ORCID Profile
0000-0002-9523-2546
Current Organisations
Nottingham University Hospitals NHS Trust
,
University of Nottingham
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Publisher: Elsevier BV
Date: 09-2022
DOI: 10.1016/J.EJPN.2022.07.004
Abstract: To explore neurological factors affecting quality of life (QoL) in children and young people with ataxia-telangiectasia (A-T), from both child and parent perspective. 24 children/young people with A-T (mean age 11.2 ± 3.5 years 13 males) and 20 parents were recruited, and 58% were reassessed after an average interval of 3.4 years. Participants completed the PedsQL QoL assessment. Participants with A-T underwent structured neurological examination. QoL data from 20 healthy controls and their parents was used for comparison. Children/young people with A-T rated their QoL higher than parental ratings across time points, with no longitudinal change. Higher age of the child participant correlated with lower parental (r = -0.43, p = .008) but not child ratings of QoL (r = -0.16, p = .380). Child and parent QoL ratings from the A-T group were lower than respective ratings from controls (η Neurological disability does not determine child/young person QoL ratings in A-T. While certain aspects of neurological disability predict parent-proxy ratings, there is no decline in QoL over time. These results may reflect resilience in the face of a complex life-limiting disorder.
Publisher: American Medical Association (AMA)
Date: 05-2022
Publisher: Radiological Society of North America (RSNA)
Date: 04-2015
Abstract: To identify statistical consensus between published studies for distribution and functional relevance of tract white matter (WM) degradation in multiple sclerosis (MS). By systematically searching online databases, tract-based spatial statistics studies were identified that compared fractional anisotropy (FA a marker for WM integrity) in MS patients to healthy control subjects, correlated FA in MS patients with physical disability, or correlated FA in MS patients with cognitive performance. Voxelwise meta-analysis was performed by using the Signed Differential Mapping method for each comparison. Moderating effects of mean age, mean physical disability score, imager magnet strength, lesion load, and number of diffusion directions were assessed by means of meta-regression. Meta-analysis was performed on data from 495 patients and 253 control subjects across 12 studies. MS diagnosis was significantly associated with widespread lower tract FA (nine studies largest cluster, 4379 voxels z = 7.1 P < .001). Greater physical disability was significantly associated with lower FA in the right posterior cingulum, left callosal splenium, right inferior fronto-occipital fasciculus, and left fornix crus (six studies 323 voxels z = 1.7 P = .001). Impaired cognition was significantly associated with lower FA in the callosal genu, thalamus, right posterior cingulum, and fornix crus (seven studies largest cluster, 980 voxels z = 2.5 P < .001). WM damage is widespread in MS with differential and only minimally overlapping distributions of low FA that relates to physical disability and cognitive impairment. The higher number of clusters of lower FA in relation to cognition and their higher z scores suggest that cerebral WM damage may have a greater relevance to cognitive dysfunction than physical disability in MS, and that low anterior callosal and thalamic FA have specific importance to cognitive status.
Publisher: BMJ
Date: 17-02-2022
DOI: 10.1136/ARCHDISCHILD-2021-323444
Abstract: Rate and severity of radiological features of physical abuse in children during the first UK-wide COVID-19 enforced national lockdown. To assess the number, type and outcome of radiological investigations for children presenting to hospital with suspected physical abuse (SPA including abusive head trauma) during the first national COVID-19 enforced lockdown compared with the prelockdown period. Multicentre, retrospective, observational, interrupted time series analysis. Eight secondary/tertiary paediatric centres between January 2018 and July 2020 inclusive. 1587 hospital assessed children undergoing radiographic skeletal surveys (SkS) and head CT imaging performed for SPA/child protection concerns. Incidence and severity of fractures identified on SkS head injury (composed of incidence rates and ratios of skull fracture, intracranial haemorrhage (ICH) and hypoxic ischaemic injury (HII)) on head CT imaging and ratio of antemortem and postmortem SkS. 1587 SkS were performed: 1282 (81%) antemortem, 762 (48%) male, and positive findings in 582 (37%). Median patient age was 6 months. There were 1.7 fractures/child prelockdown versus 1.1 fractures/child during lockdown. There was no difference between positive/negative SkS rates, the absolute ratio of antemortem ostmortem SkS or absolute numbers of head injury occurring between January 2018 and February 2020 and the lockdown period April–July 2020. Likewise, prelockdown incidence and rates of skull fracture 30/244 (12%), ICH 28/220 (13%) and HIE 10/205 (5%) were similar to lockdown, 142/1304 (11%), 171/1152 (15%) and 68/1089 (6%), respectively. The first UK COVID-19 lockdown did not lead to an increase in either the number of antemortem or postmortem radiological investigations performed for SPA, or the number or severity of fractures and intracranial injuries identified by these investigations.
