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1. Feasibility of comparing medical management and surgery (with neurosurgery or stereotactic radiosurgery) with medical management alone in people with symptomatic brain cavernoma – protocol for the Cavernomas: A Randomised Effectiveness (CARE) pilot trial

Author: Khalid Hamandi, Julie Woodfield, Smriti Agarwal, Richard Edwards, John Williamson, Ravindran Visagan, Rustam Al-Shahi Salman, Howard Brydon, Diederik Bulters, Dawn Hennigan, Paul Leach, Conor Mallucci, Nitin Mukerji, Marios Papadopoulos, Nicholas Ross, Martin Tisdall, Carole Turner, Shungu Ushewokunze, Raghu Vindlacheruvu, Paul Brennan, Phil White, Sophie Hunter, Karen Coy, Julia Wade, James Stewart, Tom Hughes, Laura Forsyth, Kirsty Harkness, David White, Rupal Shah, Sanjay Bhate, Neil Kitchen, Peter J Hutchinson, Emanuel Cirstea, Ramesh Nair, Rebecca Hall, Varduhi Cahill, Tom Hayton, Silvia Tarantino, Christin Eltze, Jack Lee, Arlo Whitehouse, Daniel Walsh, Jacqueline Stephen, Nicola Phillips, Steff Lewis, Susan Davies, Mathew Guilfoyle, Peter S Hall, Andrew Stoddart, Francesca Colombo, Emma Richards, Greg James, Sarah Illingworth, William B Lo, Andrew Bacon, Vijeya Ganesan, Sabina Patel, Aileen R Neilson, Felicia Jennings, Saba Raza-Knight, Andrew Brodbelt, Aswin Chari, Hasan Asif, Ian Kamaly-Asl, Milan Makwana, Zubair Tahir, Allan MacRaild, Grace Vassallo, Ian Anderson, Daniel Holsgrove, Carole Chambers, Sandra Williams, Francesca Spickett-Jones, Marios C Papadopoulos, John Preston, Edward White, Adel Helmy, Sarah Ali, John Reid, Daniel Brown, Louis Taylor, Christopher Uff, Patrick Grover, Azra Banaras, Linetty Makawa, Anil Israni, Richard J Edwards, William Muirhead, Daniel Brooks, Debbie Brown, Ciaran Scott Hill, Kerry Smith, Beth Atkinson, Michelle Fawcett, Sifelani Tshuma, Oliver Kennion, Jo Howe, James J M Loan, Philip Clatworthy, Claire Hudson, Rebecca Hodnett, Madalina Roman, Mary Sikaonga, Elaine Kinsella, Mario Teo, Venetia Giannakaki, James Loan, Lauren Harris, Jack Wildman, Emmanuel Chavredakis, Nihal Gurusinghe, Alex Rossdeutsch, Anthony Wiggins, Giannis Sokratous, Lucie Ferguson, Shakeelah Patel, Sonia Raj, Oishik Raha, Janneke van Beijnum, Pragnesh Bhatt, Anna Bjornson, Nicole Broomes, Alistair Bullen, Julian Cahill, Mihai Danciut, Ronneil Digpal, Ioannis Fouyas, Lauren S Harris, Sohail Majeed, Matthias Radatz, Oliver Wroe Wright, Jessica Teasdale, Michelle Coakley, Drahoslav Sokol, Chandru Kaliaperumal, Mairi MacDonald, Sarah Risbridger, Siobhan Kearney, Ellaine Bosetta, Thomas Doke, Sonny Coskuner, Christine Kamara, Jonathan Gardner, Imron Hamina, Kishor Chaudhari, Liliana Chapas, Karen Caldwell, Sarah Holland, Tamara Tajsic, Rachael Dore, Taya Anderson, Shelley Mayor, Laura O'Malley, Samantha Glover, Janice Irvine, Annika Walch, Farah Muir, Eng Tah Goh, Andrew McDarby, Michelle Bates, Rebecca Hancox, Claudia Kate Auyeung, Elizabeth Goff, Deanna Stephens, Borislava Borislavova, Ruth Worner, Sandeep Buddha, Lisa Tucker, Sandra Dymond, Andrew Mallick, Dymona McAleer, Belinda Gunning, Emma Clarkson, Cathy Stoneley, Jibril Osman Farah, Niamh Bohnacker, Rosette Marimon, Lydia Parker, Puneet Sharma, Dan Holsgrove, Danielle McLaughlan, Tracey Marsden, Kathryn Cawley, Hellen Raffalli, Imedla Mayor, Dipek Ram, Rebecca Keeping, Katie Hennessy, Ammar Kadhim, Md Moidul Islam, Manjunath Prasad, Cheryl Webster, Vicky Slater, Saffnan Mohamed, Saba Raza Knight, Terri-Louise Cromie, Allan Brown, Ruth Pennington, Charlene Campbell, Anthony Ghosh, Teresa Fitzpatrick, Mohammed Patel, Winnington Ruiz, Mirriam Taylor, Divina Anyog, Katarzyna Tluchowska, Jackson Nolasco, Kleopatra Angelopoulou, Bethany Welch, Ida Ponce, Lucy Bailey, Mia Marsden, Angelene Cope, Deepthy Blesson, Rachel Sutton, Mary Kambafwile, and Jade McAndrew
Subjects: Medicine
Abstract: Introduction The top research priority for cavernoma, identified by a James Lind Alliance Priority setting partnership was ‘Does treatment (with neurosurgery or stereotactic radiosurgery) or no treatment improve outcome for people diagnosed with a cavernoma?’ This pilot randomised controlled trial (RCT) aims to determine the feasibility of answering this question in a main phase RCT.Methods and analysis We will perform a pilot phase, parallel group, pragmatic RCT involving approximately 60 children or adults with mental capacity, resident in the UK or Ireland, with an unresected symptomatic brain cavernoma. Participants will be randomised by web-based randomisation 1:1 to treatment with medical management and with surgery (neurosurgery or stereotactic radiosurgery) versus medical management alone, stratified by prerandomisation preference for type of surgery. In addition to 13 feasibility outcomes, the primary clinical outcome is symptomatic intracranial haemorrhage or new persistent/progressive focal neurological deficit measured at 6 monthly intervals. An integrated QuinteT Recruitment Intervention (QRI) evaluates screening logs, audio recordings of recruitment discussions, and interviews with recruiters and patients/parents/carers to identify and address barriers to participation. A Patient Advisory Group has codesigned the study and will oversee its progress.Ethics and dissemination This study was approved by the Yorkshire and The Humber—Leeds East Research Ethics Committee (21/YH/0046). We will submit manuscripts to peer-reviewed journals, describing the findings of the QRI and the Cavernomas: A Randomised Evaluation (CARE) pilot trial. We will present at national specialty meetings. We will disseminate a plain English summary of the findings of the CARE pilot trial to participants and public audiences with input from, and acknowledgement of, the Patient Advisory Group.Trial registration number ISRCTN41647111.
Published: 2023
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2. Prognostic indicators and outcomes of hospitalised COVID-19 patients with neurological disease: An individual patient data meta-analysis

Author: Bhagteshwar Singh, Suzannah Lant, Sofia Cividini, Jonathan W. S. Cattrall, Lynsey C. Goodwin, Laura Benjamin, Benedict D. Michael, Ayaz Khawaja, Aline de Moura Brasil Matos, Walid Alkeridy, Andrea Pilotto, Durjoy Lahiri, Rebecca Rawlinson, Sithembinkosi Mhlanga, Evelyn C. Lopez, Brendan F. Sargent, Anushri Somasundaran, Arina Tamborska, Glynn Webb, Komal Younas, Yaqub Al Sami, Heavenna Babu, Tristan Banks, Francesco Cavallieri, Matthew Cohen, Emma Davies, Shalley Dhar, Anna Fajardo Modol, Hamzah Farooq, Jeffrey Harte, Samuel Hey, Albert Joseph, Dileep Karthikappallil, Daniel Kassahun, Gareth Lipunga, Rachel Mason, Thomas Minton, Gabrielle Mond, Joseph Poxon, Sophie Rabas, Germander Soothill, Marialuisa Zedde, Konstantin Yenkoyan, Bruce Brew, Erika Contini, Lucette Cysique, Xin Zhang, Pietro Maggi, Vincent van Pesch, Jérome Lechien, Sven Saussez, Alex Heyse, Maria Lúcia Brito Ferreira, Cristiane N. Soares, Isabel Elicer, Laura Eugenín-von Bernhardi, Waleng Ñancupil Reyes, Rong Yin, Mohammed A. Azab, Foad Abd-Allah, Ahmed Elkady, Simon Escalard, Jean-Christophe Corvol, Cécile Delorme, Pierre Tattevin, Kévin Bigaut, Norbert Lorenz, Daniel Hornuss, Jonas Hosp, Siegbert Rieg, Dirk Wagner, Benjamin Knier, Paul Lingor, Andrea Sylvia Winkler, Athena Sharifi-Razavi, Shima T. Moein, SeyedAhmad SeyedAlinaghi, Saeidreza JamaliMoghadamSiahkali, Mauro Morassi, Alessandro Padovani, Marcello Giunta, Ilenia Libri, Simone Beretta, Sabrina Ravaglia, Matteo Foschi, Paolo Calabresi, Guido Primiano, Serenella Servidei, Nicola Biagio Mercuri, Claudio Liguori, Mariangela Pierantozzi, Loredana Sarmati, Federica Boso, Silvia Garazzino, Sara Mariotto, Kimani N. Patrick, Oana Costache, Alexander Pincherle, Frederikus A. Klok, Roger Meza, Verónica Cabreira, Sofia R. Valdoleiros, Vanessa Oliveira, Igor Kaimovsky, Alla Guekht, Jasmine Koh, Eva Fernández Díaz, José María Barrios-López, Cristina Guijarro-Castro, Álvaro Beltrán-Corbellini, Javier Martínez-Poles, Alba María Diezma-Martín, Maria Isabel Morales-Casado, Sergio García García, Gautier Breville, Matteo Coen, Marjolaine Uginet, Raphaël Bernard-Valnet, Renaud Du Pasquier, Yildiz Kaya, Loay H. Abdelnour, Claire Rice, Hamish Morrison, Sylviane Defres, Saif Huda, Noelle Enright, Jane Hassell, Lucio D’Anna, Matthew Benger, Laszlo Sztriha, Eamon Raith, Krishna Chinthapalli, Ross Nortley, Ross Paterson, Arvind Chandratheva, David J. Werring, Samir Dervisevic, Kirsty Harkness, Ashwin Pinto, Dinesh Jillella, Scott Beach, Kulothungan Gunasekaran, Ivan Rocha Ferreira Da Silva, Krishna Nalleballe, Jonathan Santoro, Tyler Scullen, Lora Kahn, Carla Y. Kim, Kiran T. Thakur, Rajan Jain, Thirugnanam Umapathi, Timothy R. Nicholson, James J. Sejvar, Eva Maria Hodel, The Brain Infections Global COVID-Neuro Network Study Group, Catrin Tudur Smith, and Tom Solomon
Subjects: Medicine, Science
Abstract: Background Neurological COVID-19 disease has been reported widely, but published studies often lack information on neurological outcomes and prognostic risk factors. We aimed to describe the spectrum of neurological disease in hospitalised COVID-19 patients; characterise clinical outcomes; and investigate factors associated with a poor outcome. Methods We conducted an individual patient data (IPD) meta-analysis of hospitalised patients with neurological COVID-19 disease, using standard case definitions. We invited authors of studies from the first pandemic wave, plus clinicians in the Global COVID-Neuro Network with unpublished data, to contribute. We analysed features associated with poor outcome (moderate to severe disability or death, 3 to 6 on the modified Rankin Scale) using multivariable models. Results We included 83 studies (31 unpublished) providing IPD for 1979 patients with COVID-19 and acute new-onset neurological disease. Encephalopathy (978 [49%] patients) and cerebrovascular events (506 [26%]) were the most common diagnoses. Respiratory and systemic symptoms preceded neurological features in 93% of patients; one third developed neurological disease after hospital admission. A poor outcome was more common in patients with cerebrovascular events (76% [95% CI 67–82]), than encephalopathy (54% [42–65]). Intensive care use was high (38% [35–41]) overall, and also greater in the cerebrovascular patients. In the cerebrovascular, but not encephalopathic patients, risk factors for poor outcome included breathlessness on admission and elevated D-dimer. Overall, 30-day mortality was 30% [27–32]. The hazard of death was comparatively lower for patients in the WHO European region. Interpretation Neurological COVID-19 disease poses a considerable burden in terms of disease outcomes and use of hospital resources from prolonged intensive care and inpatient admission; preliminary data suggest these may differ according to WHO regions and country income levels. The different risk factors for encephalopathy and stroke suggest different disease mechanisms which may be amenable to intervention, especially in those who develop neurological symptoms after hospital admission.
