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  • 1
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    Bleeding with intensive versus guideline antiplatelet therapy in acute cerebral ischaemia
    Springer Science and Business Media LLC ; 2023
    In:  Scientific Reports Vol. 13, No. 1 ( 2023-07-20)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2023-07-20)
    Abstract: Intensive antiplatelet therapy did not reduce recurrent stroke/transient ischaemic attack (TIA) events as compared with guideline treatment in the Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke (TARDIS) trial, but did increase the frequency and severity of bleeding. In this pre-specified analysis, we investigated predictors of bleeding and the association of bleeding with outcome. TARDIS was an international prospective randomised open-label blinded-endpoint trial in participants with ischaemic stroke or TIA within 48 h of onset. Participants were randomised to 30 days of intensive antiplatelet therapy (aspirin, clopidogrel, dipyridamole) or guideline-based therapy (either clopidogrel alone or combined aspirin and dipyridamole). Bleeding was defined using the International Society on Thrombosis and Haemostasis five-level ordered categorical scale: fatal, major, moderate, minor, none. Of 3,096 participants, bleeding severity was: fatal 0.4%, major 1.5%, moderate 1.2%, minor 11.4%, none 85.5%. Major/fatal bleeding was increased with intensive as compared with guideline therapy: 39 vs. 17 participants, adjusted hazard ratio 2.21, 95% CI 1.24–3.93, p  = 0.007. Bleeding events diverged between treatment groups in the 8–35 day period but not in the 0–7 or 36–90 day epochs. In multivariate analysis more, and more severe, bleeding events were seen with increasing age, female sex, pre-morbid dependency, increased time to randomisation, prior major bleed, prior antiplatelet therapy and in those randomised to triple vs guideline antiplatelet therapy. More severe bleeding was associated with worse clinical outcomes across multiple physical, emotional and quality of life domains. Trial registration ISRCTN47823388 .
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-023-38474-2
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2615211-3
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  • 2
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    Quantitative CT radiomics-based models for prediction of haematoma expansion and poor functional outcome in primary intracerebral haemorrhage
    Springer Science and Business Media LLC ; 2021
    In:  European Radiology Vol. 31, No. 10 ( 2021-10), p. 7945-7959
    Details
    In: European Radiology, Springer Science and Business Media LLC, Vol. 31, No. 10 ( 2021-10), p. 7945-7959
    Abstract: To test radiomics-based features extracted from noncontrast CT of patients with spontaneous intracerebral haemorrhage for prediction of haematoma expansion and poor functional outcome and compare them with radiological signs and clinical factors. Materials and methods Seven hundred fifty-four radiomics-based features were extracted from 1732 scans derived from the TICH-2 multicentre clinical trial. Features were harmonised and a correlation-based feature selection was applied. Different elastic-net parameterisations were tested to assess the predictive performance of the selected radiomics-based features using grid optimisation. For comparison, the same procedure was run using radiological signs and clinical factors separately. Models trained with radiomics-based features combined with radiological signs or clinical factors were tested. Predictive performance was evaluated using the area under the receiver operating characteristic curve (AUC) score. Results The optimal radiomics-based model showed an AUC of 0.693 for haematoma expansion and an AUC of 0.783 for poor functional outcome. Models with radiological signs alone yielded substantial reductions in sensitivity. Combining radiomics-based features and radiological signs did not provide any improvement over radiomics-based features alone. Models with clinical factors had similar performance compared to using radiomics-based features, albeit with low sensitivity for haematoma expansion. Performance of radiomics-based features was boosted by incorporating clinical factors, with time from onset to scan and age being the most important contributors for haematoma expansion and poor functional outcome prediction, respectively. Conclusion Radiomics-based features perform better than radiological signs and similarly to clinical factors on the prediction of haematoma expansion and poor functional outcome. Moreover, combining radiomics-based features with clinical factors improves their performance. Key Points • Linear models based on CT radiomics-based features perform better than radiological signs on the prediction of haematoma expansion and poor functional outcome in the context of intracerebral haemorrhage. • Linear models based on CT radiomics-based features perform similarly to clinical factors known to be good predictors. However, combining these clinical factors with radiomics-based features increases their predictive performance.