Publisher: Wiley
Date: 04-12-2018
DOI: 10.1002/HBM.24411
Publisher: SAGE Publications
Date: 16-12-2011
Abstract: To investigate two approaches to treating patients with persistent dressing problems and cognitive difficulties following stroke. Pilot randomized controlled trial. Inpatient stroke rehabilitation service. Seventy consecutive stroke patients with persistent dressing problems and accompanying cognitive difficulties at two weeks after their stroke. Patients were randomly allocated to six weeks of either a systematic neuropsychological approach, based on analysis of dressing problems and further cognitive testing, or to the control group who received conventional (functional) dressing practice. Both groups received treatment three times a week in accordance with two separately prepared manuals. Nottingham Stroke Dressing Assessment (NSDA), Line Cancellation, 10-hole peg transfer test, Object Decision, Gesture Imitation. Patients were assessed at six weeks after randomization by an independent assessor masked to group allocation. Both neuropsychological and functional groups improved performance on the NSDA over the treatment period (31% and 22%, respectively) but there was no significant difference between groups at six weeks. However, the neuropsychological group showed a significantly greater improvement on a line cancellation test of visual neglect ( t(62) = 2.1, P 0.05) and a planned subanalysis for those with right hemisphere damage showed a trend towards better dressing outcome ( P = 0.07, one-tailed). Results demonstrate the potential benefits of a systematic neuropsychological approach to dressing therapy, particularly for patients with right hemisphere damage. This study suggests the need for a phase III study evaluating the efficacy of a systematic neuropsychological approach in treating dressing difficulties, targeting patients with right hemisphere stroke and visuospatial impairments.
Publisher: Mary Ann Liebert Inc
Date: 05-2015
Publisher: Elsevier BV
Date: 2020
Publisher: BMJ
Date: 02-2018
DOI: 10.1136/BMJOPEN-2017-019930
Abstract: To test whether administration of the antifibrinolytic drug tranexamic acid (TXA) in patients with spontaneous intracerebral haemorrhage (SICH) leads to increased prevalence of diffusion-weighted MRI-defined hyperintense ischaemic lesions (primary hypothesis) or reduced perihaematomal oedema volume, perihaematomal diffusion restriction and residual MRI-defined SICH-related tissue damage (secondary hypotheses). MRI substudy nested within the double-blind randomised controlled Tranexamic Acid for Hyperacute Primary Intracerebral Haemorrhage (TICH)-2 trial ( ISRCTN93732214 ). International multicentre hospital-based study. Eligible adults consented and randomised in the TICH-2 trial who were also able to undergo MRI scanning. To address the primary hypothesis, a s le size of n=280 will allow detection of a 10% relative increase in prevalence of diffusion-weighted imaging (DWI) hyperintense lesions in the TXA group with 5% significance, 80% power and 5% imaging data rejection. TICH-2 MRI substudy participants will undergo MRI scanning using a standardised protocol at day ~5 and day ~90 after randomisation. Clinical assessments, randomisation to TXA or placebo and participant follow-up will be performed as per the TICH-2 trial protocol. The TICH-2 MRI substudy will test whether TXA increases the incidence of new DWI-defined ischaemic lesions or reduces perihaematomal oedema or final ICH lesion volume in the context of SICH. The TICH-2 trial obtained ethical approval from East Midlands - Nottingham 2 Research Ethics Committee (12/EM/0369) and an amendment to allow the TICH-2 MRI sub study was approved in April 2015 (amendment number SA02/15). All findings will be published in peer-reviewed journals. The primary outcome results will also be presented at a relevant scientific meeting. ISRCTN93732214 Pre-results.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2016
