ORCID Profile
0000-0002-4816-8991
Current Organisations
The University of Edinburgh
,
University of Oxford
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Publisher: BMJ
Date: 13-01-2013
DOI: 10.1136/PRACTNEUROL-2012-000465
Abstract: Diagnosing stroke is not always straightforward. Stroke mimics such as Todd's paresis or hemiplegic migraine account for between a fifth and a quarter of suspected strokes (depending on the setting in which they are assessed). Stroke chameleons can arise when the tempo of symptom onset is not apoplectic or if the loss of function is not clearly consistent with a deficit within an arterial territory. Thrombolysis and secondary prevention have much to offer patients with stroke chameleons, though those with stroke mimics may be harmed by these treatments and have more to gain from other therapies.
Publisher: Springer Science and Business Media LLC
Date: 30-11-2011
Publisher: BMJ
Date: 06-2021
DOI: 10.1136/BMJOPEN-2020-043906
Abstract: Clinical trials are the gold standard for testing interventions. COVID-19 has further raised their public profile and emphasised the need to deliver better, faster, more efficient trials for patient benefit. Considerable overlap exists between data required for trials and data already collected routinely in electronic healthcare records (EHRs). Opportunities exist to use these in innovative ways to decrease duplication of effort and speed trial recruitment, conduct and follow-up. The National Institute of Health Research (NIHR), Health Data Research UK and Clinical Practice Research Datalink co-organised a national workshop to accelerate the agenda for ‘data-enabled clinical trials’. Showcasing successful ex les and imagining future possibilities, the plenary talks, panel discussions, group discussions and case studies covered: design/feasibility recruitment conduct/follow-up collecting benefits/harms and analysis/interpretation. Some notable studies have successfully accessed and used EHR to identify potential recruits, support randomised trials, deliver interventions and supplement/replace trial-specific follow-up. Some outcome measures are already reliably collected others, like safety, need detailed work to meet regulatory reporting requirements. There is a clear need for system interoperability and a ‘route map’ to identify and access the necessary datasets. Researchers running regulatory-facing trials must carefully consider how data quality and integrity would be assessed. An experience-sharing forum could stimulate wider adoption of EHR-based methods in trial design and execution. EHR offer opportunities to better plan clinical trials, assess patients and capture data more efficiently, reducing research waste and increasing focus on each trial’s specific challenges. The short-term emphasis should be on facilitating patient recruitment and for postmarketing authorisation trials where research-relevant outcome measures are readily collectable. Sharing of case studies is encouraged. The workshop directly informed NIHR’s funding call for ambitious data-enabled trials at scale. There is the opportunity for the UK to build upon existing data science capabilities to identify, recruit and monitor patients in trials at scale.
Publisher: Cold Spring Harbor Laboratory
Date: 13-10-2023
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-07-2020
DOI: 10.1212/WNL.0000000000009924
Abstract: In UK Biobank (UKB), a large population-based prospective study, cases of many diseases are ascertained through linkage to routinely collected, coded national health datasets. We assessed the accuracy of these for identifying incident strokes. In a regional UKB subpopulation (n = 17,249), we identified all participants with ≥1 code signifying a first stroke after recruitment (incident stroke-coded cases) in linked hospital admission, primary care, or death record data. Stroke physicians reviewed their full electronic patient records (EPRs) and generated reference standard diagnoses. We evaluated the number and proportion of cases that were true-positives (i.e., positive predictive value [PPV]) for all codes combined and by code source and type. Of 232 incident stroke-coded cases, 97% had EPR information available. Data sources were 30% hospital admission only, 39% primary care only, 28% hospital and primary care, and 3% death records only. While 42% of cases were coded as unspecified stroke type, review of EPRs enabled a pathologic type to be assigned in %. PPVs (95% confidence intervals) were 79% (73%–84%) for any stroke (89% for hospital admission codes, 80% for primary care codes) and 83% (74%–90%) for ischemic stroke. PPVs for small numbers of death record and hemorrhagic stroke codes were low but imprecise. Stroke and ischemic stroke cases in UKB can be ascertained through linked health datasets with sufficient accuracy for many research studies. Further work is needed to understand the accuracy of death record and hemorrhagic stroke codes and to develop scalable approaches for better identifying stroke types.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2006
Publisher: Springer Science and Business Media LLC
Date: 11-01-2018
Publisher: Elsevier BV
Date: 09-2016
Publisher: Research Square Platform LLC
Date: 25-02-2019
DOI: 10.21203/RS.2.56/V2
Abstract: Background: For adults surviving stroke due to spontaneous (non-traumatic) intracerebral haemorrhage (ICH) who had taken an antithrombotic (i.e. anticoagulant or antiplatelet) drug for the prevention of vaso-occlusive disease before the ICH, it is unclear whether starting antiplatelet drugs modifies the risks of recurrent ICH, haemorrhagic events, vaso-occlusive events, or a composite of all serious vascular events compared to avoiding antiplatelet drugs. Methods/design: The REstart or STop Antithrombotics Randomised Trial (RESTART) is an investigator-led, parallel group, open, assessor-blind, randomised trial comparing starting versus avoiding antiplatelet drugs for adults surviving antithrombotic-associated ICH. Recruitment began on 22 May 2013 and ended on 31 May 2018. Follow-up ended on 30 November 2018. This update to the protocol describes the statistical analysis plan (version 1.7, finalised on 25 January 2019). Database lock and un-blinding occured on 29 January 2019, after which the un-blinded trial statistician conducted the final analyses according to this statistical analysis plan. Discussion: Final results of RESTART will be analysed and disseminated in May 2019. Trial registration: ISRCTN registry 71907627. Prospectively registered on 25 April 2013. The trial is funded by a British Heart Foundation special project grant (SP/12/2/29422) and a travel fellowship (FS/13/72/30531). The trial sponsor is the Academic and Clinical Central Office for Research and Development (ACCORD), which is a partnership between the University of Edinburgh and NHS Lothian Health Board.
