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133 results on '"Chappell, F."'

1. Blood-brain barrier leakage hotspots collocating with brain lesions due to sporadic and monogenic small vessel disease.

Author

Rudilosso, S., Stringer, M.S., Thrippleton, M., Chappell, F., Blair, G.W., Jaime Garcia, D., Doubal, F., Hamilton, I., Janssen, E., Kopczak, A., Ingrisch, M., Kerkhofs, D., Backes, W.H., Staals, J., Duering, M., Dichgans, M., Wardlaw, J.M., Rudilosso, S., Stringer, M.S., Thrippleton, M., Chappell, F., Blair, G.W., Jaime Garcia, D., Doubal, F., Hamilton, I., Janssen, E., Kopczak, A., Ingrisch, M., Kerkhofs, D., Backes, W.H., Staals, J., Duering, M., Dichgans, M., and Wardlaw, J.M.

Abstract

01 september 2023, Item does not contain fulltext, Blood-brain barrier (BBB) is known to be impaired in cerebral small vessel disease (SVD), and is measurable by dynamic-contrast enhancement (DCE)-MRI. In a cohort of 69 patients (42 sporadic, 27 monogenic SVD), who underwent 3T MRI, including DCE and cerebrovascular reactivity (CVR) sequences, we assessed the relationship of BBB-leakage hotspots to SVD lesions (lacunes, white matter hyperintensities (WMH), and microbleeds). We defined as hotspots the regions with permeability surface area product highest decile on DCE-derived maps within the white matter. We assessed factors associated with the presence and number of hotspots corresponding to SVD lesions in multivariable regression models adjusted for age, WMH volume, number of lacunes, and SVD type. We identified hotspots at lacune edges in 29/46 (63%) patients with lacunes, within WMH in 26/60 (43%) and at the WMH edges in 34/60 (57%) patients with WMH, and microbleed edges in 4/11 (36%) patients with microbleeds. In adjusted analysis, lower WMH-CVR was associated with presence and number of hotspots at lacune edges, and higher WMH volume with hotspots within WMH and at WMH edges, independently of the SVD type. In conclusion, SVD lesions frequently collocate with high BBB-leakage in patients with sporadic and monogenic forms of SVD.

Published
2023

2. Impact of Cerebral Microbleeds in Stroke Patients with Atrial Fibrillation.

Author

Soo, Y., Zietz, A., Yiu, B., Mok, V.C.T., Polymeris, A.A., Seiffge, D., Ambler, G., Wilson, D., Leung, T.W.H., Tsang, S.F., Chu, W., Abrigo, J., Cheng, C., Lee, K.J., Lim, J.S., Shiozawa, M., Koga, M., Chabriat, H., Hennerici, M., Wong, Y.K., Mak, H., Collet, R., Inamura, S., Yoshifuji, K., Arsava, E.M., Horstmann, S., Purrucker, J., Lam, B.Y.K., Wong, A., Kim, Y.D., Song, T.J., Lemmens, R., Eppinger, S., Gattringer, T., Uysal, E., Demirelli, D.S., Bornstein, N.M., Assayag, E.B., Hallevi, H., Molad, J., Nishihara, M., Tanaka, J., Coutts, S.B., Kappelle, L.J., Al-Shahi Salman, R., Jager, Rolf, Lip, G.Y.H., Goeldlin, M.B., Panos, L.D., Mas, J.L., Legrand, Laurence, Karayiannis, C., Phan, T., Bellut, M., Chappell, F., Makin, S., Hayden, D., Williams, D., Dam-Nolen, D.H.K. Van, Nederkoorn, P.J., Barbato, C., Browning, S., Wiegertjes, K., Tuladhar, A.M., Mendyk, A.M., Köhler, S., Oostenburgge, R. van, Zhou, Ying, Xu, Chao, Hilal, S., Gyanwali, B., Chen, C, Lou, M., Staals, J., Bordet, R., Kandiah, N., Leeuw, F.E. de, Simister, R., Hendrikse, Jeroen, Wardlaw, J., Kelly, P., Fluri, F., Srikanth, V., Calvet, D., Jung, S., Kwa, V.I.H., Smith, E.E., Hara, H., Yakushiji, Y., Orken, D.N., Fazekas, F., Thijs, V., Heo, J.H., Veltkamp, R., Ay, H., Imaizumi, T., Lau, K.K., Jouvent, E., Toyoda, K., Yoshimura, S., Bae, H.J., Martí-Fàbregas, J., Prats-Sánchez, L., Lyrer, P., Best, J. de, Werring, D., Engelter, S.T., Peters, Nils, Soo, Y., Zietz, A., Yiu, B., Mok, V.C.T., Polymeris, A.A., Seiffge, D., Ambler, G., Wilson, D., Leung, T.W.H., Tsang, S.F., Chu, W., Abrigo, J., Cheng, C., Lee, K.J., Lim, J.S., Shiozawa, M., Koga, M., Chabriat, H., Hennerici, M., Wong, Y.K., Mak, H., Collet, R., Inamura, S., Yoshifuji, K., Arsava, E.M., Horstmann, S., Purrucker, J., Lam, B.Y.K., Wong, A., Kim, Y.D., Song, T.J., Lemmens, R., Eppinger, S., Gattringer, T., Uysal, E., Demirelli, D.S., Bornstein, N.M., Assayag, E.B., Hallevi, H., Molad, J., Nishihara, M., Tanaka, J., Coutts, S.B., Kappelle, L.J., Al-Shahi Salman, R., Jager, Rolf, Lip, G.Y.H., Goeldlin, M.B., Panos, L.D., Mas, J.L., Legrand, Laurence, Karayiannis, C., Phan, T., Bellut, M., Chappell, F., Makin, S., Hayden, D., Williams, D., Dam-Nolen, D.H.K. Van, Nederkoorn, P.J., Barbato, C., Browning, S., Wiegertjes, K., Tuladhar, A.M., Mendyk, A.M., Köhler, S., Oostenburgge, R. van, Zhou, Ying, Xu, Chao, Hilal, S., Gyanwali, B., Chen, C, Lou, M., Staals, J., Bordet, R., Kandiah, N., Leeuw, F.E. de, Simister, R., Hendrikse, Jeroen, Wardlaw, J., Kelly, P., Fluri, F., Srikanth, V., Calvet, D., Jung, S., Kwa, V.I.H., Smith, E.E., Hara, H., Yakushiji, Y., Orken, D.N., Fazekas, F., Thijs, V., Heo, J.H., Veltkamp, R., Ay, H., Imaizumi, T., Lau, K.K., Jouvent, E., Toyoda, K., Yoshimura, S., Bae, H.J., Martí-Fàbregas, J., Prats-Sánchez, L., Lyrer, P., Best, J. de, Werring, D., Engelter, S.T., and Peters, Nils

Abstract

01 juli 2023, Contains fulltext : 294348.pdf (Publisher’s version ) (Open Access), OBJECTIVES: Cerebral microbleeds are associated with the risks of ischemic stroke and intracranial hemorrhage, causing clinical dilemmas for antithrombotic treatment decisions. We aimed to evaluate the risks of intracranial hemorrhage and ischemic stroke associated with microbleeds in patients with atrial fibrillation treated with vitamin K antagonists, direct oral anticoagulants, antiplatelets, and combination therapy (i.e. concurrent oral anticoagulant and antiplatelet). METHODS: We included patients with documented atrial fibrillation from the pooled individual patient data analysis by the Microbleeds International Collaborative Network. Risks of subsequent intracranial hemorrhage and ischemic stroke were compared between patients with and without microbleeds, stratified by antithrombotic use. RESULTS: A total of 7,839 patients were included. The presence of microbleeds was associated with an increased relative risk of intracranial hemorrhage (adjusted hazard ratio [aHR] = 2.74, 95% confidence interval = 1.76-4.26) and ischemic stroke (aHR = 1.29, 95% confidence interval = 1.04-1.59). For the entire cohort, the absolute incidence of ischemic stroke was higher than intracranial hemorrhage regardless of microbleed burden. However, for the subgroup of patients taking combination of anticoagulant and antiplatelet therapy, the absolute risk of intracranial hemorrhage exceeded that of ischemic stroke in those with 2 to 4 microbleeds (25 vs 12 per 1,000 patient-years) and ≥ 11 microbleeds (94 vs 48 per 1,000 patient-years). INTERPRETATION: Patients with atrial fibrillation and high burden of microbleeds receiving combination therapy have a tendency of higher rate of intracranial hemorrhage than ischemic stroke, with potential for net harm. Further studies are needed to help optimize stroke preventive strategies in this high-risk group. ANN NEUROL 2023;94:61-74.

Published
2023

4. A daily temperature rhythm in the human brain predicts survival after brain injury

Author

Rzechorzek, N, Thrippleton, M, Chappell, F, Mair, G, Ercole, A, Cabeleira, M, Citerio, G, Rhodes, J, Marshall, I, O'Neill, J, Rzechorzek, Nina M, Thrippleton, Michael J, Chappell, Francesca M, Mair, Grant, Ercole, Ari, Cabeleira, Manuel, Citerio, Giuseppe, Rhodes, Jonathan, Marshall, Ian, O'Neill, John S, Rzechorzek, N, Thrippleton, M, Chappell, F, Mair, G, Ercole, A, Cabeleira, M, Citerio, G, Rhodes, J, Marshall, I, O'Neill, J, Rzechorzek, Nina M, Thrippleton, Michael J, Chappell, Francesca M, Mair, Grant, Ercole, Ari, Cabeleira, Manuel, Citerio, Giuseppe, Rhodes, Jonathan, Marshall, Ian, and O'Neill, John S

Abstract

Patients undergo interventions to achieve a 'normal' brain temperature; a parameter that remains undefined for humans. The profound sensitivity of neuronal function to temperature implies the brain should be isothermal, but observations from patients and non-human primates suggest significant spatiotemporal variation. We aimed to determine the clinical relevance of brain temperature in patients by establishing how much it varies in healthy adults. We retrospectively screened data for all patients recruited to the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) High Resolution Intensive Care Unit Sub-Study. Only patients with direct brain temperature measurements and without targeted temperature management were included. To interpret patient analyses, we prospectively recruited 40 healthy adults (20 males, 20 females, 20-40 years) for brain thermometry using magnetic resonance spectroscopy. Participants were scanned in the morning, afternoon, and late evening of a single day. In patients (n = 114), brain temperature ranged from 32.6 to 42.3°C and mean brain temperature (38.5 ± 0.8°C) exceeded body temperature (37.5 ± 0.5°C, P < 0.0001). Of 100 patients eligible for brain temperature rhythm analysis, 25 displayed a daily rhythm, and the brain temperature range decreased in older patients (P = 0.018). In healthy participants, brain temperature ranged from 36.1 to 40.9°C; mean brain temperature (38.5 ± 0.4°C) exceeded oral temperature (36.0 ± 0.5°C) and was 0.36°C higher in luteal females relative to follicular females and males (P = 0.0006 and P < 0.0001, respectively). Temperature increased with age, most notably in deep brain regions (0.6°C over 20 years, P = 0.0002), and varied spatially by 2.41 ± 0.46°C with highest temperatures in the thalamus. Brain temperature varied by time of day, especially in deep regions (0.86°C, P = 0.0001), and was lowest at night. From the healthy data we built HEATWAVE - a 4D map of

Published
2022

5. Clinical associations and prognostic significance of enlarged perivascular spaces in patients with previous ischaemic stroke or tia: a pooled analysis of individual patient data.

Author

Best J.G., Ambler G., Wilson D., Du H., Lee K.-J., Lim J.-S., Teo K.C., Mak H.K.F., Kim Y.D., Song T.-J., Demirelli D.S., Nishihara M., Yoshikawa M., Kubacka M., Zietz A., Al-Shahi Salman R., Jager H.R., Lip G.Y.H., Panos L.D., Goeldlin M.B., Slater L.-A., Karayiannis C., Phan T., Franke M., Abrigo J., Cheng C., Leung T., Chu W., Chappell F., Makin S., Van Dam-Nolen D.H.K., Kooi M.E., Kohler S., Staals J., Bordet R., Dubost F., Wardlaw J., Soo Y., Fluri F., Srikanth V., Jung S., Peters N., Hara H., Yakushiji Y., Orken D.N., Heo J.H., Lau K.K., Bae H.-J., Werring D.J., Best J.G., Ambler G., Wilson D., Du H., Lee K.-J., Lim J.-S., Teo K.C., Mak H.K.F., Kim Y.D., Song T.-J., Demirelli D.S., Nishihara M., Yoshikawa M., Kubacka M., Zietz A., Al-Shahi Salman R., Jager H.R., Lip G.Y.H., Panos L.D., Goeldlin M.B., Slater L.-A., Karayiannis C., Phan T., Franke M., Abrigo J., Cheng C., Leung T., Chu W., Chappell F., Makin S., Van Dam-Nolen D.H.K., Kooi M.E., Kohler S., Staals J., Bordet R., Dubost F., Wardlaw J., Soo Y., Fluri F., Srikanth V., Jung S., Peters N., Hara H., Yakushiji Y., Orken D.N., Heo J.H., Lau K.K., Bae H.-J., and Werring D.J.