Published: 2022

3. Potential missed opportunities to prevent ischaemic stroke: prospective multicentre cohort study of atrial fibrillation-associated ischaemic stroke and TIA

Author: Gregory Y H Lip, Michael Power, Martin M Brown, Matthew Smith, Christopher Price, Tarek Yousry, Gargi Banerjee, David J Werring, Gareth Ambler, Michelle Davis, Chris Patterson, Keith Muir, Krishna Dani, Julie Staals, Jon Scott, Pankaj Sharma, Duncan Wilson, Clare Shakeshaft, Hannah Cohen, Kirsty Harkness, Louise Shaw, Jane Sword, Roland Veltkamp, Deborah Kelly, Frances Harrington, Marc Randall, Karim Mahawish, Abduelbaset Elmarim, Bernard Esisi, Claire Cullen, Arumug Nallasivam, Adrian Barry, Christine Roffe, John Coyle, Ahamad Hassan, Caroline Lovelock, Jonathan Birns, David Cohen, L Sekaran, Adrian Parry-Jones, Anthea Parry, David Hargroves, Harald Proschel, Prabel Datta, Khaled Darawil, Aravindakshan Manoj, Mathew Burn, Elio GialloMbardo, Nigel Smyth, Syed Mansoor, Ijaz Anwar, Rachel Marsh, Sissi Ispoglou, Dinesh Chadha, Mathuri Prabhakaran, Sanjeevikumar Meenakishundaram, Vinodh Krishnamurthy, Prasanna Aghoram, Michael McCormick, Nikola Sprigg Paul O’Mahony, Peter Wilkinson, Simon Leach, Sarah Caine, Ilse Burger, Gunaratam Gunathilagan, Paul Guyler, Hedley Emsley, Dulka Manawadu, Kath Pasco, Maam Mamun, Robert Luder, Mahmud Sajid, James Okwera, Elizabeth Warburton, Kari Saastamoinen, Timothy England, Janet Putterill, Enrico Flossman, David Mangion, Appu Suman, John Corrigan, Enas Lawrence, Djamil Vahidassr, Janice O’Connell, Mark White, Martin Cooper, Lillian Choy, David Seiffge, Andreas Charidimou, H R Jäger, Azlisham Mohd Nor, and Al-Shahi Salman Rustam
Subjects: Medicine
Abstract: Objective We report on: (1) the proportion of patients with known atrial fibrillation (AF); and (2) demographic, clinical or radiological differences between patients with known AF (and not treated) and patients with newly diagnosed AF, in a cohort of patients who presented with ischaemic stroke or transient ischaemic attack (TIA) not previously treated with anticoagulation.Design We reviewed cross-sectional baseline demographic and clinical data from a prospective observational cohort study, (CROMIS-2).Setting Patients were recruited from 79 hospital stroke centres throughout the UK and one centre in the Netherlands.Participants Patients were eligible if they were adults who presented with ischaemic stroke or TIA and AF and had not been previously treated with oral anticoagulation.Main outcome measures Proportion of patients with known AF before index ischaemic stroke or TIA from a cohort of patients who have not been previously treated with oral anticoagulation. Secondary analysis includes the comparison of CHA2DS2-VASc and HAS-BLED scores and other demographics and risk factors between those with newly diagnosed AF and those with previously known AF.Results Of 1470 patients included in the analysis (mean age 76 years (SD 10)), 622 (42%) were female; 999 (68%) patients had newly diagnosed AF and 471 (32%) patients had known AF. Of the 471 patients with known AF, 68% had a strong indication for anticoagulation and 89% should have been considered for anticoagulation based upon CHA2DS2-VASc score. Patients with known AF were more likely to have a prior history of dementia (4% vs 2%, p=0.02) and had higher HAS-BLED scores (median 3 vs 2). CHA2DS2-VASc, other risk factors and demographics were similar.Conclusions About 1/3 of patients who present with stroke and have AF who have not been treated with oral anticoagulation have previously known AF. Of these patients, at least 68% were not adequately treated with oral anticoagulation.Trial registration number NCT02513316.
Published: 2019
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4. 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: Henry Ma, Eleni Sakka, Hugues Chabriat, Duncan Wilson, Appu Suman, Peter J. Kelly, SL Ho, Charlotte Zerna, Eric Jouvent, Lawrence K.S. Wong, Anthea Parry, Frances Harrington, Jan Stam, Christopher Patterson, Rustam Al-Shahi Salman, Shigeru Inamura, Krishna A Dani, Henry Houlden, Sebastian Thilemann, Kotaro Iida, Chao Xu, Eunbin Ko, Daniel Guisado-Alonso, Urs Fischer, Caroline E. Lovelock, Man Yu Tse, Wing Chi Fong, Azlisham Mohd Nor, Clare Shakeshaft, Philippe Maeder, Henrik Gensicke, Stefan T. Engelter, James Okwera, Christopher Chen, Dulka Manawadu, John F. Corrigan, Efrat Kliper, Shelagh B. Coutts, Alexander P. Leff, Kam Tat Leung, Chathuri Yatawara, Leopold Hertzberger, M. Eline Kooi, Kazuhisa Yoshifuji, Hing Lung Ip, Keon-Joo Lee, Sanjeevikumar Meenakishundaram, Hiroyuki Irie, Marc Randall, Hatice Ozkan, Hideo Hara, Jill Abrigo, Raquel Delgado-Mederos, Shaloo Singhal, Enrico Flossmann, Beatriz Gómez-Ansón, Paul O'Mahony, Carmen Barbato, Ahamad Hassan, Francesca M Chappell, Harald Proschel, Vincent Mok, Masashi Nishihara, Lakshmanan Sekaran, Derya Selcuk Demirelli, Chu Peng Hoi, Hakan Ay, Joan Martí-Fàbregas, Rebeca Marín, Anne Cristine Guevarra, Martin Cooper, Einor Ben Assayag, Anne-Marie Mendyk, Christine Roffe, Myung Suk Jang, Maarten van Gemert, Hannah Cohen, Jae-Sung Lim, YK Wong, Bonnie Y.K. Lam, Janet Putterill, Wouter Schoonewille, Nick S. Ward, Nikola Sprigg, Kui Kai Lau, Bernard Esisi, Peter M. Rothwell, Henk Verbiest, Kirsty Harkness, Elisa Merino, Gareth Ambler, Arumug Nallasivam, Nigel Smyth, Paul A. Armitage, Heinrich Mattle, Pol Camps-Renom, Martin M. Brown, David Cohen, Min Lou, Pankaj Sharma, Sarah Gunkel, Elles Douven, Andreas Charidimou, Djamil Vahidassr, Cathy Soufan, Alexandros A Polymeris, Michael G. Hennerici, Chris Moran, Rachel Marsh, Mahmud Sajid, Kyohei Fujita, David J. Werring, Joanna M. Wardlaw, Derek Hayden, Joseph Kwan, Timothy J. England, Jaap van der Sande, Luis Prats-Sánchez, Paul Guyler, Ryan Hoi Kit Cheung, Koon-Ho Chan, Frank-Erik de Leeuw, Simone Browning, Jon Scott, Adrian Barry, Alejandro Martínez-Domeño, Luc Bracoub, Dinesh Chadha, Ijaz Anwar, Deborah Kelly, Moon-Ku Han, Anil M. Tuladhar, Thomas Gattringer, Fiona Carty, Abduelbaset Elmarim, Syed Mansoor, Enrico Flossman, Dilek Necioglu Orken, Jane Sword, Velandai Srikanth, Ping Wing Ng, Thomas W. Leung, Richard Shek-kwan Chang, Hans Rolf Jäger, Marwan El-Koussy, Jeroen Hendrikse, Khaled Darawil, Kazunori Toyoda, Mathuri Prabhakaran, Karim Mahawish, Ethem Murat Arsava, Jihoon Kang, Kwok Kui Wong, Michael Power, Felix Fluri, Enas Lawrence, Maam Mamun, Sissi Ispoglou, Mathew Burn, Siu Hung Li, Henry K.F. Mak, Kaori Miwa, Els De Schryver, Franz Fazekas, Jonathan G. Best, Louise Shaw, Hen Hallevi, Keith W. Muir, Ilse Burger, Adrian Wong, Nils Peters, Susana Muñoz-Maniega, Yusuke Yakushiji, David Calvet, Mark White, Michael McCormick, Vinodh Krishnamurthy, David Hargroves, Jan C. Purrucker, Tae Jin Song, Masayuki Shiozawa, Noortje A.M. Maaijwee, Prasanna Aghoram, Nicolas Christ, Lino Ramos, Yannie Soo, Thanh G. Phan, Parashkev Nachev, David J. Seiffge, Kim Wiegertjes, Leo H. Bonati, Chahin Pachai, Oi Ling Chan, Yvo B.W.E.M. Roos, Santiago Medrano-Martorell, Natan M. Bornstein, Elizabeth A. Warburton, Richard Li, Prabel Datta, Pascal P. Gratz, Edmund Ka Ming Wong, Hedley C. A. Emsley, Marie-Yvonne Douste-Blazy, Gunaratam Gunathilagan, Nagaendran Kandiah, Masatoshi Koga, Roland Veltkamp, Lee-Anne Slater, Suk Fung Tsang, Beom Joon Kim, Simon Jung, Zeynep Tanriverdi, Sarah Caine, Peter J. Koudstaal, Laurence Legrand, Kari Saastamoinen, Ale Algra, Jean-Louis Mas, Christine Delmaire, Fidel Nuñez, Robert J. van Oostenbrugge, Sebastian Eppinger, Lillian Choy, Robert Luder, Vincent I.H. Kwa, Aad van der Lugt, Marie Dominique Fratacci, Stephen Makin, Layan Akijian, Régis Bordet, Mi Hwa Yang, Ying Zhou, Elio Giallombardo, Adrian R Parry-Jones, John S. Thornton, Amos D. Korczyn, Narayanaswamy Venketasubramanian, David J. Williams, Aravindakshan Manoj, Julie Staals, Solveig Horstmann, Dianne H.K. van Dam-Nolen, Claire Cullen, Benjamin Wagner, Jun Tanaka, Martin Dennis, Stef Bakker, Gregory Y.H. Lip, L. Jaap Kappelle, Robin Lemmens, Achim Gass, David Mangion, Matthew Smith, Toshio Imaizumi, Wenyan Liu, Jeremy Molad, Christopher Price, Paul J. Nederkoorn, P. J. A. M. Brouwers, Vincent Thijs, Sze Ho Ma, Mark Schembri, Peter Wilkinson, Janice E. O’Connell, Karen Ma, John Ly, Leonidas Panos, Chung Yan Chan, Toshihiro Ide, Christopher Traenka, Joost Jöbsis, Gargi Banerjee, Paul Berntsen, Michael J. Thrippleton, Raymond T.F. Cheung, Christopher Karayiannis, Werner H. Mess, Robert Simister, Jayesh Modi Medanta, Syuhei Ikeda, John Mitchell, Linxin Li, Mauro S.B. Silva, Eric Vicaut, John Coyle, Shoichiro Sato, Michelle Davis, Jonathan Birns, Richard J. Perry, Sean M. Murphy, KC Teo, Maria del C. Valdés Hernández, Bibek Gyanwali, Tarek A. Yousry, Kath Pasco, Sebastian Köhler, Joachim Fladt, Edward S. Hui, Philippe Lyrer, Young Dae Kim, Anna K. Heye, Eric E. Smith, Saima Hilal, Ender Uysal, Ji Hoe Heo, Ysoline Beigneux, Cisca Linn, Hee-Joon Bae, Simon Leach, Winnie C.W. Chu, Ronil V. Chandra, Neurology, ACS - Atherosclerosis & ischemic syndromes, ANS - Neurovascular Disorders, MUMC+: HZC Med Staf Spec Klinische Neurofys (9), RS: Carim - B06 Imaging, MUMC+: HZC Klinische Neurofysiologie (5), Klinische Neurowetenschappen, Psychiatrie & Neuropsychologie, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, MUMC+: MA Neurologie (3), RS: Carim - B05 Cerebral small vessel disease, MUMC+: Hersen en Zenuw Centrum (3), MUMC+: MA Med Staf Spec Neurologie (9), RS: NUTRIM - R1 - Obesity, diabetes and cardiovascular health, Beeldvorming, and MUMC+: DA BV Klinisch Fysicus (9)
Subjects: Adult, Male, Risk, EXTERNAL VALIDATION, medicine.medical_specialty, Neurology, MODELS, Clinical Neurology, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Fibrinolytic Agents, Recurrence, Internal medicine, Antithrombotic, Humans, Medicine, Prospective cohort study, 610 Medicine & health, Stroke, METAANALYSIS, Aged, Ischemic Stroke, Science & Technology, medicine.diagnostic_test, business.industry, Proportional hazards model, Magnetic resonance imaging, Middle Aged, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], medicine.disease, Magnetic Resonance Imaging, Ischemic Attack, Transient, ATRIAL-FIBRILLATION, Cardiology, Female, Neurology (clinical), Neurosciences & Neurology, business, Intracranial Hemorrhages, Life Sciences & Biomedicine, 030217 neurology & neurosurgery, Fibrinolytic agent, Cohort study
Abstract: Contains fulltext : 235277.pdf (Publisher’s version ) (Closed access) BACKGROUND: Balancing the risks of recurrent ischaemic stroke and intracranial haemorrhage is important for patients treated with antithrombotic therapy after ischaemic stroke or transient ischaemic attack. However, existing predictive models offer insufficient performance, particularly for assessing the risk of intracranial haemorrhage. We aimed to develop new risk scores incorporating clinical variables and cerebral microbleeds, an MRI biomarker of intracranial haemorrhage and ischaemic stroke risk. METHODS: We did a pooled analysis of individual-patient data from the Microbleeds International Collaborative Network (MICON), which includes 38 hospital-based prospective cohort studies from 18 countries. All studies recruited participants with previous ischaemic stroke or transient ischaemic attack, acquired baseline MRI allowing quantification of cerebral microbleeds, and followed-up participants for ischaemic stroke and intracranial haemorrhage. Participants not taking antithrombotic drugs were excluded. We developed Cox regression models to predict the 5-year risks of intracranial haemorrhage and ischaemic stroke, selecting candidate predictors on biological relevance and simplifying models using backward elimination. We derived integer risk scores for clinical use. We assessed model performance in internal validation, adjusted for optimism using bootstrapping. The study is registered on PROSPERO, CRD42016036602. FINDINGS: The included studies recruited participants between Aug 28, 2001, and Feb 4, 2018. 15 766 participants had follow-up for intracranial haemorrhage, and 15 784 for ischaemic stroke. Over a median follow-up of 2 years, 184 intracranial haemorrhages and 1048 ischaemic strokes were reported. The risk models we developed included cerebral microbleed burden and simple clinical variables. Optimism-adjusted c indices were 0·73 (95% CI 0·69-0·77) with a calibration slope of 0·94 (0·81-1·06) for the intracranial haemorrhage model and 0·63 (0·62-0·65) with a calibration slope of 0·97 (0·87-1·07) for the ischaemic stroke model. There was good agreement between predicted and observed risk for both models. INTERPRETATION: The MICON risk scores, incorporating clinical variables and cerebral microbleeds, offer predictive value for the long-term risks of intracranial haemorrhage and ischaemic stroke in patients prescribed antithrombotic therapy for secondary stroke prevention; external validation is warranted. FUNDING: British Heart Foundation and Stroke Association.