Publisher: Elsevier BV
Date: 03-2008
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2017
DOI: 10.1161/CIRCIMAGING.116.004976
Abstract: Combined positron emission tomography (PET) and computed tomography (CT) can assess both anatomy and biology of carotid atherosclerosis. We sought to assess whether 18 F-fluoride or 18 F-fluorodeoxyglucose can identify culprit and high-risk carotid plaque. We performed 18 F-fluoride and 18 F-fluorodeoxyglucose PET/CT in 26 patients after recent transient ischemic attack or minor ischemic stroke: 18 patients with culprit carotid stenosis awaiting carotid endarterectomy and 8 controls without culprit carotid atheroma. We compared standardized uptake values in the clinically adjudicated culprit to the contralateral asymptomatic artery, and assessed the relationship between radiotracer uptake and plaque phenotype or predicted cardiovascular risk (ASSIGN score [Assessing Cardiovascular Risk Using SIGN Guidelines to Assign Preventive Treatment]). We also performed micro PET/CT and histological analysis of excised plaque. On histological and micro PET/CT analysis, 18 F-fluoride selectively highlighted microcalcification. Carotid 18 F-fluoride uptake was increased in clinically adjudicated culprit plaques compared with asymptomatic contralateral plaques (log 10 standardized uptake value mean 0.29±0.10 versus 0.23±0.11, P =0.001) and compared with control patients (log 10 standardized uptake value mean 0.29±0.10 versus 0.12±0.11, P =0.001). 18 F-Fluoride uptake correlated with high-risk plaque features (remodeling index [ r =0.53, P =0.003], plaque burden [ r =0.51, P =0.004]), and predicted cardiovascular risk [ r =0.65, P =0.002]). Carotid 18 F-fluorodeoxyglucose uptake appeared to be increased in 7 of 16 culprit plaques, but no overall differences in uptake were observed in culprit versus contralateral plaques or control patients. However, 18 F-fluorodeoxyglucose did correlate with predicted cardiovascular risk ( r =0.53, P =0.019), but not with plaque phenotype. 18 F-Fluoride PET/CT highlights culprit and phenotypically high-risk carotid plaque. This has the potential to improve risk stratification and selection of patients who may benefit from intervention.
Publisher: Springer Science and Business Media LLC
Date: 05-03-2018
Publisher: SAGE Publications
Date: 14-03-2013
DOI: 10.1111/J.1747-4949.2012.00973.X
Abstract: Stroke survivors experience complex combinations of impairments, activity limitations, and participation restrictions. The essential components of stroke rehabilitation remain elusive. Determining efficacy in randomized controlled trials (RCTs) is challenging there is no commonly agreed primary outcome measure for rehabilitation trials. Clinical guidelines depend on proof of efficacy in RCTs and meta-analyses. However, erse trial aims, differing methods, inconsistent data collection, and use of multiple assessment tools hinder comparability across trials. Consistent data collection in acute stroke trials has facilitated meta-analyses to inform trial design and clinical practice. With few exceptions, inconsistent data collection has hindered similar progress in stroke rehabilitation research. There is an urgent need for the routine collection of a core dataset of common variables in rehabilitation trials. The European Stroke Organisation Outcomes Working Group, the National Institutes of Neurological Disorders and Stroke Common Data Elements project, and the Collaborative Stroke Audit and Research project have called for consistency in data collection in stroke trials. Standardizing data collection can decrease study start up times, facilitate data sharing, and inform clinical guidelines. Although achieving consensus on which outcome measures to use in stroke rehabilitation trials is a considerable task, perhaps a feasible starting point is to achieve consistency in the collection of data on demography, stroke severity, and stroke onset to inclusion times. Longer term goals could include the development of a consensus process to establish the core dataset. This should be endorsed by researchers, funders, and journal editors in order to facilitate sustainable change.
Publisher: SAGE Publications
Date: 08-2006
Publisher: Elsevier BV
Date: 10-2018
DOI: 10.1016/J.YMPEV.2018.06.024
Abstract: The radiation of symbiotic copepods (Crustacea: Copepoda) living in association with stony corals (Cnidaria: Scleractinia) is considered host-specific and linked to the phylogenetic ersification of their hosts. However, symbiotic copepods are poorly investigated, occurrence records are mostly anecdotal, and no explicit analysis exists regarding their relationship with the hosts. Here, we analysed the occurrence of symbiotic copepods on different co-occurring and phylogenetically closely related scleractinian corals. We used an innovative approach of DNA extraction from single microscopic specimens that preserves the shape of the organisms for integrative morphological studies. The rationale of the study involved: (i) s ling of mushroom corals (Fungiidae) belonging to 13 species and eight genera on different reefs along the Saudi coastline in the Red Sea, (ii) extraction of all the associated copepods, (iii) morphological screening and identification of copepod species, (iv) use of DNA taxonomy on mitochondrial and nuclear markers to determine species boundaries for morphologically unknown copepod species, (v) reconstruction of phylogenies to understand their evolutionary relationships, and (vi) analysis of the ecological drivers of the occurrence, ersity and host specificity of the copepods. The seven species of coral-associated copepods, all new to science, did not show any statistically significant evidence of host-specificity or other pattern of ecological association. We thus suggest that, contrary to most assumptions and previous anecdotal evidence on this coral-copepod host-symbiont system, the association between copepods and their host corals is rather labile, not strict, and not phylogenetically constrained, changing our perception on evolutionary patterns and processes in symbiotic copepods.