DOI: 10.1161/STROKEAHA.115.010368
Abstract: The Efficacy of Nitric Oxide in Stroke (ENOS) trial found that transdermal glyceryl trinitrate (GTN, a nitric oxide donor) lowered blood pressure but did not improve functional outcome in patients with acute stroke. However, GTN was associated with improved outcome if patients were randomized within 6 hours of stroke onset. In this prespecified subgroup analysis, the effect of GTN (5 mg/d for 7 days) versus no GTN was studied in 629 patients with intracerebral hemorrhage presenting within 48 hours and with systolic blood pressure ≥140 mm Hg. The primary outcome was the modified Rankin Scale at 90 days. Mean blood pressure at baseline was 172/93 mm Hg and significantly lower (difference −7.5/−4.2 mm Hg both P ≤0.05) on day 1 in 310 patients allocated to GTN when compared with 319 randomized to no GTN. No difference in the modified Rankin Scale was observed between those receiving GTN versus no GTN (adjusted odds ratio for worse outcome with GTN, 1.04 95% confidence interval, 0.78–1.37 P =0.84). In the subgroup of 61 patients randomized within 6 hours, GTN improved functional outcome with a shift in the modified Rankin Scale (odds ratio, 0.22 95% confidence interval, 0.07–0.69 P =0.001). There was no significant difference in the rates of serious adverse events between GTN and no GTN. In patients with intracerebral hemorrhage within 48 hours of onset, GTN lowered blood pressure was safe but did not improve functional outcome. Very early treatment might be beneficial but needs assessment in further studies. URL: www.isrctn.com/ISRCTN99414122 . Unique identifier: 99414122.
Publisher: Radiological Society of North America (RSNA)
Date: 07-2022
Abstract: Background Diffuse midline gliomas (DMG) are characterized by a high incidence of
Publisher: Oxford University Press (OUP)
Date: 06-2018
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 27-12-2019
DOI: 10.1212/WNL.0000000000008881
Abstract: To assess the association of baseline imaging markers of cerebral small vessel disease (SVD) and brain frailty with clinical outcome after acute stroke in the Efficacy of Nitric Oxide in Stroke (ENOS) trial. ENOS randomized 4,011 patients with acute stroke ( hours of onset) to transdermal glyceryl trinitrate (GTN) or no GTN for 7 days. The primary outcome was functional outcome (modified Rankin Scale [mRS] score) at day 90. Cognition was assessed via telephone at day 90. Stroke syndrome was classified with the Oxfordshire Community Stroke Project classification. Brain imaging was adjudicated masked to clinical information and treatment and assessed SVD (leukoaraiosis, old lacunar infarcts/lacunes, atrophy) and brain frailty (leukoaraiosis, atrophy, old vascular lesions/infarcts). Analyses used ordinal logistic regression adjusted for prognostic variables. In all participants and those with lacunar syndrome (LACS 1,397, 34.8%), baseline CT imaging features of SVD and brain frailty were common and independently associated with unfavorable shifts in mRS score at day 90 (all participants: SVD score odds ratio [OR] 1.15, 95% confidence interval [CI] 1.07–1.24 brain frailty score OR 1.25, 95% CI 1.17–1.34 those with LACS: SVD score OR 1.30, 95% CI 1.15–1.47, brain frailty score OR 1.28, 95% CI 1.14–1.44). Brain frailty was associated with worse cognitive scores at 90 days in all participants and in those with LACS. Baseline imaging features of SVD and brain frailty were common in lacunar stroke and all stroke, predicted worse prognosis after all acute stroke with a stronger effect in lacunar stroke, and may aid future clinical decision-making. ISRCTN99414122.