    Type of Medium: Online Resource
    ISSN: 0938-7994 , 1432-1084
    URL: Article
    DOI: 10.1007/s00330-021-07826-9
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 1472718-3
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  • 3
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    Predictive value of prostate calcification for future cancer occurrence: a retrospective long-term follow-up cohort study
    British Institute of Radiology ; 2023
    In:  The British Journal of Radiology
    Details
    In: The British Journal of Radiology, British Institute of Radiology
    Abstract: Although prostate calcification is often identified on pelvic CT images, calcification itself is usually not considered clinically significant. A recent histological study proposed an association between prostate calcification and prostate cancer occurrence. Our aim was to determine the predictive value of prostate calcifications for future prostate cancer occurrence. Methods: We retrospectively analysed male patients (≥50 years old) without prior prostate cancer history, who underwent unenhanced pelvic CT between April 2010 and March 2011, and followed-up until December 2021. Cox proportional hazards models were used to assess prostate cancer risk with prostate calcification (defined as a high-density area larger than 3 mm with CT attenuation values ≥ 130 HU), controlling for age, body mass index (BMI), hypertension and diabetes mellitus. Results: A total of 636 male patients (mean age, 68 years ± 9 [standard deviation]) were evaluated. At the end of follow-up, prostate cancer had been more frequently diagnosed in patients with prostate calcification than those without prostate calcification (6.5% vs  2.6%). Multivariate analysis revealed that prostate calcification on CT was a significant predictor of future prostate cancer occurrence (hazard ratio [HR] , 2.7; 95% CI: 1.20, 5.91; p = 0.016). No statistical differences were observed in any other factors. Conclusion: Prostate calcification may be a significant predictor of future prostate cancer occurrence, and may be used for risk stratification and to guide screening protocols. Advances in knowledge: Presence of prostate calcification on unenhanced CT scan was associated with increased incidence of prostate cancer occurrence on long term follow-up.
    Type of Medium: Online Resource
    ISSN: 0007-1285 , 1748-880X
    URL: Article
    DOI: 10.1259/bjr.20221110
    RVK:
    XA 34700
    Language: English
    Publisher: British Institute of Radiology
    Publication Date: 2023
    detail.hit.zdb_id: 1468548-6
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  • 4
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    Subjective discomfort in children receiving 3 T MRI and experienced adults’ perspective on children’s tolerability of 7 T: a cross-sectional questionnaire survey
    BMJ ; 2014
    In:  BMJ Open Vol. 4, No. 10 ( 2014-10), p. e006094-
    Details
    In: BMJ Open, BMJ, Vol. 4, No. 10 ( 2014-10), p. e006094-
    Abstract: To explore the possible discomfort perceived by children participating in 7 T MRI research, and the age range in which children are most likely to tolerate it well. Design A cross-sectional survey using age-appropriate questionnaires containing six measures of subjective discomfort (general discomfort, dizziness, noisiness, claustrophobia and feeling of cold or warm). Setting For children, 3 T clinical scanner in a tertiary referral teaching hospital; for adults, 3 and 7 T scanner in a university research building. Participants Non-sedated children and young people under 18 years of age who underwent 3 T clinical MRI for brain or musculoskeletal scans and adult volunteers attending 7 T with or without 3 T for brain scans. Results 83% (89/107) of involved individuals returned questionnaires. The most common discomfort among 31 children receiving 3 T MRI was noisiness (39%), followed by cold (19%), general discomfort (16%), dizziness (13%) and claustrophobia (10%). The noise was reported more frequently in children younger than 12 years than those older (p=0.021). The most common discomfort for 58 adults receiving 7 T MRI was noisiness (43%). In adults, there was a higher frequency of general discomfort during 7 than 3 T scans (p=0.031). More than 85% of adult respondents thought children aged 12–17 years would tolerate 7 T scans well, but only 35% and 15% thought children aged 10–11 and 8–9 years, respectively, would. Conclusions Noisiness was the most common discomfort across all ages in 3 and 7 T scanners. Although general discomfort was more common during 7 than 3 T scans in adults, most adults thought children aged 12 years or more would tolerate 7 T MRI well. Cautious enrolment of children in 7 T MRI study is warranted, but until there is more evidence of how well those aged 12 years or more tolerate 7 T MRI, we would caution against enrolling younger children.
    Type of Medium: Online Resource
    ISSN: 2044-6055 , 2044-6055
    URL: Article
    DOI: 10.1136/bmjopen-2014-006094
    Language: English
    Publisher: BMJ
    Publication Date: 2014
    detail.hit.zdb_id: 2599832-8
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  • 5
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    Trial protocol: Feasibility of neuromodulation with connectivity-guided intermittent theta-burst stimulation for improving cognition in multiple sclerosis
    Walter de Gruyter GmbH ; 2023
    In:  Open Medicine Vol. 18, No. 1 ( 2023-09-28)
    Details
    In: Open Medicine, Walter de Gruyter GmbH, Vol. 18, No. 1 ( 2023-09-28)
    Abstract: Cognitive impairment in multiple sclerosis (MS) can adversely impact participation in employment, activities of daily living, and wider society. It affects 40–70% of people living with MS (pwMS). There are few effective treatments for cognitive impairment in people with MS. Neuromodulation with intermittent theta-burst stimulation (iTBS) has potential for treating cognitive impairment in pwMS. This single-centre mixed-methods feasibility randomised controlled trial (NCT04931953) will assess feasibility, acceptability, and tolerability of procedures used for applying iTBS for improving cognitive performance in pwMS. Participants will be randomised into three intervention groups with varying lengths of iTBS treatment (from 1 to 4 weeks) and a sham-control group. Quantitative data will be collected at three time points (baseline, end of intervention, and 8-week follow-up). End of the intervention semi-structured interviews will explore the views and experiences of the participants receiving the intervention, analysed using framework analysis. Quantitative and qualitative data will be synthesised to explore the impact of the iTBS intervention. Ethical approval has been received from the Health Research Authority (21/LO/0506) and recruitment started in June 2022. The results will inform the design of an RCT of the efficacy of iTBS as a therapeutic intervention for cognitive impairment in pwMS.