Publisher: Elsevier BV
Date: 08-2013
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2013
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2016
DOI: 10.1161/STROKEAHA.116.013644
Abstract: Thrombolytic therapy with intravenous alteplase within 4.5 hours of ischemic stroke onset increases the overall likelihood of an excellent outcome (no, or nondisabling, symptoms). Any improvement in functional outcome distribution has value, and herein we provide an assessment of the effect of alteplase on the distribution of the functional level by treatment delay, age, and stroke severity. Prespecified pooled analysis of 6756 patients from 9 randomized trials comparing alteplase versus placebo/open control. Ordinal logistic regression models assessed treatment differences after adjustment for treatment delay, age, stroke severity, and relevant interaction term(s). Treatment with alteplase was beneficial for a delay in treatment extending to 4.5 hours after stroke onset, with a greater benefit with earlier treatment. Neither age nor stroke severity significantly influenced the slope of the relationship between benefit and time to treatment initiation. For the observed case mix of patients treated within 4.5 hours of stroke onset (mean 3 hours and 20 minutes), the net absolute benefit from alteplase (ie, the difference between those who would do better if given alteplase and those who would do worse) was 55 patients per 1000 treated (95% confidence interval, 13–91 P =0.004). Treatment with intravenous alteplase initiated within 4.5 hours of stroke onset increases the chance of achieving an improved level of function for all patients across the age spectrum, including the over 80s and across all severities of stroke studied (top versus bottom fifth means: 22 versus 4) the earlier that treatment is initiated, the greater the benefit.
Publisher: Informa UK Limited
Date: 10-2003
DOI: 10.1080/02688690310001611251
Abstract: Spontaneous intracranial hypotension presenting with confusion and coma has rarely been reported. A case is presented and the clinical features of spontaneous intracranial hypotension are discussed.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 23-04-2007
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 13-11-2006
DOI: 10.1212/01.WNL.0000242704.60275.E9
Abstract: We prospectively recorded CSF opening pressure in 242 adults who had a lumbar puncture with concomitant measurement of weight and height. The 95% reference interval for lumbar CSF opening pressure was 10 to 25 cm CSF. Body mass index had a small but clinically insignificant influence on CSF opening pressure.
Publisher: SAGE Publications
Date: 24-11-2017
Abstract: The recommended maximum age and time window for intravenous alteplase treatment of acute ischemic stroke differs between the Europe Union and United States. We compared the effects of alteplase in cohorts defined by the current Europe Union or United States marketing approval labels, and by hypothetical revisions of the labels that would remove the Europe Union upper age limit or extend the United States treatment time window to 4.5 h. We assessed outcomes in an in idual-patient-data meta-analysis of eight randomized trials of intravenous alteplase (0.9 mg/kg) versus control for acute ischemic stroke. Outcomes included: excellent outcome (modified Rankin score 0–1) at 3–6 months, the distribution of modified Rankin score, symptomatic intracerebral hemorrhage, and 90-day mortality. Alteplase increased the odds of modified Rankin score 0–1 among 2449/6136 (40%) patients who met the current European Union label and 3491 (57%) patients who met the age-revised label (odds ratio 1.42, 95% CI 1.21−1.68 and 1.43, 1.23−1.65, respectively), but not in those outside the age-revised label (1.06, 0.90−1.26). By 90 days, there was no increased mortality in the current and age-revised cohorts (hazard ratios 0.98, 95% CI 0.76−1.25 and 1.01, 0.86–1.19, respectively) but mortality remained higher outside the age-revised label (1.19, 0.99–1.42). Similarly, alteplase increased the odds of modified Rankin score 0-1 among 1174/6136 (19%) patients who met the current US approval and 3326 (54%) who met a 4.5-h revised approval (odds ratio 1.55, 1.19−2.01 and 1.37, 1.17−1.59, respectively), but not for those outside the 4.5-h revised approval (1.14, 0.97−1.34). By 90 days, no increased mortality remained for the current and 4.5-h revised label cohorts (hazard ratios 0.99, 0.77−1.26 and 1.02, 0.87–1.20, respectively) but mortality remained higher outside the 4.5-h revised approval (1.17, 0.98–1.41). An age-revised European Union label or 4.5-h-revised United States label would each increase the number of patients deriving net benefit from alteplase by 90 days after acute ischemic stroke, without excess mortality.
Publisher: Elsevier BV
Date: 06-2016
DOI: 10.1053/J.AJKD.2015.12.028
Abstract: Cognitive impairment is associated with poorer quality of life, risk for hospitalization, and mortality. Cognitive impairment is common in people with end-stage kidney disease treated with hemodialysis, yet the severity and specific cognitive deficits are uncertain. Systematic review and meta-analysis. Adults receiving hemodialysis compared with the general population, people with non-dialysis-dependent chronic kidney disease (NDD-CKD), people receiving peritoneal dialysis, or people with nondialyzed chronic kidney failure. Randomized controlled trials, cohort or cross-sectional studies without language restriction. Validated neuropsychological tests of cognition. Cognitive test scores, aggregated by cognitive domain: orientation and attention, perception, memory, language, construction and motor performance, concept formation and reasoning, and executive functions. 42 studies of 3,522 participants. Studies were of high or uncertain risk of bias, assessed by the Newcastle-Ottawa Scale. People treated with hemodialysis had worse cognition than the general population, particularly in attention (n=22 standardized mean difference [SMD], -0.93 95% CI, -1.18 to -0.68). Hemodialysis patients performed better than nondialyzed patients with chronic kidney failure in attention (n=6 SMD, 0.70 95% CI, 0.45 to 0.96) and memory (n=6 SMD, 0.36 95% CI, 0.08 to 0.63), but had poorer memory than the general population (n=16 SMD, -0.41 95% CI, -0.91 to 0.09) and people with NDD-CKD (n=5 SMD, -0.40 95% CI, -0.60 to -0.21). There were insufficient data to show other differences among people receiving hemodialysis and those receiving peritoneal dialysis or with NDD-CKD. Potentially biased studies, not wholly adjusted for education. High heterogeneity, mainly due to the large variety of tests used to assess cognition. People treated with hemodialysis have impaired cognitive function compared to the general population, particularly in the domains of orientation and attention and executive function. Cognitive deficits in specific domains should be further explored in this population and should be considered when approaching education and chronic disease management.