Abstract

Background and aims: Enlarged perivascular spaces are an emerging marker of cerebral small vessel disease (CSVD) and might predict future stroke. However, results from existing studies vary. We aimed to clarify this through a large multicentre analysis. Method(s): We pooled individual patient data from a consortium of prospective observational studies. Participants had recent ischaemic stroke or TIA, underwent baseline MRI, and were followed up for ischaemic stroke and symptomatic intracranial haemorrhage (ICH). Perivascular spaces in the basal ganglia (BGPVS) and centrum semiovale (CSOPVS) were rated using a validated visual scale. We investigated clinical and radiological associations cross-sectionally using multinomial logistic regression, and prospective associations with ischaemic stroke and ICH using Cox regression. Result(s): We included 7,778 participants from 16 studies. Over a median follow-up of 1.47 years, 80 ICH and 424 ischaemic strokes occurred. BGPVS were associated with increasing age, hypertension, hyperlipidaemia, previous ischaemic stroke, previous ICH, lacunes, cerebral microbleeds (CMBs) and white matter hyperintensities. CSOPVS showed similar but weaker associations. Prospectively, after adjusting for potential confounders including CMBs, BGPVS were associated with ischaemic stroke (11-20 BGPVS: HR 1.20, 95% CI 0.93-1.54; 21+ BGPVS: HR 1.50, 95% CI 1.10-2.06; overall p = 0.040), but not ICH. CSOPVS were not associated with either outcome. Conclusion(s): In patients with ischaemic stroke or TIA, increasing BGPVS burden is associated with more severe CSVD and greater ischaemic stroke risk. Neither BGPVS nor CSOPVS were independently associated with future ICH, suggesting that CMBs are a more informative marker for intracranial bleeding risk in this population. (Figure Presented).

Published
2022

6. Development of imaging-based risk scores for prediction of intracranial haemorrhage and ischaemic stroke in patients taking antithrombotic therapy after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies

Author

Best, J.G., Ambler, G., Wilson, D., Lee, K.J., Lim, J.S., Shiozawa, M., Koga, M., Li, L, Lovelock, C., Chabriat, H., Hennerici, M., Wong, Y.K., Mak, H.K.F., Prats-Sanchez, L., Martínez-Domeño, A., Inamura, S., Yoshifuji, K., Arsava, E.M., Horstmann, S., Purrucker, J., Lam, B.Y.K., Wong, A., Kim, Y.D., Song, T.J., Lemmens, R., Eppinger, S., Gattringer, T., Uysal, E., Tanriverdi, Z., Bornstein, N.M., Assayag, E. Ben, Hallevi, H., Molad, J., Nishihara, M., Tanaka, J., Coutts, S.B., Polymeris, A., Wagner, B., Seiffge, D.J., Lyrer, P., Algra, A., Kappelle, L.J., Al-Shahi Salman, R., Jäger, H.R., Lip, G.Y.H., Fischer, U., El-Koussy, M., Mas, J.L., Legrand, Laurence, Karayiannis, C., Phan, T., Gunkel, S., Christ, N., Abrigo, J., Leung, T., Chu, W., Chappell, F., Makin, S., Hayden, D., Williams, D.J., Mess, W.H., Nederkoorn, P.J., Barbato, C., Browning, S., Wiegertjes, K., Tuladhar, A.M., Maaijwee, N., Guevarra, A.C., Yatawara, C., Mendyk, A.M., Delmaire, C., Köhler, S., Oostenbrugge, R van, Zhou, Y, Xu, Chao, Hilal, S., Gyanwali, B., Chen, C, Lou, M., Staals, J., Bordet, R., Kandiah, N., Leeuw, F.E. de, Simister, R., Hendrikse, Jeroen, Kelly, P.J., Wardlaw, J., Soo, Y., Fluri, F., Srikanth, V., Calvet, D., Jung, S., Kwa, V.I.H., Engelter, S.T., Peters, Nils, Smith, E.E., Hara, H., Yakushiji, Y., Orken, D.N., Best, J.G., Ambler, G., Wilson, D., Lee, K.J., Lim, J.S., Shiozawa, M., Koga, M., Li, L, Lovelock, C., Chabriat, H., Hennerici, M., Wong, Y.K., Mak, H.K.F., Prats-Sanchez, L., Martínez-Domeño, A., Inamura, S., Yoshifuji, K., Arsava, E.M., Horstmann, S., Purrucker, J., Lam, B.Y.K., Wong, A., Kim, Y.D., Song, T.J., Lemmens, R., Eppinger, S., Gattringer, T., Uysal, E., Tanriverdi, Z., Bornstein, N.M., Assayag, E. Ben, Hallevi, H., Molad, J., Nishihara, M., Tanaka, J., Coutts, S.B., Polymeris, A., Wagner, B., Seiffge, D.J., Lyrer, P., Algra, A., Kappelle, L.J., Al-Shahi Salman, R., Jäger, H.R., Lip, G.Y.H., Fischer, U., El-Koussy, M., Mas, J.L., Legrand, Laurence, Karayiannis, C., Phan, T., Gunkel, S., Christ, N., Abrigo, J., Leung, T., Chu, W., Chappell, F., Makin, S., Hayden, D., Williams, D.J., Mess, W.H., Nederkoorn, P.J., Barbato, C., Browning, S., Wiegertjes, K., Tuladhar, A.M., Maaijwee, N., Guevarra, A.C., Yatawara, C., Mendyk, A.M., Delmaire, C., Köhler, S., Oostenbrugge, R van, Zhou, Y, Xu, Chao, Hilal, S., Gyanwali, B., Chen, C, Lou, M., Staals, J., Bordet, R., Kandiah, N., Leeuw, F.E. de, Simister, R., Hendrikse, Jeroen, Kelly, P.J., Wardlaw, J., Soo, Y., Fluri, F., Srikanth, V., Calvet, D., Jung, S., Kwa, V.I.H., Engelter, S.T., Peters, Nils, Smith, E.E., Hara, H., Yakushiji, Y., and Orken, D.N.

Abstract

Item does not contain fulltext, BACKGROUND: Balancing the risks of recurrent ischaemic stroke and intracranial haemorrhage is important for patients treated with antithrombotic therapy after ischaemic stroke or transient ischaemic attack. However, existing predictive models offer insufficient performance, particularly for assessing the risk of intracranial haemorrhage. We aimed to develop new risk scores incorporating clinical variables and cerebral microbleeds, an MRI biomarker of intracranial haemorrhage and ischaemic stroke risk. METHODS: We did a pooled analysis of individual-patient data from the Microbleeds International Collaborative Network (MICON), which includes 38 hospital-based prospective cohort studies from 18 countries. All studies recruited participants with previous ischaemic stroke or transient ischaemic attack, acquired baseline MRI allowing quantification of cerebral microbleeds, and followed-up participants for ischaemic stroke and intracranial haemorrhage. Participants not taking antithrombotic drugs were excluded. We developed Cox regression models to predict the 5-year risks of intracranial haemorrhage and ischaemic stroke, selecting candidate predictors on biological relevance and simplifying models using backward elimination. We derived integer risk scores for clinical use. We assessed model performance in internal validation, adjusted for optimism using bootstrapping. The study is registered on PROSPERO, CRD42016036602. FINDINGS: The included studies recruited participants between Aug 28, 2001, and Feb 4, 2018. 15 766 participants had follow-up for intracranial haemorrhage, and 15 784 for ischaemic stroke. Over a median follow-up of 2 years, 184 intracranial haemorrhages and 1048 ischaemic strokes were reported. The risk models we developed included cerebral microbleed burden and simple clinical variables. Optimism-adjusted c indices were 0·73 (95% CI 0·69-0·77) with a calibration slope of 0·94 (0·81-1·06) for the intracranial haemorrhage model and 0·63 (0·62-0·65) with

Published
2021

7. Development of imaging-based risk scores for prediction of intracranial haemorrhage and ischaemic stroke in patients taking antithrombotic therapy after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies.

Author

Best J.G., Ambler G., Wilson D., Lee K.-J., Lim J.-S., Shiozawa M., Koga M., Li L., Lovelock C., Chabriat H., Hennerici M., Wong Y.K., Mak H.K.F., Prats-Sanchez L., Martinez-Domeno A., Inamura S., Yoshifuji K., Arsava E.M., Horstmann S., Purrucker J., Lam B.Y.K., Wong A., Kim Y.D., Song T.-J., Lemmens R., Eppinger S., Gattringer T., Uysal E., Tanriverdi Z., Bornstein N.M., Ben Assayag E., Hallevi H., Molad J., Nishihara M., Tanaka J., Coutts S.B., Polymeris A., Wagner B., Seiffge D.J., Lyrer P., Algra A., Kappelle L.J., Al-Shahi Salman R., Jager H.R., Lip G.Y.H., Fischer U., El-Koussy M., Mas J.-L., Legrand L., Karayiannis C., Phan T., Gunkel S., Christ N., Abrigo J., Leung T., Chu W., Chappell F., Makin S., Hayden D., Williams D.J., Mess W.H., Nederkoorn P.J., Barbato C., Browning S., Wiegertjes K., Tuladhar A.M., Maaijwee N., Guevarra A.C., Yatawara C., Mendyk A.-M., Delmaire C., Kohler S., van Oostenbrugge R., Zhou Y., Xu C., Hilal S., Gyanwali B., Chen C., Lou M., Staals J., Bordet R., Kandiah N., de Leeuw F.-E., Simister R., Hendrikse J., Kelly P.J., Wardlaw J., Soo Y., Fluri F., Srikanth V., Calvet D., Jung S., Kwa V.I.H., Engelter S.T., Peters N., Smith E.E., Hara H., Yakushiji Y., Orken D.N., Fazekas F., Thijs V., Heo J.H., Mok V., Veltkamp R., Ay H., Imaizumi T., Gomez-Anson B., Lau K.K., Jouvent E., Rothwell P.M., Toyoda K., Bae H.-J., Marti-Fabregas J., Werring D.J., Harkness K., Shaw L., Sword J., Mohd Nor A., Sharma P., Kelly D., Harrington F., Randall M., Smith M., Mahawish K., Elmarim A., Esisi B., Cullen C., Nallasivam A., Price C., Barry A., Roffe C., Coyle J., Hassan A., Birns J., Cohen D., Sekaran L., Parry-Jones A., Parry A., Hargroves D., Proschel H., Datta P., Darawil K., Manoj A., Burn M., Patterson C., Giallombardo E., Smyth N., Mansoor S., Anwar I., Marsh R., Ispoglou S., Chadha D., Prabhakaran M., Meenakishundaram S., O'Connell J., Scott J., Krishnamurthy V., Aghoram P., McCormick M., Sprigg N., O'Mahony P., Cooper M., Choy L., Wilkinson P., Leach S., Caine S., Burger I., Gunathilagan G., Guyler P., Emsley H., Davis M., Manawadu D., Pasco K., Mamun M., Luder R., Sajid M., Okwera J., Warburton E., Saastamoinen K., England T., Putterill J., Flossman E., Power M., Dani K., Mangion D., Suman A., Corrigan J., Lawrence E., Vahidassr D., Shakeshaft C., Brown M., Charidimou A., Cohen H., Banerjee G., Houlden H., White M., Yousry T., Flossmann E., Muir K., Gratz P., Mattle H., Panos L., Korczyn A., Kliper E., Maeder P., Gass A., Pachai C., Bracoub L., Douste-Blazy M.-Y., Fratacci M.D., Vicaut E., Sato S., Miwa K., Fujita K., Ide T., Ma H., Ly J., Singhal S., Chandra R., Slater L.-A., Soufan C., Moran C., Traenka C., Thilemann S., Fladt J., Gensicke H., Bonati L., Kim B.J., Han M.-K., Kang J., Ko E., Yang M.H., Jang M.S., Murphy S., Carty F., Akijian L., Thornton J., Schembri M., Douven E., Delgado-Mederos R., Marin R., Camps-Renom P., Guisado-Alonso D., Nunez F., Medrano-Martorell S., Merino E., Iida K., Ikeda S., Irie H., Demirelli D.S., Medanta J.M., Zerna C., Hernandez M.V., Armitage P., Heye A., Munoz-Maniega S., Sakka E., Thrippleton M., Dennis M., Beigneux Y., Silva M., Venketasubramanian N., Ho S.L., Cheung R.T.F., Chan K.H., Teo K.C., Hui E., Kwan J.S.K., Chang R., Tse M.Y., Hoi C.P., Chan C.Y., Chan O.L., Cheung R.H.K., Wong E.K.M., Leung K.T., Tsang S.F., Ip H.L., Ma S.H., Ma K., Fong W.C., Li S.H., Li R., Ng P.W., Wong K.K., Liu W., Wong L., Ramos L., De Schryver E., Jobsis J., van der Sande J., Brouwers P., Roos Y., Stam J., Bakker S., Verbiest H., Schoonewille W., Linn C., Hertzberger L., van Gemert M., Berntsen P., Van Dam-Nolen D., Kooi M.E., Van der Lugt A., Koudstaal P., Leff A., Ward N., Nachev P., Perry R., Ozkan H., Mitchell J., Best J.G., Ambler G., Wilson D., Lee K.-J., Lim J.-S., Shiozawa M., Koga M., Li L., Lovelock C., Chabriat H., Hennerici M., Wong Y.K., Mak H.K.F., Prats-Sanchez L., Martinez-Domeno A., Inamura S., Yoshifuji K., Arsava E.M., Horstmann S., Purrucker J., Lam B.Y.K., Wong A., Kim Y.D., Song T.-J., Lemmens R., Eppinger S., Gattringer T., Uysal E., Tanriverdi Z., Bornstein N.M., Ben Assayag E., Hallevi H., Molad J., Nishihara M., Tanaka J., Coutts S.B., Polymeris A., Wagner B., Seiffge D.J., Lyrer P., Algra A., Kappelle L.J., Al-Shahi Salman R., Jager H.R., Lip G.Y.H., Fischer U., El-Koussy M., Mas J.-L., Legrand L., Karayiannis C., Phan T., Gunkel S., Christ N., Abrigo J., Leung T., Chu W., Chappell F., Makin S., Hayden D., Williams D.J., Mess W.H., Nederkoorn P.J., Barbato C., Browning S., Wiegertjes K., Tuladhar A.M., Maaijwee N., Guevarra A.C., Yatawara C., Mendyk A.-M., Delmaire C., Kohler S., van Oostenbrugge R., Zhou Y., Xu C., Hilal S., Gyanwali B., Chen C., Lou M., Staals J., Bordet R., Kandiah N., de Leeuw F.-E., Simister R., Hendrikse J., Kelly P.J., Wardlaw J., Soo Y., Fluri F., Srikanth V., Calvet D., Jung S., Kwa V.I.H., Engelter S.T., Peters N., Smith E.E., Hara H., Yakushiji Y., Orken D.N., Fazekas F., Thijs V., Heo J.H., Mok V., Veltkamp R., Ay H., Imaizumi T., Gomez-Anson B., Lau K.K., Jouvent E., Rothwell P.M., Toyoda K., Bae H.-J., Marti-Fabregas J., Werring D.J., Harkness K., Shaw L., Sword J., Mohd Nor A., Sharma P., Kelly D., Harrington F., Randall M., Smith M., Mahawish K., Elmarim A., Esisi B., Cullen C., Nallasivam A., Price C., Barry A., Roffe C., Coyle J., Hassan A., Birns J., Cohen D., Sekaran L., Parry-Jones A., Parry A., Hargroves D., Proschel H., Datta P., Darawil K., Manoj A., Burn M., Patterson C., Giallombardo E., Smyth N., Mansoor S., Anwar I., Marsh R., Ispoglou S., Chadha D., Prabhakaran M., Meenakishundaram S., O'Connell J., Scott J., Krishnamurthy V., Aghoram P., McCormick M., Sprigg N., O'Mahony P., Cooper M., Choy L., Wilkinson P., Leach S., Caine S., Burger I., Gunathilagan G., Guyler P., Emsley H., Davis M., Manawadu D., Pasco K., Mamun M., Luder R., Sajid M., Okwera J., Warburton E., Saastamoinen K., England T., Putterill J., Flossman E., Power M., Dani K., Mangion D., Suman A., Corrigan J., Lawrence E., Vahidassr D., Shakeshaft C., Brown M., Charidimou A., Cohen H., Banerjee G., Houlden H., White M., Yousry T., Flossmann E., Muir K., Gratz P., Mattle H., Panos L., Korczyn A., Kliper E., Maeder P., Gass A., Pachai C., Bracoub L., Douste-Blazy M.-Y., Fratacci M.D., Vicaut E., Sato S., Miwa K., Fujita K., Ide T., Ma H., Ly J., Singhal S., Chandra R., Slater L.-A., Soufan C., Moran C., Traenka C., Thilemann S., Fladt J., Gensicke H., Bonati L., Kim B.J., Han M.-K., Kang J., Ko E., Yang M.H., Jang M.S., Murphy S., Carty F., Akijian L., Thornton J., Schembri M., Douven E., Delgado-Mederos R., Marin R., Camps-Renom P., Guisado-Alonso D., Nunez F., Medrano-Martorell S., Merino E., Iida K., Ikeda S., Irie H., Demirelli D.S., Medanta J.M., Zerna C., Hernandez M.V., Armitage P., Heye A., Munoz-Maniega S., Sakka E., Thrippleton M., Dennis M., Beigneux Y., Silva M., Venketasubramanian N., Ho S.L., Cheung R.T.F., Chan K.H., Teo K.C., Hui E., Kwan J.S.K., Chang R., Tse M.Y., Hoi C.P., Chan C.Y., Chan O.L., Cheung R.H.K., Wong E.K.M., Leung K.T., Tsang S.F., Ip H.L., Ma S.H., Ma K., Fong W.C., Li S.H., Li R., Ng P.W., Wong K.K., Liu W., Wong L., Ramos L., De Schryver E., Jobsis J., van der Sande J., Brouwers P., Roos Y., Stam J., Bakker S., Verbiest H., Schoonewille W., Linn C., Hertzberger L., van Gemert M., Berntsen P., Van Dam-Nolen D., Kooi M.E., Van der Lugt A., Koudstaal P., Leff A., Ward N., Nachev P., Perry R., Ozkan H., and Mitchell J.

