevalence of incidental brain findings, calculated by meta-analysis of pooled proportions using DerSimonian-Laird weights in a random effects model. Results In 16 studies, 135 of 19 559 people had neoplastic incidental brain findings (prevalence 0.70%, 95% confidence interval 0.47% to 0.98%), and prevalence increased with age (χ2 for linear trend, P=0.003). In 15 studies, 375 of 15 559 people had non-neoplastic incidental brain findings (prevalence 2.0%, 1.1% to 3.1%, excluding white matter hyperintensities, silent infarcts, and microbleeds). The number of asymptomatic people needed to scan to detect any incidental brain finding was 37. The prevalence of incidental brain findings was higher in studies using high resolution MRI sequences than in those using standard resolution sequences (4.3% v 1.7%, P<0.001). The prevalence of neoplastic incidental brain findings increased with age. Conclusions Incidental findings on brain MRI are common, prevalence increases with age, and detection is more likely using high resolution MRI sequences than standard resolution sequences. These findings deserve to be mentioned when obtaining informed consent for brain MRI in research and clinical practice but are not sufficient to justify screening healthy asymptomatic people.
International Journal of Stroke | 2014
Thorsten Steiner; Rustam Al-Shahi Salman; Ronnie Beer; Hanne Christensen; Charlotte Cordonnier; László Csiba; Michael Forsting; Sagi Harnof; Catharina J.M. Klijn; Derk Krieger; A. David Mendelow; Carlos A. Molina; Joan Montaner; Karsten Overgaard; Jesper Petersson; Risto O. Roine; Erich Schmutzhard; Karsten Schwerdtfeger; Christian Stapf; Turgut Tatlisumak; Brenda Thomas; Danilo Toni; Andreas Unterberg; Markus Wagner
Background Intracerebral hemorrhage (ICH) accounted for 9% to 27% of all strokes worldwide in the last decade, with high early case fatality and poor functional outcome. In view of recent randomized controlled trials (RCTs) of the management of ICH, the European Stroke Organisation (ESO) has updated its evidence-based guidelines for the management of ICH. Method A multidisciplinary writing committee of 24 researchers from 11 European countries identified 20 questions relating to ICH management and created recommendations based on the evidence in RCTs using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results We found moderate- to high-quality evidence to support strong recommendations for managing patients with acute ICH on an acute stroke unit, avoiding hemostatic therapy for acute ICH not associated with antithrombotic drug use, avoiding graduated compression stockings, using intermittent pneumatic compression in immobile patients, and using blood pressure lowering for secondary prevention. We found moderate-quality evidence to support weak recommendations for intensive lowering of systolic blood pressure to <140 mmHg within six-hours of ICH onset, early surgery for patients with a Glasgow Coma Scale score 9–12, and avoidance of corticosteroids. Conclusion These guidelines inform the management of ICH based on evidence for the effects of treatments in RCTs. Outcome after ICH remains poor, prioritizing further RCTs of interventions to improve outcome.
JAMA | 2011
Janneke van Beijnum; H. Bart van der Worp; Dennis R. Buis; Rustam Al-Shahi Salman; L. Jaap Kappelle; Gabriel J.E. Rinkel; Jan Willem Berkelbach van der Sprenkel; W. Peter Vandertop; Ale Algra; Catharina J.M. Klijn
CONTEXT Outcomes following treatment of brain arteriovenous malformations (AVMs) with microsurgery, embolization, stereotactic radiosurgery (SRS), or combinations vary greatly between studies. OBJECTIVES To assess rates of case fatality, long-term risk of hemorrhage, complications, and successful obliteration of brain AVMs after interventional treatment and to assess determinants of these outcomes. DATA SOURCES We searched PubMed and EMBASE to March 1, 2011, and hand-searched 6 journals from January 2000 until March 2011. STUDY SELECTION AND DATA EXTRACTION We identified studies fulfilling predefined inclusion criteria. We used Poisson regression analyses to explore associations of patient and study characteristics