Publisher: S. Karger AG
Date: 2015
DOI: 10.1159/000441098
Abstract: b i Background: /i /b Recent evidence suggests that stroke is increasing as a cause of morbidity and mortality in younger adults, where it carries particular significance for working in iduals. Accurate and up-to-date estimates of stroke burden are important for planning stroke prevention and management in younger adults. b i Objectives: /i /b This study aims to estimate prevalence, mortality and disability-adjusted life years (DALYs) and their trends for total, ischemic stroke (IS) and hemorrhagic stroke (HS) in the world for 1990-2013 in adults aged 20-64 years. b i Methodology: /i /b Stroke prevalence, mortality and DALYs were estimated using the Global Burden of Disease (GBD) 2013 methods. All available data on rates of stroke incidence, excess mortality, prevalence and death were collected. Statistical models were used along with country-level covariates to estimate country-specific stroke burden. Stroke-specific disability weights were used to compute years lived with disability and DALYs. Means and 95% uncertainty intervals (UIs) were calculated for prevalence, mortality and DALYs. The median of the percent change and 95% UI were determined for the period from 1990 to 2013. b i Results: /i /b In 2013, in younger adults aged 20-64 years, the global prevalence of HS was 3,725,085 cases (95% UI 3,548,098-3,871,018) and IS was 7,258,216 cases (95% UI 6,996,272-7,569,403). Globally, between 1990 and 2013, there were significant increases in absolute numbers and prevalence rates of both HS and IS for younger adults. There were 1,483,707 (95% UI 1,340,579-1,658,929) stroke deaths globally among younger adults but the number of deaths from HS (1,047,735 (95% UI 945,087-1,184,192)) was significantly higher than the number of deaths from IS (435,972 (95% UI 354,018-504,656)). There was a 20.1% (95% UI -23.6 to -10.3) decline in the number of total stroke deaths among younger adults in developed countries but a 36.7% (95% UI 26.3-48.5) increase in developing countries. Death rates for all strokes among younger adults declined significantly in developing countries from 47 (95% UI 42.6-51.7) in 1990 to 39 (95% UI 35.0-43.8) in 2013. Death rates for all strokes among younger adults also declined significantly in developed countries from 33.3 (95% UI 29.8-37.0) in 1990 to 23.5 (95% UI 21.1-26.9) in 2013. A significant decrease in HS death rates for younger adults was seen only in developed countries between 1990 and 2013 (19.8 (95% UI 16.9-22.6) and 13.7 (95% UI 12.1-15.9)) per 100,000). No significant change was detected in IS death rates among younger adults. The total DALYs from all strokes in those aged 20-64 years was 51,429,440 (95% UI 46,561,382-57,320,085). Globally, there was a 24.4% (95% UI 16.6-33.8) increase in total DALY numbers for this age group, with a 20% (95% UI 11.7-31.1) and 37.3% (95% UI 23.4-52.2) increase in HS and IS numbers, respectively. b i Conclusions: /i /b Between 1990 and 2013, there were significant increases in prevalent cases, total deaths and DALYs due to HS and IS in younger adults aged 20-64 years. Death and DALY rates declined in both developed and developing countries but a significant increase in absolute numbers of stroke deaths among younger adults was detected in developing countries. Most of the burden of stroke was in developing countries. In 2013, the greatest burden of stroke among younger adults was due to HS. While the trends in declining death and DALY rates in developing countries are encouraging, these regions still fall far behind those of developed regions of the world. A more aggressive approach toward primary prevention and increased access to adequate healthcare services for stroke is required to substantially narrow these disparities.