Abstract

Background: Balancing the risks of recurrent ischaemic stroke and intracranial haemorrhage is important for patients treated with antithrombotic therapy after ischaemic stroke or transient ischaemic attack. However, existing predictive models offer insufficient performance, particularly for assessing the risk of intracranial haemorrhage. We aimed to develop new risk scores incorporating clinical variables and cerebral microbleeds, an MRI biomarker of intracranial haemorrhage and ischaemic stroke risk. Method(s): We did a pooled analysis of individual-patient data from the Microbleeds International Collaborative Network (MICON), which includes 38 hospital-based prospective cohort studies from 18 countries. All studies recruited participants with previous ischaemic stroke or transient ischaemic attack, acquired baseline MRI allowing quantification of cerebral microbleeds, and followed-up participants for ischaemic stroke and intracranial haemorrhage. Participants not taking antithrombotic drugs were excluded. We developed Cox regression models to predict the 5-year risks of intracranial haemorrhage and ischaemic stroke, selecting candidate predictors on biological relevance and simplifying models using backward elimination. We derived integer risk scores for clinical use. We assessed model performance in internal validation, adjusted for optimism using bootstrapping. The study is registered on PROSPERO, CRD42016036602. Finding(s): The included studies recruited participants between Aug 28, 2001, and Feb 4, 2018. 15 766 participants had follow-up for intracranial haemorrhage, and 15 784 for ischaemic stroke. Over a median follow-up of 2 years, 184 intracranial haemorrhages and 1048 ischaemic strokes were reported. The risk models we developed included cerebral microbleed burden and simple clinical variables. Optimism-adjusted c indices were 0.73 (95% CI 0.69-0.77) with a calibration slope of 0.94 (0.81-1.06) for the intracranial haemorrhage model and 0.63 (0.62-0.65) w

Published
2021

8. The complication rate among people with diabetes at low risk of foot ulceration in Fife, UK: an analysis of routinely collected data

Author

Heggie, R., Chappell, F., Crawford, F., Martin, A., Gupta, S., Hawkins, N., Horne, M., Leese, G.P., and Lewsey, J.

Abstract

Aims:\ud \ud To estimate the rate at which people with diabetes and a low risk of foot ulceration change diabetic foot ulceration risk status over time, and to estimate the rate of ulceration, amputation and death among this population.\ud \ud Methods:\ud \ud We conducted an observational study of 10 421 people with diabetes attending foot screening in an outpatient setting in NHS Fife, UK, using routinely collected data from a national diabetes register, NHS SCI Diabetes. We estimated the proportion of people who changed risk status and the cumulative incidence of ulceration, amputation and death, respectively, among people with diabetes at low risk of diabetic foot ulceration at 2‐year follow‐up.\ud \ud Results:\ud \ud At 2‐year follow‐up, 5.1% (95% CI 4.7, 5.6) of people with diabetes classified as low risk at their first visit had progressed to moderate risk. The cumulative incidence of ulceration, amputation and death was 0.4% (95% CI 0.3, 0.6), 0.1% (95% CI 0.1, 0.2) and 3.4% (95% CI 3.1, 3.8), respectively.\ud \ud Conclusions:\ud \ud At 2‐year follow‐up, 5% of people at low risk of diabetic foot ulceration changed clinical risk status and

Published
2020

10. 30 Informant-Reported Decline Associates with Silent Acute Stroke Lesions and Worse Small Vessel Disease in Mild Stroke Patients

Author

Clancy, U, primary, Garcia, D J, additional, Hewins, W, additional, Stringer, M, additional, Thrippleton, M, additional, Chappell, F M, additional, Brown, R, additional, Blair, G, additional, Arteaga, C, additional, Valdes-Hernadez, M, additional, Wiseman, S, additional, Hamilton, I, additional, Job, D, additional, Doubal, F N, additional, and Wardlaw, J M, additional

Published
2021
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14. Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies

Author

Wilson, D., Ambler, G., Lee, K.J., Lim, J.S., Shiozawa, M., Koga, M., Li, L, Lovelock, C., Chabriat, H., Hennerici, M., Wong, Y.K., Mak, H.K.F., Prats-Sanchez, L., Martinez-Domeno, A., Inamura, S., Yoshifuji, K., Arsava, E.M., Horstmann, S., Purrucker, J., Lam, B.Y.K., Wong, A., Kim, Y.D., Song, T.J., Schrooten, M., Lemmens, R., Eppinger, S., Gattringer, T., Uysal, E., Tanriverdi, Z., Bornstein, N.M., Assayag, E.B., Hallevi, H., Tanaka, J., Hara, H., Coutts, S.B., Hert, L., Polymeris, A., Seiffge, D.J., Lyrer, P., Algra, A., Kappelle, J., Al-Shahi Salman, R., Jager, H.R., Lip, G.Y.H., Mattle, H.P., Panos, L.D., Mas, J.L., Legrand, L., Karayiannis, C., Phan, T., Gunkel, S., Christ, N., Abrigo, J., Leung, T., Chu, W., Chappell, F., Makin, S., Hayden, D., Williams, D.J., Kooi, M.E., Dam-Nolen, D.H.K., Barbato, C., Browning, S., Wiegertjes, K., Tuladhar, A.M., Maaijwee, N., Guevarra, C., Yatawara, C., Mendyk, A.M., Delmaire, C., Kohler, S., Oostenbrugge, R van, Zhou, Y, Xu, C., Hilal, S., Gyanwali, B., Chen, C, Lou, M., Staals, J., Bordet, R., Kandiah, N., Leeuw, F.E. de, Simister, R., Lugt, A. van der, Kelly, P.J., Wardlaw, J.M., Soo, Y., Fluri, F., Srikanth, V., Calvet, D., Jung, S., Kwa, V.I.H., Engelter, S.T., Peters, N, Smith, E.E., Yakushiji, Y., Orken, D.N., Fazekas, F., Marti-Fabregas, J., Werring, D.J., Wilson, D., Ambler, G., Lee, K.J., Lim, J.S., Shiozawa, M., Koga, M., Li, L, Lovelock, C., Chabriat, H., Hennerici, M., Wong, Y.K., Mak, H.K.F., Prats-Sanchez, L., Martinez-Domeno, A., Inamura, S., Yoshifuji, K., Arsava, E.M., Horstmann, S., Purrucker, J., Lam, B.Y.K., Wong, A., Kim, Y.D., Song, T.J., Schrooten, M., Lemmens, R., Eppinger, S., Gattringer, T., Uysal, E., Tanriverdi, Z., Bornstein, N.M., Assayag, E.B., Hallevi, H., Tanaka, J., Hara, H., Coutts, S.B., Hert, L., Polymeris, A., Seiffge, D.J., Lyrer, P., Algra, A., Kappelle, J., Al-Shahi Salman, R., Jager, H.R., Lip, G.Y.H., Mattle, H.P., Panos, L.D., Mas, J.L., Legrand, L., Karayiannis, C., Phan, T., Gunkel, S., Christ, N., Abrigo, J., Leung, T., Chu, W., Chappell, F., Makin, S., Hayden, D., Williams, D.J., Kooi, M.E., Dam-Nolen, D.H.K., Barbato, C., Browning, S., Wiegertjes, K., Tuladhar, A.M., Maaijwee, N., Guevarra, C., Yatawara, C., Mendyk, A.M., Delmaire, C., Kohler, S., Oostenbrugge, R van, Zhou, Y, Xu, C., Hilal, S., Gyanwali, B., Chen, C, Lou, M., Staals, J., Bordet, R., Kandiah, N., Leeuw, F.E. de, Simister, R., Lugt, A. van der, Kelly, P.J., Wardlaw, J.M., Soo, Y., Fluri, F., Srikanth, V., Calvet, D., Jung, S., Kwa, V.I.H., Engelter, S.T., Peters, N, Smith, E.E., Yakushiji, Y., Orken, D.N., Fazekas, F., Marti-Fabregas, J., and Werring, D.J.

Abstract

Contains fulltext : 208975.pdf (publisher's version ) (Open Access), BACKGROUND: Cerebral microbleeds are a neuroimaging biomarker of stroke risk. A crucial clinical question is whether cerebral microbleeds indicate patients with recent ischaemic stroke or transient ischaemic attack in whom the rate of future intracranial haemorrhage is likely to exceed that of recurrent ischaemic stroke when treated with antithrombotic drugs. We therefore aimed to establish whether a large burden of cerebral microbleeds or particular anatomical patterns of cerebral microbleeds can identify ischaemic stroke or transient ischaemic attack patients at higher absolute risk of intracranial haemorrhage than ischaemic stroke. METHODS: We did a pooled analysis of individual patient data from cohort studies in adults with recent ischaemic stroke or transient ischaemic attack. Cohorts were eligible for inclusion if they prospectively recruited adult participants with ischaemic stroke or transient ischaemic attack; included at least 50 participants; collected data on stroke events over at least 3 months follow-up; used an appropriate MRI sequence that is sensitive to magnetic susceptibility; and documented the number and anatomical distribution of cerebral microbleeds reliably using consensus criteria and validated scales. Our prespecified primary outcomes were a composite of any symptomatic intracranial haemorrhage or ischaemic stroke, symptomatic intracranial haemorrhage, and symptomatic ischaemic stroke. We registered this study with the PROSPERO international prospective register of systematic reviews, number CRD42016036602. FINDINGS: Between Jan 1, 1996, and Dec 1, 2018, we identified 344 studies. After exclusions for ineligibility or declined requests for inclusion, 20 322 patients from 38 cohorts (over 35 225 patient-years of follow-up; median 1.34 years [IQR 0.19-2.44]) were included in our analyses. The adjusted hazard ratio [aHR] comparing patients with cerebral microbleeds to those without was 1.35 (95% CI 1.20-1.50) for the composite outcome of intr

Published
2019

15. Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies.