    Type of Medium: Online Resource
    ISSN: 2391-5463
    URL: Article
    DOI: 10.1515/med-2023-0814
    Language: English
    Publisher: Walter de Gruyter GmbH
    Publication Date: 2023
    detail.hit.zdb_id: 2829380-0
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  • 6
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    Investigating Microstructural Changes in White Matter in Multiple Sclerosis: A Systematic Review and Meta-Analysis of Neurite Orientation Dispersion and Density Imaging
    MDPI AG ; 2021
    In:  Brain Sciences Vol. 11, No. 9 ( 2021-08-29), p. 1151-
    Details
    In: Brain Sciences, MDPI AG, Vol. 11, No. 9 ( 2021-08-29), p. 1151-
    Abstract: Multiple sclerosis (MS) is characterised by widespread damage of the central nervous system that includes alterations in normal-appearing white matter (NAWM) and demyelinating white matter (WM) lesions. Neurite orientation dispersion and density imaging (NODDI) has been proposed to provide a precise characterisation of WM microstructures. NODDI maps can be calculated for the Neurite Density Index (NDI) and Orientation Dispersion Index (ODI), which estimate orientation dispersion and neurite density. Although NODDI has not been widely applied in MS, this technique is promising in investigating the complexity of MS pathology, as it is more specific than diffusion tensor imaging (DTI) in capturing microstructural alterations. We conducted a meta-analysis of studies using NODDI metrics to assess brain microstructural changes and neuroaxonal pathology in WM lesions and NAWM in patients with MS. Three reviewers conducted a literature search of four electronic databases. We performed a random-effect meta-analysis and the extent of between-study heterogeneity was assessed with the I2 statistic. Funnel plots and Egger’s tests were used to assess publication bias. We identified seven studies analysing 374 participants (202 MS and 172 controls). The NDI in WM lesions and NAWM were significantly reduced compared to healthy WM and the standardised mean difference of each was −3.08 (95%CI −4.22 to (−1.95), p ≤ 0.00001, I2 = 88%) and −0.70 (95%CI −0.99 to (−0.40), p ≤ 0.00001, I2 = 35%), respectively. There was no statistically significant difference of the ODI in MS WM lesions and NAWM compared to healthy controls. This systematic review and meta-analysis confirmed that the NDI is significantly reduced in MS lesions and NAWM than in WM from healthy participants, corresponding to reduced intracellular signal fraction, which may reflect underlying damage or loss of neurites.
    Type of Medium: Online Resource
    ISSN: 2076-3425
    URL: Article
    DOI: 10.3390/brainsci11091151
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2651993-8
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  • 7
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    EPEN-24. SIOP EPENDYMOMA II: CENTRAL EPENDYMOMA MANAGEMENT ADVISORY GROUP – THE UK EXPERIENCE
    Oxford University Press (OUP) ; 2020
    In:  Neuro-Oncology Vol. 22, No. Supplement_3 ( 2020-12-04), p. iii312-iii312
    Details
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 22, No. Supplement_3 ( 2020-12-04), p. iii312-iii312
    Abstract: Paediatric Ependymoma is the second most common malignant brain tumour of childhood with approximately 50% of cases recurring. It has been described as a “surgical” disease since patients who have undergone a gross total surgical resection (GTR) have a better prognosis than those who have a subtotal resection (STR). Analysis of the UKCCSG/SIOP 1992 04 clinical trial has shown that only 49% of cases had a GTR, with 5-year survival rates for STR of 22–47% and GTR of 67–80%. As part of the SIOP II Ependymoma trial the UK established a panel of experts in the treatment of Ependymoma from Neuro-oncology, Neuro-radiology and Neuro-surgery. Meeting weekly, cases are discussed to provide a consensus on radiological review, ensuring central pathological review, trial stratification and whether further surgery should be advocated on any particular case. Evaluation of the first 68 UK patients has shown a GTR in 47/68 (69%) of patients and STR in 21/68 (31%) of patients. Following discussion at EMAG it was felt that 9/21 (43%) STR patients could be offered early second look surgery. Following this 2nd look surgery the number of cases with a GTR increased to 56/68 (82%). There has been a clear increase in the number of patients for whom a GTR has been achieved following discussion at EMAG and prior to them moving forwards with their oncological treatment. This can only have beneficial effects in decreasing their risk of tumour recurrence or CSF dissemination and also in reducing the target volume for radiotherapy.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    URL: Article
    DOI: 10.1093/neuonc/noaa222.161
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2094060-9
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  • 8
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    Disproportionate Expression of ATM in Cerebellar Cortex During Human Neurodevelopment
