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2. Oral anticoagulants in the oldest old with recent stroke and atrial fibrillation

Author

Polymeris, A. A., Macha, K., Paciaroni, M., Wilson, D., Koga, M., Cappellari, M., Schaedelin, S., Zietz, A., Peters, N., Seiffge, D. J., Haupenthal, D., Gassmann, L., De Marchis, G. M., Wang, R., Gensicke, H., Stoll, S., Thilemann, S., Avramiotis, N. S., Bonetti, B., Tsivgoulis, G., Ambler, G., Alberti, A., Yoshimura, S., Brown, M. M., Shiozawa, M., Lip, G. Y. H., Venti, M., Acciarresi, M., Tanaka, K., Mosconi, M. G., Takagi, M., Jager, R. H., Muir, K., Inoue, M., Schwab, S., Bonati, L. H., Lyrer, P. A., Toyoda, K., Caso, V., Werring, D. J., Kallmunzer, B., Engelter, S. T., Traenka, C., Hert, L., Wagner, B., Schaub, F., Meya, L., Fladt, J., Dittrich, T., Fisch, U., Volbers, B., Siedler, G., Bovi, P., Tomelleri, G., Micheletti, N., Zivelonghi, C., Emiliani, A., Parry-Jones, A., Patterson, C., Price, C., Elmarimi, A., Parry, A., Nallasivam, A., Nor, A. M., Esis, B., Bruce, D., Bhaskaran, B., Roffe, C., Cullen, C., Holmes, C., Cohen, D., Hargroves, D., Mangion, D., Chadha, D., Vahidassr, D., Manawadu, D., Giallombardo, E., Warburton, E., Flossman, E., Gunathilagan, G., Proschel, H., Emsley, H., Anwar, I., Burger, I., Okwera, J., Putterill, J., O'Connell, J., Bamford, J., Corrigan, J., Scott, J., Birns, J., Kee, K., Saastamoinen, K., Pasco, K., Dani, K., Sekaran, L., Choy, L., Iveson, L., Mamun, M., Sajid, M., Cooper, M., Burn, M., Smith, M., Power, M., Davis, M., Smyth, N., Veltkamp, R., Sharma, P., Guyler, P., O'Mahony, P., Wilkinson, P., Datta, P., Aghoram, P., Marsh, R., Luder, R., Meenakishundaram, S., Subramonian, S., Leach, S., Ispoglou, S., Andole, S., England, T., Manoj, A., Harrington, F., Rehman, H., Sword, J., Staals, J., Mahawish, K., Harkness, K., Shaw, L., Mccormich, M., Sprigg, N., Mansoor, S., Krishnamurthy, V., Giustozzi, M., Agnelli, G., Becattini, C., D'Amore, C., Cimini, L. A., Bandini, F., Liantinioti, C., Chondrogianni, M., Yaghi, S., Furie, K. L., Tadi, P., Zedde, M., Abdul-Rahim, A. H., Lees, K. R., Carletti, M., Rigatelli, A., Putaala, J., Tomppo, L., Tatlisumak, T., Marcheselli, S., Pezzini, A., Poli, L., Padovani, A., Vannucchi, V., Masotti, L., Sohn, S. -I., Lorenzini, G., Tassi, R., Guideri, F., Acampa, M., Martini, G., Ntaios, G., Athanasakis, G., Makaritsis, K., Karagkiozi, E., Vadikolias, K., Mumoli, N., Galati, F., Sacco, S., Tiseo, C., Corea, F., Ageno, W., Bellesini, M., Colombo, G., Silvestrelli, G., Ciccone, A., Lanari, A., Scoditti, U., Denti, L., Mancuso, M., Maccarrone, M., Ulivi, L., Orlandi, G., Giannini, N., Tassinari, T., De Lodovici, M. L., Rueckert, C., Baldi, A., Toni, D., Letteri, F., Pieroni, A., Giuntini, M., Lotti, E. M., Flomin, Y., Kargiotis, O., Karapanayiotides, T., Monaco, S., Baronello, M. M., Csiba, L., Szabo, L., Chiti, A., Giorli, E., Del Sette, M., Imberti, D., Zabzuni, D., Doronin, B., Volodina, V., Michel, P., Vanacker, P., Barlinn, K., Pallesen, L. -P., Barlinn, J., Deleu, D., Melikyan, G., Ibrahim, F., Akhtar, N., Gourbali, V., Todo, K., Kimura, K., Shibazaki, K., Yagita, Y., Furui, E., Itabashi, R., Terasaki, T., Shiokawa, Y., Hirano, T., Suzuki, R., Kamiyama, K., Nakagawara, J., Takizawa, S., Homma, K., Okuda, S., Okada, Y., Maeda, K., Kameda, T., Kario, K., Nagakane, Y., Hasegawa, Y., Akiyama, H., Shibuya, S., Mochizuki, H., Ito, Y., Nakashima, T., Matsuoka, H., Takamatsu, K., Nishiyama, K., Endo, K., Miyagi, T., Osaki, M., Kobayashi, J., Okata, T., Tanaka, E., Sakamoto, Y., Tokunaga, K., Takizawa, H., Takasugi, J., Matsubara, S., Higashida, K., Matsuki, T., Kinoshita, N., Ide, T., Yoshimoto, T., Ando, D., Fujita, K., Kumamoto, M., Kamimura, T., Kikuno, M., Mizoguchi, T., and Sato, T.

Subjects
Male, medicine.medical_specialty, Vitamin K, medicine.drug_class, 610 Medicine & health, Aged, 80 and over, Atrial Fibrillation, Factor Xa Inhibitors, Female, Humans, Stroke, Continuous variable, Internal medicine, 80 and over, medicine, Aged, Proportional hazards model, business.industry, Anticoagulant, Confounding, Atrial fibrillation, Patient data, medicine.disease, Oldest old, Neurology, Neurology (clinical), 610 Medizin und Gesundheit, business
Abstract

Objective: To investigate the safety and effectiveness of direct oral anticoagulants (DOAC) versus vitamin K antagonists (VKA) after recent stroke in patients with atrial fibrillation (AF) aged ≥85 years. Methods: Individual patient data analysis from seven prospective stroke cohorts. We compared DOAC versus VKA treatment among patients with AF and recent stroke (≥85y = 0.65, 95%-CI [0.52, 0.81]) and < 85 years (HR = 0.79, 95%-CI [0.66, 0.95]) in simple (p interaction = 0.129), adjusted (p interaction = 0.094) or weighted (p interaction = 0.512) models. Analyses on recurrent stroke, ICH and death separately were consistent with the primary analysis, as were sensitivity analyses using age dichotomized at 90 years and as a continuous variable. DOAC had a similar net clinical benefit in patients aged ≥85 (+1.73 to +2.66) and < 85 years (+1.90 to +3.36 events/100 patient-years for ICH-weights 1.5 to 3.1). Interpretation: The favorable profile of DOAC over VKA in patients with AF and recent stroke was maintained in the oldest old. ANN NEUROL 2021.

Published
2022
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3. Oral Anticoagulants in the Oldest Old with Recent Stroke and Atrial Fibrillation