Published: 2021
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5. Safety and efficacy of losartan for the reduction of brain atrophy in clinically diagnosed Alzheimer's disease (the RADAR trial): a double-blind, randomised, placebo-controlled, phase 2 trial

Author: Patrick Gavin Kehoe, Nicholas Turner, Beth Howden, Lina Jarutyte, Shona Louise Clegg, Ian Brian Malone, Josephine Barnes, Casper Nielsen, Carole Hélène Sudre, Aileen Wilson, Ngoc Jade Thai, Peter Sinclair Blair, Elizabeth Coulthard, Janet Athene Lane, Peter Passmore, Jodi Taylor, Henk-Jan Mutsaerts, David Lee Thomas, Nick Charles Fox, Ian Wilkinson, Yoav Ben-Shlomo, Kirsty Harkness, Tarun Kuruvilla, Rupert McShane, Peter Connelly, Gordon Duncan, Lucy Calvert, Alasdair Lawrie, Matthew Sheridan, Eric Jackson, Bernard Udeze, Stephen Pearson, Tobias Langheinrich, Suvarna Wagle, Joseph Butchart, Ajay Macharouthu, Andrew Donaldson, Wendy Neil, Vivek Pattan, David Findlay, Alan Thomas, Robert Barber, Andrew Byrne, Madhusudan Dalvi, Rashi Negi, Bernadette McGuinness, Radiology and nuclear medicine, and Neurology
Subjects: medicine.medical_specialty, Angiotensin II receptor antagonist, Blood Pressure, Placebo, Losartan, State Medicine, law.invention, Randomized controlled trial, Double-Blind Method, law, Alzheimer Disease, Internal medicine, medicine, media_common.cataloged_instance, Humans, European union, Stroke, media_common, business.industry, Brain, Articles, Middle Aged, medicine.disease, Angiotensin II, Clinical trial, Treatment Outcome, Neurology (clinical), Atrophy, business, medicine.drug
Abstract: BACKGROUND: Drugs modifying angiotensin II signalling could reduce Alzheimer's disease pathology, thus decreasing the rate of disease progression. We investigated whether the angiotensin II receptor antagonist losartan, compared with placebo, could reduce brain volume loss, as a measure of disease progression, in clinically diagnosed mild-to-moderate Alzheimer's disease.METHODS: In this double-blind, multicentre, randomised controlled trial, eligible patients aged 55 years or older, previously untreated with angiotensin II drugs and diagnosed (National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria) with mild-to-moderate Alzheimer's disease, and who had capacity to consent, were recruited from 23 UK National Health Service hospital trusts. After undergoing a 4-week, open-label phase of active treatment then washout, participants were randomly assigned (1:1) oral over-encapsulated preparations of either 100 mg losartan (after an initial two-dose titration stage) or matched placebo daily for 12 months. Randomisation, minimised by age and baseline medial temporal lobe atrophy score, was undertaken online or via pin-access service by telephone. Participants, their study companions, and study personnel were masked to group assignment. The primary outcome, analysed by the intention-to-treat principle (ie, participants analysed in the group to which they were randomised, without imputation for missing data), was change in whole brain volume between baseline and 12 months, measured using volumetric MRI and determined by boundary shift interval (BSI) analysis. The trial is registered with the International Standard Randomised Controlled Trial Register (ISRCTN93682878) and the European Union Drug Regulating Authorities Clinical Trials Database (EudraCT 2012-003641-15), and is completed.FINDINGS: Between July 22, 2014, and May 17, 2018, 261 participants entered the open-label phase. 211 were randomly assigned losartan (n=105) or placebo (n=106). Of 197 (93%) participants who completed the study, 171 (81%) had complete primary outcome data. The mean brain volume (BSI) reduction was 19·1 mL (SD 10·3) in the losartan group and 20·0 mL (10·8) in the placebo group. The difference in total volume reduction between groups was -2·29 mL (95% CI -6·46 to 0·89; p=0·14). The number of adverse events was low (22 in the losartan group and 20 in the placebo group) with no differences between treatment groups. There was one treatment-related death per treatment group.INTERPRETATION: 12 months of treatment with losartan was well tolerated but was not effective in reducing the rate of brain atrophy in individuals with clinically diagnosed mild-to-moderate Alzheimer's disease. Further research is needed to assess the potential therapeutic benefit from earlier treatment in patients with milder cognitive impairment or from longer treatment periods.FUNDING: Efficacy and Mechanism Evaluation Programme (UK Medical Research Council and National Institute for Health Research).
Published: 2021
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6. Effects of oral anticoagulation for atrial fibrillation after spontaneous intracranial haemorrhage: a randomised, open-label, assessor-blinded, pilot phase, non-inferiority trial

Author: Rustam Al-Shahi Salman, Catriona Keerie, Jacqueline Stephen, Steff Lewis, John Norrie, Martin S. Dennis, David E. Newby, Joanna M. Wardlaw, Gregory Y.H. Lip, Adrian Parry-Jones, Philip M. White, Colin Baigent, Dan Lasserson, Colin Oliver, Fiach O'Mahony, Shannon Amoils, John Bamford, Jane Armitage, Jonathan Emberson, Gabriël J.R. Rinkel, Gordon Lowe, Karen Innes, Kasia Adamczuk, Lynn Dinsmore, Jonathan Drever, Garry Milne, Allan Walker, Aidan Hutchison, Carol Williams, Ruth Fraser, Rosemary Anderson, Kate Covil, Kelly Stewart, Jessica Rees, Peter Hall, Alistair Bullen, Andrew Stoddart, Tom J. Moullaali, Jeb Palmer, Eleni Sakka, Joanne Perthen, Nicola Lyttle, Neshika Samarasekera, Allan MacRaild, Seona Burgess, Jessica Teasdale, Michelle Coakley, Pat Taylor, Gordon Blair, William Whiteley, Susan Shenkin, Una Clancy, Malcolm Macleod, Rachel Sutherland, Tom Moullaali, Amanda Barugh, Christine Lerpiniere, Fiona Moreton, Nicholas Fethers, Tal Anjum, Manju Krishnan, Peter Slade, Sharon Storton, Marie Williams, Caroline Davies, Lynda Connor, Glyn Gainard, Carl Murphy, Mark Barber, Derek Esson, James Choulerton, Louise Shaw, Suzanne Lucas, Sarah Hierons, Joanne Avis, Andrew Stone, Lukuman Gbadamoshi, Telma Costa, Lauren Pearce, Kirsty Harkness, Emma Richards, Jo Howe, Christine Kamara, Ralf Lindert, Ali Ali, Jahanzeb Rehan, Sarah Chapman, Maria Edwards, Raj Bathula, David Cohen, Joseph Devine, Mushiya Mpelembue, Priya Yesupatham, Swati Chhabra, Gbadebo Adewetan, Robert Ballantine, Daniel Brooks, Gemma Smith, Gill Rogers, Stuart Marsden, Sarah Clark, Ami Wilkinson, Ellen Brown, Lynsey Stephenson, Khin Nyo, Annie Abraham, Yogish Pai, Gek Shim, Vidya Baliga, Anand Nair, Matthew Robinson, Catherine Hawksworth, Jill Greig, Irfan Alam, Tonicha Nortcliffe, Ridha Ramiz, Ryan Shaw, Stephanie Lee, Tracy Marsden, Jane Perez, Emily Birleson, Rajendra Yadava, Mirriam Sangombe, Sam Stafford, Tom Hughes, Lucy Knibbs, Bethan Morse, Stefan Schwarz, Benjamin Jelley, Susan White, Bella Richard, Heidi Lawson, Sally Moseley, Michelle Tayler, Mandy Edwards, Claire Triscott, Rebecca Wallace, Angela Hall, Amanda Dell, Khalid Rashed, Sarah Board, Clare Buckley, Alfonso Tanate, Tressy Pitt-Kerby, Kate Beesley, Jess Perry, Christine Hellyer, Paul Guyler, Nisha Menon, Sharon Tysoe, Raji Prabakaran, Martin Cooper, Anoja Rajapakse, Inez Wynter, Susan Smith, Nic Weir, Cherish Boxall, Hannah Yates, Simon Smith, Pamela Crawford, James Marigold, Fiona Smith, Jake Harvey, Sue Evans, Laura Baldwin, Sarah Hammond, Paul Mudd, Angela Bowring, Samantha Keenan, Kevin Thorpe, Mohammad Haque, Joanne Taaffe, Natalie Temple, Tracey Peachey, Kim Wells, Fiona Haines, Nicola Butterworth-Cowin, Zoey Horne, Radim Licenik, Hayley Boughton, Timothy England, Amanda Hedstrom, Brian Menezes, Ruth Davies, Venetia Johnson, Simon Whittingham-Jones, David Werring, Sabaa Obarey, Caroline Watchurst, Amy Ashton, Shez Feerick, Nina Francia, Azra Banaras, Daniel Epstein, Marilena Marinescu, Annick Williams, Anna Robinson, Fiona Humphries, Ijaz Anwar, Arunkumar Annamalai, Susan Crawford, Vicky Collins, Lorna Shepherd, Elaine Siddle, Justin Penge, Sam Qureshi, Vinodh Krishnamurthy, Vasileios Papavasileiou, Dean Waugh, Emelda Veraque, Nathan Douglas, Numan Khan, Sankaranarayanan Ramachandran, Peter Sommerville, Anthony Rudd, Sagal Kullane, Ajay Bhalla, Jonathan Birns, Rowshanara Ahmed, Meegan Gibbons, Eva Klamerus, Benjie Cendreda, Keith Muir, Nicola Day, Angela Welch, Wilma Smith, Jennifer Elliot, Salwa Eltawil, Ammad Mahmood, Kim Hatherley, Shirley Mitchell, Harjit Bains, Lauren Quinn, Rachel Teal, Ivie Gbinigie, George Harston, Phil Mathieson, Gary Ford, Ursula Schulz, James Kennedy, Kirubananthan Nagaratnam, Kiran Bangalore, Neelima Bhupathiraju, Chris Wharton, Ken Fotherby, Ahmad Nasar, Angie Stevens, Angela Willberry, Rachel Evans, Baljinder Rai, Chloe Blake, Kamy Thavanesan, Gail Hann, Tanith Changuion, Sara Nix, Amanda Whiting, Michelle Dharmasiri, Louise Mallon, Marketa Keltos, Nigel Smyth, Charlotte Eglinton, John Duffy, Ela Tone, Lucy Sykes, Emily Porter, Carolyn Fitton, Nikolaos Kirkineziadis, Gillian Cluckie, Kate Kennedy, Sarah Trippier, Rebecca Williams, Elizabeth Hayter, James Rackie, Bhavini Patel, Ghatala Rita, Adrian Blight, Val Jones, Liqun Zhang, Lillian Choy, Anthony Pereira, Brian Clarke, Samer Al-Hussayni, Lynn Dixon, Andrew Young, Adrian Bergin, David Broughton, Senthil