Publisher: BMJ
Date: 06-2023
Publisher: Cold Spring Harbor Laboratory
Date: 23-09-2021
DOI: 10.1101/2021.09.21.21263298
Abstract: Cerebral microbleeds (CMBs) appear as small, circular, well defined hypointense lesions of a few mm in size on T2*-weighted gradient recalled echo (T2*-GRE) images and appear enhanced on susceptibility weighted images (SWI). Due to their small size, contrast variations and other mimics (e.g. blood vessels), CMBs are highly challenging to detect automatically. In large datasets (e.g. the UK Biobank dataset), exhaustively labelling CMBs manually is difficult and time consuming. Hence it would be useful to preselect candidate CMB subjects in order to focus on those for manual labelling, which is essential for training and testing automated CMB detection tools on these datasets. In this work, we aim to detect CMB candidate subjects from a larger dataset, UK Biobank, using a machine learning-based, computationally light pipeline. For our evaluation, we used 3 different datasets, with different intensity characteristics, acquired with different scanners. They include the UK Biobank dataset and two clinical datasets with different pathological conditions. We developed and evaluated our pipelines on different types of images, consisting of SWI or GRE images. We also used the UK Biobank dataset to compare our approach with alternative CMB preselection methods using non-imaging factors and/or imaging data. Finally, we evaluated the pipeline’s generalisability across datasets. Our method provided subject-level detection accuracy 80% on all the datasets (withindataset results), and showed good generalisability across datasets, providing a consistent accuracy of over 80%, even when evaluated across different modalities.
Publisher: Mary Ann Liebert Inc
Date: 03-2020
Publisher: Wiley
Date: 25-10-2019
DOI: 10.1111/ENE.14084
Publisher: British Institute of Radiology
Date: 10-05-2018
DOI: 10.1259/BJR.20170719
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2022
DOI: 10.1161/STROKEAHA.121.035191
Abstract: Seeking consent rapidly in acute stroke trials is crucial as interventions are time sensitive. We explored the association between consent pathways and time to enrollment in the TICH-2 (Tranexamic Acid in Intracerebral Haemorrhage-2) randomized controlled trial. Consent was provided by patients or by a relative or an independent doctor in incapacitated patients, using a 1-stage (full written consent) or 2-stage (initial brief consent followed by full written consent post-randomization) approach. The computed tomography-to-randomization time according to consent pathways was compared using the Kruskal-Wallis test. Multivariable logistic regression was performed to identify variables associated with onset-to-randomization time of ≤3 hours. Of 2325 patients, 817 (35%) gave self-consent using 1-stage (557 68%) or 2-stage consent (260 32%). For 1507 (65%), consent was provided by a relative (1 stage, 996 [66%] 2 stage, 323 [21%]) or a doctor (all 2-stage, 188 [12%]). One patient did not record prerandomization consent, with written consent obtained subsequently. The median (interquartile range) computed tomography-to-randomization time was 55 (38–93) minutes for doctor consent, 55 (37–95) minutes for 2-stage patient, 69 (43–110) minutes for 2-stage relative, 75 (48–124) minutes for 1-stage patient, and 90 (56–155) minutes for 1-stage relative consents ( P .001). Two-stage consent was associated with onset-to-randomization time of ≤3 hours compared with 1-stage consent (adjusted odds ratio, 1.9 [95% CI, 1.5–2.4]). Doctor consent increased the odds (adjusted odds ratio, 2.3 [1.5–3.5]) while relative consent reduced the odds of randomization ≤3 hours (adjusted odds ratio, 0.10 [0.03–0.34]) compared with patient consent. Only 2 of 771 patients (0.3%) in the 2-stage pathways withdrew consent when full consent was sought later. Two-stage consent process did not result in higher withdrawal rates or loss to follow-up. The use of initial brief consent was associated with shorter times to enrollment, while maintaining good participant retention. Seeking written consent from relatives was associated with significant delays. URL: www.isrctn.com Unique identifier: ISRCTN93732214.
Publisher: SAGE Publications
Date: 09-07-2016
Abstract: Outcome after intracerebral hemorrhage remains poor. Tranexamic acid is easy to administer, readily available, inexpensive, and effective in other hemorrhagic conditions. This randomized trial aims to test the hypothesis that intravenous tranexamic acid given within 8 h of spontaneous intracerebral hemorrhage reduces death or dependency. Phase III prospective double-blind randomized placebo-controlled trial. Participants within 8 h of spontaneous intracerebral hemorrhage are randomized to receive either intravenous tranexamic acid 1 g 10 min bolus followed by 1 g 8 h infusion, or placebo. A trial of 2000 participants (300 from start-up phase and 1700 from main phase) will have 90% power to detect an ordinal shift of the modified Rankin Scale with odds ratio 0.79. The primary outcome is death or dependency measured by ordinal shift analysis of the 7 level mRS at day 90. Secondary outcomes are neurological impairment at day 7 and disability, quality of life, cognition, and mood at day 90. Safety outcomes are death, serious adverse events, thromboembolic events, and seizures. Cost outcomes are length of stay in hospital, readmission, and institutionalization. This pragmatic trial is assessing efficacy of tranexamic acid after spontaneous intracerebral hemorrhage. Recruitment started in 2013 as of 15th January 2016 1355 participants have been enrolled, from 95 centers in seven countries. Recruitment is due to end in 2017. TICH-2 Trial is registered as ISRCTN93732214.