with case fatality, complications, long-term risk of hemorrhage, and successful brain AVM obliteration. DATA SYNTHESIS We identified 137 observational studies including 142 cohorts, totaling 13,698 patients and 46,314 patient-years of follow-up. Case fatality was 0.68 (95% CI, 0.61-0.76) per 100 person-years overall, 1.1 (95% CI, 0.87-1.3; n = 2549) after microsurgery, 0.50 (95% CI, 0.43-0.58; n = 9436) after SRS, and 0.96 (95% CI, 0.67-1.4; n = 1019) after embolization. Intracranial hemorrhage rates were 1.4 (95% CI, 1.3-1.5) per 100 person-years overall, 0.18 (95% CI, 0.10-0.30) after microsurgery, 1.7 (95% CI, 1.5-1.8) after SRS, and 1.7 (95% CI, 1.3-2.3) after embolization. More recent studies were associated with lower case-fatality rates (rate ratio [RR], 0.972; 95% CI, 0.955-0.989) but increased rates of hemorrhage (RR, 1.02; 95% CI, 1.00-1.03). Male sex (RR, 0.964; 95% CI, 0.945-0.984), small brain AVMs (RR, 0.988; 95% CI, 0.981-0.995), and those with strictly deep venous drainage (RR, 0.975; 95% CI, 0.960-0.990) were associated with lower case fatality. Lower hemorrhage rates were associated with male sex (RR, 0.976, 95% CI, 0.964-0.988), small brain AVMs (RR, 0.988, 95% CI, 0.980-0.996), and brain AVMs with deep venous drainage (0.982, 95% CI, 0.969-0.996). Complications leading to permanent neurological deficits or death occurred in a median 7.4% (range, 0%-40%) of patients after microsurgery, 5.1% (range, 0%-21%) after SRS, and 6.6% (range, 0%-28%) after embolization. Successful brain AVM obliteration was achieved in 96% (range, 0%-100%) of patients after microsurgery, 38% (range, 0%-75%) after SRS, and 13% (range, 0%-94%) after embolization. CONCLUSIONS Although case fatality after treatment has decreased over time, treatment of brain AVM remains associated with considerable risks and incomplete efficacy. Randomized controlled trials comparing different treatment modalities appear justified.
Stroke | 2010
Caroline E. Lovelock; Charlotte Cordonnier; Hiromitsu Naka; Rustam Al-Shahi Salman; Cathie Sudlow; Takatoshi Sorimachi; David J. Werring; Simone M. Gregoire; Toshio Imaizumi; Seung-Hoon Lee; Dennis Briley; Peter M. Rothwell
Background and Purpose— Cerebral microbleeds (MB) are potential risk factors for intracerebral hemorrhage (ICH), but it is unclear if they are a contraindication to using antithrombotic drugs. Insights could be gained by pooling data on MB frequency stratified by antithrombotic use in cohorts with ICH and ischemic stroke (IS)/transient ischemic attack (TIA). Methods— We performed a systematic review of published and unpublished data from cohorts with stroke or TIA to compare the presence of MB in: (1) antithrombotic users vs nonantithrombotic users with ICH; (2) antithrombotic users vs nonusers with IS/TIA; and (3) ICH vs ischemic events stratified by antithrombotic use. We also analyzed published and unpublished follow-up data to determine the risk of ICH in antithrombotic users with MB. Results— In a pooled analysis of 1460 ICH and 3817 IS/TIA, MB were more frequent in ICH vs IS/TIA in all treatment groups, but the excess increased from 2.8 (odds ratio; range, 2.3–3.5) in nonantithrombotic users to 5.7 (range, 3.4–9.7) in antiplatelet users and 8.0 (range, 3.5–17.8) in warfarin users (P difference=0.01). There was also an excess of MB in warfarin users vs nonusers with ICH (OR, 2.7; 95% CI, 1.6–4.4; P<0.001) but none in warfarin users with IS/TIA (OR, 1.3; 95% CI, 0.9–1.7; P=0.33; P difference=0.01). There was a smaller excess of MB in antiplatelet users vs nonusers with ICH (OR, 1.7; 95% CI, 1.3–2.3; P<0.001), but findings were similar for antiplatelet users with IS/TIA (OR, 1.4; 95% CI, 1.2–1.7; P<0.001; P difference=0.25). In pooled follow-up data for 768 antithrombotic users, presence of MB at baseline was associated with a substantially increased risk of subsequent ICH (OR, 12.1; 95% CI, 3.4–42.5; P<0.001). Conclusions— The excess of MB in warfarin users with ICH compared to other groups suggests that MB increase the risk of warfarin-associated ICH. Limited prospective data corroborate these findings, but larger prospective studies are urgently required.