Author

Polymeris, A.A. Macha, K. Paciaroni, M. Wilson, D. Koga, M. Cappellari, M. Schaedelin, S. Zietz, A. Peters, N. Seiffge, D.J. Haupenthal, D. Gassmann, L. De Marchis, G.M. Wang, R. Gensicke, H. Stoll, S. Thilemann, S. Avramiotis, N.S. Bonetti, B. Tsivgoulis, G. Ambler, G. Alberti, A. Yoshimura, S. Brown, M.M. Shiozawa, M. Lip, G.Y.H. Venti, M. Acciarresi, M. Tanaka, K. Mosconi, M.G. Takagi, M. Jäger, R.H. Muir, K. Inoue, M. Schwab, S. Bonati, L.H. Lyrer, P.A. Toyoda, K. Caso, V. Werring, D.J. Kallmünzer, B. Engelter, S.T. Engelter, S.T. Lyrer, P.A. Bonati, L.H. Seiffge, D.J. Traenka, C. Polymeris, A.A. Zietz, A. Peters, N. De Marchis, G.M. Thilemann, S. Avramiotis, N.S. Gensicke, H. Hert, L. Wagner, B. Schaub, F. Meya, L. Fladt, J. Dittrich, T. Fisch, U. Macha, K. Haupenthal, D. Gassmann, L. Wang, R. Stoll, S. Schwab, S. Volbers, B. Siedler, G. Kallmünzer, B. Cappellari, M. Bonetti, B. Bovi, P. Tomelleri, G. Micheletti, N. Zivelonghi, C. Emiliani, A. Parry-Jones, A. Patterson, C. Price, C. Elmarimi, A. Parry, A. Nallasivam, A. Nor, A.M. Esis, B. Bruce, D. Bhaskaran, B. Roffe, C. Cullen, C. Holmes, C. Cohen, D. Hargroves, D. Mangion, D. Chadha, D. Vahidassr, D. Manawadu, D. Giallombardo, E. Warburton, E. Flossman, E. Gunathilagan, G. Proschel, H. Emsley, H. Anwar, I. Burger, I. Okwera, J. Putterill, J. O’Connell, J. Bamford, J. Corrigan, J. Scott, J. Birns, J. Kee, K. Saastamoinen, K. Pasco, K. Dani, K. Sekaran, L. Choy, L. Iveson, L. Mamun, M. Sajid, M. Cooper, M. Burn, M. Smith, M. Power, M. Davis, M. Smyth, N. Veltkamp, R. Sharma, P. Guyler, P. O’Mahony, P. Wilkinson, P. Datta, P. Aghoram, P. Marsh, R. Luder, R. Meenakishundaram, S. Subramonian, S. Leach, S. Ispoglou, S. Andole, S. England, T. Manoj, A. Harrington, F. Rehman, H. Sword, J. Staals, J. Mahawish, K. Harkness, K. Shaw, L. McCormich, M. Sprigg, N. Mansoor, S. Krishnamurthy, V. Giustozzi, M. Acciarresi, M. Agnelli, G. Becattini, C. Alberti, A. D’Amore, C. Cimini, L.A. Bandini, F. Tsivgoulis, G. Liantinioti, C. Chondrogianni, M. Yaghi, S. Furie, K.L. Tadi, P. Zedde, M. Abdul-Rahim, A.H. Lees, K.R. Bovi, P. Carletti, M. Rigatelli, A. Cappellari, M. Putaala, J. Tomppo, L. Tatlisumak, T. Marcheselli, S. Pezzini, A. Poli, L. Padovani, A. Vannucchi, V. Masotti, L. Sohn, S.-I. Lorenzini, G. Tassi, R. Guideri, F. Acampa, M. Martini, G. Ntaios, G. Athanasakis, G. Makaritsis, K. Karagkiozi, E. Vadikolias, K. Mumoli, N. Galati, F. Sacco, S. Tiseo, C. Corea, F. Ageno, W. Bellesini, M. Colombo, G. Silvestrelli, G. Ciccone, A. Lanari, A. Scoditti, U. Denti, L. Mancuso, M. Maccarrone, M. Ulivi, L. Orlandi, G. Giannini, N. Tassinari, T. De Lodovici, M.L. Rueckert, C. Baldi, A. Toni, D. Letteri, F. Pieroni, A. Giuntini, M. Lotti, E.M. Flomin, Y. Kargiotis, O. Karapanayiotides, T. Monaco, S. Baronello, M.M. Csiba, L. Szabó, L. Chiti, A. Giorli, E. Del Sette, M. Imberti, D. Zabzuni, D. Doronin, B. Volodina, V. Michel, P. Vanacker, P. Barlinn, K. Pallesen, L.-P. Barlinn, J. Deleu, D. Melikyan, G. Ibrahim, F. Akhtar, N. Gourbali, V. Todo, K. Kimura, K. Shibazaki, K. Yagita, Y. Furui, E. Itabashi, R. Terasaki, T. Shiokawa, Y. Hirano, T. Suzuki, R. Kamiyama, K. Nakagawara, J. Takizawa, S. Homma, K. Okuda, S. Okada, Y. Maeda, K. Kameda, T. Kario, K. Nagakane, Y. Hasegawa, Y. Akiyama, H. Shibuya, S. Mochizuki, H. Ito, Y. Nakashima, T. Matsuoka, H. Takamatsu, K. Nishiyama, K. Tanaka, K. Endo, K. Miyagi, T. Osaki, M. Kobayashi, J. Okata, T. Tanaka, E. Sakamoto, Y. Tokunaga, K. Takizawa, H. Takasugi, J. Matsubara, S. Higashida, K. Matsuki, T. Kinoshita, N. Shiozawa, M. Ide, T. Yoshimoto, T. Ando, D. Fujita, K. Kumamoto, M. Kamimura, T. Kikuno, M. Mizoguchi, T. Sato, T. NOACISP-LONGTERM, Erlangen Registry, CROMIS-2, RAF, RAF-DOAC, SAMURAI-NVAF Verona Registry Collaborators

Abstract

Objective: To investigate the safety and effectiveness of direct oral anticoagulants (DOAC) versus vitamin K antagonists (VKA) after recent stroke in patients with atrial fibrillation (AF) aged ≥85 years. Methods: Individual patient data analysis from seven prospective stroke cohorts. We compared DOAC versus VKA treatment among patients with AF and recent stroke (

Published
2022

4. Quantitative CT radiomics-based models for prediction of haematoma expansion and poor functional outcome in primary intracerebral haemorrhage

Author

Pszczolkowski, S, Manzano-Patron, J P, Law, Z K, Krishnan, K, Ali, A, Bath, P M, Sprigg, N, and Dineen, R A

Abstract

ObjectivesTo test radiomics-based features extracted from noncontrast CT of patients with spontaneous intracerebral haemorrhage for prediction of haematoma expansion and poor functional outcome and compare them with radiological signs and clinical factors.Materials and methodsSeven hundred fifty-four radiomics-based features were extracted from 1732 scans derived from the TICH-2 multicentre clinical trial. Features were harmonised and a correlation-based feature selection was applied. Different elastic-net parameterisations were tested to assess the predictive performance of the selected radiomics-based features using grid optimisation. For comparison, the same procedure was run using radiological signs and clinical factors separately. Models trained with radiomics-based features combined with radiological signs or clinical factors were tested. Predictive performance was evaluated using the area under the receiver operating characteristic curve (AUC) score.ResultsThe optimal radiomics-based model showed an AUC of 0.693 for haematoma expansion and an AUC of 0.783 for poor functional outcome. Models with radiological signs alone yielded substantial reductions in sensitivity. Combining radiomics-based features and radiological signs did not provide any improvement over radiomics-based features alone. Models with clinical factors had similar performance compared to using radiomics-based features, albeit with low sensitivity for haematoma expansion. Performance of radiomics-based features was boosted by incorporating clinical factors, with time from onset to scan and age being the most important contributors for haematoma expansion and poor functional outcome prediction, respectively.ConclusionRadiomics-based features perform better than radiological signs and similarly to clinical factors on the prediction of haematoma expansion and poor functional outcome. Moreover, combining radiomics-based features with clinical factors improves their performance.

Published
2021

5. Effect of Glyceryl Trinitrate on Hemodynamics in Acute Stroke

Author

Appleton, J, Woodhouse, L, Bereczki, D, Berge, E, Christensen, H, Collins, R, Gommans, J, Ntaios, G, Ozturk, S, Szatmari, S, Wardlaw, J, Sprigg, N, Rothwell, P, Bath, P, and Investigators, Enos

Subjects
Aged, 80 and over, Male, Time Factors, Original Contributions, Clinical Sciences, blood pressure, Middle Aged, hemodynamics, Administration, Cutaneous, Stroke, Nitroglycerin, glyceryl trinitrate, Acute Disease, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, heart rate, Humans, Female, hemorrhage, Aged
Abstract

Supplemental Digital Content is available in the text., Background and Purpose— Increased blood pressure (BP), heart rate, and their derivatives (variability, pulse pressure, rate-pressure product) are associated with poor clinical outcome in acute stroke. We assessed the effects of glyceryl trinitrate (GTN) on hemodynamic parameters and these on outcome in participants in the ENOS trial (Efficacy of Nitric Oxide in Stroke). Methods— Four thousand and eleven patients with acute stroke and raised BP were randomized within 48 hours of onset to transdermal GTN or no GTN for 7 days. Peripheral hemodynamics were measured at baseline (3 measures) and daily (2 measures) during treatment. Between-visit BP variability over days 1 to 7 (as SD) was assessed in quintiles. Functional outcome was assessed as modified Rankin Scale and cognition as telephone mini-mental state examination at day 90. Analyses were adjusted for baseline prognostic variables. Data are mean difference or odds ratios with 95% CI. Results— Increased baseline BP (diastolic, variability), heart rate, and rate-pressure product were each associated with unfavorable functional outcome at day 90. Increased between-visit systolic BP variability was associated with an unfavourable shift in modified Rankin Scale (highest quintile adjusted odds ratio, 1.65; 95% CI, 1.37–1.99), worse cognitive scores (telephone mini-mental state examination: highest quintile adjusted mean difference, −2.03; 95% CI, −2.84 to −1.22), and increased odds of death at day 90 (highest quintile adjusted odds ratio, 1.57; 95% CI, 1.12–2.19). GTN lowered BP and rate-pressure product and increased heart rate at day 1 and reduced between-visit systolic BP variability. Conclusions— Increased between-visit BP variability was associated with poor functional and cognitive outcomes and increased death 90 days after acute stroke. In addition to lowering BP and rate-pressure product, GTN reduced between-visit systolic BP variability. Agents that lower BP variability in acute stroke require further study.