Publisher: Public Library of Science (PLoS)
Date: 24-08-2015
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2014
DOI: 10.1161/STROKEAHA.113.004362
Abstract: Intravenous recombinant tissue-type plasminogen activator (r-tPA), despite a risk of early symptomatic intracranial hemorrhage (sICH), is of net clinical benefit to acute stroke patients. We tested if predictive models could identify patients least likely to be harmed by sICH or those who gained no net benefit. We used the Third International Stroke Trial (IST-3) trial data set, an international, multicenter, open treatment randomized trial of 0.9 mg/kg r-tPA versus control in 3035 patients with acute ischemic stroke. We compared the discrimination and calibration of previously developed predictive models for ICH and poststroke poor outcome and developed a new model using variables selected by systematic review. We calculated the absolute and relative risk reduction of death or dependency with r-tPA in patients at a low, medium, or high predicted risk of sICH or poor functional outcome. Prediction models for sICH or poor outcome (Hemorrhage After Thrombolysis [HAT] Sugar, Early Infarct Signs, Dense Artery, Age, National Institutes of Health (NIH) Stroke Score (SEDAN) Glucose Race Age Sex Pressure Stroke Severity [GRASPS] Stroke Thrombolytic Predictive Instrument Dense Artery, Rankin Score, Age, Glucose, Onset to Treatment Time, NIHSS [DRAGON] Totaled Health Risks in Vascular Events [THRIVE] our new model and a model with National Institutes of Health Stroke Scale and age) had similar area under receiver operator characteristic curves (AUROCC) to predict sICH ( P for difference .05). The simplest model (with covariates National Institutes of Health Stroke Scale and age) predicted both sICH (AUROCC, 0.63 95% CI, 0.58–0.68) and poststroke poor functional outcome (AUROCC, 0.80 95% CI, 0.77–0.82) similarly to complex models. There was no evidence that the effect of r-tPA in patients at high predicted risk of sICH or poor functional outcome after stroke was less than in those at lower risk. There is a clinically relevant net positive effect of r-tPA in patients with acute stroke at a high predicted risk of sICH or poor functional outcome. URL: www.controlled-trials.com . Unique identifier: ISRCTN25765518.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2015
DOI: 10.1161/STROKEAHA.115.010319
Abstract: In patients with acute ischemic stroke, a high blood pressure or a highly variable blood pressure is a common reason for withholding thrombolytic treatment, but guidelines recommend a conservative approach to active blood pressure lowering in this setting. We have performed exploratory analyses to study the clinical effects of blood pressure and early blood pressure–lowering treatment in patients included in a randomized-controlled trial of thrombolytic treatment for acute ischemic stroke. The Third International Stroke Trial (IST-3) randomized 3035 patients with ischemic stroke to recombinant tissue-type plasminogen activator 0.9 mg/kg or open control within 6 hours of symptom onset. Blood pressure was measured at randomization, at start of treatment, and at 30 minutes and 1 and 24 hours after start of treatment, and the use of blood pressure–lowering treatment during the first 24 hours was recorded. We have characterized blood pressure by mean systolic blood pressure at baseline, by variability of systolic blood pressure (expressed by the standard deviation and the range between the lowest and the highest pressure), and by the change in systolic blood pressure from baseline to 24 hours. We used logistic regression analysis to explore the associations of blood pressure characteristics or blood pressure–lowering treatment with early adverse events, early death, and functional outcome at 6 months, after adjustment for key prognostic variables. High baseline blood pressure and high blood pressure variability during the first 24 hours were associated with higher numbers of early adverse events and early deaths, and for several analyses, the differences were statistically significant. A larger decline in blood pressure and the use of blood pressure–lowering treatment during the first 24 hours were associated with a reduced risk of poor outcome at 6 months (odds ratio, 0.93 95% confidence interval, 0.89–0.97 P =0.001 and odds ratio, 0.78 95% confidence interval, 0.65–0.93 P =0.007, respectively), irrespective of whether the patient was given recombinant tissue-type plasminogen activator ( P values for interaction .05). Among patients with ischemic stroke who are candidates for thrombolytic treatment, high baseline blood pressure and a large pressure variability during the first 24 hours may be associated with a poor prognosis, whereas a large reduction in blood pressure and the use of blood pressure–lowering treatment during the first 24 hours may be associated with a favorable prognosis. These data support the rationale for further trials of agents that lower blood pressure or reduce blood pressure variability in the acute phase of ischemic stroke. URL: www.clinicaltrials.gov . Unique identifier: NCT00120003.
Publisher: American Medical Association (AMA)
Date: 10-2021
Publisher: Elsevier BV
Date: 07-2022
Publisher: BMJ
Date: 17-08-2009
DOI: 10.1136/BMJ.B3016
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-12-2015
Publisher: Elsevier BV
Date: 05-2015
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2022
DOI: 10.1161/STROKEAHA.122.039082
Abstract: The utility of magnetic resonance imaging (MRI) brain in patients with transient or minor neurological symptoms is uncertain. We sought to determine the proportion of participants with transient or minor neurological symptoms who had MRI evidence of acute ischemia at different clinical probabilities of transient ischemic attack (TIA) or minor stroke. Cohort of participants with transient or minor neurological symptoms from emergency and outpatient settings. Clinicians at different levels of training gave each participant a diagnostic probability (probable when TIA/stroke was the most likely differential diagnosis possible when TIA/stroke was not the most likely differential diagnosis or uncertain when diagnostic probability could not be given) before 1.5 or 3T brain MRI ≤5 days from onset. Post hoc, each clinical syndrome was defined blind to MRI findings as National Institute of Neurological Disorders and Stroke criteria TIA/stroke International Headache Society criteria migraine aura non-TIA focal symptoms or nonfocal symptoms. MRI evidence of acute ischemia was defined by 2 reads of MRI. Stroke was ascertained for at least 90 days and up to 18 months after recruitment. Two hundred seventy-two participated (47% female, mean age 60, SD 14), 58% with MRI ≤2 days of onset. Most (92%) reported focal symptoms. MR evidence of acute ischemia was found, for stroke/TIA clinical probabilities of probable 23 out of 75 (31% [95% CI, 21%–42%]) possible 26 out of 151 (17% [12%–24%]) and uncertain 9 out of 43, (20% [10%–36%]). MRI evidence of acute ischemia was found in National Institute of Neurological Disorders and Stroke criteria TIA/stroke 40 out of 95 (42% [32%–53%]) migraine aura 4 out of 38 (11% [3%–25%]) non-TIA focal symptoms 16 out of 99 (16% [10%–25%]) and no focal features 1 out of 29 (3% [0%–18%]). After MRI, a further 14 (5% [95% CI, 3–8]) would be treated with an antiplatelet drug compared with treatment plan before MRI. By 18 months, a new ischemic stroke occurred in 9 out of 61 (18%) patients with MRI evidence of acute ischemia and 2 out of 211 (1%) without (age-adjusted hazard ratio, 13 [95% CI, 3–62] P .0001). MRI evidence of acute brain ischemia was found in about 1 in 6 transient or minor neurological symptoms patients with a nonstroke/TIA initial diagnosis or uncertain diagnosis. Methods to determine the clinical and cost-effectiveness of MRI are needed in this population.