Raghunathan, Benjamin Jackson, Jason Appleton, Gwendoline Wilkes, Amanda Buck, Carla Richardson, Judith Clarke, Lucy Fleming, Gemma Squires, Zhe Law, Camille Hutchinson, Vera Cvoro, Mandy Couser, Amanda McGregor, Sean McAuley, Susan Pound, Patricia Cochrane, Clare Holmes, Peter Murphy, Nicola Devitt, Mairead Osborn, Amy Steele, Lucy Belle Guthrie, Elizabeth Smith, Jonathan Hewitt, Natalie Chaston, Min Myint, Andrew Smith, Louise Fairlie, Michelle Davis, Beth Atkinson, Stephen Woodward, Valerie Hogg, Michelle Fawcett, Louise Finlay, Anand Dixit, Eleanor Cameron, Breffni Keegan, Jim Kelly, Dónal Concannon, Dipankar Dutta, Deborah Ward, Jon Glass, Susan O'Connell, Joseph Ngeh, Alison O'Kelly, Emma Williams, Suzanne Ragab, Damian Jenkinson, Judith Dube, Laura Gleave, Jacqui Leggett, Nisha Kissoon, Louise Southern, Utpal Naghotra, Maria Bokhari, Beverley McClelland, Katja Adie, Abhijit Mate, Frances Harrington, Ali James, Elizabeth Swanson, Terri Chant, Miriam Naccache, Abbie Coutts, Gillian Courtauld, Sarah Whurr, Sue Webber, Emily Shead, Robert Luder, Maneesh Bhargava, Elodie Murali, Larissa Cuenoud, Kath Pasco, O Speirs, Lianne Chapman, Linda Inskip, Lisa Kavanagh, Meena Srinivasan, Nichola Motherwell, Indranil Mukherjee, Louise Tonks, Denise Donaldson, Heather Button, Rebecca Wilcox, Fran Hurford, Rachel Logan, Andy Taylor, Tracie Arden, Michael Carpenter, Prabal Datta, Tajammal Zahoor, Linda Jackson, Ann Needle, Andrew Stanners, Imran Ghouri, Donna Exley, Salman Akhtar, Hollie Brooke, Shannen Beadle, Eoin O'Brien, Jobbin Francis, Joanne McGee, Elaine Amis, Jennifer Mitchell, Sarah Finlay, Devesh Sinha, Csilla Manoczki, Sam King, James Tarka, Sumita Choudhary, Jegamalini Premaruban, Dorothy Sutton, Pradeep Kumar, Charlotte Culmsee, Caroline Winckley, Holly Davies, Hilary Thatcher, Evangelos Vasileiadis, Basaam Aweid, Melinda Holden, Cathy Mason, Thant Hlaing, Gladys Madzamba, Tanya Ingram, Michelle Linforth, Claire Cullen, Nibu Thomas, John France, Afaq Saulat, Biju Bhaskaran, Pauline Fitzell, Kathleen Horan, Catherine Manyoni, Josie Garfield-Smith, Hannah Griffin, Stacey Atkins, Joan Redome, Girish Muddegowda, Holly Maguire, Adrian Barry, Nenette Abano, Resti Varquez, Joanne Hiden, Susan Lyjko, Alda Remegoso, Kay Finney, Adrian Butler, Martin Strecker, Mary Joan MaCleod, Janice Irvine, Sandra Nelson, German Guzmangutierrez, Jacqueline Furnace, Vicky Taylor, Hawraman Ramadan, Kim Storton, Sohail Hassan, Eman Abdus Sami, Ruth Bellfield, Kelvin Stewart, Outi Quinn, Chris Patterson, Hedley Emsley, Bindu Gregary, Shakeel Ahmed, Shakeelah Patel, Sonia Raj, Sulaiman Sultan, Fiona Wright, Peter Langhorne, Ruth Graham, Terry Quinn, and Kate McArthur
Subjects: Adult, medicine.medical_specialty, Adolescent, medicine.drug_class, Population, Minimisation (clinical trials), Intracranial haemorrhage, subarachnoid haemorrhage, antiplatelet therapy, law.invention, Randomized controlled trial, law, Internal medicine, Atrial Fibrillation, Medicine, Humans, atrial fibrillation, Prospective Studies, education, Adverse effect, Stroke, oral anticoagulation, education.field_of_study, business.industry, Hazard ratio, intraventricular haemorrhage, Anticoagulants, Atrial fibrillation, intracerebral haemorrhage, Vitamin K antagonist, medicine.disease, United Kingdom, subdural haemorrhage, Neurology (clinical), business, Intracranial Hemorrhages, randomised controlled trial
Abstract: Summary Background Oral anticoagulation reduces the rate of systemic embolism for patients with atrial fibrillation by two-thirds, but its benefits for patients with previous intracranial haemorrhage are uncertain. In the Start or STop Anticoagulants Randomised Trial (SoSTART), we aimed to establish whether starting is non-inferior to avoiding oral anticoagulation for survivors of intracranial haemorrhage who have atrial fibrillation. Methods SoSTART was a prospective, randomised, open-label, assessor-masked, parallel-group, pilot phase trial done at 67 hospitals in the UK. We recruited adults (aged ≥18 years) who had survived at least 24 h after symptomatic spontaneous intracranial haemorrhage, had atrial fibrillation, and had a CHA2DS2-VASc score of at least 2. Web-based computerised randomisation incorporating a minimisation algorithm allocated participants (1:1) to start or avoid long-term (≥1 year) full treatment dose open-label oral anticoagulation. The participants assigned to start oral anticoagulation received either a direct oral anticoagulant or vitamin K antagonist, and the group assigned to avoid oral anticoagulation received standard clinical practice (antiplatelet agent or no antithrombotic agent). The primary outcome was recurrent symptomatic spontaneous intracranial haemorrhage, and was adjudicated by an individual masked to treatment allocation. All outcomes were ascertained for at least 1 year after randomisation and assessed in the intention-to-treat population of all randomly assigned participants, using Cox proportional hazards regression adjusted for minimisation covariates. We planned a sample size of 190 participants (one-sided p=0·025, power 90%, allowing for non-adherence) based on a non-inferiority margin of 12% (or adjusted hazard ratio [HR] of 3·2). This trial is registered with ClinicalTrials.gov (NCT03153150) and is complete. Findings Between March 29, 2018, and Feb 27, 2020, consent was obtained at 61 sites for 218 participants, of whom 203 were randomly assigned at a median of 115 days (IQR 49–265) after intracranial haemorrhage onset. 101 were assigned to start and 102 to avoid oral anticoagulation. Participants were followed up for median of 1·2 years (IQR 0·97–1·95; completeness 97·2%). Starting oral anticoagulation was not non-inferior to avoiding oral anticoagulation: eight (8%) of 101 in the start group versus four (4%) of 102 in the avoid group had intracranial haemorrhage recurrences (adjusted HR 2·42 [95% CI 0·72–8·09]; p=0·152). Serious adverse events occurred in 17 (17%) participants in the start group and 15 (15%) in the avoid group. 22 (22%) patients in the start group and 11 (11%) patients in the avoid group died during the study. Interpretation Whether starting oral anticoagulation was non-inferior to avoiding it for people with atrial fibrillation after intracranial haemorrhage was inconclusive, although rates of recurrent intracranial haemorrhage were lower than expected. In view of weak evidence from analyses of three composite secondary outcomes, the possibility that oral anticoagulation might be superior for preventing symptomatic major vascular events should be investigated in adequately powered randomised trials. Funding British Heart Foundation, Medical Research Council, Chest Heart & Stroke Scotland.
Published: 2021
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7. Fully automated cognitive screening tool based on assessment of speech and language

Author: Bahman Mirheidari, Kirsty Harkness, Ronan O’Malley, Traci Walker, Daniel Blackburn, Markus Reuber, Heidi Christensen, and Annalena Venneri
Subjects: medicine.medical_specialty, business.industry, Cognitive disorder, Psychological intervention, Cognition, Disease, medicine.disease, 030227 psychiatry, 03 medical and health sciences, Psychiatry and Mental health, 0302 clinical medicine, Physical medicine and rehabilitation, Fully automated, Cognitive screening, Verbal fluency test, Medicine, Dementia, Surgery, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: IntroductionRecent years have seen an almost sevenfold rise in referrals to specialist memory clinics. This has been associated with an increased proportion of patients referred with functional cognitive disorder (FCD), that is, non-progressive cognitive complaints. These patients are likely to benefit from a range of interventions (eg, psychotherapy) distinct from the requirements of patients with neurodegenerative cognitive disorders. We have developed a fully automated system, ‘CognoSpeak’, which enables risk stratification at the primary–secondary care interface and ongoing monitoring of patients with memory concerns.MethodsWe recruited 15 participants to each of four groups: Alzheimer’s disease (AD), mild cognitive impairment (MCI), FCD and healthy controls. Participants responded to 12 questions posed by a computer-presented talking head. Automatic analysis of the audio and speech data involved speaker segmentation, automatic speech recognition and machine learning classification.ResultsCognoSpeak could distinguish between participants in the AD or MCI groups and those in the FCD or healthy control groups with a sensitivity of 86.7%. Patients with MCI were identified with a sensitivity of 80%.DiscussionOur fully automated system achieved levels of accuracy comparable to currently available, manually administered assessments. Greater accuracy should be achievable through further system training with a greater number of users, the inclusion of verbal fluency tasks and repeat assessments. The current data supports CognoSpeak’s promise as a screening and monitoring tool for patients with MCI. Pending confirmation of these findings, it may allow clinicians to offer patients at low risk of dementia earlier reassurance and relieve pressures on specialist memory services.