Published
2019

9. Rates, Risks and Routes to Reduce Vascular Dementia (R4VaD), a UK wide multicentre prospective observational cohort study of cognition after stroke: Protocol

Author

Doubal, F, Brown, R, Backhouse, E, Woodhouse, L, Bath, P, Quinn, T, Robinson, T, Markus, HS, McManus, R, Werring, DJ, O'Brien, John, Sprigg, N, Parry-Jones, A, Touyz, RM, Williams, S, Mah, YH, Emslie, H, Markus, Hugh [0000-0002-9794-5996], O'Brien, John [0000-0002-0837-5080], and Apollo - University of Cambridge Repository

Subjects
Stroke, cognition, observational, dementia
Abstract

Background: Stroke commonly affects cognition and, by definition, much vascular dementia follows stroke. However, there are fundamental limitations in our understanding of vascular cognitive impairment, restricting understanding of prevalence, trajectories, mechanisms, prevention, treatment, and patient service needs. Aims: Rates, Risks and Routes to Reduce Vascular Dementia (R4VaD) is an observational cohort study of post-stroke cognition. We aim to recruit a wide range of patients with stroke, presenting to geographically diverse UK hospitals, into a longitudinal study to determine rates of, and risk factors for, cognitive and related impairments after stroke, to assess potential mechanisms and improve prediction models. Methods: We will recruit at least 2000 patients within six weeks of stroke with or without capacity to consent, and collect baseline demographic, clinical, socioeconomic, lifestyle, cognitive, neuropsychiatric and informant data using streamlined patient centred methods appropriate to the stage after stroke. We will obtain more detailed assessments at 4-8 weeks after the baseline assessment and follow-up by phone and post yearly to at least 2 years. We will assess diagnostic neuroimaging in all, and high-sensitivity inflammatory markers, genetics, blood pressure (BP) and diffusion tensor imaging in mechanistic sub-studies. Planned Outputs: R4VaD will provide reliable data on long-term cognitive function after stroke, stratified by prior cognition, stroke- and patient-related variables, and improved risk prediction. It will create a platform enabling sharing of data, imaging and samples. Participants will be consented for re-contact, facilitating future clinical trials, and providing a resource for the stroke and dementia research communities.

Published
2021

10. 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

11. Rates, risks and routes to reduce vascular dementia (R4vad), a UK-wide multicentre prospective observational cohort study of cognition after stroke:Protocol

Author

Wardlaw, J.M., Doubal, F., Brown, R., Backhouse, E., Woodhouse, L., Bath, P., Quinn, T.J., Robinson, T., Markus, H.S., McManus, R., O’Brien, J.T., Werring, D.J., Sprigg, N., Parry-Jones, A., Touyz, R.M., Williams, S., Mah, Y.-H., Emsley, H., Investigators, the R4VaD, Wardlaw, J.M., Doubal, F., Brown, R., Backhouse, E., Woodhouse, L., Bath, P., Quinn, T.J., Robinson, T., Markus, H.S., McManus, R., O’Brien, J.T., Werring, D.J., Sprigg, N., Parry-Jones, A., Touyz, R.M., Williams, S., Mah, Y.-H., Emsley, H., and Investigators, the R4VaD

Abstract

Background: Stroke commonly affects cognition and, by definition, much vascular dementia follows stroke. However, there are fundamental limitations in our understanding of vascular cognitive impairment, restricting understanding of prevalence, trajectories, mechanisms, prevention, treatment and patient-service needs. Aims: Rates, Risks and Routes to Reduce Vascular Dementia (R4VaD) is an observational cohort study of post-stroke cognition. We aim to recruit a wide range of patients with stroke, presenting to geographically diverse UK hospitals, into a longitudinal study to determine rates of, and risk factors for, cognitive and related impairments after stroke, to assess potential mechanisms and improve prediction models. Methods: We will recruit at least 2000 patients within six weeks of stroke with or without capacity to consent and collect baseline demographic, clinical, socioeconomic, lifestyle, cognitive, neuropsychiatric and informant data using streamlined patient-centred methods appropriate to the stage after stroke. We will obtain more detailed assessments at four to eight weeks after the baseline assessment and follow-up by phone and post yearly to at least two years. We will assess diagnostic neuroimaging in all and high-sensitivity inflammatory markers, genetics, blood pressure and diffusion tensor imaging in mechanistic sub-studies. Planned outputs: R4VaD will provide reliable data on long-term cognitive function after stroke, stratified by prior cognition, stroke- and patient-related variables and improved risk prediction. It will create a platform enabling sharing of data, imaging and samples. Participants will be consented for re-contact, facilitating future clinical trials and providing a resource for the stroke and dementia research communities. © European Stroke Organisation 2020.

Published
2021

12. Rates, risks and routes to reduce vascular dementia (R4vad), a UK-wide multicentre prospective observational cohort study of cognition after stroke : Protocol

Author

Wardlaw, J.M., Doubal, F., Brown, R., Backhouse, E., Woodhouse, L., Bath, P., Quinn, T.J., Robinson, T., Markus, H.S., McManus, R., O’Brien, J.T., Werring, D.J., Sprigg, N., Parry-Jones, A., Touyz, R.M., Williams, S., Mah, Y.-H., Emsley, H., Investigators, the R4VaD, Wardlaw, J.M., Doubal, F., Brown, R., Backhouse, E., Woodhouse, L., Bath, P., Quinn, T.J., Robinson, T., Markus, H.S., McManus, R., O’Brien, J.T., Werring, D.J., Sprigg, N., Parry-Jones, A., Touyz, R.M., Williams, S., Mah, Y.-H., Emsley, H., and Investigators, the R4VaD

Abstract

Background: Stroke commonly affects cognition and, by definition, much vascular dementia follows stroke. However, there are fundamental limitations in our understanding of vascular cognitive impairment, restricting understanding of prevalence, trajectories, mechanisms, prevention, treatment and patient-service needs. Aims: Rates, Risks and Routes to Reduce Vascular Dementia (R4VaD) is an observational cohort study of post-stroke cognition. We aim to recruit a wide range of patients with stroke, presenting to geographically diverse UK hospitals, into a longitudinal study to determine rates of, and risk factors for, cognitive and related impairments after stroke, to assess potential mechanisms and improve prediction models. Methods: We will recruit at least 2000 patients within six weeks of stroke with or without capacity to consent and collect baseline demographic, clinical, socioeconomic, lifestyle, cognitive, neuropsychiatric and informant data using streamlined patient-centred methods appropriate to the stage after stroke. We will obtain more detailed assessments at four to eight weeks after the baseline assessment and follow-up by phone and post yearly to at least two years. We will assess diagnostic neuroimaging in all and high-sensitivity inflammatory markers, genetics, blood pressure and diffusion tensor imaging in mechanistic sub-studies. Planned outputs: R4VaD will provide reliable data on long-term cognitive function after stroke, stratified by prior cognition, stroke- and patient-related variables and improved risk prediction. It will create a platform enabling sharing of data, imaging and samples. Participants will be consented for re-contact, facilitating future clinical trials and providing a resource for the stroke and dementia research communities. © European Stroke Organisation 2020.