The Lancet | 2014
Rustam Al-Shahi Salman; Elaine Beller; Jonathan Kagan; Elina Hemminki; Robert Phillips; Julian Savulescu; Malcolm R. Macleod; Janet Wisely; Iain Chalmers
After identification of an important research question and selection of an appropriate study design, waste can arise from the regulation, governance, and management of biomedical research. Obtaining regulatory and governance approval has become increasingly burdensome and disproportionate to the conceivable risks to research participants. Regulation and governance involve interventions that are assumed to be justified in the interests of patients and the public, but they can actually compromise these interests. Inefficient management of the procedural conduct of research is wasteful, especially if it results in poor recruitment and retention of participants in well designed studies addressing important questions. These sources of waste can be minimised if the following four recommendations are addressed. First, regulators should use their influence to reduce other causes of waste and inefficiency in research. Second, regulators and policy makers should work with researchers, patients, and health professionals to streamline and harmonise the laws, regulations, guidelines, and processes that govern whether and how research can be done, and ensure that they are proportionate to the plausible risks associated with the research. Third, researchers and research managers should increase the efficiency of recruitment, retention, data monitoring, and data sharing in research through use of research designs known to reduce inefficiencies, and further research should be done to learn how efficiency can be increased. Finally, everyone, particularly those responsible for health-care systems, should promote integration of research into everyday clinical practice. Regulators and researchers should monitor adherence to each of these recommendations and publish metrics.
Stroke | 2009
Charlotte Cordonnier; Gillian M. Potter; Caroline Jackson; Fergus N. Doubal; Sarah Keir; Cathie Sudlow; Joanna M. Wardlaw; Rustam Al-Shahi Salman
Background and Purpose— If the diagnostic and prognostic significance of brain microbleeds (BMBs) are to be investigated and used for these purposes in clinical practice, observer variation in BMB assessment must be minimized. Methods— Two doctors used a pilot rating scale to describe the number and distribution of BMBs (round, low-signal lesions, <10 mm diameter on gradient echo MRI) among 264 adults with stroke or TIA. They were blinded to clinical data and their counterpart’s ratings. Disagreements were adjudicated by a third observer, who informed the development of a new Brain Observer MicroBleed Scale (BOMBS), which was tested in a separate cohort of 156 adults with stroke. Results— In the pilot study, agreement about the presence of ≥1 BMB in any location was moderate (&kgr;=0.44; 95% CI, 0.32-0.56), but agreement was worse in lobar locations (&kgr;=0.44; 95% CI, 0.30-0.58) than in deep (&kgr;=0.62; 95% CI, 0.48-0.76) or posterior fossa locations (&kgr;=0.66; 95% CI, 0.47-0.84). Using BOMBS, agreement about the presence of ≥1 BMB improved in any location (&kgr;=0.68; 95% CI, 0.49-0.86) and in lobar locations (&kgr;=0.78; 95% CI, 0.60-0.97). Conclusion— Interrater reliability concerning the presence of BMBs was moderate to good, and could be improved with the use of the BOMBS rating scale, which takes into account the main sources of interrater disagreement identified by our pilot scale.
PLOS Biology | 2013
Konstantinos K. Tsilidis; Orestis A. Panagiotou; Emily S. Sena; Eleni Aretouli; Evangelos Evangelou; David W. Howells; Rustam Al-Shahi Salman; Malcolm R. Macleod; John P. A. Ioannidis
The evaluation of 160 meta-analyses of animal studies on potential treatments for neurological disorders reveals that the number of statistically significant results was too large to be true, suggesting biases.
Journal of Neurology, Neurosurgery, and Psychiatry | 2014
Michael Tin Chung Poon; Arthur Fonville; Rustam Al-Shahi Salman
Background and aim There is uncertainty about the long-term prognosis after spontaneous intracerebral haemorrhage (ICH). Therefore, we systematically reviewed the literature for studies reporting long-term survival and ICH recurrence, and their predictors. Methods We searched Ovid Medline 1946–2011 inclusive for cohort studies of ≥50 patients reporting long-term (>30 days) outcome after ICH. Two reviewers independently extracted data from each study. We meta-analysed 1-year and 5-year survival data from population-based studies using a random effects model (and quantified inconsistency using the I2 statistic). Results We identified 122 eligible studies. The pooled estimate of 1-year survival was 46% (95% CI 43% to 49%; nine population-based studies (n=2408); I2=27%) and 5-year survival was 29% (95% CI 26% to 33%; three population-based studies (n=699); I2=6%). In 27 cohort studies, predictors most consistently associated with death were increasing age, decreasing Glasgow Coma Scale score, increasing ICH volume, presence of intraventricular haemorrhage, and deep/infratentorial ICH location. The annual risk of recurrent ICH varied from 1.3% to 7.4% in nine studies and this risk was higher after lobar ICH than non-lobar ICH in two of three hospital-based studies. Four studies reporting the risks of recurrent ICH and ischaemic stroke after ICH found no significant differences between these risks. Conclusions Less than a half of patients with ICH survive 1 year and less than a third survive 5 years. Risks of recurrent ICH and ischaemic stroke after ICH appear similar after ICH, provoking uncertainties about the use of antithrombotic drugs.