    Springer Science and Business Media LLC ; 2023
    In:  The Cerebellum
    Details
    In: The Cerebellum, Springer Science and Business Media LLC
    Abstract: Cerebellar neurodegeneration is a classical feature of ataxia telangiectasia (A-T), an autosomal recessive condition caused by loss-of-function mutation of the ATM gene, a gene with multiple regulatory functions. The increased vulnerability of cerebellar neurones to degeneration compared to cerebral neuronal populations in individuals with ataxia telangiectasia implies a specific importance of intact ATM function in the cerebellum. We hypothesised that there would be elevated transcription of ATM in the cerebellar cortex relative to ATM expression in other grey matter regions during neurodevelopment in individuals without A-T. Using ATM transcription data from the BrainSpan Atlas of the Developing Human Brain, we demonstrate a rapid increase in cerebellar ATM expression relative to expression in other brain regions during gestation and remaining elevated during early childhood, a period corresponding to the emergence of cerebellar neurodegeneration in ataxia telangiectasia patients. We then used gene ontology analysis to identify the biological processes represented in the genes correlated with cerebellar ATM expression. This analysis demonstrated that multiple processes are associated with expression of ATM in the cerebellum, including cellular respiration, mitochondrial function, histone methylation, and cell-cycle regulation, alongside its canonical role in DNA double-strand break repair. Thus, the enhanced expression of ATM in the cerebellum during early development may be related to the specific energetic demands of the cerebellum and its role as a regulator of these processes.
    Type of Medium: Online Resource
    ISSN: 1473-4230
    URL: Article
    DOI: 10.1007/s12311-023-01560-2
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2071266-2
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  • 9
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    Dorsolateral prefrontal circuit effective connectivity mediates the relationship between white matter structure and PASAT ‐3 performance in multiple sclerosis
    Wiley ; 2021
    In:  Human Brain Mapping Vol. 42, No. 2 ( 2021-02), p. 495-509
    Details
    In: Human Brain Mapping, Wiley, Vol. 42, No. 2 ( 2021-02), p. 495-509
    Abstract: Three decades ago a series of parallel circuits were described involving the frontal cortex and deep grey matter structures, with putative roles in control of motor and oculomotor function, cognition, behaviour and emotion. The circuit comprising the dorsolateral prefrontal cortex, caudate, globus pallidus and thalamus has a putative role in regulating executive functions. The aim of this study is to investigate effective connectivity (EC) of the dorsolateral‐prefrontal circuit and its association with PASAT‐3 performance in people with multiple sclerosis(MS). We use Granger causality analysis of resting‐state functional MRI from 52 people with MS and 36 healthy people to infer that reduced EC in the afferent limb of the dorsolateral prefrontal circuit occurs in the people with MS with cognitive dysfunction (left: p = .006; right: p = .029), with bilateral EC reductions in this circuit resulting in more severe cognitive dysfunction than unilateral reductions alone ( p = .002). We show that reduced EC in the afferent limb of the dorsolateral prefrontal circuit mediates the relationship between cognitive performance and macrostrucutral and microstructural alterations of white matter tracts in components of the circuit. Specificity is shown by the absence of any relationship between cognition and EC in the analogous and anatomically proximal motor circuit. We demonstrate good stability of the EC measures in people with MS over an interval averaging 8‐months. Key positive and negative results are replicated in an independent cohort of people with MS. Our findings identify the dorsolateral prefrontal circuit as a potential target for therapeutic strategies aimed at improving cognition in people with MS.
    Type of Medium: Online Resource
    ISSN: 1065-9471 , 1097-0193
    URL: Issue
    URL: Article
    DOI: 10.1002/hbm.v42.2
    DOI: 10.1002/hbm.25239
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 1492703-2
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  • 10
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    Computed tomography (CT) angiography for confirmation of the clinical diagnosis of brain death
    Wiley ; 2014
    In:  Cochrane Database of Systematic Reviews Vol. 2018, No. 12 ( 2014-03-31)
    Details
    In: Cochrane Database of Systematic Reviews, Wiley, Vol. 2018, No. 12 ( 2014-03-31)
    Type of Medium: Online Resource
    ISSN: 1465-1858
    URL: Article
    DOI: 10.1002/14651858.CD009694.pub2
    Language: English
    Publisher: Wiley
    Publication Date: 2014
    detail.hit.zdb_id: 2038950-4
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