Author

Jung S., van Dam-Nolen D.H.K., Douven E., Delgado-Mederos, R., Marin R., Camps-Renom P., Guisado-Alonso D., Nunez F., Medrano-Martorell S., Merino E., Iida K., Ikeda S., Nishihara M., Irie H., Demirelli D.S., Medanta J.M., Zerna C., Hernandez M.V., Armitage P., Heye A., Munoz-Maniega S., Sakka E., Thrippleton M., Dennis M., Beigneux Y., Silva M., Venketasubramanian N., Ho S.L., Cheung R.T.F., Chan K.H., Teo K.C., Hui E., Kwan J.S.K., Chang R., Tse M.Y., Hoi C.P., Chan C.Y., Chan O.L., Cheung R.H.K., Wong E.K.M., Leung K.T., Tsang S.F., Ip H.L., Ma S.H., Ma K., Fong W.C., Li S.H., Li R., Ng P.W., Wong K.K., Liu W., Wong L., Ramos L., De Schryver E., Jobsis J., van der Sande J., Brouwers P., Roos Y., Stam J., Bakker S., Verbiest H., Schoonewille W., Linn C., Hertzberger L., van Gemert M., Berntsen P., Hendrikse J., Nederkoorn P., Mess W., Koudstaal P., Leff A., Ward N., Nachev P., Perry R., Ozkan H., Mitchell J., Wilson D., Ambler G., Lee K.-J., Lim J.-S., Shiozawa M., Koga M., Li L., Lovelock C., Chabriat H., Hennerici M., Wong Y.K., Mak H.K.F., Prats-Sanchez L., Martinez-Domeno A., Inamura S., Yoshifuji K., Arsava E.M., Horstmann S., Purrucker J., Lam B.Y.K., Wong A., Kim Y.D., Song T.-J., Schrooten M., Lemmens R., Eppinger S., Gattringer T., Uysal E., Tanriverdi Z., Bornstein N.M., Assayag E.B., Hallevi H., Tanaka J., Hara H., Coutts S.B., Hert L., Polymeris A., Seiffge D.J., Lyrer P., Algra A., Kappelle J., Al-Shahi Salman R., Jager H.R., Lip G.Y.H., Mattle H.P., Panos L.D., Mas J.-L., Legrand L., Karayiannis C., Phan T., Gunkel S., Christ N., Abrigo J., Leung T., Chu W., Chappell F., Makin S., Hayden D., Williams D.J., Kooi M.E., Barbato C., Browning S., Wiegertjes K., Tuladhar A.M., Maaijwee N., Guevarra C., Yatawara C., Mendyk A.-M., Delmaire C., Kohler S., van Oostenbrugge R., Zhou Y., Xu C., Hilal S., Gyanwali B., Chen C., Lou M., Staals J., Bordet R., Kandiah N., de Leeuw F.-E., Simister R., van der Lugt A., Kelly P.J., Wardlaw J.M., Soo Y., Fluri F., Srikanth V., Calvet D., Kwa V.I.H., Engelter S.T., Peters N., Smith E.E., Yakushiji Y., Orken D.N., Fazekas F., Thijs V., Heo J.H., Mok V., Veltkamp R., Ay H., Imaizumi T., Gomez-Anson B., Lau K.K., Jouvent E., Rothwell P.M., Toyoda K., Bae H.-J., Marti-Fabregas J., Werring D.J., Harkness K., Shaw L., Sword J., Mohd Nor A., Sharma P., Kelly D., Harrington F., Randall M., Smith M., Mahawish K., Elmarim A., Esisi B., Cullen C., Nallasivam A., Price C., Barry A., Roffe C., Coyle J., Hassan A., Birns J., Cohen D., Sekaran L., Parry-Jones A., Parry A., Hargroves D., Proschel H., Datta P., Darawil K., Manoj A., Burn M., Patterson C., Giallombardo E., Smyth N., Mansoor S., Anwar I., Marsh R., Ispoglou S., Chadha D., Prabhakaran M., Meenakishundaram S., O'Connell J., Scott J., Krishnamurthy V., Aghoram P., McCormick M., Sprigg N., O'Mahony P., Cooper M., Choy L., Wilkinson P., Leach S., Caine S., Burger I., Gunathilagan G., Guyler P., Emsley H., Davis M., Manawadu D., Pasco K., Mamun M., Luder R., Sajid M., Okwera J., Warburton E., Saastamoinen K., England T., Putterill J., Flossman E., Power M., Dani K., Mangion D., Suman A., Corrigan J., Lawrence E., Vahidassr D., Shakeshaft C., Brown M., Charidimou A., Cohen H., Banerjee G., Houlden H., White M., Yousry T., Flossmann E., Muir K., El-Koussy M., Gratz P., Molad J., Korczyn A., Kliper E., Maeder P., Gass A., Pachai C., Bracoub L., Douste-Blazy M.-Y., Fratacci M.D., Vicaut E., Sato S., Miwa K., Fujita K., Ide T., Ma H., Ly J., Singhal S., Chandra R., Slater L.-A., Soufan C., Moran C., Traenka C., Thilemann S., Fladt J., Gensicke H., Bonati L., Kim B.J., Han M.-K., Kang J., Ko E., Yang M.H., Jang M.S., Murphy S., Carty F., Akijian L., Thornton J., Schembri M., Jung S., van Dam-Nolen D.H.K., Douven E., Delgado-Mederos, R., Marin R., Camps-Renom P., Guisado-Alonso D., Nunez F., Medrano-Martorell S., Merino E., Iida K., Ikeda S., Nishihara M., Irie H., Demirelli D.S., Medanta J.M., Zerna C., Hernandez M.V., Armitage P., Heye A., Munoz-Maniega S., Sakka E., Thrippleton M., Dennis M., Beigneux Y., Silva M., Venketasubramanian N., Ho S.L., Cheung R.T.F., Chan K.H., Teo K.C., Hui E., Kwan J.S.K., Chang R., Tse M.Y., Hoi C.P., Chan C.Y., Chan O.L., Cheung R.H.K., Wong E.K.M., Leung K.T., Tsang S.F., Ip H.L., Ma S.H., Ma K., Fong W.C., Li S.H., Li R., Ng P.W., Wong K.K., Liu W., Wong L., Ramos L., De Schryver E., Jobsis J., van der Sande J., Brouwers P., Roos Y., Stam J., Bakker S., Verbiest H., Schoonewille W., Linn C., Hertzberger L., van Gemert M., Berntsen P., Hendrikse J., Nederkoorn P., Mess W., Koudstaal P., Leff A., Ward N., Nachev P., Perry R., Ozkan H., Mitchell J., Wilson D., Ambler G., Lee K.-J., Lim J.-S., Shiozawa M., Koga M., Li L., Lovelock C., Chabriat H., Hennerici M., Wong Y.K., Mak H.K.F., Prats-Sanchez L., Martinez-Domeno A., Inamura S., Yoshifuji K., Arsava E.M., Horstmann S., Purrucker J., Lam B.Y.K., Wong A., Kim Y.D., Song T.-J., Schrooten M., Lemmens R., Eppinger S., Gattringer T., Uysal E., Tanriverdi Z., Bornstein N.M., Assayag E.B., Hallevi H., Tanaka J., Hara H., Coutts S.B., Hert L., Polymeris A., Seiffge D.J., Lyrer P., Algra A., Kappelle J., Al-Shahi Salman R., Jager H.R., Lip G.Y.H., Mattle H.P., Panos L.D., Mas J.-L., Legrand L., Karayiannis C., Phan T., Gunkel S., Christ N., Abrigo J., Leung T., Chu W., Chappell F., Makin S., Hayden D., Williams D.J., Kooi M.E., Barbato C., Browning S., Wiegertjes K., Tuladhar A.M., Maaijwee N., Guevarra C., Yatawara C., Mendyk A.-M., Delmaire C., Kohler S., van Oostenbrugge R., Zhou Y., Xu C., Hilal S., Gyanwali B., Chen C., Lou M., Staals J., Bordet R., Kandiah N., de Leeuw F.-E., Simister R., van der Lugt A., Kelly P.J., Wardlaw J.M., Soo Y., Fluri F., Srikanth V., Calvet D., Kwa V.I.H., Engelter S.T., Peters N., Smith E.E., Yakushiji Y., Orken D.N., Fazekas F., Thijs V., Heo J.H., Mok V., Veltkamp R., Ay H., Imaizumi T., Gomez-Anson B., Lau K.K., Jouvent E., Rothwell P.M., Toyoda K., Bae H.-J., Marti-Fabregas J., Werring D.J., Harkness K., Shaw L., Sword J., Mohd Nor A., Sharma P., Kelly D., Harrington F., Randall M., Smith M., Mahawish K., Elmarim A., Esisi B., Cullen C., Nallasivam A., Price C., Barry A., Roffe C., Coyle J., Hassan A., Birns J., Cohen D., Sekaran L., Parry-Jones A., Parry A., Hargroves D., Proschel H., Datta P., Darawil K., Manoj A., Burn M., Patterson C., Giallombardo E., Smyth N., Mansoor S., Anwar I., Marsh R., Ispoglou S., Chadha D., Prabhakaran M., Meenakishundaram S., O'Connell J., Scott J., Krishnamurthy V., Aghoram P., McCormick M., Sprigg N., O'Mahony P., Cooper M., Choy L., Wilkinson P., Leach S., Caine S., Burger I., Gunathilagan G., Guyler P., Emsley H., Davis M., Manawadu D., Pasco K., Mamun M., Luder R., Sajid M., Okwera J., Warburton E., Saastamoinen K., England T., Putterill J., Flossman E., Power M., Dani K., Mangion D., Suman A., Corrigan J., Lawrence E., Vahidassr D., Shakeshaft C., Brown M., Charidimou A., Cohen H., Banerjee G., Houlden H., White M., Yousry T., Flossmann E., Muir K., El-Koussy M., Gratz P., Molad J., Korczyn A., Kliper E., Maeder P., Gass A., Pachai C., Bracoub L., Douste-Blazy M.-Y., Fratacci M.D., Vicaut E., Sato S., Miwa K., Fujita K., Ide T., Ma H., Ly J., Singhal S., Chandra R., Slater L.-A., Soufan C., Moran C., Traenka C., Thilemann S., Fladt J., Gensicke H., Bonati L., Kim B.J., Han M.-K., Kang J., Ko E., Yang M.H., Jang M.S., Murphy S., Carty F., Akijian L., Thornton J., and Schembri M.

Abstract

Background: Cerebral microbleeds are a neuroimaging biomarker of stroke risk. A crucial clinical question is whether cerebral microbleeds indicate patients with recent ischaemic stroke or transient ischaemic attack in whom the rate of future intracranial haemorrhage is likely to exceed that of recurrent ischaemic stroke when treated with antithrombotic drugs. We therefore aimed to establish whether a large burden of cerebral microbleeds or particular anatomical patterns of cerebral microbleeds can identify ischaemic stroke or transient ischaemic attack patients at higher absolute risk of intracranial haemorrhage than ischaemic stroke. Method(s): We did a pooled analysis of individual patient data from cohort studies in adults with recent ischaemic stroke or transient ischaemic attack. Cohorts were eligible for inclusion if they prospectively recruited adult participants with ischaemic stroke or transient ischaemic attack; included at least 50 participants; collected data on stroke events over at least 3 months follow-up; used an appropriate MRI sequence that is sensitive to magnetic susceptibility; and documented the number and anatomical distribution of cerebral microbleeds reliably using consensus criteria and validated scales. Our prespecified primary outcomes were a composite of any symptomatic intracranial haemorrhage or ischaemic stroke, symptomatic intracranial haemorrhage, and symptomatic ischaemic stroke. We registered this study with the PROSPERO international prospective register of systematic reviews, number CRD42016036602. Finding(s): Between Jan 1, 1996, and Dec 1, 2018, we identified 344 studies. After exclusions for ineligibility or declined requests for inclusion, 20 322 patients from 38 cohorts (over 35 225 patient-years of follow-up; median 1.34 years [IQR 0.19-2.44]) were included in our analyses. The adjusted hazard ratio [aHR] comparing patients with cerebral microbleeds to those without was 1.35 (95% CI 1.20-1.50) for the composite outcome of