Published: 2021

8. Bayesian Inference Associates Rare KDR Variants with Specific Phenotypes in Pulmonary Arterial Hypertension

Author: Emilia M. Swietlik, Daniel Greene, Na Zhu, Karyn Megy, Marcella Cogliano, Smitha Rajaram, Divya Pandya, Tobias Tilly, Katie A. Lutz, Carrie C.L. Welch, Michael W. Pauciulo, Laura Southgate, Jennifer M. Martin, Carmen M. Treacy, Christopher J. Penkett, Jonathan C. Stephens, Harm J. Bogaard, Colin Church, Gerry Coghlan, Anna W. Coleman, Robin Condliffe, Christina A. Eichstaedt, Mélanie Eyries, Henning Gall, Stefano Ghio, Barbara Girerd, Ekkehard Grünig, Simon Holden, Luke Howard, Marc Humbert, David G. Kiely, Gabor Kovacs, Jim Lordan, Rajiv D. Machado, Robert V. MacKenzie Ross, Colm McCabe, Shahin Moledina, David Montani, Horst Olschewski, Joanna Pepke-Zaba, Laura Price, Christopher J. Rhodes, Werner Seeger, Florent Soubrier, Jay Suntharalingam, Mark R. Toshner, Anton Vonk Noordegraaf, John Wharton, James M. Wild, Stephen John Wort, Allan Lawrie, Martin R. Wilkins, Richard C. Trembath, Yufeng Shen, Wendy K. Chung, Andrew J. Swift, William C. Nichols, Nicholas W. Morrell, Stefan Gräf, Stephen Abbs, Lara Abulhoul, Julian Adlard, Munaza Ahmed, Timothy J. Aitman, Hana Alachkar, David J. Allsup, Philip Ancliff, Richard Antrobus, Ruth Armstrong, Gavin Arno, Sofie Ashford, William J. Astle, Anthony Attwood, Paul Aurora, Christian Babbs, Chiara Bacchelli, Tamam Bakchoul, Siddharth Banka, Tadbir Bariana, Julian Barwell, Joana Batista, Helen E. Baxendale, Phil L. Beales, David L. Bennett, Agnieszka Bierzynska, Tina Biss, Maria A.K. Bitner-Glindzicz, Graeme C. Black, Marta Bleda, Iulia Blesneac, Detlef Bockenhauer, Sara Boyce, John R. Bradley, Gerome Breen, Paul Brennan, Carole Brewer, Matthew Brown, Andrew C. Browning, Michael J. Browning, Rachel J. Buchan, Matthew S. Buckland, Teofila Bueser, Carmen Bugarin Diz, John Burn, Siobhan O. Burns, Oliver S. Burren, Nigel Burrows, Carolyn Campbell, Gerald Carr-White, Keren Carss, Ruth Casey, Mark J. Caulfield, Jenny Chambers, John Chambers, Melanie M.Y. Chan, Floria Cheng, Patrick F. Chinnery, Manali Chitre, Martin T. Christian, Jill Clayton-Smith, Maureen Cleary, Naomi Clements Brod, Elizabeth Colby, Trevor R.P. Cole, Janine Collins, Peter W. Collins, Cecilia J. Compton, H. Terence Cook, Stuart Cook, Nichola Cooper, Paul A. Corris, Nicola S. Curry, Matthew J. Daniels, Mehul Dattani, Louise C. Daugherty, John Davis, Anthony De Soyza, Sri V.V. Deevi, Timothy Dent, Charu Deshpande, Eleanor F. Dewhurst, Peter H. Dixon, Sofia Douzgou, Kate Downes, Anna M. Drazyk, Elizabeth Drewe, Daniel Duarte, Tina Dutt, J. David M. Edgar, Karen Edwards, William Egner, Melanie N. Ekani, Perry Elliott, Wendy N. Erber, Marie Erwood, Maria C. Estiu, Dafydd Gareth Evans, Gillian Evans, Tamara Everington, Hiva Fassihi, Remi Favier, Debra Fletcher, Frances A. Flinter, R. Andres Floto, Tom Fowler, James Fox, Amy J. Frary, Courtney E. French, Kathleen Freson, Mattia Frontini, Abigail Furnell, Daniel P. Gale, Vijeya Ganesan, Michael Gattens, Hossein-Ardeschir Ghofrani, J. Simon R. Gibbs, Kate Gibson, Kimberly C. Gilmour, Nicholas S. Gleadall, Sarah Goddard, Keith Gomez, Pavels Gordins, David Gosal, Jodie Graham, Luigi Grassi, Lynn Greenhalgh, Andreas Greinacher, Paolo Gresele, Philip Griffiths, Sofia Grigoriadou, Detelina Grozeva, Mark Gurnell, Scott Hackett, Charaka Hadinnapola, Rosie Hague, William M. Hague, Matthias Haimel, Matthew Hall, Helen L. Hanson, Eshika Haque, Kirsty Harkness, Andrew R. Harper, Claire L. Harris, Daniel Hart, Ahamad Hassan, Grant Hayman, Alex Henderson, Archana Herwadkar, Jonathan Hoffman, Rita Horvath, Henry Houlden, Arjan C. Houweling, Fengyuan Hu, Gavin Hudson, Aarnoud P. Huissoon, Matthew Hurles, Melita Irving, Louise Izatt, Roger James, Sally A. Johnson, Stephen Jolles, Jennifer Jolley, Dragana Josifova, Neringa Jurkute, Mary A. Kasanicki, Hanadi Kazkaz, Rashid Kazmi, Peter Kelleher, Anne M Kelly, Wilf Kelsall, Carly Kempster, Nathalie Kingston, Nils Koelling, Myrto Kostadima, Ania Koziell, Roman Kreuzhuber, Taco W. Kuijpers, Ajith Kumar, Dinakantha Kumararatne, Manju A. Kurian, Michael A. Laffan, Fiona Lalloo, Michele Lambert, Hana Lango Allen, D. Mark Layton, Claire Lentaigne, Tracy Lester, Adam P. Levine, Rachel Linger, Hilary Longhurst, Lorena E. Lorenzo, Eleni Louka, Paul A. Lyons, Bella Madan, Eamonn R. Maher, Jesmeen Maimaris, Samantha Malka, Sarah Mangles, Rutendo Mapeta, Kevin J. Marchbank, Stephen Marks, Hugh S. Markus, Hanns-Ulrich Marschall, Andrew Marshall, Mary Mathias, Emma Matthews, Heather Maxwell, Paul McAlinden, Mark I. McCarthy, Harriet McKinney, Stuart Meacham, Adam J. Mead, Sarju G. Mehta, Michel Michaelides, Carolyn Millar, Shehla N. Mohammed, Anthony T. Moore, Monika Mozere, Keith W. Muir, Andrew D. Mumford, Andrea H. Nemeth, William G. Newman, Michael Newnham, Sadia Noorani, Paquita Nurden, Jennifer O’Sullivan, Samya Obaji, Chris Odhams, Steven Okoli, Andrea Olschewski, Kai Ren Ong, S. Helen Oram, Elizabeth Ormondroyd, Willem H. Ouwehand, Claire Palles, Sofia Papadia, Soo-Mi Park, David Parry, Smita Patel, Joan Paterson, Andrew Peacock, Simon H. Pearce, Kathelijne Peerlinck, Romina Petersen, Clarissa Pilkington, Kenneth E.S. Poole, Bethan Psaila, Angela Pyle, Richard Quinton, Shamima Rahman, Anupama Rao, F. Lucy Raymond, Paula J. Rayner-Matthews, Augusto Rendon, Tara Renton, Andrew S.C. Rice, Alex Richter, Leema Robert, Irene Roberts, Sarah J. Rose, Robert Ross-Russell, Catherine Roughley, Noemi B.A. Roy, Deborah M. Ruddy, Omid Sadeghi-Alavijeh, Moin A. Saleem, Nilesh Samani, Crina Samarghitean, Alba Sanchis-Juan, Ravishankar B. Sargur, Robert N. Sarkany, Simon Satchell, Sinisa Savic, Genevieve Sayer, John A. Sayer, Laura Scelsi, Andrew M. Schaefer, Sol Schulman, Richard Scott, Marie Scully, Claire Searle, Arjune Sen, W.A. Carrock Sewell, Denis Seyres, Neil Shah, Olga Shamardina, Susan E. Shapiro, Adam C. Shaw, Keith Sibson, Lucy Side, Ilenia Simeoni, Michael A. Simpson, Matthew C. Sims, Suthesh Sivapalaratnam, Damian Smedley, Katherine R. Smith, Kenneth G.C. Smith, Katie Snape, Nicole Soranzo, Olivera Spasic-Boskovic, Simon Staines, Emily Staples, Hannah Stark, Kathleen E. Stirrups, Alex Stuckey, Petros Syrris, R. Campbell Tait, Kate Talks, Rhea Y.Y. Tan, Jenny C. Taylor, John M. Taylor, James E. Thaventhiran, Andreas C. Themistocleous, David Thomas, Ellen Thomas, Moira J. Thomas, Patrick Thomas, Kate Thomson, Adrian J. Thrasher, Chantal Thys, Marc Tischkowitz, Catherine Titterton, Cheng-Hock Toh, Ian P. Tomlinson, Matthew Traylor, Paul Treadaway, Salih Tuna, Ernest Turro, Philip Twiss, Tom Vale, Chris Van Geet, Natalie van Zuydam, Anthony M Vandersteen, Marta Vazquez-Lopez, Julie von Ziegenweidt, Annette Wagner, Quinten Waisfisz, Neil Walker, Suellen M. Walker, James S. Ware, Hugh Watkins, Christopher Watt, Andrew R. Webster, Lucy Wedderburn, Wei Wei, Steven B. Welch, Julie Wessels, Sarah K. Westbury, John-Paul Westwood, Deborah Whitehorn, James Whitworth, Andrew O.M. Wilkie, Catherine Williamson, Brian T. Wilson, Edwin K.S. Wong, Nicholas Wood, Yvette Wood, Christopher Geoffrey Woods, Emma R. Woodward, Austen Worth, Michael Wright, Katherine Yates, Patrick F.K. Yong, Timothy Young, Ping Yu, Patrick Yu-Wai-Man, Eliska Zlamalova, Russel Hirsch, R. James White, Marc Simon, David Badesch, Erika Rosenzweig, Charles Burger, Murali Chakinala, Thenappan Thenappan, Greg Elliott, Robert Simms, Harrison Farber, Robert Frantz, Jean Elwing, Nicholas Hill, Dunbar Ivy, James Klinger, Steven Nathan, Ronald Oudiz, Ivan Robbins, Robert Schilz, Terry Fortin, Jeffrey Wilt, Delphine Yung, Eric Austin, Ferhaan Ahmad, Nitin Bhatt, Tim Lahm, Adaani Frost, Zeenat Safdar, Zia Rehman, Robert Walter, Fernando Torres, Sahil Bakshi, Stephen Archer, Rahul Argula, Christopher Barnett, Raymond Benza, Ankit Desai, Veeranna Maddipati, University of Cambridge [UK] (CAM), Columbia University [New York], University of Sheffield [Sheffield], University of Cincinnati (UC), St George's, University of London, Vrije Universiteit Amsterdam [Amsterdam] (VU), Golden Jubilee National Hospital, Glasgow, Royal Free Hospital [London, UK], Heidelberg University Hospital [Heidelberg], Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Technische Hochschule Mittelhessen - University of Applied Sciences [Giessen] (THM), Fondazione IRCCS Policlinico San Matteo, Hypertension pulmonaire : physiopathologie et innovation thérapeutique (HPPIT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Universität Heidelberg [Heidelberg], Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Imperial College London, Royal Hallamshire Hospital, University of Graz, Freeman Hospital, Royal United Hospitals Bath (RUH), Great Ormond Street Hospital for Children [London] (GOSH), Royal Papworth Hospital, Cambridge Biomedical Campus, Cambridge, United Kingdom., King‘s College London, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Karl-Franzens-Universität [Graz, Autriche], Pulmonary medicine, ACS - Pulmonary hypertension & thrombosis, Swietlik, Emilia [0000-0002-4095-8489], Megy, Karyn [0000-0002-2826-3879], Tilly, Tobias [0000-0002-6762-5342], Stephens, Jonathan [0000-0003-2020-9330], Toshner, Mark [0000-0002-3969-6143], Morrell, Nicholas [0000-0001-5700-9792], Graf, Stefan [0000-0002-1315-8873], Apollo - University of Cambridge Repository, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Karl-Franzens-Universität Graz, HAL-SU, Gestionnaire, British Heart Foundation, and The Academy of Medical Sciences
Subjects: 0301 basic medicine, Candidate gene, Cardiac & Cardiovascular Systems, genetic association studies, 030204 cardiovascular system & hematology, Biology, Bayesian inference, 03 medical and health sciences, 0302 clinical medicine, Missing heritability problem, pulmonary hypertension, medicine, Family history, Gene, Genetics & Heredity, Genetics, family history, Science & Technology, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Kinase insert domain receptor, computed tomography, General Medicine, Original Articles, medicine.disease, Pulmonary hypertension, Phenotype, 3. Good health, 030104 developmental biology, Cardiovascular System & Cardiology, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Life Sciences & Biomedicine, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, vascular endothelial growth factor receptor
Abstract: Supplemental Digital Content is available in the text., Background: Approximately 25% of patients with pulmonary arterial hypertension (PAH) have been found to harbor rare mutations in disease-causing genes. To identify missing heritability in PAH, we integrated deep phenotyping with whole-genome sequencing data using Bayesian statistics. Methods: We analyzed 13 037 participants enrolled in the NBR study (NIHR BioResource—Rare Diseases), of which 1148 were recruited to the PAH domain. To test for genetic associations between genes and selected phenotypes of pulmonary hypertension, we used the Bayesian rare variant association method BeviMed. Results: Heterozygous, high impact, likely loss-of-function variants in the kinase insert domain receptor (KDR) gene were strongly associated with significantly reduced transfer coefficient for carbon monoxide (posterior probability=0.989) and older age at diagnosis (posterior probability=0.912). We also provide evidence for familial segregation of a rare nonsense KDR variant with these phenotypes. On computed tomographic imaging of the lungs, a range of parenchymal abnormalities were observed in the 5 patients harboring these predicted deleterious variants in KDR. Four additional PAH cases with rare likely loss-of-function variants in KDR were independently identified in the US PAH Biobank cohort with similar phenotypic characteristics. Conclusions: The Bayesian inference approach allowed us to independently validate KDR, which encodes for the VEGFR2 (vascular endothelial growth factor receptor 2), as a novel PAH candidate gene. Furthermore, this approach specifically associated high impact likely loss-of-function variants in the genetically constrained gene with distinct phenotypes. These findings provide evidence for KDR being a clinically actionable PAH gene and further support the central role of the vascular endothelium in the pathobiology of PAH.