Published
2021

23. SiPP (Stroke in Pregnancy and Postpartum): A prospective, observational, international, multicentre study on pathophysiological mechanisms, clinical profile, management and outcome of cerebrovascular diseases in pregnant and postpartum women

Author

Lorenzano, S. Kremer, C. Pavlovic, A. Jovanovic, D.R. Sandset, E.C. Christensen, H. Bushnell, C. Arsovska, A. Sprigg, N. Roffe, C. Ijäs, P. Gdovinova, Z. Alexandrov, A. Zedde, M. Tassi, R. Acciaresi, M. Lantz, M. Sunnerhagen, K. Zarkov, M. Rantanen, K. Perren, F. Iversen, H.K. Kruuse, C. Slowik, A. Palazzo, P. Korv, J. Fromm, A. Lovrencic-Huzjan, A. Korompoki, E. Fonseca, A.C. Gall, S.L. Brunner, F. Caso, V. Sacco, S. for the SiPP Trial Investigators ESO-WISE Group

Abstract

Rationale: Cerebrovascular diseases associated with pregnancy and postpartum period are uncommon; however, they can have an important impact on health of both women and foetus or newborn. Aims: To evaluate the frequency, characteristics and management of cerebrovascular events in pregnant/postpartum women, to clarify pathophysiological mechanisms underlying the occurrence of these events including biomolecular aspects, and to assess the short- and long-term cerebrovascular and global cardiovascular outcome of these patients, their predictors and infant outcome. Methods and design: This is an observational, prospective, multicentre, international case–control study. The study will include patients with cerebrovascular events during pregnancy and/or within six months after delivery. For each included case, two controls will be prospectively recruited: one pregnant or puerperal subject without any history of cerebrovascular event and one non-pregnant or non-puerperal subject with a recent cerebrovascular event. All controls will be matched by age, ethnicity and type of cerebrovascular event with their assigned cases. The pregnant controls will be matched also by pregnancy weeks/trimester. Follow-up will last 24 months for the mother and 12 months for the infant. Summary: To better understand causes and outcomes of uncommon conditions like pregnancy/postpartum-related cerebrovascular events, the development of multisite, multidisciplinary registry-based studies, such as the Stroke in Pregnancy and Postpartum study, is needed in order to collect an adequate number of patients, draw reliable conclusions and give definite recommendations on their management. © European Stroke Organisation 2019.

Published
2020

24. A scoping review of psychoeducational interventions for people after transient ischemic attack and minor stroke

Author

Kontou, E, Kettlewell, J, Condon, L, Thomas, S, Lee, AR, Sprigg, N, Watkins, Caroline Leigh, Walker, M, Shokraneh, F, Kontou, E, Kettlewell, J, Condon, L, Thomas, S, Lee, AR, Sprigg, N, Watkins, Caroline Leigh, Walker, M, and Shokraneh, F

Abstract

Background: Psychoeducation can provide information and support to cope with the physical and emotional effects of a health condition. This scoping review aimed to identify the evidence regarding psychoeducational interventions for people after a Transient Ischaemic Attack (TIA) and minor stroke. Methods: This review was conducted in accordance with the PRISMA Extension for Scoping Reviews. Three electronic databases (MEDLINE, Embase, PsycINFO) were searched for articles on interventions related to psychoeducational support post TIA and minor/mild stroke. Search retrieved 3722 articles. Three reviewers independently screened titles, abstracts, full-texts, and then extracted data for included studies. Study quality was assessed using the JADAD scale. TIDieR checklist was used to describe interventions. Results: Fifteen RCTs were included. Twelve studies were of high quality (JADAD score ≥2), two were low quality. A total of 1500 participants were recruited across the studies. Definition of TIA and minor stroke were unclear, leading to the exclusion of several studies. Various interventions were included, including education/psychoeducation (n=4); exercise and lifestyle advice (n=3); telephone-based education/counselling (n=3); secondary prevention education (n=1); motivational interviewing (n=2); self-management (n=2). Interventions were inconsistently described, with information missing about who delivered it and tailoring. Conclusions: Definitions of stroke severity are not adequately reported. There are variety of interventions including education about a range of stroke-specific topics. Many interventions are not adequately defined, thus making it difficult to determine if the aim was to provide information or support to promote self-management and wellbeing post TIA/minor stroke. There is a need for a more in-depth systematic review to develop a clear definition of psychoeducation.

Published
2020

25. Significant variation in mortality and functional outcome after acute ischaemic stroke between western countries: data from the Tinzaparin in Acute Ischaemic Stroke Trial (TAIST)

Author

Gray, L.J., Sprigg, N., Bath, P.M.W., Sorensen, P., Lindenstrom, E., Boysen, G., De Deyn, P.P., Friis, P., Leys, D., Marttila, R., Olsson, J.-E., O'Neill, D., Ringelstein, B., van der Sande, J.-J., and Turpie, A.G.G.

Subjects
Stroke (Disease) -- Care and treatment, Stroke (Disease) -- Patient outcomes, Stroke (Disease) -- Research, Health, Psychology and mental health
Published
2006

35. Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Author

Al-Shahi Salman, Rustam, Dennis, MS, Sandercock, PAG, Sudlow, CLM, Wardlaw, JM, Whiteley, WN, Murray, GD, Stephen, J, Newby, DE, Sprigg, N, Werring, DJ, White, PM, Baigent, Colin, Lasserson, Daniel, Sullivan, Frank, Carrie, Johanna, Rojas, Javier, Amoils, Shannon, Bamford, John, Armitage, Jane, Rinkel, Gabriel, Lowe, Gordon, Emberson, Jonathan, Innes, Karen, Dinsmore, Lynn, Drever, Jonathan, Williams, Carol, Perry, David, McGill, Connor, Buchanan, David, Walker, Allan, Hutchison, Aidan, Matthews, Christopher, Fraser, Ruth, McGrath, Aileen, Deary, Ann, Anderson, Rosemary, Walker, Pauli, Hansen, Christian, Parker, Richard, Rodriguez, Aryelly, Macleod, MR, Gattringer, Thomas, Palmer, Jeb, Sakka, Eleni, Adil-Smith, Jennifer, Minks, David, Mitra, Dipayan, Bhatnagar, Priya, du Plessis, Johannes, Joshi, Yogish, Lerpiniere, Christine, O'Brien, Richard, Burgess, Seona, Mead, Gillian, Paulton, Ruth, Doubal, Fergus, McCormick, Katrina, Hunter, Neil, Taylor, Pat, Parakramawansha, Ruwan, Perry, Jack, Blair, Gordon, MacRaild, Allan, Parry-Jones, Adrian, Johnes, Mary, Lee, Stephanie, Shaw, Kelly Marie, Burger, Ilse, Punter, Martin, Ingham, Andrea, Perez, Jane, Naing, Zin, Morell, Jordi, Marsden, Tracy, Hall, Andrea, Marshall, Sally, Harrison, Louise, Jarapa, Rowilson, Wood, Edith, O'Loughlin, Victoria, Cohen, David, Davies, Silvie, Njoku, Kelechi, Mpelembue, Mushiya, Burgess, Laura, Licenik, Radim, Ngwako, Mmua, Nisar, Nabeela, Niranchanan, Rangah, Roganova, Tatjana, Bathula, Rajaram, Devine, Joseph, David, Anette, Oshodi, Anne, Guo, Fenglin, Owoyele, Emmanuelle, Sukdeo, Varthi, Ballantine, Robert, Abbdul-saheb, Mudhar, Chamberlain, Angela, Chandrakumar, Aberami, Poku, Philip, Harkness, Kirsty, Blank, Catrin, Richards, Emma, Ali, Ali, Kibutu, Faith, Balitska, Olesia, Birchall, Kathryn, Bayliss, Pauline, Doyle, Clare, Stocks, Kathy, Majis, Arshad, Howe, Jo, Kamara, Christine, Barron, Luke, Maatouk, Ahmad, Lindert, Ralf, Dakin, Katy, Redgrave, Jessica, Bhaskaran, Biju, Salih, Isam, Kelly, Debs, Szabo, Susan, Tomlin, Dawn, Bearne, Helen, Buxton, Jean, Fitzell, Pauline, Ayres, Georgina, Saulat, Afaq, Horan, Kathleen, Garfield-Smith, Joanne, Bhakri, Harbens, Guyler, Paul, Sinha, Devesh, Loganathan, Thayalini, Siddiqui, Amber, Siddiqui, Anwer, Coward, Lucy, Kunhunny, Swapna, Tysoe, Sharon, Orath Prabakaran, Rajalakshmi, Kelavkar, Shyam, Rashmi, Sindhu, Ngo, David, Ng, Kheng Xiong, Menon, Nisha, Shah, Sweni, Barber, Mark, Esson, Derek, Brodie, Fiona, Anjum, Talat, Wani, Mushtaq, Krishnan, Manju, Quinn, Leanne, Spencer, Jayne, Jones, Terry, Thompson-Jones, Helen, Dacey, Lynne, Chenna, Srikanth, Storton, Sharon, Thomas, Sarah, Beaty, Teresa, Treadwell, Shelley, Davies, Caroline, Tucker, Susan, Connor, Lynda, Slade, Peter, Gainard, Glyn, Muddegowda, Girish, Sanyal, Ranjan, Remegoso, Alda, Abano, Nenette, Causley, Chelsea, Carpio, Racquel, Stevens, Stephanie, Butler, Adrian, Varquez, Resti, Denic, Hayley, Alipio, Francis, Moores, Andrew, Barry, Adrian, Maguire, Holly, Grocott, Jeanette, Finney, Kay, Lyjko, Sue, Roffe, Christine, Hiden, Joanne, Ferdinand, Phillip, Cvoro, Vera, Ullah, Khalil, Chapman, Nicola, Couser, Mandy, Pound, Susan, Mcauley, Sean, Raghunathan, Senthil, Shelton, Faye, Hedstrom, Amanda, Godfrey, Margi, Havard, Diane, Buck, Amanda, Krishnan, Kailash, Gilzeane, Nicola, Roffe, Jack, Clarke, Judith, Whittamore, Katherine, Sheikh, Saima, Keshvara, Rekha, Jordan, Carla, Jackson, Benjamin, Wilkes, Gwendoline, Appleton, Jason, Law, Zhe, Matias, Oliver, Vasileiadis, Evangelos, Mason, Cathy, Parry, Anthea, Landers, Geraldine, Holden, Melinda, Aweid, Basaam, Rashed, Khalid, Balian, Linda, Vickers, Carinna, Keeling, Elizabeth, Board, Sarah, Allison, Joanna, Buckley, Clare, Williams-Yesson, Barbara, Board, Joanne, Pitt-Kerby, Tressy, Tanate, Alfonso, Wood, Diane, Kini, Manohar, Chadha, Dinesh, Walstow, Deborah, Fong, Rosanna, Luder, Robert, Adesina, Tolu, Gallagher, Jill, Bridger, Hayley, Murali, Elodie, Bhargava, Maneesh, van Someren, Chloe, Harrington, Frances, Mate, Abhijit, James, Ali, Courtauld, Gillian, Schofield, Christine, Adie, Katja, Lucas, Linda, Bond, Kirsty, Maund, Bev, Ellis, Sam, Mudd, Paul, James, Martin, Keenan, Samantha, Bowring, Angela, Cageao, Julie, Kingwell, Hayley, Roughan, Caroline, Hemsley, Anthony, Sword, Jane, Strain, David, Miller, Keniesha, Goff, Anita, Gupwell, Karin, Thorpe, Kevin, Emsley, Hedley, Punekar, Shuja, McLoughlin, Alison, Sultan, Sulaiman, Gregory, Bindu, Raj, Sonia, Doyle, Donna, Muir, Keith, Smith, Wilma, Welch, Angela, Moreton, Fiona, Cheripelli, Bharath Kumar, El Tawil, Salwa, Kalladka, Dheeraj, Huang, Xuya, Day, Nicola, Ramachandran, Sankaranarayana, Crosbie, Caroline, Elliot, Jennifer, Rudd, Tony, Marks, Katherine, Bhalla, Ajay, Birns, Jonathan, Kullane, Sagal, Weir, Nic, Allen, Christopher, Pressly, Vanessa, Crawford, Pam, Battersby-Wood, Emma, Blades, Alex, Egerton, Shuna, Walters, Ashleigh, Evans, Sue, Marigold, James Richard, Smith, Fiona, Howard, Gabriella, Gartrell, Imogen, Smith, Simon, Creeden, Robyn, Cox, Chloe, Boxall, Cherish, Hewitt, Jonathan, Nott, Claire, Sarah, Procter, Whiteman, Jessica, Buckle, Steve, Wallace, Rebecca, Mardania, Rina, Gray, Jane, Triscott, Claire, Nair, Anand, Greig, Jill, Rana, Pratap, Robinson, Matthew, Alam, Mohammad Irfan, Wilson, Duncan, Watchurst, Caroline, Brezitski, Maria, Crook, Luci, Jones, Ifan, Banaras, Azra, Patel, Krishna, Erande, Renuka, Hogan, Caroline, Hostettler, Isabel, Ashton, Amy, Feerick, Shez, Francia, Nina, Oji, Nnebuife, Elliott, Emma, Al-Mayhani, Talal, Dutta, Dipankar, Brown, Pauline, Ward, Deborah, Davis, Fiona, Turfrey, Jennifer, Hughes, Chloe, Collins, Kayleigh, Bakawala, Rehana, O'Connell, Susan, Glass, Jon, Broughton, David, Tryambake, Dinesh, Dixon, Lynn, Chapman, Kath, Young, Andrew, Bergin, Adrian, Sigsworth, Andrew, Manoj, Aravind, Fletcher, Glyn, Lopez, Paula, Cox, Penelope, Wilkinson, Mark, Fitzsimmons, Paul, Sharma, Nikhil, Choulerton, James, Button, Denise, Dow, Lindsey, Gbadamoshi, Lukuman, Avis, Joanne, Madigan, Barbara, McCann, Stephanie, Shaw, Louise, Howcroft, Deborah, Lucas, Suzanne, Stone, Andrew, Cluckie, Gillian, Lovelock, Caroline, Clarke, Brian, Chopra, Neha, Clarke, Natasha, Patel, Bhavini, Kennedy, Kate, Williams, Rebecca, Blight, Adrian, O'Reilly, Joanna, Orefo, Chukwuka, Dayal, Nilofer, Ghatala, Rita, Adedoyin, Temi, Watson, Fran, Trippier, Sarah, Choy, Lillian, Moynihan, Barry, Khan, Usman, Jones, Val, Jeyaraj, Naomi, Kerin, Lourda, Thavanesan, Kamy, Tiwari, Divya, Cox, Chantel, Ljubez, Anja, Tucker, Laura, Iqbal, Arshi, Bagnall, Caroline, Keltos, Marketa, Roberts, Josh, Jupp, Becky, Ovington, Catherine, Rogers, Emily, David, Owen, Bell, Jo, Longland, Barbara, Hann, Gail, Cooper, Martin, Nasar, Mohammad, Rajapakse, Anoja, Wynter, Inez, Anwar, Ijaz, Skinner, Helen, Nozedar, Tarn, McArdle, Damian, Kumar, Balakrishna, Crawford, Susan, Annamalai, Arunkumar, Ramshaw, Alex, Holmes, Clare, Caine, Sarah, Osborn, Mairead, Dodd, Emily, Murphy, Peter, Devitt, Nicola, Baker, Pauline, Steele, Amy, Guthrie, Lucy Belle, Clarke, Samantha, Hassan, Ahamad, Waugh, Dean, Veraque, Emelda, Makawa, Linetty, Kambafwile, Mary, Randall, Marc, Papavasileiou, Vasileios, Cullen, Claire, Peters, Jenny, Thant, Hlaing, Ingram, Tanya, Zoe, Mellor, Durairaj, Ramesh, Harrison, Melanie, Stevenson, Sarah, Shackcloth, Daniela, Ewing, Jordan, Sutton, Victoria, McCarron, Mark, McKee, Jacqueline, Doherty, Mandy, McVerry, Ferghal, Blair, Caroline, MacLeod, Mary, Irvine, Janice, Gow, Heather, Furnace, Jacqueline, Joyson, Anu, Jagpal, Baljit, Ross, Sarah, Klaasen, Katrina, Nelson, Sandra, Clarke, Rebecca, Crouch, Nichola, MacLennan, Beverly, Taylor, Vicky, Epstein, Daniel, Shukla, Avani, Krishnamurthy, Vinodh, Nicholas, Paul, Qureshi, Sammie, Webber, Adam, Penge, Justin, Ramadan, Hawraman, Maguire, Stuart, Patterson, Chris, Bellfield, Ruth, Hairsine, Brigid, Stewart, Kelvin, Hooley, Michaela, Quinn, Outi, Richard, Bella, Moseley, Sally, Edwards, Mandy, Lawson, Heidi, Tayler, Michelle, Pai, Yogish, Dhakal, Mahesh, Esisi, Bernard, Dima, Sofia, Smith, Gemma