Publisher: SAGE Publications
Date: 11-2006
DOI: 10.1111/J.1747-4949.2006.00059.X
Abstract: High blood pressure (BP) is common in acute stroke and is independently associated with a poor outcome. Many patients with acute stroke are taking antihypertensive medications. To test the safety and efficacy of 7 days of transdermal glyceryl trinitrate (GTN, 5 mg/day) vs. no GTN in patients with acute stroke patients taking antihypertensive therapy immediately before their stroke are also randomised to continue vs. stop this temporarily. ENOS is a prospective international multicentre single-blind randomised-controlled trial in 5000 patients with acute ( 48 h of onset) ischaemic or haemorrhagic stroke. The primary outcome is combined death and dependency (modified Rankin scale 2) at 90 days measured by blinded central telephone follow-up. Secondary outcomes include: BP over the 7 days of treatment death, impairment (Scandinavian stroke scale), recurrence, and neuroimaging at 7 days discharge disposition, disability (Barthel index), cognition (mini-mental status examination) and quality of life (EuroQoL). The s le size will allow an absolute difference in death/dependency of 5% to be detected with 90% power at 5% significance for GTN versus no GTN. Randomisation and data collection are performed over a secure Internet site with real-time data validation. Neuroimaging and serious adverse events are adjudicated blinded to treatment.
Publisher: Wiley
Date: 29-09-2016
DOI: 10.1002/HBM.23414
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-03-2021
Abstract: Antiplatelet therapy increases the risk of hematoma expansion in intracerebral hemorrhage (ICH) while the effect on functional outcome is uncertain. This is an exploratory analysis of the TICH‐2 (Tranexamic Acid in Intracerebral Hemorrhage‐2) double‐blind, randomized, placebo‐controlled trial, which studied the efficacy of tranexamic acid in patients with spontaneous ICH within 8 hours of onset. Multivariable logistic regression and ordinal regression were performed to explore the relationship between pre‐ICH antiplatelet therapy, and 24‐hour hematoma expansion and day 90 modified Rankin Scale score, as well as the effect of tranexamic acid. Of 2325 patients, 611 (26.3%) had pre‐ICH antiplatelet therapy. They were older (mean age, 75.7 versus 66.5 years), more likely to have ischemic heart disease (25.4% versus 2.7%), ischemic stroke (36.2% versus 6.3%), intraventricular hemorrhage (40.2% versus 27.5%), and larger baseline hematoma volume (mean, 28.1 versus 22.6 mL) than the no‐antiplatelet group. Pre‐ICH antiplatelet therapy was associated with a significantly increased risk of hematoma expansion (adjusted odds ratio [OR], 1.28 95% CI, 1.01–1.63), a shift toward unfavorable outcome in modified Rankin Scale (adjusted common OR, 1.58 95% CI, 1.32–1.91) and a higher risk of death at day 90 (adjusted OR, 1.63 95% CI, 1.25–2.11). Tranexamic acid reduced the risk of hematoma expansion in the overall patients with ICH (adjusted OR, 0.76 95% CI, 0.62–0.93) and antiplatelet subgroup (adjusted OR, 0.61 95% CI, 0.41–0.91) with no significant interaction between pre‐ICH antiplatelet therapy and tranexamic acid (P interaction=0.248). Antiplatelet therapy is independently associated with hematoma expansion and unfavorable functional outcome. Tranexamic acid reduced hematoma expansion regardless of prior antiplatelet therapy use. URL: www.isrctn.com Unique identifier: ISRCTN93732214.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-07-2021
DOI: 10.1097/MAO.0000000000003281
Abstract: Brain magnetic resonance imaging in patients with cochlear implants (CIs) is impacted by image artefacts. The optimal positioning of the CI to minimize artefacts is unknown. This study aimed to characterize the dependence of the extent and distribution of the artefact on CI positioning. Three normally hearing in iduals underwent magnetic resonance imaging using a standard T1-weighted 3D sequence. Scans were acquired with a non-functioning CI placed underneath a swimming cap at four plausible scalp positions on each side, and without the CI in situ. The artefact in each image was assessed quantitatively using voxel-based techniques. Two radiologists also independently rated the likely impact of the artefact on the detection of pathology for 20 neuroradiological locations. The procedure was well tolerated. The most postero-inferior CI positions resulted in the smallest apparent artefacts. Radiological evaluations suggested that artefacts would likely limit pathology detection in the ipsilateral temporal, parietal, and occipital lobes, regardless of CI location. Pathology detection in contralateral structures and anterior corpus callosum was rarely affected. Certain CI locations appeared to selectively spare ipsilateral structures, for ex le, postero-inferior CI locations selectively spared ipsilateral midbrain, deep grey matter, and frontal lobes. A CI placed under a swimming cap is a feasible tool for observing the effect of CI location on image usability within a single subject and potentially informing surgical planning. Regardless of CI placement, artefacts involving ipsilateral parietal, temporal, and occipital lobes severely limited diagnostic image utility. Between 35% and 70% of neuroradiological features were deemed unaffected by the implant.