Publisher: BMJ
Date: 22-11-2018
DOI: 10.1136/BMJ.K4577
Abstract: To determine prevalence and types of potentially serious incidental findings on magnetic resonance imaging (MRI) in apparently asymptomatic adults, describe factors associated with potentially serious incidental findings, and summarise information on follow-up and final diagnoses. Systematic review and meta-analyses. Citation searches of relevant articles and authors’ files in Medline and Embase (from inception to 25 April 2017). Eligible studies included prevalence and types of incidental findings detected among apparently asymptomatic adults undergoing MRI of the brain, thorax, abdomen, or brain and body. Data on study population and methods, prevalence and types of incidental findings, and final diagnoses were extracted. Pooled prevalence was estimated by random effects meta-analysis, and heterogeneity by τ 2 statistics. Prevalence of potentially serious incidental findings on MRI of the brain, thorax, abdomen, and brain and body. Of 5905 retrieved studies, 32 (0.5%) met the inclusion criteria (n=27 643 participants). Pooled prevalence of potentially serious incidental findings was 3.9% (95% confidence interval 0.4% to 27.1%) on brain and body MRI, 1.4% (1.0% to 2.1%) on brain MRI, 1.3% (0.2% to 8.1%) on thoracic MRI, and 1.9% (0.3% to 12.0%) on abdominal MRI. Pooled prevalence rose after including incidental findings of uncertain potential seriousness (12.8% (3.9% to 34.3%), 1.7% (1.1% to 2.6%), 3.0% (0.8% to 11.3%), and 4.5% (1.5% to 12.9%), respectively). There was generally substantial heterogeneity among included studies. About half the potentially serious incidental findings were suspected malignancies (brain, 0.6% (95% confidence interval 0.4% to 0.9%) thorax, 0.6% (0.1% to 3.1%) abdomen, 1.3% (0.2% to 9.3%) brain and body, 2.3% (0.3% to 15.4%)). There were few informative data on potential sources of between-study variation or factors associated with potentially serious incidental findings. Limited data suggested that relatively few potentially serious incidental findings had serious final diagnoses (48/234, 20.5%). A substantial proportion of apparently asymptomatic adults will have potentially serious incidental findings on MRI, but little is known of their health consequences. Systematic, long term follow-up studies are needed to better inform on these consequences and the implications for policies on feedback of potentially serious incidental findings. Prospero CRD42016029472.
Publisher: Elsevier BV
Date: 11-2014
Publisher: Springer Science and Business Media LLC
Date: 25-03-2019
Publisher: SAGE Publications
Date: 09-03-2012
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2015
DOI: 10.1161/STROKEAHA.114.006573
Abstract: Our aim was to identify whether particular subgroups of patients had an unacceptably high risk of symptomatic intracranial hemorrhage or low chance of benefit when treated with alteplase (recombinant tissue-type plasminogen activator). Third International Stroke Trial was an international randomized trial of the intravenous (IV) recombinant plasminogen activator alteplase (0.9 mg/kg) versus control in 3035 (1515 versus 1520) patients. We analyzed the effect of recombinant tissue-type plasminogen activator on 6-month functional outcome, early death, and symptomatic intracranial hemorrhage (both ≤7 days). We tested for any differences in treatment effect between subgroups by a test of interaction. Our 13 protocol prespecified subgroups were time to randomization, age, sex, stroke subtype, atrial fibrillation, early ischemic change (clinician and expert panel), prior antiplatelet use, stroke severity, diastolic and systolic blood pressure at randomization, center’s thrombolysis experience, and trial phase. Analyses were adjusted for key baseline prognostic factors. There were no significant interactions in the subgroups analyzed that were consistent across all 3 outcomes. Treatment with recombinant tissue-type plasminogen activator increased the odds of symptomatic intracranial hemorrhage by a greater amount in patients taking prior antiplatelets than those who were not ( P =0.019 for test of interaction), but had no clear detrimental effect on functional outcome at 6 months in this group ( P =0.781 for test of interaction). Among the types of patient in the Third International Stroke Trial, this secondary analysis did not identify any subgroups for whom treatment should be avoided. Given the limitations of the analysis, we found no clear evidence to avoid treatment in patients with prior ischemic stroke, diabetes mellitus, or hypertension. URL: www.controlled-trials.com . Unique identifier: ISRCTN25765518. www.controlled-trials.com/ISRCTN25765518 .
Publisher: Elsevier BV
Date: 06-2019
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2014
DOI: 10.1161/STROKEAHA.114.006890
Abstract: Prompt thrombolytic therapy with intravenous alteplase reduces disability after acute ischemic stroke. In an exploratory analysis, we examined whether long-term survival varied by baseline characteristics after alteplase. In this open-treatment, international, randomized, controlled trial, ischemic stroke patients were randomly allocated hours of onset to intravenous alteplase (0.9 mg/kg) plus standard care (n=1515) or standard care alone (n=1520). We followed patients to death, censoring when last known to be alive. We grouped patients by delay to randomization, and good or poor predicted prognosis (calculated from baseline National Institutes of Health Stroke Scale [NIHSS] score and age). We present absolute mortality differences between treated and control groups at 7 days, 6 months, and 18 months poststroke. Alteplase was not associated with a significant increase in mortality within 18 months (0.6% [95% confidence interval (CI), −2.9% to +4.2] P =0.72] in all patients with complete vital status (99.9%, 3034/3035). In patients randomized hours of stroke, 18-month mortality was lower in the alteplase-treated group than the control group (40.6% [95% CI, 42.6–52.7] versus 47.8% [95% CI, 35.5–45.3] P =0.0434]. The difference in 18-month mortality between alteplase-treated and control patients was greater in patients who were randomized early ( hours) compared with late (3–6 hours +9% [95% CI, 1–17] P =0.0317). Alteplase led to a greater improvement in 18-month survival in patients with a poor prognosis than in patients with a good prognosis (+8% [95% CI, 2–14] P =0.0091). These exploratory analyses of the third International Stroke Trial (IST-3) trial support improving acute stroke patients’ access to earlier alteplase treatment, treatment of patients with poor prognosis, and further randomized controlled trials in minor stroke to replicate these findings. URL: www.controlled-trials.com . Unique identifier: ISRCTN25765518.