Published
2019

16. Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies

Author

Wilson, D. (Duncan), Ambler, G. (Gareth), Lee, K.-J. (Keon-Joo), Lim, J.-S. (Jae-Sung), Shiozawa, M. (Masayuki), Koga, M. (Masatoshi), Li, L. (Linxin), Lovelock, C. (Caroline), Chabriat, H. (Hugues), Hennerici, M.G. (Michael), Wong, Y.K. (Yuen Kwun), Mak, H.K.F. (Henry Ka Fung), Prats-Sánchez, L. (Luis), Martínez-Domeño, A. (Alejandro), Inamura, S. (Shigeru), Yoshifuji, K. (Kazuhisa), Arsava, E.M. (Ethem Murat), Horstmann, S. (Solveig), Purrucker, J. (Jan), Lam, B.Y.K. (Bonnie Yin Ka), Wong, A. (Adrian), Kim, Y.D. (Young Dae), Song, T.-J. (Tae-Jin), Schrooten, M. (Maarten), Lemmens, R. (Robin), Eppinger, S. (Sebastian), Gattringer, T. (Thomas), Uysal, E. (Ender), Tanriverdi, Z. (Zeynep), Bornstein, S.R. (Stefan), Assayag, E.B. (Einor Ben), Hallevi, H. (Hen), Tanaka, J. (Jun), Hara, H. (Hideo), Coutts, S.B. (Shelagh B), Hert, L. (Lisa), Polymeris, A. (Alexandros), Seiffge, D.J. (David J), Lyrer, P.A. (Philippe), Algra, A. (Ale), Kappelle, L.J. (Jaap), Al-Shahi Salman, R. (Rustam), Jäger, H.R. (Rolf), Lip, G.Y.H. (Gregory Y H), Mattle, H., Panos, L.D. (Leonidas D), Mas, J.L. (J.), Legrand, L. (Laurence), Karayiannis, C. (Christopher), Phan, T.G. (Thanh), Gunkel, S. (Sarah), Christ, N. (Nicolas), Abrigo, J. (Jill), Leung, T. (Thomas), Chu, W. (Winnie), Chappell, F. (Francesca), Makin, S. (Stephen), Hayden, D. (Derek), Williams, D.J. (David J), Kooi, M.E. (M. Eline), van Dam-Nolen, D.H.K. (Dianne H K), Barbato, C. (Carmen), Browning, S. (Simone), Wiegertjes, K. (Kim), Tuladhar, A.M. (Anil M.), Maaijwee, N. (Noortje), Guevarra, C. (Christine), Yatawara, C. (Chathuri), Mendyk, A.-M. (Anne-Marie), Delmaire, C. (Christine), Köhler, S. (Sebastian), Oostenbrugge, R.J. (Robert) van, Zhou, Y. (Ying), Xu, C. (Chao), Hilal, S. (Saima), Gyanwali, B. (Bibek), Chen, C. (Christopher), Lou, M. (Min), Staals, J. (Julie), Bordet, R. (Régis), Kandiah, N. (Nagaendran), Leeuw, H.F. (Frank) de, Simister, R. (Robert), Lugt, A. (Aad) van der, Kelly, P.J. (Peter J), Wardlaw, J.M. (J.), Soo, Y. (Yannie), Fluri, F. (Felix), Srikanth, V. (Velandai), Calvet, D. (David), Jung, S. (Simon), Kwa, V.I.H., Engelter, S.T. (Stefan), Peters, N. (Nils), Smith, E.E. (Eric), Yakushiji, Y. (Yusuke), Orken, D.N. (Dilek Necioglu), Fazekas, F. (Franz), Thijs, V. (Vincent), Heo, J.H. (Ji Hoe), Mok, V. (Vincent), Veltkamp, R. (Roland), Ay, H. (Hakan), Imaizumi, T. (Toshio), Gomez-Anson, B. (Beatriz), Lau, K.K. (Kui Kai), Jouvent, E. (Eric), Rothwell, P.M. (Peter), Toyoda, K. (Kazunori), Bae, H.-J. (Hee-Joon), Marti-Fabregas, J. (Joan), Werring, D.J. (David), Harkness, K. (Kirsty), Shaw, L. (Louise), Sword, J. (Jane), Mohd Nor, A. (Azlisham), Sharma, P. (Pankaj), Kelly, D. (Deborah), Harrington, F. (Frances), Randall, M. (Marc), Smith, M. (Matthew), Mahawish, K. (Karim), Elmarim, A. (Abduelbaset), Esisi, B. (Bernard), Cullen, C. (Claire), Nallasivam, A. (Arumug), Price, C. (Christopher), Barry, A. (Adrian), Roffe, C. (Christine), Coyle, J. (John), Hassan, A. (Ahamad), Birns, J. (Jonathan), Cohen, D. (David), Sekaran, L. (Lakshmanan), Parry-Jones, A. (Adrian), Parry, A. (Anthea), Hargroves, D. (David), Proschel, H. (Harald), Datta, P. (Prabel), Darawil, K. (Khaled), Manoj, A. (Aravindakshan), Burn, M. (Mathew), Patterson, C. (Chris), Giallombardo, E. (Elio), Smyth, N. (Nigel), Mansoor, S. (Syed), Anwar, I. (Ijaz), Marsh, R. (Rachel), Ispoglou, S. (Sissi), Chadha, D. (Dinesh), Prabhakaran, M. (Mathuri), Meenakishundaram, S. (Sanjeevikumar), O'Connell, J. (Janice), Scott, J. (Jon), Krishnamurthy, V. (Vinodh), Aghoram, P. (Prasanna), McCormick, M. (Michael), Sprigg, N. (Nikola), O'Mahony, P. (Paul), Cooper, M. (Martin), Choy, L. (Lillian), Wilkinson, P. (Peter), Leach, S. (Simon), Caine, S. (Sarah), Burger, I. (Ilse), Gunathilagan, G. (Gunaratam), Guyler, P. (Paul), Emsley, H. (Hedley), Davis, M. (Michelle), Manawadu, D. (Dulka), Pasco, K. (Kath), Mamun, M. (Maam), Luder, R. (Robert), Sajid, M. (Mahmud), Okwera, J. (James), Warburton, E. (Elizabeth), Saastamoinen, K. (Kari), England, T. (Timothy), Putterill, J. (Janet), Flossman, E. (Enrico), Power, M. (Michael), Dani, K. (Krishna), Mangion, D. (David), Suman, A. (Appu), Corrigan, J. (John), Lawrence, E. (Enas), Vahidassr, D. (Djamil), Shakeshaft, C. (Clare), Brown, M. (Martin), Charidimou, A. (Andreas), Cohen, H. (Hannah), Banerjee, G. (Gargi), Houlden, H. (Henry), White, M. (Mark), Yousry, T. (Tarek), Flossmann, E. (Enrico), Muir, K. (Keith), El-Koussy, M. (Marwan), Gratz, P. (Pascal), Molad, J. (Jeremy), Korczyn, A.D. (A.), Kliper, E. (Efrat), Maeder, P. (Philippe), Gass, A. (Achim), Pachai, C. (Chahin), Bracoub, L. (Luc), Douste-Blazy, M.-Y. (Marie-Yvonne), Fratacci, M.D. (Marie Dominique), Vicaut, E. (Eric), Sato, S. (Shoichiro), Miwa, K. (Kaori), Fujita, K. (Kyohei), Ide, T. (Toshihiro), Ma, H. (Henry), Ly, J. (John), Singhal, S. (Shahoo), Chandra, R. (Ronil), Slater, L.-A. (Lee-Anne), Soufan, C. (Cathy), Moran, C. (Christopher), Traenka, C. (Christopher), Thilemann, S. (Sebastian), Fladt, J. (Joachim), Gensicke, H. (Henrik), Bonati, L. (Leo), Kim, B.J. (Beom Joon), Han, M.-K. (Moon-Ku), Kang, J. (Jihoon), Ko, E. (Eunbin), Yang, M.H. (Mi Hwa), Jang, M.S. (Myung Suk), Murphy, S. (Sean), Carty, F. (Fiona), Akijian, L. (Layan), Thornton, J. (John), Schembri, M. (Mark), Douven, E. (Elles), Delgado-Mederos;, R. (Raquel), Marín, R. (Rebeca), Camps-Renom, P. (Pol), Guisado-Alonso, D. (Daniel), Nuñez, F. (Fidel), Medrano-Martorell, S. (Santiago), Merino, E. (Elisa), Iida, K. (Kotaro), Ikeda, S. (Syuhei), Nishihara, M. (Masashi), Irie, H. (Hiroyuki), Demirelli, D.S. (Derya Selcuk), Medanta, J.M. (Jayesh Modi), Zerna, C. (Charlotte), Hernández, M.V. (Maria Valdés), Armitage, P. (Paul), Heye, A. (Anna), Muñoz Maniega, S. (Susana), Sakka, E. (Eleni), Thrippleton, M. (Michael), Dennis, M.S. (M.), Beigneux, Y. (Ysoline), Silva, M. (Mauro), Venketasubramanian, N. (Narayanaswamy), Ho, S.L. (Shu Leung), Cheung, R.T.F. (Raymond Tak Fai), Chan, K.H. (Koon Ho), Teo, K.C. (Kay Cheong), Hui, E. (Edward), Kwan, J.S.K. (Joseph Shiu Kwong), Chang, R. (Richard), Tse, M.Y. (Man Yu), Hoi, C.P. (Chu Peng), Chan, C.Y. (Chung Yan), Chan, O.L. (Oi Ling), Cheung, R.H.K. (Ryan Hoi Kit), Wong, E.K.M. (Edmund Ka Ming), Leung, K.T. (Kam Tat), Tsang, S.F. (Suk Fung), Ip, H.L. (Hing Lung), Ma, S.H. (Sze Ho), Ma, K. (Karen), Fong, W.C. (Wing Chi), Li, S.H. (Siu Hung), Li, R. (Richard), Ng, P.W. (Ping Wing), Wong, K.K. (Kwok Kui), Liu, W. (Wenyan), Wong, L. (Lawrence), Ramos, L. (Lino), Schryver, E.L.L.M. (Els) de, Jöbsis, J. (Joost), van der Sande, J. (Jaap), Brouwers, P.J. (Paul), Roos, Y.B.W.E.M. (Yvo), Stam, J. (Jan), Bakker, S.L.M. (Stef), Verbiest, H. (Henk), Schoonewille, W. (Wouter), Linn, C. (Cisca), Hertzberger, L., Gemert, M. (Maarten) van, Berntsen, P. (Paul), Hendrikse, J. (Jeroen), Nederkoorn, P.J. (Paul), Mess, W.H. (Werner), Koudstaal, P.J. (Peter), Leff, A. (Alexander), Ward, N. (Nicholas), Nachev, P. (Parashkev), Perry, R. (Richard), Ozkan, H. (Hatice), Mitchell, J. (John), Wilson, D. (Duncan), Ambler, G. (Gareth), Lee, K.-J. (Keon-Joo), Lim, J.-S. (Jae-Sung), Shiozawa, M. (Masayuki), Koga, M. (Masatoshi), Li, L. (Linxin), Lovelock, C. (Caroline), Chabriat, H. (Hugues), Hennerici, M.G. (Michael), Wong, Y.K. (Yuen Kwun), Mak, H.K.F. (Henry Ka Fung), Prats-Sánchez, L. (Luis), Martínez-Domeño, A. (Alejandro), Inamura, S. (Shigeru), Yoshifuji, K. (Kazuhisa), Arsava, E.M. (Ethem Murat), Horstmann, S. (Solveig), Purrucker, J. (Jan), Lam, B.Y.K. (Bonnie Yin Ka), Wong, A. (Adrian), Kim, Y.D. (Young Dae), Song, T.-J. (Tae-Jin), Schrooten, M. (Maarten), Lemmens, R. (Robin), Eppinger, S. (Sebastian), Gattringer, T. (Thomas), Uysal, E. (Ender), Tanriverdi, Z. (Zeynep), Bornstein, S.R. (Stefan), Assayag, E.B. (Einor Ben), Hallevi, H. (Hen), Tanaka, J. (Jun), Hara, H. (Hideo), Coutts, S.B. (Shelagh B), Hert, L. (Lisa), Polymeris, A. (Alexandros), Seiffge, D.J. (David J), Lyrer, P.A. (Philippe), Algra, A. (Ale), Kappelle, L.J. (Jaap), Al-Shahi Salman, R. (Rustam), Jäger, H.R. (Rolf), Lip, G.Y.H. (Gregory Y H), Mattle, H., Panos, L.D. (Leonidas D), Mas, J.L. (J.), Legrand, L. (Laurence), Karayiannis, C. (Christopher), Phan, T.G. (Thanh), Gunkel, S. (Sarah), Christ, N. (Nicolas), Abrigo, J. (Jill), Leung, T. (Thomas), Chu, W. (Winnie), Chappell, F. (Francesca), Makin, S. (Stephen), Hayden, D. (Derek), Williams, D.J. (David J), Kooi, M.E. (M. Eline), van Dam-Nolen, D.H.K. (Dianne H K), Barbato, C. (Carmen), Browning, S. (Simone), Wiegertjes, K. (Kim), Tuladhar, A.M. (Anil M.), Maaijwee, N. (Noortje), Guevarra, C. (Christine), Yatawara, C. (Chathuri), Mendyk, A.-M. (Anne-Marie), Delmaire, C. (Christine), Köhler, S. (Sebastian), Oostenbrugge, R.J. (Robert) van, Zhou, Y. (Ying), Xu, C. (Chao), Hilal, S. (Saima), Gyanwali, B. (Bibek), Chen, C. (Christopher), Lou, M. (Min), Staals, J. (Julie), Bordet, R. (Régis), Kandiah, N. (Nagaendran), Leeuw, H.F. (Frank) de, Simister, R. (Robert), Lugt, A. (Aad) van der, Kelly, P.J. (Peter J), Wardlaw, J.M. (J.), Soo, Y. (Yannie), Fluri, F. (Felix), Srikanth, V. (Velandai), Calvet, D. (David), Jung, S. (Simon), Kwa, V.I.H., Engelter, S.T. (Stefan), Peters, N. (Nils), Smith, E.E. (Eric), Yakushiji, Y. (Yusuke), Orken, D.N. (Dilek Necioglu), Fazekas, F. (Franz), Thijs, V. (Vincent), Heo, J.H. (Ji Hoe), Mok, V. (Vincent), Veltkamp, R. (Roland), Ay, H. (Hakan), Imaizumi, T. (Toshio), Gomez-Anson, B. (Beatriz), Lau, K.K. (Kui Kai), Jouvent, E. (Eric), Rothwell, P.M. (Peter), Toyoda, K. (Kazunori), Bae, H.-J. (Hee-Joon), Marti-Fabregas, J. (Joan), Werring, D.J. (David), Harkness, K. (Kirsty), Shaw, L. (Louise), Sword, J. (Jane), Mohd Nor, A. (Azlisham), Sharma, P. (Pankaj), Kelly, D. (Deborah), Harrington, F. (Frances), Randall, M. (Marc), Smith, M. (Matthew), Mahawish, K. (Karim), Elmarim, A. (Abduelbaset), Esisi, B. (Bernard), Cullen, C. (Claire), Nallasivam, A. (Arumug), Price, C. (Christopher), Barry, A. (Adrian), Roffe, C. (Christine), Coyle, J. (John), Hassan, A. (Ahamad), Birns, J. (Jonathan), Cohen, D. (David), Sekaran, L. (Lakshmanan), Parry-Jones, A. (Adrian), Parry, A. (Anthea), Hargroves, D. (David), Proschel, H. (Harald), Datta, P. (Prabel), Darawil, K. (Khaled), Manoj, A. (Aravindakshan), Burn, M. (Mathew), Patterson, C. (Chris), Giallombardo, E. (Elio), Smyth, N. (Nigel), Mansoor, S. (Syed), Anwar, I. (Ijaz), Marsh, R. (Rachel), Ispoglou, S. (Sissi), Chadha, D. (Dinesh), Prabhakaran, M. (Mathuri), Meenakishundaram, S. (Sanjeevikumar), O'Connell, J. (Janice), Scott, J. (Jon), Krishnamurthy, V. (Vinodh), Aghoram, P. (Prasanna), McCormick, M. (Michael), Sprigg, N. (Nikola), O'Mahony, P. (Paul), Cooper, M. (Martin), Choy, L. (Lillian), Wilkinson, P. (Peter), Leach, S. (Simon), Caine, S. (Sarah), Burger, I. (Ilse), Gunathilagan, G. (Gunaratam), Guyler, P. (Paul), Emsley, H. (Hedley), Davis, M. (Michelle), Manawadu, D. (Dulka), Pasco, K. (Kath), Mamun, M. (Maam), Luder, R. (Robert), Sajid, M. (Mahmud), Okwera, J. (James), Warburton, E. (Elizabeth), Saastamoinen, K. (Kari), England, T. (Timothy), Putterill, J. (Janet), Flossman, E. (Enrico), Power, M. (Michael), Dani, K. (Krishna), Mangion, D. (David), Suman, A. (Appu), Corrigan, J. (John), Lawrence, E. (Enas), Vahidassr, D. (Djamil), Shakeshaft, C. (Clare), Brown, M. (Martin), Charidimou, A. (Andreas), Cohen, H. (Hannah), Banerjee, G. (Gargi), Houlden, H. (Henry), White, M. (Mark), Yousry, T. (Tarek), Flossmann, E. (Enrico), Muir, K. (Keith), El-Koussy, M. (Marwan), Gratz, P. (Pascal), Molad, J. (Jeremy), Korczyn, A.D. (A.), Kliper, E. (Efrat), Maeder, P. (Philippe), Gass, A. (Achim), Pachai, C. (Chahin), Bracoub, L. (Luc), Douste-Blazy, M.-Y. (Marie-Yvonne), Fratacci, M.D. (Marie Dominique), Vicaut, E. (Eric), Sato, S. (Shoichiro), Miwa, K. (Kaori), Fujita, K. (Kyohei), Ide, T. (Toshihiro), Ma, H. (Henry), Ly, J. (John), Singhal, S. (Shahoo), Chandra, R. (Ronil), Slater, L.-A. (Lee-Anne), Soufan, C. (Cathy), Moran, C. (Christopher), Traenka, C. (Christopher), Thilemann, S. (Sebastian), Fladt, J. (Joachim), Gensicke, H. (Henrik), Bonati, L. (Leo), Kim, B.J. (Beom Joon), Han, M.-K. (Moon-Ku), Kang, J. (Jihoon), Ko, E. (Eunbin), Yang, M.H. (Mi Hwa), Jang, M.S. (Myung Suk), Murphy, S. (Sean), Carty, F. (Fiona), Akijian, L. (Layan), Thornton, J. (John), Schembri, M. (Mark), Douven, E. (Elles), Delgado-Mederos;, R. (Raquel), Marín, R. (Rebeca), Camps-Renom, P. (Pol), Guisado-Alonso, D. (Daniel), Nuñez, F. (Fidel), Medrano-Martorell, S. (Santiago), Merino, E. (Elisa), Iida, K. (Kotaro), Ikeda, S. (Syuhei), Nishihara, M. (Masashi), Irie, H. (Hiroyuki), Demirelli, D.S. (Derya Selcuk), Medanta, J.M. (Jayesh Modi), Zerna, C. (Charlotte), Hernández, M.V. (Maria Valdés), Armitage, P. (Paul), Heye, A. (Anna), Muñoz Maniega, S. (Susana), Sakka, E. (Eleni), Thrippleton, M. (Michael), Dennis, M.S. (M.), Beigneux, Y. (Ysoline), Silva, M. (Mauro), Venketasubramanian, N. (Narayanaswamy), Ho, S.L. (Shu Leung), Cheung, R.T.F. (Raymond Tak Fai), Chan, K.H. (Koon Ho), Teo, K.C. (Kay Cheong), Hui, E. (Edward), Kwan, J.S.K. (Joseph Shiu Kwong), Chang, R. (Richard), Tse, M.Y. (Man Yu), Hoi, C.P. (Chu Peng), Chan, C.Y. (Chung Yan), Chan, O.L. (Oi Ling), Cheung, R.H.K. (Ryan Hoi Kit), Wong, E.K.M. (Edmund Ka Ming), Leung, K.T. (Kam Tat), Tsang, S.F. (Suk Fung), Ip, H.L. (Hing Lung), Ma, S.H. (Sze Ho), Ma, K. (Karen), Fong, W.C. (Wing Chi), Li, S.H. (Siu Hung), Li, R. (Richard), Ng, P.W. (Ping Wing), Wong, K.K. (Kwok Kui), Liu, W. (Wenyan), Wong, L. (Lawrence), Ramos, L. (Lino), Schryver, E.L.L.M. (Els) de, Jöbsis, J. (Joost), van der Sande, J. (Jaap), Brouwers, P.J. (Paul), Roos, Y.B.W.E.M. (Yvo), Stam, J. (Jan), Bakker, S.L.M. (Stef), Verbiest, H. (Henk), Schoonewille, W. (Wouter), Linn, C. (Cisca), Hertzberger, L., Gemert, M. (Maarten) van, Berntsen, P. (Paul), Hendrikse, J. (Jeroen), Nederkoorn, P.J. (Paul), Mess, W.H. (Werner), Koudstaal, P.J. (Peter), Leff, A. (Alexander), Ward, N. (Nicholas), Nachev, P. (Parashkev), Perry, R. (Richard), Ozkan, H. (Hatice), and Mitchell, J. (John)