Published: 2020
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9. Medical management with interventional therapy versus medical management alone for unruptured brain arteriovenous malformations (ARUBA):final follow-up of a multicentre, non-blinded, randomised controlled trial

Author: Alessandra Biondi, Jessica Overbey, Michael K. Parides, Kirsty Harkness, Rustam Al-Shahi Salman, Richard B. Libman, Andreas Hartmann, H. Bart van der Worp, Rüdiger von Kummer, Charlotte Cordonnier, Ellen Moquete, Emmanuel Houdart, Christian Stapf, Helen Kim, Marco Antonio Stefani, Jay P. Mohr, Catharina J.M. Klijn, John Pile-Spellman, and Alan J. Moskowitz
Subjects: Adult, Intracranial Arteriovenous Malformations, Male, medicine.medical_specialty, Pediatrics, Radiosurgery, Stroke/epidemiology, Neurosurgical Procedures, law.invention, Intracranial Arteriovenous Malformations/drug therapy, 03 medical and health sciences, Embolization, 0302 clinical medicine, All institutes and research themes of the Radboud University Medical Center, Randomized controlled trial, law, medicine, Humans, Neurosurgical Procedures/methods, 030212 general & internal medicine, Radiosurgery/methods, Adverse effect, Stroke, Intention-to-treat analysis, business.industry, Incidence (epidemiology), Hazard ratio, Arteriovenous Fistula/drug therapy, Middle Aged, medicine.disease, Interim analysis, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], Embolization, Therapeutic, Treatment Outcome, Arteriovenous Fistula, Female, Neurology (clinical), Neurosurgery, Embolization, Therapeutic/methods, business, Therapeutic/methods, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: BackgroundIn A Randomized trial of Unruptured Brain Arteriovenous malformations (ARUBA), randomisation was halted at a mean follow-up of 33·3 months after a prespecified interim analysis showed that medical management alone was superior to the combination of medical management and interventional therapy in preventing symptomatic stroke or death. We aimed to study whether these differences persisted through 5-years' follow-up.MethodsARUBA was a non-blinded, randomised trial done at 39 clinical centres in nine countries. Adults (age ≥18 years) diagnosed with an unruptured brain arteriovenous malformation, who had never undergone interventional therapy, and were considered by participating clinical centres to be suitable for intervention to eradicate the lesion, were eligible for inclusion. Patients were randomly assigned (1:1) by a web-based data collection system, stratified by clinical centre in a random permuted block design with block sizes of two, four, and six, to medical management alone or with interventional therapy (neurosurgery, embolisation, or stereotactic radiotherapy, alone or in any combination, sequence, or number). Although patients and investigators at a given centre were not masked to treatment assignment, investigators at other centres and those in the clinical coordinating centre were not informed of assignment or outcomes at any of the centres. The primary outcome was time to death or symptomatic stroke confirmed by imaging, assessed by a neurologist at each centre not involved in the management of participants' care, and monitored by an independent committee using an adaptive approach with interim analyses. Enrolment began on April 4, 2007, and was halted on April 15, 2013, after which follow-up continued until July 15, 2015. All analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, NCT00389181.FindingsOf 1740 patients screened, 226 were randomly assigned to medical management alone (n=110) or medical management plus interventional therapy (n=116). During a mean follow-up of 50·4 months (SD 22·9), the incidence of death or symptomatic stroke was lower with medical management alone (15 of 110, 3·39 per 100 patient-years) than with medical management with interventional therapy (41 of 116, 12·32 per 100 patient-years; hazard ratio 0·31, 95% CI 0·17 to 0·56). Two patients in the medical management group and four in the interventional therapy group (two attributed to intervention) died during follow-up. Adverse events were observed less often in patients allocated to medical management compared with interventional therapy (283 vs 369; 58·97 vs 78·73 per 100 patient-years; risk difference −19·76, 95% CI −30·33 to −9·19).InterpretationAfter extended follow-up, ARUBA showed that medical management alone remained superior to interventional therapy for the prevention of death or symptomatic stroke in patients with an unruptured brain arteriovenous malformation. The data concerning the disparity in outcomes should affect standard specialist practice and the information presented to patients. The even longer-term risks and differences between the two therapeutic approaches remains uncertain.FundingNational Institute of Neurological Disorders and Stroke for the randomisation phase and Vital Projects Fund for the follow-up phase.
Published: 2020
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10. Cognitive Impairment Before Atrial Fibrillation-Related Ischemic Events:Neuroimaging and Prognostic Associations

Author: Gargi Banerjee, Edgar Chan, Gareth Ambler, Duncan Wilson, Lisa Cipolotti, Clare Shakeshaft, Hannah Cohen, Tarek Yousry, Rustam Al‐Shahi Salman, Gregory Y. H. Lip, Keith W. Muir, Martin M. Brown, Hans Rolf Jäger, David J. Werring, Louise Shaw, Kirsty Harkness, Jane Sword, Azlisham Mohd Nor, Pankaj Sharma, Deborah Kelly, Frances Harrington, Marc Randall, Matthew Smith, Karim Mahawish, Abduelbaset Elmarim, Bernard Esisi, Claire Cullen, Arumug Nallasivam, Christopher Price, Adrian Barry, Christine Roffe, John Coyle, Ahamad Hassan, Caroline Lovelock, Jonathan Birns, David Cohen, L. Sekaran, Adrian Parry‐Jones, Anthea Parry, David Hargroves, Harald Proschel, Prabel Datta, Khaled Darawil, Aravindakshan Manoj, Mathew Burn, Chris Patterson, Elio Giallombardo, Nigel Smyth, Syed Mansoor, Ijaz Anwar, Rachel Marsh, Sissi Ispoglou, Dinesh Chadha, Mathuri Prabhakaran, Sanjeevikumar Meenakishundaram, Janice O'Connell, Jon Scott, Vinodh Krishnamurthy, Prasanna Aghoram, Michael McCormick, Paul O'Mahony, Martin Cooper, Lillian Choy, Peter Wilkinson, Simon Leach, Sarah Caine, Ilse Burger, Gunaratam Gunathilagan, Paul Guyler, Hedley Emsley, Michelle Davis, Dulka Manawadu, Kath Pasco, Maam Mamun, Robert Luder, Mahmud Sajid, James Okwera, Julie Staals, Elizabeth Warburton, Kari Saastamoinen, Timothy England, Janet Putterill, Enrico Flossman, Michael Power, Krishna Dani, David Mangion, Appu Suman, John Corrigan, Enas Lawrence, and Djamil Vahidassr
Subjects: medicine.medical_specialty, Neuroimaging, Neuropsychological Tests, Brain ischemia, Disability Evaluation, Cognition, Leukoencephalopathies, Predictive Value of Tests, Modified Rankin Scale, Internal medicine, Atrial Fibrillation, Prevalence, medicine, Humans, Cognitive Dysfunction, atrial fibrillation, Prospective Studies, Cognitive decline, Vascular dementia, Stroke, Original Research, Ischemic Stroke, cognitive impairment, business.industry, cerebral small vessel disease, Transient Ischemic Attack (TIA), Atrial fibrillation, vascular dementia, Odds ratio, Prognosis, medicine.disease, United Kingdom, Hyperintensity, brain ischemia, Functional Status, Ischemic Attack, Transient, Cerebral Small Vessel Diseases, Cardiology, Cardiology and Cardiovascular Medicine, business
Abstract: Background It is likely that a proportion of poststroke cognitive impairment is sometimes attributable to unidentified prestroke decline; prestroke cognitive function is also clinically relevant because it is associated with poor functional outcomes, including death. We investigated the radiological and prognostic associations of preexisting cognitive impairment in patients with ischemic stroke or transient ischemic attack associated with atrial fibrillation. Methods and Results We included 1102 patients from the prospective multicenter observational CROMIS ‐2 (Clinical Relevance of Microbleeds in Stroke 2) atrial fibrillation study. Preexisting cognitive impairment was identified using the 16‐item Informant Questionnaire for Cognitive Decline in the Elderly. Functional outcome was measured using the modified Rankin scale. Preexisting cognitive impairment was common (n=271; 24.6%). The presence of lacunes (odds ratio [OR], 1.50; 95% CI , 1.03–1.05; P =0.034), increasing periventricular white matter hyperintensity grade (per grade increase, OR , 1.38; 95% CI , 1.17–1.63; P OR , 1.26; 95% CI , 1.05–1.51; P =0.011), and medial temporal atrophy grade (per grade increase, OR , 1.61; 95% CI , 1.34–1.95; P mRS >2; adjusted OR , 2.43; 95% CI , 1.42–4.20; P =0.001). Conclusions Preexisting cognitive impairment in patients with atrial fibrillation–associated ischemic stroke or transient ischemic attack is common, and associated with imaging markers of cerebral small vessel disease and neurodegeneration, as well as with longer‐term functional outcome. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 02513316.