Publisher: Elsevier BV
Date: 07-2023
Publisher: Elsevier BV
Date: 05-2018
Publisher: Elsevier BV
Date: 05-2016
Publisher: Cold Spring Harbor Laboratory
Date: 09-07-2023
DOI: 10.1101/2023.07.08.23292404
Abstract: Impaired attention performance is a significant burden to people with multiple sclerosis (MS). Brain connectivity fluctuates with transitions between cognitive states, so measurement of network dynamics during these conditions may help to understand MS-related attention impairment. In people with MS and healthy controls, attention was measured using the Attention Network Test. 3T MRI was used to measure structural connectivity and both static and dynamic functional connectivity in the attention-related fronto-parietal network (FPN) at rest and during an attentionally-demanding task. Groups were compared on connectivity of the FPN during rest and task performance. Relationships between network connectivity and attention performance were tested using linear regression. The s le comprised 37 people with MS and 23 matched controls. At rest, people with MS had significantly lower structural connectivity (R 2 =0.13, p=0.004), lower static functional connectivity (R 2 =0.07, p=0.032) and higher dynamic functional connectivity (R 2 =0.08, p=0.026) of the FPN. Higher dynamic connectivity was significantly associated with poorer attention performance in people with MS (R 2 =0.20, p=0.008). During attention-task performance, static functional connectivity was greater in people with MS than controls (R 2 =0.10, p=0.008). The task-induced reduction in static connectivity (relative to rest) was directly related to attention performance (R 2 =0.23, p .001). Increased dynamic functional connectivity of the FPN at rest may be a useful indicator of deficits in sustained attention in people with MS. The transition from rest to active-attentive state is accompanied by an increase in dynamic connectivity, and decrease in static connectivity which may be helpful in understanding aetiology and treatment of attention impairment.