Abstract

Background: Cerebral microbleeds are a neuroimaging biomarker of stroke risk. A crucial clinical question is whether cerebral microbleeds indicate patients with recent ischaemic stroke or transient ischaemic attack in whom the rate of future intracranial haemorrhage is likely to exceed that of recurrent ischaemic stroke when treated with antithrombotic drugs. We therefore aimed to establish whether a large burden of cerebral microbleeds or particular anatomical patterns of cerebral microbleeds can identify ischaemic stroke or transient ischaemic attack patients at higher absolute risk of intracranial haemorrhage than ischaemic stroke. Methods: We did a pooled analysis of individual patient data from cohort studies in adults with recent ischaemic stroke or transient ischaemic attack. Cohorts were eligible for inclusion if they prospectively recruited adult participants with ischaemic stroke or

Published
2019
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17. Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies

Author

Wilson, D, Ambler, G, Lee, K-J, Lim, J-S, Shiozawa, M, Koga, M, Li, L, Lovelock, C, Chabriat, H, Hennerici, M, Wong, YK, Mak, HKF, Prats-Sanchez, L, Martinez-Domeno, A, Inamura, S, Yoshifuji, K, Arsava, EM, Horstmann, S, Purrucker, J, Lam, BYK, Wong, A, Kim, YD, Song, T-J, Schrooten, M, Lemmens, R, Eppinger, S, Gattringer, T, Uysal, E, Tanriverdi, Z, Bornstein, NM, Ben Assayag, E, Hallevi, H, Tanaka, J, Hara, H, Coutts, SB, Hert, L, Polymeris, A, Seiffge, DJ, Lyrer, P, Algra, A, Kappelle, J, Salman, RA-S, Jager, HR, Lip, GYH, Mattle, HP, Panos, LD, Mas, J-L, Legrand, L, Karayiannis, C, Phan, T, Gunkel, S, Christ, N, Abrigo, J, Leung, T, Chu, W, Chappell, F, Makin, S, Hayden, D, Williams, DJ, Kooi, ME, van Dam-Nolen, DHK, Barbato, C, Browning, S, Wiegertjes, K, Tuladhar, AM, Maaijwee, N, Guevarra, C, Yatawara, C, Mendyk, A-M, Delmaire, C, Kohler, S, van Oostenbrugge, R, Zhou, Y, Xu, C, Hilal, S, Gyanwali, B, Chen, C, Lou, M, Staals, J, Bordet, R, Kandiah, N, de Leeuw, F-E, Simister, R, van der Lugt, A, Kelly, PJ, Wardlaw, JM, Soo, Y, Fluri, F, Srikanth, V, Calvet, D, Jung, S, Kwa, VIH, Engelter, ST, Peters, N, Smith, EE, Yakushiji, Y, Orken, DN, Fazekas, F, Thijs, V, Heo, JH, Mok, V, Veltkamp, R, Ay, H, Imaizumi, T, Gomez-Anson, B, Lau, KK, Jouvent, E, Rothwell, PM, Toyoda, K, Bae, H-J, Marti-Fabregas, J, Werring, DJ, Wilson, D, Ambler, G, Lee, K-J, Lim, J-S, Shiozawa, M, Koga, M, Li, L, Lovelock, C, Chabriat, H, Hennerici, M, Wong, YK, Mak, HKF, Prats-Sanchez, L, Martinez-Domeno, A, Inamura, S, Yoshifuji, K, Arsava, EM, Horstmann, S, Purrucker, J, Lam, BYK, Wong, A, Kim, YD, Song, T-J, Schrooten, M, Lemmens, R, Eppinger, S, Gattringer, T, Uysal, E, Tanriverdi, Z, Bornstein, NM, Ben Assayag, E, Hallevi, H, Tanaka, J, Hara, H, Coutts, SB, Hert, L, Polymeris, A, Seiffge, DJ, Lyrer, P, Algra, A, Kappelle, J, Salman, RA-S, Jager, HR, Lip, GYH, Mattle, HP, Panos, LD, Mas, J-L, Legrand, L, Karayiannis, C, Phan, T, Gunkel, S, Christ, N, Abrigo, J, Leung, T, Chu, W, Chappell, F, Makin, S, Hayden, D, Williams, DJ, Kooi, ME, van Dam-Nolen, DHK, Barbato, C, Browning, S, Wiegertjes, K, Tuladhar, AM, Maaijwee, N, Guevarra, C, Yatawara, C, Mendyk, A-M, Delmaire, C, Kohler, S, van Oostenbrugge, R, Zhou, Y, Xu, C, Hilal, S, Gyanwali, B, Chen, C, Lou, M, Staals, J, Bordet, R, Kandiah, N, de Leeuw, F-E, Simister, R, van der Lugt, A, Kelly, PJ, Wardlaw, JM, Soo, Y, Fluri, F, Srikanth, V, Calvet, D, Jung, S, Kwa, VIH, Engelter, ST, Peters, N, Smith, EE, Yakushiji, Y, Orken, DN, Fazekas, F, Thijs, V, Heo, JH, Mok, V, Veltkamp, R, Ay, H, Imaizumi, T, Gomez-Anson, B, Lau, KK, Jouvent, E, Rothwell, PM, Toyoda, K, Bae, H-J, Marti-Fabregas, J, and Werring, DJ

Abstract

BACKGROUND: Cerebral microbleeds are a neuroimaging biomarker of stroke risk. A crucial clinical question is whether cerebral microbleeds indicate patients with recent ischaemic stroke or transient ischaemic attack in whom the rate of future intracranial haemorrhage is likely to exceed that of recurrent ischaemic stroke when treated with antithrombotic drugs. We therefore aimed to establish whether a large burden of cerebral microbleeds or particular anatomical patterns of cerebral microbleeds can identify ischaemic stroke or transient ischaemic attack patients at higher absolute risk of intracranial haemorrhage than ischaemic stroke. METHODS: We did a pooled analysis of individual patient data from cohort studies in adults with recent ischaemic stroke or transient ischaemic attack. Cohorts were eligible for inclusion if they prospectively recruited adult participants with ischaemic stroke or transient ischaemic attack; included at least 50 participants; collected data on stroke events over at least 3 months follow-up; used an appropriate MRI sequence that is sensitive to magnetic susceptibility; and documented the number and anatomical distribution of cerebral microbleeds reliably using consensus criteria and validated scales. Our prespecified primary outcomes were a composite of any symptomatic intracranial haemorrhage or ischaemic stroke, symptomatic intracranial haemorrhage, and symptomatic ischaemic stroke. We registered this study with the PROSPERO international prospective register of systematic reviews, number CRD42016036602. FINDINGS: Between Jan 1, 1996, and Dec 1, 2018, we identified 344 studies. After exclusions for ineligibility or declined requests for inclusion, 20 322 patients from 38 cohorts (over 35 225 patient-years of follow-up; median 1·34 years [IQR 0·19-2·44]) were included in our analyses. The adjusted hazard ratio [aHR] comparing patients with cerebral microbleeds to those without was 1·35 (95% CI 1·20-1·50) for the composite outcome of intr

Published
2019

20. Rationale, design and methodology of the image analysis protocol for studies of patients with cerebral small vessel disease and mild stroke

Author

Hernandez, M.D.C.V., Armitage, P.A., Thrippleton, M.J., Chappell, F., Sandeman, E., Maniega, S.M., Shuler, K., and Wardlaw, J.M.