Published: 2020
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11. Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Author: Rustam Al-Shahi Salman, David P Minks, Dipayan Mitra, Mark A Rodrigues, Priya Bhatnagar, Johann C du Plessis, Yogish Joshi, Martin S Dennis, Gordon D Murray, David E Newby, Peter A G Sandercock, Nikola Sprigg, Jacqueline Stephen, Cathie L M Sudlow, David J Werring, William N Whiteley, Joanna M Wardlaw, Philip M White, Colin Baigent, Daniel Lasserson, Frank Sullivan, Johanna Carrie, Javier Rojas, Shannon Amoils, John Bamford, Jane Armitage, Gabriel Rinkel, Gordon Lowe, Jonathan Emberson, Karen Innes, Lynn Dinsmore, Jonathan Drever, Carol Williams, David Perry, Connor McGill, David Buchanan, Allan Walker, Aidan Hutchison, Christopher Matthews, Ruth Fraser, Aileen McGrath, Ann Deary, Rosemary Anderson, Pauli Walker, Christian Hansen, Richard Parker, Aryelly Rodriguez, Malcolm Macleod, Thomas Gattringer, Jeb Palmer, Eleni Sakka, Jennifer Adil-Smith, David Minks, Johannes du Plessis, Christine Lerpiniere, Richard O'Brien, Seona Burgess, Gillian Mead, Ruth Paulton, Fergus Doubal, Katrina McCormick, Neil Hunter, Pat Taylor, Ruwan Parakramawansha, Jack Perry, Gordon Blair, Allan MacRaild, Adrian Parry-Jones, Mary Johnes, Stephanie Lee, Kelly Marie Shaw, Ilse Burger, Martin Punter, Andrea Ingham, Jane Perez, Zin Naing, Jordi Morell, Tracy Marsden, Andrea Hall, Sally Marshall, Louise Harrison, Rowilson Jarapa, Edith Wood, Victoria O'Loughlin, David Cohen, Silvie Davies, Kelechi Njoku, Mushiya Mpelembue, Laura Burgess, Radim Licenik, Mmua Ngwako, Nabeela Nisar, Rangah Niranchanan, Tatjana Roganova, Rajaram Bathula, Joseph Devine, Anette David, Anne Oshodi, Fenglin Guo, Emmanuelle Owoyele, Varthi Sukdeo, Robert Ballantine, Mudhar Abbdul-saheb, Angela Chamberlain, Aberami Chandrakumar, Philip Poku, Kirsty Harkness, Catrin Blank, Emma Richards, Ali Ali, Faith Kibutu, Olesia Balitska, Kathryn Birchall, Pauline Bayliss, Clare Doyle, Kathy Stocks, Arshad Majis, Jo Howe, Christine Kamara, Luke Barron, Ahmad Maatouk, Ralf Lindert, Katy Dakin, Jessica Redgrave, Biju Bhaskaran, Isam Salih, Debs Kelly, Susan Szabo, Dawn Tomlin, Helen Bearne, Jean Buxton, Pauline Fitzell, Georgina Ayres, Afaq Saulat, Kathleen Horan, Joanne Garfield-Smith, Harbens Bhakri, Paul Guyler, Devesh Sinha, Thayalini Loganathan, Amber Siddiqui, Anwer Siddiqui, Lucy Coward, Swapna Kunhunny, Sharon Tysoe, Rajalakshmi Orath Prabakaran, Shyam Kelavkar, Sindhu Rashmi, David Ngo, Kheng Xiong Ng, Nisha Menon, Sweni Shah, Mark Barber, Derek Esson, Fiona Brodie, Talat Anjum, Mushtaq Wani, Manju Krishnan, Leanne Quinn, Jayne Spencer, Terry Jones, Helen Thompson-Jones, Lynne Dacey, Srikanth Chenna, Sharon Storton, Sarah Thomas, Teresa Beaty, Shelley Treadwell, Caroline Davies, Susan Tucker, Lynda Connor, Peter Slade, Glyn Gainard, Girish Muddegowda, Ranjan Sanyal, Alda Remegoso, Nenette Abano, Chelsea Causley, Racquel Carpio, Stephanie Stevens, Adrian Butler, Resti Varquez, Hayley Denic, Francis Alipio, Andrew Moores, Adrian Barry, Holly Maguire, Jeanette Grocott, Kay Finney, Sue Lyjko, Christine Roffe, Joanne Hiden, Phillip Ferdinand, Vera Cvoro, Khalil Ullah, Nicola Chapman, Mandy Couser, Susan Pound, Sean Mcauley, Senthil Raghunathan, Faye Shelton, Amanda Hedstrom, Margi Godfrey, Diane Havard, Amanda Buck, Kailash Krishnan, Nicola Gilzeane, Jack Roffe, Judith Clarke, Katherine Whittamore, Saima Sheikh, Rekha Keshvara, Carla Jordan, Benjamin Jackson, Gwendoline Wilkes, Jason Appleton, Zhe Law, Oliver Matias, Evangelos Vasileiadis, Cathy Mason, Anthea Parry, Geraldine Landers, Melinda Holden, Basaam Aweid, Khalid Rashed, Linda Balian, Carinna Vickers, Elizabeth Keeling, Sarah Board, Joanna Allison, Clare Buckley, Barbara Williams-Yesson, Joanne Board, Tressy Pitt-Kerby, Alfonso Tanate, Diane Wood, Manohar Kini, Dinesh Chadha, Deborah Walstow, Rosanna Fong, Robert Luder, Tolu Adesina, Jill Gallagher, Hayley Bridger, Elodie Murali, Maneesh Bhargava, Chloe van Someren, Frances Harrington, Abhijit Mate, Ali James, Gillian Courtauld, Christine Schofield, Katja Adie, Linda Lucas, Kirsty Bond, Bev Maund, Sam Ellis, Paul Mudd, Martin James, Samantha Keenan, Angela Bowring, Julie Cageao, Hayley Kingwell, Caroline Roughan, Anthony Hemsley, Jane Sword, David Strain, Keniesha Miller, Anita Goff, Karin Gupwell, Kevin Thorpe, Hedley Emsley, Shuja Punekar, Alison McLoughlin, Sulaiman Sultan, Bindu Gregory, Sonia Raj, Donna Doyle, Keith Muir, Wilma Smith, Angela Welch, Fiona Moreton, Bharath Kumar Cheripelli, Salwa El Tawil, Dheeraj Kalladka, Xuya Huang, Nicola Day, Sankaranarayanan Ramachandran, Caroline Crosbie, Jennifer Elliot, Tony Rudd, Katherine Marks, Ajay Bhalla, Jonathan Birns, Sagal Kullane, Nic Weir, Christopher Allen, Vanessa Pressly, Pam Crawford, Emma Battersby-Wood, Alex Blades, Shuna Egerton, Ashleigh Walters, Sue Evans, James Richard Marigold, Fiona Smith, Gabriella Howard, Imogen Gartrell, Simon Smith, Robyn Creeden, Chloe Cox, Cherish Boxall, Jonathan Hewitt, Claire Nott, Procter Sarah, Jessica Whiteman, Steve Buckle, Rebecca Wallace, Rina Mardania, Jane Gray, Claire Triscott, Anand Nair, Jill Greig, Pratap Rana, Matthew Robinson, Mohammad Irfan Alam, David Werring, Duncan Wilson, Caroline Watchurst, Maria Brezitski, Luci Crook, Ifan Jones, Azra Banaras, Krishna Patel, Renuka Erande, Caroline Hogan, Isabel Hostettler, Amy Ashton, Shez Feerick, Nina Francia, Nnebuife Oji, Emma Elliott, Talal Al-Mayhani, Martin Dennis, Cathie Sudlow, William Whiteley, Dipankar Dutta, Pauline Brown, Deborah Ward, Fiona Davis, Jennifer Turfrey, Chloe Hughes, Kayleigh Collins, Rehana Bakawala, Susan O'Connell, Jon Glass, David Broughton, Dinesh Tryambake, Lynn Dixon, Kath Chapman, Andrew Young, Adrian Bergin, Andrew Sigsworth, Aravind Manoj, Glyn Fletcher, Paula Lopez, Penelope Cox, Mark Wilkinson, Paul Fitzsimmons, Nikhil Sharma, James Choulerton, Denise Button, Lindsey Dow, Lukuman Gbadamoshi, Joanne Avis, Barbara Madigan, Stephanie McCann, Louise Shaw, Deborah Howcroft, Suzanne Lucas, Andrew Stone, Gillian Cluckie, Caroline Lovelock, Brian Clarke, Neha Chopra, Natasha Clarke, Bhavini Patel, Kate Kennedy, Rebecca Williams, Adrian Blight, Joanna O'Reilly, Chukwuka Orefo, Nilofer Dayal, Rita Ghatala, Temi Adedoyin, Fran Watson, Sarah Trippier, Lillian Choy, Barry Moynihan, Usman Khan, Val Jones, Naomi Jeyaraj, Lourda Kerin, Kamy Thavanesan, Divya Tiwari, Chantel Cox, Anja Ljubez, Laura Tucker, Arshi Iqbal, Caroline Bagnall, Marketa Keltos, Josh Roberts, Becky Jupp, Catherine Ovington, Emily Rogers, Owen David, Jo Bell, Barbara Longland, Gail Hann, Martin Cooper, Mohammad Nasar, Anoja Rajapakse, Inez Wynter, Ijaz Anwar, Helen Skinner, Tarn Nozedar, Damian McArdle, Balakrishna Kumar, Susan Crawford, Arunkumar Annamalai, Alex Ramshaw, Clare Holmes, Sarah Caine, Mairead Osborn, Emily Dodd, Peter Murphy, Nicola Devitt, Pauline Baker, Amy Steele, Lucy Belle Guthrie, Samantha Clarke, Ahamad Hassan, Dean Waugh, Emelda Veraque, Linetty Makawa, Mary Kambafwile, Marc Randall, Vasileios Papavasileiou, Claire Cullen, Jenny Peters, Hlaing Thant, Tanya Ingram, Mellor Zoe, Ramesh Durairaj, Melanie Harrison, Sarah Stevenson, Daniela Shackcloth, Jordan Ewing, Victoria Sutton, Mark McCarron, Jacqueline McKee, Mandy Doherty, Ferghal McVerry, Caroline Blair, Mary MacLeod, Janice Irvine, Heather Gow, Jacqueline Furnace, Anu Joyson, Baljit Jagpal, Sarah Ross, Katrina Klaasen, Sandra Nelson, Rebecca Clarke, Nichola Crouch, Beverly MacLennan, Vicky Taylor, Daniel Epstein, Avani Shukla, Vinodh Krishnamurthy, Paul Nicholas, Sammie Qureshi, Adam Webber, Justin Penge, Hawraman Ramadan, Stuart Maguire, Chris Patterson, Ruth Bellfield, Brigid Hairsine, Kelvin Stewart, Michaela Hooley, Outi Quinn, Bella Richard, Sally Moseley, Mandy Edwards, Heidi Lawson, Michelle Tayler, Yogish Pai, Mahesh Dhakal, Bernard Esisi, Sofia Dima, Gemma Marie Smith, Mark Garside, Muhammad Naeem, Vidya Baliga, Gill Rogers, Ellen Brown, David Bruce, Rachel Hayman, Susan Clayton, Ed Gamble, Rebecca Grue, Bethan Charles, Adam Hague, Sujata Blane, Caroline Lambert, Afnan Chaudhry, Thomas Harrison, Kari Saastamoinen, Dionne Hove, Laura Howaniec, Gemma Grimwood, Ozlem Redjep, Fiona Humphries, Lucia Argandona, Larissa Cuenoud, Esther Erumere, Sageet Amlani, Grace Auld, Afraim Salek-Haddadi, Ursula Schulz, James Kennedy, Gary Ford, Philip Mathieson, Ian Reckless, Rachel Teal, Giulia Lenti, George Harston, Eoin O'Brien, Joanne Mcgee, Jennifer Mitchell, Elaine Amis, Dominic Handley, Siobhan Kelly, George Zachariah, Jobbin Francis, Sarah Crisp, Juliana Sesay, Sarah Finlay, Helen Hayhoe, Niamh Hannon, Tom Hughes, Bethan Morse, Henry De Berker, Emma Tallantyre, Ahmed Osman, Susan White, Stefan Schwarz, Benjamin Jelley, Rajendra Yadava, Khalid Azhar, Julie Reddan, Mirriam Sangombe, Samantha Stafford, Ken Fotherby, Debbie Morgan, Farrukh Baig, Karla Jennings-Preece, Donna Butler, Nasar Ahmad, Angela Willberry, Angela Stevens, Baljinder Rai, Prasad Siddegowda, Peter Howard, Lisa Hyatt, Tracey Dobson, David Jarrett, Suheil Ponnambath, Jane Tandy, Yasmin Harrington-Davies, Rebecca Butler, Claire James, Stacey Valentine, Anne Suttling, Peter Langhorne, Gillian Kerr, Fiona Wright, Ruth Graham, Christine McAlpine, Mohammad Shahzad Iqbal, Louise Humphreys, Kath Pasco, Olga Balazikova, Ashraf Nasim, Cassilda Peixoto, Louise Gallagher, Shahrzad Shahmehri, Sandip Ghosh, Elizabeth Barrie, Danielle Gilmour, Margo Henry, Tom Webb, Linda Cowie, Hannah Rudenko, Shanni McDonald, Natasha Schumacher, Susannah Walker, Tracey Cosier, Anna Verrion, Eva Beranova, Audrey Thomson, Marius Venter, Arindam Kar, Sheila Mashate, Kirsten Harvey, Léjeune Gardener, Vinh Nguyen, Omid Halse, Olivia Geraghty, Beth Hazel, Peter Wilding, Victoria Tilley, Tim Cassidy, Beverley McClelland, Maria Bokhari, Timothy England, Mohana Maddula, Richard Donnelly, Paul Findlay, Ashish Macaden, Ian Shread, Charlotte Barr, Azlisham Mohd Nor, Claire Brown, Nicola Persad, Charlotte Eglinton, Marie Weinling, Benjamin Hyams, Alex Shah, John Baker, Anthony Byrne, Caroline McGhee, Amanda Smart, Claire Copeland, Michael Carpenter, Marion Walker, Richard Davey, Ann Needle, Razik Fathima, Gavin Bateman, Prabal Datta, Andrew Stanners, Linda Jackson, Julie Ball, Michelle Davis, Natalie Atkinson, Michelle Fawcett, Teresa Thompson, Helen Guy, Valerie Hogg, Carole Hays, Stephen Woodward, Mohammad Haque, Eluzai