Marie, Garside, Mark, Naeem, Muhammad, Baliga, Vidya, Rogers, Gill, Brown, Ellen, Bruce, David, Hayman, Rachel, Clayton, Susan, Gamble, Ed, Grue, Rebecca, Charles, Bethan, Hague, Adam, Blane, Sujata, Lambert, Caroline, Chaudhry, Afnan, Harrison, Thomas, Saastamoinen, Kari, Hove, Dionne, Howaniec, Laura, Grimwood, Gemma, Redjep, Ozlem, Humphries, Fiona, Argandona, Lucia, Cuenoud, Larissa, Erumere, Esther, Amlani, Sageet, Auld, Grace, Salek-Haddadi, Afraim, Schulz, Ursula, Kennedy, James, Ford, Gary, Mathieson, Philip, Reckless, Ian, Teal, Rachel, Lenti, Giulia, Harston, George, O'Brien, Eoin, Mcgee, Joanne, Mitchell, Jennifer, Amis, Elaine, Handley, Dominic, Kelly, Siobhan, Zachariah, George, Francis, Jobbin, Crisp, Sarah, Sesay, Juliana, Finlay, Sarah, Hayhoe, Helen, Hannon, Niamh, Hughes, Tom, Morse, Bethan, De Berker, Henry, Tallantyre, Emma, Osman, Ahmed, White, Susan, Schwarz, Stefan, Jelley, Benjamin, Yadava, Rajendra, Azhar, Khalid, Reddan, Julie, Sangombe, Mirriam, Stafford, Samantha, Fotherby, Ken, Morgan, Debbie, Baig, Farrukh, Jennings-Preece, Karla, Butler, Donna, Ahmad, Nasar, Willberry, Angela, Stevens, Angela, Rai, Baljinder, Siddegowda, Prasad, Howard, Peter, Hyatt, Lisa, Dobson, Tracey, Jarrett, David, Ponnambath, Suheil, Tandy, Jane, Harrington-Davies, Yasmin, Butler, Rebecca, James, Claire, Valentine, Stacey, Suttling, Anne, Langhorne, Peter, Kerr, Gillian, Wright, Fiona, Graham, Ruth, McAlpine, Christine, Iqbal, Mohammad Shahzad, Humphreys, Louise, Pasco, Kath, Balazikova, Olga, Nasim, Ashraf, Peixoto, Cassilda, Gallagher, Louise, Shahmehri, Shahrzad, Ghosh, Sandip, Barrie, Elizabeth, Gilmour, Danielle, Henry, Margo, Webb, Tom, Cowie, Linda, Rudenko, Hannah, McDonald, Shanni, Schumacher, Natasha, Walker, Susannah, Cosier, Tracey, Verrion, Anna, Beranova, Eva, Thomson, Audrey, Venter, Marius, Kar, Arindam, Mashate, Sheila, Harvey, Kirsten, Gardener, Léjeune, Nguyen, Vinh, Halse, Omid, Geraghty, Olivia, Hazel, Beth, Wilding, Peter, Tilley, Victoria, Cassidy, Tim, McClelland, Beverley, Bokhari, Maria, England, Timothy, Maddula, Mohana, Donnelly, Richard, Findlay, Paul, Macaden, Ashish, Shread, Ian, Barr, Charlotte, Mohd Nor, Azlisham, Brown, Claire, Persad, Nicola, Eglinton, Charlotte, Weinling, Marie, Hyams, Benjamin, Shah, Alex, Baker, John, Byrne, Anthony, McGhee, Caroline, Smart, Amanda, Copeland, Claire, Carpenter, Michael, Walker, Marion, Davey, Richard, Needle, Ann, Fathima, Razik, Bateman, Gavin, Datta, Prabal, Stanners, Andrew, Jackson, Linda, Ball, Julie, Davis, Michelle, Atkinson, Natalie, Fawcett, Michelle, Thompson, Teresa, Guy, Helen, Hogg, Valerie, Hays, Carole, Woodward, Stephen, Haque, Mohammad, Hakim, Eluzai, Symonds, Stuart, Maanoosi, Mehran, Herman, Jane, Black, Toby, Miriam, Skelton, Clarke, Caroline, Anthony, Alpha, Tribbeck, Michele, Cronin, Julie, Mead, Denise, Fennelly, Ruth, McIlmoyle, James, Dickinson, Christina, Jeffs, Carol, Anwar, Sajjad, Howard, Joanne, Jones, Kirsty, Dhar, Saikat, Clay, Caroline, Siddiq, Muhammad, Ivatts, Simone, Baird, Yolanda, Sally, Moore, Amey, Isobel, Newton, Sophie, Clayton-Evans, Lisa, Chadbourn, Indra, Rayessa, Rayessa, Naylor, Charde, Rodgers, Alicia, Wilson, Lisa, Wilson, Sarah, Clarkson, Emma, Davies, Ruth, Owings, Paula, Sangster, Graeme, Gott, Valerie, Little, Victoria, Weir, Pauline, Cherian, Suja, Jose, Deepa, Moroney, Helen, Downham, Susan, Dodd, Angela, Vettimootal Johnson, Venetia, Codd, Laura, Robinson, Naomi, Ahmed, Ashraf, Albazzaz, Mo, Johnson, Sharon, Denniss, Carol, Cunningham, Mishell, Zahoor, Tajammal, Webster, Timothy, Leason, Sandra, Haider, Syed, Chatterjee, Kausic, Nallasivan, Arumugam, Perkins, Charlotte, Seagrave, Samantha, Jenkins, Colin, Price, Fiona, Hughes, Claire, Mercer, Lily, Hussain, Malik, Brown, Sarah, Harvey, Miriam, Homan, Jane, Khan, Mohammad, Whiting, Robert, Foote, Leanne, Hunt, Nicholas, Durman, Helen, Brotherton, Lucy, Foot, Jayne, Pawley, Corinne, Foster, Eliza, Whitcher, Alison, Metcalf, Kneale, Jagger, Jenny, McDonald, Susan, Waterfield, Kelly, Sutton, Patrick, Shinh, Naval, Anversha, Ajmal, Ravenhill, Garth, Greenwood, Richard, Saada, Janak, Wiltshire, Alison, Perfitt, Rebekah, Andole, Sreeman, Gadapa, Naveen, Dunne, Karen, Krommyda, Magdalini, Burssens, Evelyne, King, Sam, Plewa, Catherine, Smyth, Nigel, Wilson, Jenny, Giallombardo, Elio, Sykes, Lucy, Kumar, Pradeep, Barker, James, Huggett, Isabel, Dunn, Linda, Culmsee, Charlotte, Thomas, Philip, Myint, Min, Brew, Helen, Majmudar, Nikhil, O'Connell, Janice, Bunea, George, Fox, Charlotte, Gulliver, Diane, Smith, Andrew, Mokoena, Betty, Sattar, Naweed, Krishnamurthy, Ramesh, Osborne, Emily, Wilson, David, Wroath, Belinda, Dynan, Kevin, Power, Michael, Thompson, Susan, Adell, Victoria, Orugun, Enoch, Poultney, Una, Glover, Rachel, Crowther, Hannah, Thornthwaite, Sarah, Wiggam, Ivan, Wallace, Aine, Kerr, Enda, Fulton, Ailsa, Hunter, Annemarie, Tauro, Suzanne, Cuddy, Sarah, Mangion, David, Hardwick, Anne, Markova, Skarlet, Lawrence, Tara, Constantin, Carmen, Fletcher, Jo, Thomas, Isobel, Pettitt, Kerry, Sekaran, Lakshmanan, Tate, Margaret, Bharaj, Kiranjit, Simon, Rohan, Justin, Frances, Sethuraman, Sakthivel, Phiri, Duke, Mohammed, Niaz, Chauhan, Meena, Elfandi, Khaled, Khan, Uzma, Eveson, David, Mistri, Amit, Manning, Lisa, Khan, Shagufta, Patel, Champa, Moqsith, Mohammed, Sattar, Saira, Lam, Man Yee, Musarrat, Kashif, Stephens, Claire, Kalathil, Latheef, Miller, Richard, Salehin, Maqsud, Gautam, Nikki, Bailey, Duncan, Amor, Kelly, Meir, Julie, Nicolson, Anne, Imam, Javed, Wood, Lisa, White, Julie, Sajid, Mahmud, Ghaly, George, Ball, Margaret, Gascoyne, Rachel, Proeschel, Harald, Sharpe, Simon, Horton, Sarah, Beaves, Emily, Jones, Stephanie, Yip, Brigitte, Bell, Murdina, MacLiver, Linda, MacInnes, Brian, Sims, Don, Hurley, Jennifer, Willmot, Mark, Sutton, Claire, Littleton, Edward, Maiden, Susan, Jones, Rachael, Cunningham, James, Green, Carole, Bates, Michelle, Shekhar, Raj, Gilham, Ellie, Ahmed, Iman, Crown, Rachel, Fuller, Tracy, Goorah, Neetish, Bell, Angela, Kelly, Christine, Singh, Arun, Walford, Jamie, Tomlinson, Benjamin, Patel, Farzana, Duberley, Stephen, Kane, Ingrid, Rajkumar, Chakravarthi, Gaylard, Jane, Breeds, Joanna, Gainsborough, Nicola, Pitt-Ford, Alexandra, Barbon, Emma, Latter, Laura, Thompson, Philip, Hervey, Simon, Krishnamoorthy, Shrivakumar, Vassallo, Joseph, Walter, Deborah, Cochrane, Helen, Srinivasan, Meena, Campbell, Robert, Donaldson, Denise, Motherwell, Nichola, Hurford, Frances, Mukherjee, Indranil, Kenton, Antony, Nyabadza, Sheila, Martin, Irene, Hunt, Benjamin, Hassan, Hardi, O'Toole, Sarah, Dallol, Bander, Putterill, Janet, Jha, Ratneshwari, Gallifent, Rachel, Kakar, Puneet, Pusalkar, Aparna, Chan, Kelly, Dangri, Puneet, Beadle, Hannah, Cook, Angela, Crabtree, Karen, Subramonian, Santhosh, Owusu-Agyei, Peter, Temple, Natalie, Butterworth-Cowin, Nicola, Ragab, Suzanne, Knops, Kerstin, Jinks, Emma, Dickson, Christine, Gleave, Laura, Dube, Judith, Leggett, Jacqui, Garcia, Tatiana, Ispoglou, Sissy, Evans, Rachel, Ankolekar, Sandeep, Hayes, Anne, Ni, Hlaing, Rahman, Bithi, Milligan, Josette, Graham, Carol, Jose, Josin, Keegan, Breffni, Kelly, Jim, Dewar, Richard, White, James, and Thomas, Kelly