Abstract

Rationale: Cerebral small vessel disease (SVD) is common in ageing and patients with dementia and stroke. Its manifestations on magnetic resonance imaging (MRI) include white matter hyperintensities, lacunes, microbleeds, perivascular spaces, small subcortical infarcts, and brain atrophy. Many studies focus only on one of these manifestations. A protocol for the differential assessment of all these features is, therefore, needed.\ud \ud Aims: To identify ways of quantifying imaging markers in research of patients with SVD and operationalize the recommendations from the STandards for ReportIng Vascular changes on nEuroimaging guidelines. Here, we report the rationale, design, and methodology of a brain image analysis protocol based on our experience from observational longitudinal studies of patients with nondisabling stroke.\ud \ud Design: The MRI analysis protocol is designed to provide quantitative and qualitative measures of disease evolution including: acute and old stroke lesions, lacunes, tissue loss due to stroke, perivascular spaces, microbleeds, macrohemorrhages, iron deposition in basal ganglia, substantia nigra and brain stem, brain atrophy, and white matter hyperintensities, with the latter separated into intense and less intense. Quantitative measures of tissue integrity such as diffusion fractional anisotropy, mean diffusivity, and the longitudinal relaxation time are assessed in regions of interest manually placed in anatomically and functionally relevant locations, and in others derived from feature extraction pipelines and tissue segmentation methods. Morphological changes that relate to cognitive deficits after stroke, analyzed through shape models of subcortical structures, complete the multiparametric image analysis protocol.\ud \ud Outcomes: Final outcomes include guidance for identifying ways to minimize bias and confounds in the assessment of SVD and stroke imaging biomarkers. It is intended that this information will inform the design of studies to examine the underlying pathophysiology of SVD and stroke, and to provide reliable, quantitative outcomes in trials of new therapies and preventative strategies.

Published
2015

21. The development and validation of a multivariable prognostic model to predict foot ulceration in diabetes using a systematic review and individual patient data meta‐analyses.

Author

Crawford, F., Cezard, G., Chappell, F. M., Young, Matthew J., Abbott, Caroline A., Boulton, Andrew J. M., Boyko, Edward J., Seelig, Amber, Kastenbauer, Thomas, Leese, Graham P., Monami, Matteo, Monteiro‐Soares, Matilde, Rith‐Najarian, Stephen J., Veves, Aristidis, Stansby, Gerard P., Sheikh, Aziz, Coates, Nikki, Jeffcoate, William J., Leech, Nicola, and Fahey, Tom

Subjects
DISEASE risk factors, DIABETIC foot, AGE distribution, CONFIDENCE intervals, EXPERIMENTAL design, RESEARCH methodology, META-analysis, MULTIVARIATE analysis, RISK assessment, SEX distribution, SYSTEMATIC reviews, LOGISTIC regression analysis, RESEARCH methodology evaluation, DISEASE duration, STATISTICAL models, ODDS ratio, PROGNOSIS, DIAGNOSIS
Abstract

Aims: Diabetes guidelines recommend screening for the risk of foot ulceration but vary substantially in the underlying evidence base. Our purpose was to derive and validate a prognostic model of independent risk factors for foot ulceration in diabetes using all available individual patient data from cohort studies conducted worldwide. Methods: We conducted a systematic review and meta‐analysis of individual patient data from 10 cohort studies of risk factors in the prediction of foot ulceration in diabetes. Predictors were selected for plausibility, availability and low heterogeneity. Logistic regression produced adjusted odds ratios (ORs) for foot ulceration by ulceration history, monofilament insensitivity, any absent pedal pulse, age, sex and diabetes duration. Results: The 10 studies contained data from 16 385 participants. A history of foot ulceration produced the largest OR [6.59 (95% CI 2.49 to 17.45)], insensitivity to a 10 g monofilament [3.18 (95% CI 2.65 to 3.82)] and any absent pedal pulse [1.97 (95% CI 1.62 to 2.39)] were consistently, independently predictive. Combining three predictors produced sensitivities between 90.0% (95% CI 69.9% to 97.2%) and 95.3% (95% CI 84.5% to 98.7%); the corresponding specificities were between 12.1% (95% CI 8.2% to 17.3%) and 63.9% (95% CI 61.1% to 66.6%). Conclusions: This prognostic model of only three risk factors, a history of foot ulceration, an inability to feel a 10 g monofilament and the absence of any pedal pulse, compares favourably with more complex approaches to foot risk assessment recommended in clinical diabetes guidelines. What's new?: Cohort studies to identify risk factors for foot ulceration in people with diabetes have been published in the biomedical literature since the early 1990s.We assembled an international data set of risk factors collected from 16 385 individuals with diabetes who took part in cohort studies to derive and validate a prognostic model of three risk factors: a history of foot ulceration, an inability to feel a 10 g monofilament and at least one absent pedal pulse.The use of only these three risk factors in foot risk assessments during annual diabetes foot checks could reduce the amount of time spent assessing risk and thereby increase the number of people with diabetes who have checks performed.The frequency of risk assessment should be considered in future research. [ABSTRACT FROM AUTHOR]

Published
2018
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24. Non-invasive imaging compared with intra-arterial angiography in the diagnosis of symptomatic carotid stenosis: a meta-analysis.

Author

Wardlaw J, Chappell F, Best JJK, Wartolowska K, Berry E, NHS Research and Development Health Technology Assessment Carotid Stenosis Imaging Group, Wardlaw, J M, Chappell, F M, Best, J J K, Wartolowska, K, and Berry, E

Abstract

Background: Accurate carotid imaging is important for effective secondary stroke prevention. Non-invasive imaging, now widely available, is replacing intra-arterial angiography for carotid stenosis, but the accuracy remains uncertain despite an extensive literature. We systematically reviewed the accuracy of non-invasive imaging compared with intra-arterial angiography for diagnosing carotid stenosis in patients with carotid territory ischaemic symptoms. Methods: We searched for articles published between 1980 and April 2004; included studies comparing non-invasive imaging with intra-arterial angiography that met Standards for Reporting of Diagnostic Accuracy (STARD) criteria; extracted data to calculate sensitivity and specificity of non-invasive imaging, to test for heterogeneity and to perform sensitivity analyses; and categorised percent stenosis by the North American Symptomatic Carotid Endarterectomy Trial (NASCET) method. Results: In 41 included studies (2541 patients, 4876 arteries), contrast-enhanced MR angiography was more sensitive (0.94, 95% CI 0.88-0.97) and specific (0.93, 95% CI 0.89-0.96) for 70-99% stenosis than Doppler ultrasound, MR angiography, and CT angiography (sensitivities 0.89, 0.88, 0.76; specificities 0.84, 0.84, 0.94, respectively). Data for 50-69% stenoses and combinations of non-invasive tests were sparse and unreliable. There was heterogeneity between studies and evidence of publication bias. Interpretation: Non-invasive tests, used cautiously, could replace intra-arterial carotid angiography for 70-99% stenosis. However, more data are required to determine their accuracy, especially at 50-69% stenoses where the balance of risk and benefit for carotid endarterectomy is particularly narrow, and to explore and overcome heterogeneity. Methodology for evaluating imaging tests should be improved; blinded, prospective studies in clinically relevant patients are essential basic characteristics. [ABSTRACT FROM AUTHOR]

Published
2006

32. Plautus: The Comedies

Author

Packman, Z. M., primary, Carrier, C., additional, Beecham, R., additional, Burroway, J., additional, Chappell, F., additional, Dillard, R., additional, Beacham, R., additional, Poster, C., additional, Slavitt, David R., additional, Bovie, Palmer, additional, Segal, E., additional, Moore, R., additional, Taylor, H., additional, Bovie, P., additional, Tatum, J., additional, Garrett, G., additional, Epstein, D., additional, and Wright, J., additional

Published
1998
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36. INFORMANT-REPORTED DECLINE ASSOCIATES WITH SILENT ACUTE STROKE LESIONS ANDWORSE SMALL VESSEL DISEASE IN MILD STROKE PATIENTS.

Author

Clancy, U., Garcia, D. J., Hewins, W., Stringer, M., Thrippleton, M., Chappell, F. M., Brown, R., Blair, G., Arteaga, C., Valdes-Hernadez, M., Wiseman, S., Hamilton, I., Job, D., Doubal, F. N., and Wardlaw, J. M.

Subjects
DIAGNOSIS of dementia, COGNITION disorders, CONFERENCES & conventions, STROKE patients, LIFE skills, EARLY diagnosis
Abstract

Introduction: Small vessel disease (SVD) commonly causes stroke and dementia. Early clinical predictors of disease progression are lacking. We aimed to determine whether informant reports of chronic cognitive/functional decline, prerequisites for dementia diagnosis, are associated with (a)baseline SVD burden, measured by Fazekas scores and (b)SVD change, measured by incident subcortical Diffusion-weighted Imaging (DWI) lesions. Method: We prospectively recruited patients with mild ischaemic stroke, performed diagnostic MRI, and invited participants to repeat MRI 3- to 6-monthly. Informants completed the Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE) prior to baseline visit, a 16-item questionnaire which assesses patients’ cognitive and functional decline in the preceding ten years. Scores range from 1–5: a score above 3.3 has high sensitivity/specificity for dementia post-stroke. We conducted linear regression with IQCODE as the dependent variable, adjusting for age, sex, baseline MoCA, disability (modified Rankin Scale). Results: We recruited 106 participants (mean age 67 years;range 40–86;33% female). Ninety-three informant questionnaires were returned. IQCODE associated with baseline Fazekas score; Fazekas 6 (β =0.28, p=0.04) vs. Fazekas 3 (β =0.03, p=0.67), R2=0.11, adjusted for age, sex, baseline MoCA, disability. IncidentDWI lesions were common (15/106; 14/15 subcortical; no active embolic sources; median 67 days post-stroke). Four were asymptomatic, two reported stroke-like symptoms and nine had neuropsychiatric/non-focal symptoms. IQCODE was higher in those with a new lesion vs. without (β =0.21, p=0.02), R2=0.09, while age (β =−0.004, p=0.19), MoCA (β =−0.006, p=0.56) and disability (β =0.06, p=0.2) were not. Conclusions: Higher SVD burden and incident, mostly “silent” stroke lesions associate more strongly with informant concerns of cognitive/functional decline than age or objective cognitive tests. These findings are novel in an ischaemic stroke population and the first to assess IQCODE/SVD progression. Future work should determine whether combining informant reports with imaging features of small vessel disease improves early detection of dementia. [ABSTRACT FROM AUTHOR]

Published
2021
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42. Back to the bat cave: An ingenious snare to lure our kids into science.

Author

Chappell, F.

Subjects
*SCIENCE
Abstract

Suggests the formation of a new group of superheroes, maybe called `The Science Squadron,' who would be drawn from different ethnic and socioeconomic backgrounds and age groups and should represent a spectrum of scientific disciplines: astronomy, zoology, Newtonian physics, chemistry, mathematics. These heroes would help reintroduce science to students not merely by lecturing, but in enlisting student aid. Possible areas for support.

Published
1992

44. A daily temperature rhythm in the human brain predicts survival after brain injury

Author

Rzechorzek, Nina M, Thrippleton, Michael J, Chappell, Francesca M, Mair, Grant, Ercole, Ari, Cabeleira, Manuel, Citerio, Giuseppe, Rhodes, Jonathan, Marshall, Ian, O'Neill, John S, Rzechorzek, N, Thrippleton, M, Chappell, F, Mair, G, Ercole, A, Cabeleira, M, Citerio, G, Rhodes, J, Marshall, I, O'Neill, J, Ercole, Ari [0000-0001-8350-8093], O'Neill, John [0000-0003-2204-6096], and Apollo - University of Cambridge Repository

Subjects
Adult, Male, Temperature, Brain, brain thermometry, brain injury, daily, mortality, Body Temperature, Hypothermia, Induced, Brain Injuries, brain temperature, Brain Injuries, Traumatic, Humans, Female, Neurology (clinical), Aged, Retrospective Studies
Abstract

Patients undergo interventions to achieve a ‘normal’ brain temperature; a parameter that remains undefined for humans. The profound sensitivity of neuronal function to temperature implies the brain should be isothermal, but observations from patients and non-human primates suggest significant spatiotemporal variation. We aimed to determine the clinical relevance of brain temperature in patients by establishing how much it varies in healthy adults. We retrospectively screened data for all patients recruited to the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury High Resolution Intensive Care Unit Sub-Study. Only patients with direct brain temperature measurements without targeted temperature management were included. To interpret patient analyses, we prospectively recruited 40 healthy adults (20 males, 20 females, 20-40 years) for brain thermometry using magnetic resonance spectroscopy. Participants were scanned in the morning, afternoon, and late evening of a single day. In patients (n=114), mean brain temperature (38.5±0.8°C) exceeded body temperature (37.5±0.5°C, P, The prospective study was funded by a Medical Research Council Clinician Scientist Fellowship awarded to N.M.R. (MR/S022023/1). J.S.O.N. is supported by the Medical Research Council (MC_UP_1201/4). Some of the data contributing to the retrospective analysis were obtained in the context of CENTER-TBI, a large collaborative project (EC grant 602150) supported by the European Union’s 7th Framework program (FP7/2007-2013). Additional funding for patient data collection was obtained from the Hannelore Kohl Stiftung (Germany), from OneMind (USA) and from Integra LifeSciences Corporation (USA). M.J.T. acknowledges funding from the NHS Lothian Research and Development Office.