Publisher: American Medical Association (AMA)
Date: 23-04-2014
Abstract: Whether conservative management is superior to interventional treatment for unruptured brain arteriovenous malformations (bAVMs) is uncertain because of the shortage of long-term comparative data. To compare the long-term outcomes of conservative management vs intervention for unruptured bAVM. Population-based inception cohort study of 204 residents of Scotland aged 16 years or older who were first diagnosed as having an unruptured bAVM during 1999-2003 or 2006-2010 and followed up prospectively for 12 years. Conservative management (no intervention) vs intervention (any endovascular embolization, neurosurgical excision, or stereotactic radiosurgery alone or in combination). Cox regression analyses, with multivariable adjustment for prognostic factors and baseline imbalances if hazards were proportional, to compare rates of the primary outcome (death or sustained morbidity of any cause by Oxford Handicap Scale [OHS] score ≥2 for ≥2 successive years [0 = no symptoms and 6 = death]) and the secondary outcome (nonfatal symptomatic stroke or death due to bAVM, associated arterial aneurysm, or intervention). Of 204 patients, 103 underwent intervention. Those who underwent intervention were younger, more likely to have presented with seizure, and less likely to have large bAVMs than patients managed conservatively. During a median follow-up of 6.9 years (94% completeness), the rate of progression to the primary outcome was lower with conservative management during the first 4 years of follow-up (36 vs 39 events 9.5 vs 9.8 per 100 person-years adjusted hazard ratio, 0.59 95% CI, 0.35-0.99), but rates were similar thereafter. The rate of the secondary outcome was lower with conservative management during 12 years of follow-up (14 vs 38 events 1.6 vs 3.3 per 100 person-years adjusted hazard ratio, 0.37 95% CI, 0.19-0.72). Among patients aged 16 years or older diagnosed as having unruptured bAVM, use of conservative management compared with intervention was associated with better clinical outcomes for up to 12 years. Longer follow-up is required to understand whether this association persists.
Publisher: Springer Science and Business Media LLC
Date: 12-2016
Publisher: Elsevier BV
Date: 10-2021
Publisher: Elsevier BV
Date: 03-2012
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2023
DOI: 10.1161/STROKEAHA.122.040529
Abstract: Anti-inflammatory therapies reduce recurrent vascular events in coronary disease. Existing studies have reported highly conflicting findings for the association of blood inflammatory markers with vascular recurrence after stroke leading to uncertainty about the potential of anti-inflammatory therapies after stroke and no consensus about the utility of measurement of inflammatory markers in current guidelines. We investigated the association between hsCRP (high-sensitivity C-reactive protein), IL-6 (interluekin-6), and recurrent major adverse cardiovascular events (MACE), and stroke from in idual participant data from 8420 patients with ischemic stroke/transient ischemic attack from 10 prospective studies. We did within-study multivariable regression analyses and then combined adjusted risk ratio (RR) by random-effects meta-analysis. During 18 920 person-years of follow-up, 1407 (16.7% [95% CI, 15.9–17.5]) patients had MACE and 1191 (14.1% [95% CI, 13.4–14.9]) patients had recurrent stroke. On bivariate analysis, baseline IL-6 was associated with MACE (RR, 1.26 [95% CI, 1.10–1.43]) and recurrent stroke (RR, 1.18 [95% CI, 1.05–1.32]), per unit increase log e IL-6. Similar associations were observed for hsCRP (MACE RR, 1.19 [95% CI, 1.09–1.29] recurrent stroke RR, 1.12 [95% CI, 1.04–1.21], per unit increase log e hsCRP). After adjustment for vascular risk factors and treatment, independent associations remained with MACE (IL-6, RR, 1.12 [95% CI, 1.04–1.21] hsCRP, RR, 1.09 [95% CI, 1.04–1.15]) and recurrent stroke (IL-6, RR, 1.09 [95% CI, 1.00–1.19] hsCRP, RR, 1.05 [95% CI, 1.00–1.11]). Comparing the top with the bottom quarters (Q4 versus Q1), IL-6 (RR, 1.35 [95% CI, 1.09–1.67]) and hsCRP (RR, 1.31 [95% CI, 1.07–1.61]) were associated with MACE after adjustment. Similar results were observed for recurrent stroke for IL-6 (RR, 1.33 [95% CI, 1.08–1.65]) but not hsCRP (RR, 1.16 [95% CI, 0.93–1.43]). Blood markers of inflammation were independently associated with vascular recurrence after stroke, strengthening the rationale for randomized trials of anti-inflammatory therapies for secondary prevention after ischemic stroke/TIA.
Publisher: SAGE Publications
Date: 03-2007
DOI: 10.1258/096914107780154530
Abstract: Objective: Some private health screening companies in the UK provide 'health check-ups' using whole-body magnetic resonance imaging (MRI), in spite of the lack of evidence demonstrating that such screening is worthwhile. We discuss the issues surrounding the use of an MRI scan as a screening test in 'health check-ups' and set out our concerns. Conclusion: Because of the five balance between the potential perils and benefits of the unselective use of brain MRI for 'health check-ups', its use should be restricted to a research setting.