Abstract

Background:\ud Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events.\ud \ud Methods:\ud The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627).\ud \ud Findings:\ud Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92).\ud \ud Interpretation:\ud These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention.

Published
2019

37. Prehospital transdermal glyceryl trinitrate for ultra-acute intracerebral hemorrhage: Data from the RIGHT-2 trial

Author

Bath, PM, Woodhouse, LJ, Krishnan, K, Appleton, JP, Anderson, CS, Berge, E, Cala, L, Dixon, M, England, TJ, Godolphin, PJ, Hepburn, T, Mair, G, Montgomery, AA, Phillips, SJ, Potter, J, Price, CI, Randall, M, Robinson, TG, Roffe, C, Rothwell, PM, Sandset, EC, Sanossian, N, Saver, JL, Siriwardena, AN, Venables, G, Wardlaw, JM, and Sprigg, N

Subjects
cardiovascular system, circulatory and respiratory physiology
Abstract

Background and Purpose- Pilot trials suggest that glyceryl trinitrate (GTN; nitroglycerin) may improve outcome when administered early after stroke onset. Methods- We undertook a multicentre, paramedic-delivered, ambulance-based, prospective randomized, sham-controlled, blinded-end point trial in adults with presumed stroke within 4 hours of ictus. Participants received transdermal GTN (5 mg) or a sham dressing (1:1) in the ambulance and then daily for three days in hospital. The primary outcome was the 7-level modified Rankin Scale at 90 days assessed by central telephone treatment-blinded follow-up. This prespecified subgroup analysis focuses on participants with an intracerebral hemorrhage as their index event. Analyses are intention-to-treat. Results- Of 1149 participants with presumed stroke, 145 (13%; GTN, 74; sham, 71) had an intracerebral hemorrhage: time from onset to randomization median, 74 minutes (interquartile range, 45-110). By admission to hospital, blood pressure tended to be lower with GTN as compared with sham: mean, 4.4/3.5 mm Hg. The modified Rankin Scale score at 90 days was nonsignificantly higher in the GTN group: adjusted common odds ratio for poor outcome, 1.87 (95% CI, 0.98-3.57). A prespecified global analysis of 5 clinical outcomes (dependency, disability, cognition, quality of life, and mood) was worse with GTN; Mann-Whitney difference, 0.18 (95% CI, 0.01-0.35; Wei-Lachin test). GTN was associated with larger hematoma and growth, and more mass effect and midline shift on neuroimaging, and altered use of hospital resources. Death in hospital but not at day 90 was increased with GTN. There were no significant between-group differences in serious adverse events. Conclusions- Prehospital treatment with GTN worsened outcomes in patients with intracerebral hemorrhage. Since these results could relate to the play of chance, confounding, or a true effect of GTN, further randomized evidence on the use of vasodilators in ultra-acute intracerebral hemorrhage is needed. Clinical Trial Registration- URL: http://www.controlled-trials.com. Unique identifier: ISRCTN26986053.

Published
2019
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38. Outcome Assessment by Central Adjudicators Versus Site Investigators in Stroke Trials: A Systematic Review and Meta-Analysis

Author

Godolphin, Peter J., Bath, Philip M., Algra, Ale, Berge, Eivind, Brown, Martin M., Chalmers, John, Duley, Lelia, Eliasziw, Misha, Gregson, John, Greving, Jacoba P., Hankey, Graeme J., Hosomi, Naohisa, Johnston, S. Claiborne, Patsko, Emily, Ranta, Annamarei, Sandset, Per Morten, Serena, Joaquin, Weimar, Christian, Montgomery, Alan A., Knipp, S. C., Giugliano, R. P., Bonati, L. H., Nagai, Y., Matsumoto, M., Barnett, H. J. M., Fox, A. J., Farrant, M., Easton, J. D., Elm, J. J., Neal, B., Arima, H., Serena, J., Davalos, A., Amarenco, P., Evans, S., Sprigg, N., Dineen, R., Eikelboom, J. W., Chen, C., Godolphin, Peter J., Bath, Philip M., Algra, Ale, Berge, Eivind, Brown, Martin M., Chalmers, John, Duley, Lelia, Eliasziw, Misha, Gregson, John, Greving, Jacoba P., Hankey, Graeme J., Hosomi, Naohisa, Johnston, S. Claiborne, Patsko, Emily, Ranta, Annamarei, Sandset, Per Morten, Serena, Joaquin, Weimar, Christian, Montgomery, Alan A., Knipp, S. C., Giugliano, R. P., Bonati, L. H., Nagai, Y., Matsumoto, M., Barnett, H. J. M., Fox, A. J., Farrant, M., Easton, J. D., Elm, J. J., Neal, B., Arima, H., Serena, J., Davalos, A., Amarenco, P., Evans, S., Sprigg, N., Dineen, R., Eikelboom, J. W., and Chen, C.

Published
2019

39. 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

40. Lowering blood pressure after acute intracerebral haemorrhage: Protocol for a systematic review and meta-analysis using individual patient data from randomised controlled trials participating in the Blood Pressure in Acute Stroke Collaboration (BASC)

Author

Moullaali, TJ, Wang, X, Woodhouse, LJ, Law, ZK, Delcourt, C, Sprigg, N, Krishnan, K, Robinson, TG, Wardlaw, JM, Al-Shahi Salman, R, Berge, E, Sandset, EC, Anderson, CS, Bath, PM, Moullaali, TJ, Wang, X, Woodhouse, LJ, Law, ZK, Delcourt, C, Sprigg, N, Krishnan, K, Robinson, TG, Wardlaw, JM, Al-Shahi Salman, R, Berge, E, Sandset, EC, Anderson, CS, and Bath, PM

Abstract

Introduction Conflicting results from multiple randomised trials indicate that the methods and effects of blood pressure (BP) reduction after acute intracerebral haemorrhage (ICH) are complex. The Blood pressure in Acute Stroke Collaboration is an international collaboration, which aims to determine the optimal management of BP after acute stroke including ICH. Methods and analysis A systematic review will be undertaken according to the Preferred Reporting Items for Systematic review and Meta-Analysis of Individual Participant Data (IPD) guideline. A search of Cochrane Central Register of Controlled Trials, EMBASE and MEDLINE from inception will be conducted to identify randomised controlled trials of BP management in adults with acute spontaneous (non-traumatic) ICH enrolled within the first 7 days of symptom onset. Authors of studies that meet the inclusion criteria will be invited to share their IPD. The primary outcome will be functional outcome according to the modified Rankin Scale. Safety outcomes will be early neurological deterioration, symptomatic hypotension and serious adverse events. Secondary outcomes will include death and neuroradiological and haemodynamic variables. Meta-analyses of pooled IPD using the intention-to-treat dataset of included trials, including subgroup analyses to assess modification of the effects of BP lowering by time to treatment, treatment strategy and patient's demographic, clinical and prestroke neuroradiological characteristics. Ethics and dissemination No new patient data will be collected nor is there any deviation from the original purposes of each study where ethical approvals were granted; therefore, further ethical approval is not required. Results will be reported in international peer-reviewed journals. PROSPERO registration number CRD42019141136.