Published
2022

45. Sex Differences in Frequency, Severity, and Distribution of Cerebral Microbleeds.

Author

Fandler-Höfler S, Eppinger S, Ambler G, Nash P, Kneihsl M, Lee KJ, Lim JS, Shiozawa M, Koga M, Li L, Lovelock C, Chabriat H, Hennerici M, Wong YK, Mak HKF, Prats-Sanchez L, Martínez-Domeño A, Inamura S, Yoshifuji K, Arsava EM, Horstmann S, Purrucker J, Lam BYK, Wong A, Kim YD, Song TJ, Lemmens R, Uysal E, Tanriverdi Z, Bornstein NM, Ben Assayag E, Hallevi H, Molad J, Nishihara M, Tanaka J, Coutts SB, Polymeris A, Wagner B, Seiffge DJ, Lyrer P, Kappelle LJ, Salman RA, Hernandez MV, Jäger HR, Lip GYH, Fischer U, El-Koussy M, Mas JL, Legrand L, Karayiannis C, Phan T, Gunkel S, Christ N, Abrigo J, Chu W, Leung T, Chappell F, Makin S, Hayden D, Williams DJ, Mess WH, Kooi ME, Barbato C, Browning S, Tuladhar AM, Maaijwee N, Guevarra AC, Mendyk AM, Delmaire C, Köhler S, van Oostenbrugge R, Zhou Y, Xu C, Hilal S, Robert C, Chen C, Lou M, Staals J, Bordet R, Kandiah N, de Leeuw FE, Simister R, Bos D, Kelly PJ, Wardlaw J, Soo Y, Fluri F, Srikanth V, Calvet D, Jung S, Kwa VIH, Engelter ST, Peters N, Smith EE, Hara H, Yakushiji Y, Orken DN, Thijs V, Heo JH, Mok V, Veltkamp R, Ay H, Imaizumi T, Lau KK, Jouvent E, Rothwell PM, Toyoda K, Bae HJ, Marti-Fabregas J, Wilson D, Best J, Fazekas F, Enzinger C, Werring DJ, and Gattringer T

Subjects
Humans, Male, Female, Aged, Middle Aged, Sex Factors, Magnetic Resonance Imaging, Prospective Studies, Severity of Illness Index, Cerebral Small Vessel Diseases epidemiology, Cerebral Small Vessel Diseases diagnostic imaging, Cerebral Small Vessel Diseases complications, Aged, 80 and over, Cohort Studies, Cerebral Hemorrhage epidemiology, Cerebral Hemorrhage diagnostic imaging, Cerebral Hemorrhage mortality
Abstract

Importance: Cerebral small vessel disease (SVD) is associated with various cerebrovascular outcomes, but data on sex differences in SVD are scarce., Objective: To investigate whether the frequency, severity, and distribution of cerebral microbleeds (CMB), other SVD markers on magnetic resonance imaging (MRI), and outcomes differ by sex., Design, Setting, and Participants: This cohort study used pooled individual patient data from the Microbleeds International Collaborative Network, including patients from 38 prospective cohort studies in 18 countries between 2000 and 2018, with clinical follow-up of at least 3 months (up to 5 years). Participants included patients with acute ischemic stroke or transient ischemic attack with available brain MRI. Data were analyzed from April to December 2023., Main Outcomes and Measures: Outcomes of interest were presence of CMB, lacunes, and severe white matter hyperintensities determined on MRI. Additionally, mortality, recurrent ischemic stroke, and intracranial hemorrhage during follow-up were assessed. Multivariable random-effects logistic regression models, Cox regression, and competing risk regression models were used to investigate sex differences in individual SVD markers, risk of recurrent cerebrovascular events, and death., Results: A total of 20 314 patients (mean [SD] age, 70.1 [12.7] years; 11 721 [57.7%] male) were included, of whom 5649 (27.8%) had CMB. CMB were more frequent in male patients, and this was consistent throughout different age groups, locations, and in multivariable models (female vs male adjusted odds ratio [aOR], 0.86; 95% CI, 0.80-0.92; P < .001). Female patients had fewer lacunes (aOR, 0.82; 95% CI, 0.74-0.90; P < .001) but a higher prevalence of severe white matter hyperintensities (aOR, 1.10; 95% CI, 1.01-1.20; P = .04) compared with male patients. A total of 2419 patients (11.9%) died during a median (IQR) follow-up of 1.4 (0.7-2.5) years. CMB presence was associated with a higher risk of mortality in female patients (hazard ratio, 1.15; 95% CI, 1.02-1.31), but not male patients (hazard ratio, 0.95; 95% CI, 0.84-1.07) (P for interaction = .01). A total of 1113 patients (5.5%) had recurrent ischemic stroke, and 189 patients (0.9%) had recurrent intracranial hemorrhage, with no sex differences., Conclusions and Relevance: This cohort study using pooled individual patient data found varying frequencies of individual SVD markers between female and male patients, indicating potential pathophysiological differences in manifestation and severity of SVD. Further research addressing differences in pathomechanisms and outcomes of SVD between female and male patients is required.

Published
2024
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46. Parasitic infections: what do paediatricians need to know?

Author

Eisen S, Nabarro L, Godbole G, Ciang-Sang T, Chappell F, and Cohen J

Abstract

Parasitic infections and the medications used to treat them may be unfamiliar to many paediatricians. Parasitic infections, however, are not uncommonly seen in children in the UK. We summarise infections which are commonly seen, currently recommended treatment and practical guidance on formulations, adverse effects and treatment choice., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2024
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47. Higher intraocular pressure is associated with slower axial growth in children with non-pathological high myopia.

Author

Yii FS, He M, Chappell F, Bernabeu MO, MacGillivray T, Dhillon B, Tatham A, and Strang N

Subjects
Child, Humans, Intraocular Pressure, Cohort Studies, Eye pathology, Refraction, Ocular, Axial Length, Eye pathology, Myopia, Glaucoma pathology
Abstract

Objectives: To investigate the association between intraocular pressure (IOP) and axial elongation rate in highly myopic children from the ZOC-BHVI High Myopia Cohort Study., Methods: 162 eyes of 81 healthy children (baseline spherical equivalent: -6.25 D to -15.50 D) aged 7-12 years with non-pathological high myopia were studied over five biennial visits. The mean (SD) follow-up duration was 5.2 (3.3) years. A linear mixed-effects model (LMM) was used to assess the association between IOP (at time point t-1) and axial elongation rate (annual rate of change in AL from t-1 to t), controlling for a pre-defined set of covariates including sex, age, central corneal thickness, anterior chamber depth and lens thickness (at t-1). LMM was also used to assess the contemporaneous association between IOP and axial length (AL) at t, controlling for the same set of covariates (at t) as before., Results: Higher IOP was associated with slower axial growth (β = -0.01, 95% CI -0.02 to -0.005, p = 0.001). There was a positive contemporaneous association between IOP and AL (β = 0.03, 95% CI 0.01-0.05, p = 0.004), but this association became progressively less positive with increasing age, as indicated by a negative interaction effect between IOP and age on AL (β = -0.01, 95% CI -0.01 to -0.003, p = 0.001)., Conclusions: Higher IOP is associated with slower rather than faster axial growth in children with non-pathological high myopia, an association plausibly confounded by the increased influence of ocular compliance on IOP., (© 2023. The Author(s).)

Published
2024
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48. Trends in Antibiotic Use in a Large Children's Hospital in London (United Kingdom): 5 Years of Point Prevalence Surveys.

Author

Meesters K, Chappell F, and Demirjian A

Abstract

Background : Antibiotics are commonly prescribed in paediatrics. As their excessive use contributes to adverse drug events, increased healthcare costs, and antimicrobial resistance, antimicrobial stewardship initiatives are essential to optimising medical care. These single-centre point prevalence surveys aimed to provide insights into antibiotic prescribing trends and identify targets for paediatric AMS activities. Methods : 14 point prevalence surveys were conducted from March 2016-April 2021, collecting data on antibiotic prescriptions, indication, adherence to guidelines, and route of administration. The UK adapted the World Health Organisation's AWaRe classification-guided antibiotic categorization. Results : 32.5% of all inpatients were on at least one antimicrobial; this remained stable during all surveys (range: 20-44%, p = 0.448). Of all prescriptions, 67.2% had an end- or review-date, and the majority was for agents in the Watch category (46.8-70.5%). Amoxicillin and clavulanate were the most frequently prescribed antibiotics (20.8%), followed by gentamicin (15.3%). Approximately 28.8% of all prescriptions were for prophylactic indications, while 7.6% of the prescriptions were not adherent to the hospital guidelines. Conclusions : This study highlights the importance of ongoing monitoring and robust AMS initiatives to ensure prudent antibiotic prescribing in paediatric healthcare. It underscores the need for tailored guidelines, educational efforts, and targeted interventions to enhance the quality of antibiotic usage, ultimately benefiting both individual patients and public health.

Published
2024
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49. Clinical Associations and Prognostic Value of MRI-Visible Perivascular Spaces in Patients With Ischemic Stroke or TIA: A Pooled Analysis

Author

Best JG, Ambler G, Wilson D, Du H, Lee KJ, Lim JS, Teo KC, Mak H, Kim YD, Song TJ, Selcuk Demirelli D, Nishihara M, Yoshikawa M, Kubacka M, Zietz A, Al-Shahi Salman R, Jäger HR, Lip GYH, Panos L, Goeldlin MB, Slater LA, Karayiannis CC, Phan TG, Bellut M, Abrigo J, Cheng C, Leung TW, Chu W, Chappell F, Makin SDJ, van Dam-Nolen DHK, Kooi ME, Köhler S, Staals J, Kuchcinski G, Bordet R, Dubost F, Wardlaw JM, Soo YOY, Fluri F, Srikanth VK, Jung S, Peters N, Hara H, Yakushiji Y, Necioglu Orken D, Heo JH, Lau GKK, Bae HJ, and Werring DJ

Subjects
Humans, Female, Aged, Male, Prognosis, Prospective Studies, Intracranial Hemorrhages, Magnetic Resonance Imaging, Cerebral Hemorrhage, Ischemic Stroke, Ischemic Attack, Transient complications, Ischemic Attack, Transient diagnostic imaging, Stroke diagnostic imaging, Cerebral Small Vessel Diseases complications, Cerebral Small Vessel Diseases diagnostic imaging
Abstract

Background and Objectives: Visible perivascular spaces are an MRI marker of cerebral small vessel disease and might predict future stroke. However, results from existing studies vary. We aimed to clarify this through a large collaborative multicenter analysis., Methods: We pooled individual patient data from a consortium of prospective cohort studies. Participants had recent ischemic stroke or transient ischemic attack (TIA), underwent baseline MRI, and were followed up for ischemic stroke and symptomatic intracranial hemorrhage (ICH). Perivascular spaces in the basal ganglia (BGPVS) and perivascular spaces in the centrum semiovale (CSOPVS) were rated locally using a validated visual scale. We investigated clinical and radiologic associations cross-sectionally using multinomial logistic regression and prospective associations with ischemic stroke and ICH using Cox regression., Results: We included 7,778 participants (mean age 70.6 years; 42.7% female) from 16 studies, followed up for a median of 1.44 years. Eighty ICH and 424 ischemic strokes occurred. BGPVS were associated with increasing age, hypertension, previous ischemic stroke, previous ICH, lacunes, cerebral microbleeds, and white matter hyperintensities. CSOPVS showed consistently weaker associations. Prospectively, after adjusting for potential confounders including cerebral microbleeds, increasing BGPVS burden was independently associated with future ischemic stroke (versus 0-10 BGPVS, 11-20 BGPVS: HR 1.19, 95% CI 0.93-1.53; 21+ BGPVS: HR 1.50, 95% CI 1.10-2.06; p = 0.040). Higher BGPVS burden was associated with increased ICH risk in univariable analysis, but not in adjusted analyses. CSOPVS were not significantly associated with either outcome., Discussion: In patients with ischemic stroke or TIA, increasing BGPVS burden is associated with more severe cerebral small vessel disease and higher ischemic stroke risk. Neither BGPVS nor CSOPVS were independently associated with future ICH.

Published
2024
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50. National point-prevalence survey of healthcare-associated infections and antimicrobial use: UK-PAS/UKHSA joint call to action for all paediatric services.

Author

Channon-Wells S, Elmes J, Muller-Pebody B, McGarrity O, Chappell F, Drysdale SB, Ashiru-Oredope D, Patel S, and Demirjian A

Subjects
Humans, Child, Prevalence, Practice Patterns, Physicians', United Kingdom epidemiology, Anti-Infective Agents therapeutic use, Cross Infection epidemiology, Cross Infection prevention & control
Abstract

The negative impact of high antimicrobial use (AMU), antimicrobial resistance and healthcare-associated infections (HCAIs) on children is concerning. However, a lack of available paediatric data makes it challenging to design and implement interventions that would improve health outcomes in this population, and impedes efforts to secure additional resources. The upcoming 2023 national point-prevalence survey of HCAIs and AMU in hospitals, led by the UK Health Security Agency, is an opportunity to collect valuable information, which will enable healthcare providers and policy makers to optimize antimicrobial stewardship and infection prevention practices in all populations, including children. These data will facilitate benchmarking and sharing of best practice, internally, nationally and internationally. This is a joint call to action asking all healthcare professionals-particularly in paediatrics-to nominate a lead for their institution and participate in this survey, to ensure appropriate paediatric representation, and help protect children from these growing threats., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Published
2023
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