Publisher: Elsevier BV
Date: 07-2019
Publisher: Elsevier BV
Date: 06-2012
Publisher: SAGE Publications
Date: 03-05-2013
DOI: 10.1111/IJS.12040
Abstract: Thrombolysis with intravenous alteplase is both effective and safe when administered to particular types of patient within 4·5 hours of having an ischemic stroke. However, the extent to which effects might vary in different types of patient is uncertain. We describe the protocol for an updated in idual patient data meta-analysis of trials of intravenous alteplase, including results from the recently reported third International Stroke Trial, in which a wide range of patients enrolled up to six-hours after stroke onset were randomized to alteplase vs. control. This protocol will specify the primary outcome for efficacy, specified prior to knowledge of the results from the third International Stroke Trial, as the proportion of patients having a ‘favorable’ stroke outcome, defined by modified Rankin Score 0–1 at final follow-up at three- to six-months. The primary analysis will be to estimate the extent to which the known benefit of alteplase on modified Rankin Score 0–1 diminishes with treatment delay, and the extent to which it is independently modified by age and stroke severity. Key secondary outcomes include effect of alteplase on death within 90 days analyses of modified Rankin Score using ordinal, rather than dichotomous, methods and effects of alteplase on symptomatic intracranial hemorrhage, fatal intracranial hemorrhage, symptomatic ischemic brain edema and early edema, effacement and/or midline shift. This collaborative meta-analysis of in idual participant data from all randomized trials of intravenous alteplase vs. control will demonstrate how the known benefits of alteplase on ischemic stroke outcome vary across different types of patient.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2015
DOI: 10.1161/STROKEAHA.114.007953
Abstract: The characteristics of intracerebral hemorrhage (ICH) may vary by ICH location because of differences in the distribution of underlying cerebral small vessel diseases. Therefore, we investigated the incidence, characteristics, and outcome of lobar and nonlobar ICH. In a population-based, prospective inception cohort study of ICH, we used multiple overlapping sources of case ascertainment and follow-up to identify and validate ICH diagnoses in 2010 to 2011 in an adult population of 695 335. There were 128 participants with first-ever primary ICH. The overall incidence of lobar ICH was similar to nonlobar ICH (9.8 [95% confidence interval, 7.7–12.4] versus 8.6 [95% confidence interval, 6.7–11.1] per 100 000 adults/y). At baseline, adults with lobar ICH were more likely to have preceding dementia (21% versus 5% P =0.01), lower Glasgow Coma Scale scores (median, 13 versus 14 P =0.03), larger ICHs (median, 38 versus 11 mL P .001), subarachnoid extension (57% versus 5% P .001), and subdural extension (15% versus 3% P =0.02) than those with nonlobar ICH. One-year case fatality was lower after lobar ICH than after nonlobar ICH (adjusted odds ratio for death at 1 year: lobar versus nonlobar ICH 0.21 95% confidence interval, 0.07–0.63 P =0.006, after adjustment for known predictors of outcome). There were 4 recurrent ICHs, which occurred exclusively in survivors of lobar ICH (annual risk of recurrent ICH after lobar ICH, 11.8% 95% confidence interval, 4.6%–28.5% versus 0% after nonlobar ICH log-rank P =0.04). The baseline characteristics and outcome of lobar ICH differ from other locations.
Publisher: SAGE Publications
Date: 25-11-2020
Abstract: Hospital-based studies have reported variable associations between outcome after spontaneous intracerebral hemorrhage and peri-hematomal edema volume. In a community-based study, we aimed to investigate the existence, strength, direction, and independence of associations between intracerebral hemorrhage and peri-hematomal edema volumes on diagnostic brain CT and one-year functional outcome and long-term survival. We identified all adults, resident in Lothian, diagnosed with first-ever, symptomatic spontaneous intracerebral hemorrhage between June 2010 and May 2013 in a community-based, prospective inception cohort study. We defined regions of interest manually and used a semi-automated approach to measure intracerebral hemorrhage volume, peri-hematomal edema volume, and the sum of these measurements (total lesion volume) on first diagnostic brain CT performed at ≤3 days after symptom onset. The primary outcome was death or dependence (scores 3–6 on the modified Rankin Scale) at one-year after intracerebral hemorrhage. Two hundred ninety-two (85%) of 342 patients (median age 77.5 y, IQR 68–83, 186 (54%) female, median time from onset to CT 6.5 h (IQR 2.9–21.7)) were dead or dependent one year after intracerebral hemorrhage. Peri-hematomal edema and intracerebral hemorrhage volumes were colinear ( R 2 = 0.77). In models using both intracerebral hemorrhage and peri-hematomal edema, 10 mL increments in intracerebral hemorrhage (adjusted odds ratio (aOR) 1.72 (95% CI 1.08–2.87) p = 0.029) but not peri-hematomal edema volume (aOR 0.92 (0.63–1.45) p = 0.69) were independently associated with one-year death or dependence. 10 mL increments in total lesion volume were independently associated with one-year death or dependence (aOR 1.24 (1.11–1.42) p = 0.0004). Total volume of intracerebral hemorrhage and peri-hematomal edema, and intracerebral hemorrhage volume alone on diagnostic brain CT, undertaken at three days or sooner, are independently associated with death or dependence one-year after intracerebral hemorrhage, but peri-hematomal edema volume is not. Anonymized summary data may be requested from the corresponding author.
Publisher: Wiley
Date: 08-2016
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for William Whiteley.