Publisher: Wiley
Date: 27-08-2022
DOI: 10.1002/ANA.26481
Abstract: We assessed whether hematoma expansion (HE) and favorable outcome differ according to type of intracerebral hemorrhage (ICH). Among participants with ICH enrolled in the TICH‐2 (Tranexamic Acid for Hyperacute Primary Intracerebral Haemorrhage) trial, we assessed baseline scans for hematoma location and presence of cerebral amyloid angiopathy (CAA) using computed tomography (CT, simplified Edinburgh criteria) and magnetic resonance imaging (MRI Boston criteria) and categorized ICH as lobar CAA, lobar non‐CAA, and nonlobar. The main outcomes were HE and favorable functional outcome. We constructed multivariate regression models and assessed treatment effects using interaction terms. A total of 2,298 out of 2,325 participants were included with available CT (98.8% median age = 71 years, interquartile range = 60‐80 years 1,014 female). Additional MRI was available in 219 patients (9.5%). Overall, 1,637 participants (71.2%) had nonlobar ICH the remaining 661 participants (28.8%) had lobar ICH, of whom 202 patients had lobar CAA‐ICH (8.8%, 173 participants according to Edinburgh and 29 participants according to Boston criteria) and 459 did not (lobar non‐CAA, 20.0%). For HE, we found a significant interaction of lobar CAA ICH with time from onset to randomization (increasing risk with time, p interaction 0.001) and baseline ICH volume (constant risk regardless of volume, p interaction 0.001) but no association between type of ICH and risk of HE or favorable outcome. Tranexamic acid significantly reduced the risk of HE (adjusted odds ratio = 0.7, 95% confidence interval = 0.6–1.0, p = 0.020) without statistically significant interaction with type of ICH ( p interaction = 0.058). Tranexamic acid was not associated with favorable outcome. Risk of HE in patients with lobar CAA‐ICH was not independently increased but seems to have different dynamics compared to other types of ICH. The time window for treatment of CAA‐ICH to prevent HE may be longer. ANN NEUROL 2022 :921–930
Publisher: National Institute for Health and Care Research
Date: 07-2019
DOI: 10.3310/HTA23350
Abstract: Tranexamic acid reduces death due to bleeding after trauma and postpartum haemorrhage. The aim of the study was to assess if tranexamic acid is safe, reduces haematoma expansion and improves outcomes in adults with spontaneous intracerebral haemorrhage (ICH). The TICH-2 (Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage) study was a pragmatic, Phase III, prospective, double-blind, randomised placebo-controlled trial. Acute stroke services at 124 hospitals in 12 countries (Denmark, Georgia, Hungary, Ireland, Italy, Malaysia, Poland, Spain, Sweden, Switzerland, Turkey and the UK). Adult patients (aged ≥ 18 years) with ICH within 8 hours of onset. Exclusion criteria were ICH secondary to anticoagulation, thrombolysis, trauma or a known underlying structural abnormality patients for whom tranexamic acid was thought to be contraindicated prestroke dependence (i.e. patients with a modified Rankin Scale [mRS] score 4) life expectancy 3 months and a Glasgow Coma Scale score of 5. Participants, allocated by randomisation, received 1 g of an intravenous tranexamic acid bolus followed by an 8-hour 1-g infusion or matching placebo (i.e. 0.9% saline). The primary outcome was functional status (death or dependency) at day 90, which was measured by the shift in the mRS score, using ordinal logistic regression, with adjustment for stratification and minimisation criteria. A total of 2325 participants (tranexamic acid, n = 1161 placebo, n = 1164) were recruited from 124 hospitals in 12 countries between 2013 and 2017. Treatment groups were well balanced at baseline. The primary outcome was determined for 2307 participants (tranexamic acid, n = 1152 placebo, n = 1155). There was no statistically significant difference between the treatment groups for the primary outcome of functional status at day 90 [adjusted odds ratio (aOR) 0.88, 95% confidence interval (CI) 0.76 to 1.03 p = 0.11]. Although there were fewer deaths by day 7 in the tranexamic acid group (aOR 0.73, 95% CI 0.53 to 0.99 p = 0.041), there was no difference in case fatality at 90 days (adjusted hazard ratio 0.92, 95% CI 0.77 to 1.10 p = 0.37). Fewer patients experienced serious adverse events (SAEs) after treatment with tranexamic acid than with placebo by days 2 ( p = 0.027), 7 ( p = 0.020) and 90 ( p = 0.039). There was no increase in thromboembolic events or seizures. Despite attempts to enrol patients rapidly, the majority of participants were enrolled and treated 4.5 hours after stroke onset. Pragmatic inclusion criteria led to a heterogeneous population of participants, some of whom had very large strokes. Although 12 countries enrolled participants, the majority (82.1%) were from the UK. Tranexamic acid did not affect a patient’s functional status at 90 days after ICH, despite there being significant modest reductions in early death (by 7 days), haematoma expansion and SAEs, which is consistent with an antifibrinolytic effect. Tranexamic acid was safe, with no increase in thromboembolic events. Future work should focus on enrolling and treating patients early after stroke and identify which participants are most likely to benefit from haemostatic therapy. Large randomised trials are needed. Current Controlled Trials ISRCTN93732214. This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment Vol. 23, No. 35. See the NIHR Journals Library website for further project information. The project was also funded by the Pragmatic Trials, UK, funding call and the Swiss Heart Foundation in Switzerland.
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
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 Robert Dineen.