Published
2019

41. Applicability of ENCHANTED trial results to current acute ischemic stroke patients eligible for intravenous thrombolysis in England and Wales: Comparison with the Sentinel Stroke National Audit Programme registry

Author

Robinson, TG, Bray, BD, Paley, L, Sprigg, N, Wang, X, Arima, H, Bath, PM, Broderick, JP, Durham, AC, Kim, JS, Lavados, PM, Lee, TH, Martins, S, Nguyen, TH, Pandian, JD, Parsons, MW, Pontes-Neto, OM, Ricci, S, Sharma, VK, Wang, J, Woodward, M, Rudd, AG, Chalmers, J, S Anderson, C, Robinson, TG, Bray, BD, Paley, L, Sprigg, N, Wang, X, Arima, H, Bath, PM, Broderick, JP, Durham, AC, Kim, JS, Lavados, PM, Lee, TH, Martins, S, Nguyen, TH, Pandian, JD, Parsons, MW, Pontes-Neto, OM, Ricci, S, Sharma, VK, Wang, J, Woodward, M, Rudd, AG, Chalmers, J, and S Anderson, C

Abstract

Background: Randomized controlled trials provide high-level evidence, but the necessity to include selected patients may limit the generalisability of their results. Methods: Comparisons were made of baseline and outcome data between patients with acute ischemic stroke (AIS) recruited into the alteplase-dose arm of the international, multi-center, Enhanced Control of Hypertension and Thrombolysis Stroke study (ENCHANTED) in the United Kingdom (UK), and alteplase-treated AIS patients registered in the UK Sentinel Stroke National Audit Programme (SSNAP) registry, over the study period June 2012 to October 2015. Results: There were 770 AIS patients (41.2% female; mean age 72 years) included in ENCHANTED at sites in England and Wales, which was 19.5% of alteplase-treated AIS patients registered in the SSNAP registry. Trial participants were significantly older, had lower baseline neurological severity, less likely Asian, and had more premorbid symptoms, hypertension and atrial fibrillation. Although ENCHANTED participants had higher rates of symptomatic intracerebral hemorrhage than those in SSNAP, there were no differences in onset-to-treatment time, levels of disability (assessed by the modified Rankin scale) at hospital discharge, and mortality over 90 days between groups. Conclusions: Despite the high level of participation, equipoise over the dose of alteplase among UK clinician investigators favored the inclusion of older, frailer, milder AIS patients in the ENCHANTED trial. Clinical trial registration: Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01422616.

Published
2019

42. 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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44. Outcome Assessment by Central Adjudicators Versus Site Investigators in Stroke Trials: A Systematic Review and Meta-Analysis

Author

Cardiovasculaire Epi Team 6, ZL Cerebrovasculaire Ziekten Medisch, Brain, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Expertisecentrum Alg., Godolphin, Peter J., Bath, Philip M., Algra, Ale, Berge, Eivind, Brown, Martin M., Chalmers, John, Duley, Lelia, Eliasziw, Misha, Gregson, John, Greving, Jacoba P., Hankey, Graeme J., Hosomi, Naohisa, Johnston, S. Claiborne, Patsko, Emily, Ranta, Annamarei, Sandset, Per Morten, Serena, Joaquin, Weimar, Christian, Montgomery, Alan A., Knipp, S. C., Giugliano, R. P., Bonati, L. H., Nagai, Y., Matsumoto, M., Barnett, H. J. M., Fox, A. J., Farrant, M., Easton, J. D., Elm, J. J., Neal, B., Arima, H., Serena, J., Davalos, A., Amarenco, P., Evans, S., Sprigg, N., Dineen, R., Eikelboom, J. W., Chen, C., Cardiovasculaire Epi Team 6, ZL Cerebrovasculaire Ziekten Medisch, Brain, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Expertisecentrum Alg., Godolphin, Peter J., Bath, Philip M., Algra, Ale, Berge, Eivind, Brown, Martin M., Chalmers, John, Duley, Lelia, Eliasziw, Misha, Gregson, John, Greving, Jacoba P., Hankey, Graeme J., Hosomi, Naohisa, Johnston, S. Claiborne, Patsko, Emily, Ranta, Annamarei, Sandset, Per Morten, Serena, Joaquin, Weimar, Christian, Montgomery, Alan A., Knipp, S. C., Giugliano, R. P., Bonati, L. H., Nagai, Y., Matsumoto, M., Barnett, H. J. M., Fox, A. J., Farrant, M., Easton, J. D., Elm, J. J., Neal, B., Arima, H., Serena, J., Davalos, A., Amarenco, P., Evans, S., Sprigg, N., Dineen, R., Eikelboom, J. W., and Chen, C.

Published
2019

45. The REstart or STop Antithrombotics Randomised Trial (RESTART) after stroke due to intracerebral haemorrhage: study protocol for a randomised controlled trial

Author

Al-Shahi Salman, R, Dennis, M S, Murray, G D, Innes, K, Drever, J, Dinsmore, L, Williams, C, White, P M, Whiteley, W N, Sandercock, P A G, Sudlow, C L M, Newby, D E, Sprigg, N, Werring, D J, Rajkumar, C, and others

Abstract

Background\ud For adults surviving stroke due to spontaneous (non-traumatic) intracerebral haemorrhage (ICH) who had taken an antithrombotic (i.e. anticoagulant or antiplatelet) drug for the prevention of vaso-occlusive disease before the ICH, it is unclear whether starting antiplatelet drugs results in an increase in the risk of recurrent ICH or a beneficial net reduction of all serious vascular events compared to avoiding antiplatelet drugs.\ud \ud Methods/design\ud The REstart or STop Antithrombotics Randomised Trial (RESTART) is an investigator-led, randomised, open, assessor-blind, parallel-group, randomised trial comparing starting versus avoiding antiplatelet drugs for adults surviving antithrombotic-associated ICH at 122 hospital sites in the United Kingdom. RESTART uses a central, web-based randomisation system using a minimisation algorithm, with 1:1 treatment allocation to which central research staff are masked. Central follow-up includes annual postal or telephone questionnaires to participants and their general (family) practitioners, with local provision of information about adverse events and outcome events. The primary outcome is recurrent symptomatic ICH. The secondary outcomes are: symptomatic haemorrhagic events; symptomatic vaso-occlusive events; symptomatic stroke of uncertain type; other fatal events; modified Rankin Scale score; adherence to antiplatelet drug(s). The magnetic resonance imaging (MRI) sub-study involves the conduct of brain MRI according to a standardised imaging protocol before randomisation to investigate heterogeneity of treatment effect according to the presence of brain microbleeds. Recruitment began on 22 May 2013. The target sample size is at least 720 participants in the main trial (at least 550 in the MRI sub-study).\ud \ud Discussion\ud Final results of RESTART will be analysed and disseminated in 2019.

Published
2018

48. Outcome Assessment by Central Adjudicators Versus Site Investigators in Stroke Trials

Author

Godolphin, Peter J., primary, Bath, Philip M., additional, Algra, Ale, additional, Berge, Eivind, additional, Brown, Martin M., additional, Chalmers, John, additional, Duley, Lelia, additional, Eliasziw, Misha, additional, Gregson, John, additional, Greving, Jacoba P., additional, Hankey, Graeme J., additional, Hosomi, Naohisa, additional, Johnston, S. Claiborne, additional, Patsko, Emily, additional, Ranta, Annamarei, additional, Sandset, Per Morten, additional, Serena, Joaquín, additional, Weimar, Christian, additional, Montgomery, Alan A., additional, Knipp, S.C., additional, Giugliano, R.P., additional, Bonati, L.H., additional, Nagai, Y., additional, Matsumoto, M., additional, Barnett, H.J.M., additional, Fox, A.J., additional, Farrant, M., additional, Easton, J.D., additional, Elm, J.J., additional, Neal, B., additional, Arima, H., additional, Dávalos, A., additional, Amarenco, P., additional, Evans, S., additional, Sprigg, N., additional, Dineen, R., additional, Eikelboom, J.W., additional, and Chen, C., additional

Published
2019
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49. 136Rates, risks and routes to reduce vascular dementia (R4VAD)

Author

Backhouse, E V, primary, Brown, R, additional, Williams, S, additional, Parry-Jones, A, additional, Werring, D, additional, Sprigg, N, additional, Touyz, R, additional, Tyrrell, P, additional, Robinson, T, additional, Rudd, A, additional, McManus, R, additional, O’Brien, J, additional, Markus, H, additional, Bath, P, additional, Quinn, T, additional, Doubal, F, additional, and Wardlaw, J M, additional

Published
2019
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