Hakim, Stuart Symonds, Mehran Maanoosi, Jane Herman, Toby Black, Skelton Miriam, Caroline Clarke, Alpha Anthony, Michele Tribbeck, Julie Cronin, Denise Mead, Ruth Fennelly, James McIlmoyle, Christina Dickinson, Carol Jeffs, Sajjad Anwar, Joanne Howard, Kirsty Jones, Saikat Dhar, Caroline Clay, Muhammad Siddiq, Simone Ivatts, Yolanda Baird, Moore Sally, Isobel Amey, Sophie Newton, Lisa Clayton-Evans, Indra Chadbourn, Rayessa Rayessa, Charde Naylor, Alicia Rodgers, Lisa Wilson, Sarah Wilson, Emma Clarkson, Ruth Davies, Paula Owings, Graeme Sangster, Valerie Gott, Victoria Little, Pauline Weir, Suja Cherian, Deepa Jose, Helen Moroney, Susan Downham, Angela Dodd, Venetia Vettimootal Johnson, Laura Codd, Naomi Robinson, Ashraf Ahmed, Mo Albazzaz, Sharon Johnson, Carol Denniss, Mishell Cunningham, Tajammal Zahoor, Timothy Webster, Sandra Leason, Syed Haider, Kausic Chatterjee, Arumugam Nallasivan, Charlotte Perkins, Samantha Seagrave, Colin Jenkins, Fiona Price, Claire Hughes, Lily Mercer, Malik Hussain, Sarah Brown, Miriam Harvey, Jane Homan, Mohammad Khan, Robert Whiting, Leanne Foote, Nicholas Hunt, Helen Durman, Lucy Brotherton, Jayne Foot, Corinne Pawley, Eliza Foster, Alison Whitcher, Kneale Metcalf, Jenny Jagger, Susan McDonald, Kelly Waterfield, Patrick Sutton, Naval Shinh, Ajmal Anversha, Garth Ravenhill, Richard Greenwood, Janak Saada, Alison Wiltshire, Rebekah Perfitt, Sreeman Andole, Naveen Gadapa, Karen Dunne, Magdalini Krommyda, Evelyne Burssens, Sam King, Catherine Plewa, Nigel Smyth, Jenny Wilson, Elio Giallombardo, Lucy Sykes, Pradeep Kumar, James Barker, Isabel Huggett, Linda Dunn, Charlotte Culmsee, Philip Thomas, Min Myint, Helen Brew, Nikhil Majmudar, Janice OConnell, George Bunea, Charlotte Fox, Diane Gulliver, Andrew Smith, Betty Mokoena, Naweed Sattar, Ramesh Krishnamurthy, Emily Osborne, David Wilson, Belinda Wroath, Kevin Dynan, Michael Power, Susan Thompson, Victoria Adell, Enoch Orugun, Una Poultney, Rachel Glover, Hannah Crowther, Sarah Thornthwaite, Ivan Wiggam, Aine Wallace, Enda Kerr, Ailsa Fulton, Annemarie Hunter, Suzanne Tauro, Sarah Cuddy, David Mangion, Anne Hardwick, Skarlet Markova, Tara Lawrence, Carmen Constantin, Jo Fletcher, Isobel Thomas, Kerry Pettitt, Lakshmanan Sekaran, Margaret Tate, Kiranjit Bharaj, Rohan Simon, Frances Justin, Sakthivel Sethuraman, Duke Phiri, Niaz Mohammed, Meena Chauhan, Khaled Elfandi, Uzma Khan, David Eveson, Amit Mistri, Lisa Manning, Shagufta Khan, Champa Patel, Mohammed Moqsith, Saira Sattar, Man Yee Lam, Kashif Musarrat, Claire Stephens, Latheef Kalathil, Richard Miller, Maqsud Salehin, Nikki Gautam, Duncan Bailey, Kelly Amor, Julie Meir, Anne Nicolson, Javed Imam, Lisa Wood, Julie White, Mahmud Sajid, George Ghaly, Margaret Ball, Rachel Gascoyne, Harald Proeschel, Simon Sharpe, Sarah Horton, Emily Beaves, Stephanie Jones, Brigitte Yip, Murdina Bell, Linda MacLiver, Brian MacInnes, Don Sims, Jennifer Hurley, Mark Willmot, Claire Sutton, Edward Littleton, Susan Maiden, Rachael Jones, James Cunningham, Carole Green, Michelle Bates, Raj Shekhar, Ellie Gilham, Iman Ahmed, Rachel Crown, Tracy Fuller, Neetish Goorah, Angela Bell, Christine Kelly, Arun Singh, Jamie Walford, Benjamin Tomlinson, Farzana Patel, Stephen Duberley, Ingrid Kane, Chakravarthi Rajkumar, Jane Gaylard, Joanna Breeds, Nicola Gainsborough, Alexandra Pitt-Ford, Emma Barbon, Laura Latter, Philip Thompson, Simon Hervey, Shrivakumar Krishnamoorthy, Joseph Vassallo, Deborah Walter, Helen Cochrane, Meena Srinivasan, Robert Campbell, Denise Donaldson, Nichola Motherwell, Frances Hurford, Indranil Mukherjee, Antony Kenton, Sheila Nyabadza, Irene Martin, Benjamin Hunt, Hardi Hassan, Sarah O'Toole, Bander Dallol, Janet Putterill, Ratneshwari Jha, Rachel Gallifent, Puneet Kakar, Aparna Pusalkar, kelly Chan, Puneet Dangri, Hannah Beadle, Angela Cook, Karen Crabtree, Santhosh Subramonian, Peter Owusu-Agyei, Natalie Temple, Nicola Butterworth-Cowin, Suzanne Ragab, Kerstin Knops, Emma Jinks, Christine Dickson, Laura Gleave, Judith Dube, Jacqui Leggett, Tatiana Garcia, Sissy Ispoglou, Rachel Evans, Sandeep Ankolekar, Anne Hayes, Hlaing Ni, Bithi Rahman, Josette Milligan, Carol Graham, Josin Jose, Breffni Keegan, Jim Kelly, Richard Dewar, James White, Kelly Thomas, Rajkumar, C, University of St Andrews. School of Medicine, University of St Andrews. Sir James Mackenzie Institute for Early Diagnosis, University of St Andrews. Population and Behavioural Science Division, University of St Andrews. Pure Mathematics, University of St Andrews. School of Psychology and Neuroscience, and University of St Andrews. School of Biology
Subjects: Male, MICROBLEEDS, 030204 cardiovascular system & hematology, AMYLOID ANGIOPATHY, Brain Ischemia, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Secondary Prevention, ACUTE ISCHEMIC-STROKE, Aged, 80 and over, Aspirin, Manchester Cancer Research Centre, medicine.diagnostic_test, Hazard ratio, Brain, Magnetic Resonance Imaging, Superficial siderosis, Cerebral Small Vessel Diseases, Stroke, Treatment Outcome, Female, medicine.drug, CT, medicine.medical_specialty, ANTITHROMBOTIC THERAPY, Clinical Neurology, Neuroimaging, Subgroup analysis, 03 medical and health sciences, Internal medicine, medicine, Journal Article, Humans, Aged, Cerebral Hemorrhage, business.industry, ResearchInstitutes_Networks_Beacons/mcrc, DAS, Magnetic resonance imaging, medicine.disease, SIGNS, ASPIRIN, Neurology (clinical), Tomography, X-Ray Computed, business, SUPERFICIAL SIDEROSIS, Platelet Aggregation Inhibitors, 030217 neurology & neurosurgery
Abstract: Background: Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy.Methods: RESTART was a prospective, randomised, open-label, blinded-endpoint, parallel-group trial at 122 hospitals in the UK that assessed whether starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. For this prespecified subgroup analysis, consultant neuroradiologists masked to treatment allocation reviewed brain CT or MRI scans performed before randomisation to confirm participant eligibility and rate features of the intracerebral haemorrhage and surrounding brain. We followed participants for primary (recurrent symptomatic intracerebral haemorrhage) and secondary (ischaemic stroke) outcomes for up to 5 years (reported elsewhere). For this report, we analysed eligible participants with intracerebral haemorrhage according to their treatment allocation in primary subgroup analyses of cerebral microbleeds on MRI and in exploratory subgroup analyses of other features on CT or MRI. The trial is registered with the ISRCTN registry, number ISRCTN71907627.Findings: Between May 22, 2013, and May 31, 2018, 537 participants were enrolled, of whom 525 (98%) had intracerebral haemorrhage: 507 (97%) were diagnosed on CT (252 assigned to start antiplatelet therapy and 255 assigned to avoid antiplatelet therapy, of whom one withdrew and was not analysed) and 254 (48%) underwent the required brain MRI protocol (122 in the start antiplatelet therapy group and 132 in the avoid antiplatelet therapy group). There were no clinically or statistically significant hazards of antiplatelet therapy on recurrent intracerebral haemorrhage in primary subgroup analyses of cerebral microbleed presence (2 or more) versus absence (0 or 1) (adjusted hazard ratio [HR] 0·30 [95% CI 0·08–1·13] vs 0·77 [0·13–4·61]; pinteraction=0·41), cerebral microbleed number 0–1 versus 2–4 versus 5 or more (HR 0·77 [0·13–4·62] vs 0·32 [0·03–3·66] vs 0·33 [0·07–1·60]; pinteraction=0·75), or cerebral microbleed strictly lobar versus other location (HR 0·52 [0·004–6·79] vs 0·37 [0·09–1·28]; pinteraction=0·85). There was no evidence of heterogeneity in the effects of antiplatelet therapy in any exploratory subgroup analyses (all pinteraction>0·05).Interpretation: Our findings exclude all but a very modest harmful effect of antiplatelet therapy on recurrent intracerebral haemorrhage in the presence of cerebral microbleeds. Further randomised trials are needed to replicate these findings and investigate them with greater precision.Funding: British Heart Foundation.
Published: 2019
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12. Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies

Author: Christopher Price, P. J. A. M. Brouwers, Vincent Thijs, Sze Ho Ma, Mark Schembri, Raymond T.F. Cheung, Christopher Karayiannis, Werner H. Mess, Robert Simister, Peter Wilkinson, Jayesh Modi Medanta, Janice E. O’Connell, Karen Ma, Martin Dennis, Sean C. Murphy, John Ly, Velandai Srikanth, Hing Lung Ip, Mathew Burn, Saima Hilal, Ijaz Anwar, Richard Shek-kwan Chang, Christopher Chen, Carmen Barbato, Hatice Ozkan, Achim Gass, Louise Shaw, Hen Hallevi, Aravindakshan Manoj, Julie Staals, Frances Harrington, Henry Houlden, Hideo Hara, Kam Tat Leung, Christopher Traenka, Jeroen Hendrikse, Keon-Joo Lee, Elio Giallombardo, Ender Uysal, Edmund Ka Ming Wong, Joost Jöbsis, Gargi Banerjee, Dulka Manawadu, Rebeca Marín, John S. Thornton, Nick S. Ward, Vinodh Krishnamurthy, Thomas W. Leung, Ji Hoe Heo, Philippe Maeder, Masatoshi Koga, Michael Power, Marc Randall, Amos D. Korczyn, Narayanaswamy Venketasubramanian, Derya Selcuk Demirelli, Richard Li, Prabel Datta, Christine Guevarra, YK Wong, Ysoline Beigneux, Cisca Linn, Solveig Horstmann, Henk Verbiest, Kirsty Harkness, Eric Vicaut, John Coyle, Shoichiro Sato, Anne Marie Mendyk, Chathuri Yatawara, Alexandros A Polymeris, Lisa Hert, Joan Martí-Fàbregas, Felix Fluri, Cathy Soufan, Djamil Vahidassr, Lakshmanan Sekaran, Chu Peng Hoi, Maarten van Gemert, Andreas Charidimou, Robert Luder, Lillian Choy, Jaap van der Sande, Hannah Cohen, Jae-Sung Lim, Maam Mamun, Vincent I.H. Kwa, Kyohei Fujita, Joseph Kwan, Syuhei Ikeda, John Mitchell, Paul Berntsen, Michael J. Thrippleton, Shelagh B. Coutts, Simone Browning, Paul Guyler, Heinrich Mattle, Elles Douven, Jonathan Birns, M. Eline Kooi, Jan Stam, Hedley C. A. Emsley, David Mangion, David Calvet, Min Lou, Yannie Soo, Santiago Medrano-Martorell, Michael G. Hennerici, Chris Moran, Thomas Gattringer, Bernard Esisi, Kazuhisa Yoshifuji, Hakan Ay, Rustam Al-Shahi Salman, Joanna M. Wardlaw, Derek Hayden, Richard J. Perry, Gunaratam Gunathilagan, Hans Rolf Jäger, Frank-Erik de Leeuw, Luis Prats-Sánchez, Pankaj Sharma, Mi Hwa Yang, Marie Yvonne Douste-Blazy, Enas Lawrence, Nils Peters, Elisa Merino, KC Teo, Ethem Murat Arsava, Luc Bracoub, Dinesh Chadha, Linxin Li, Nikola Sprigg, Adrian R Parry-Jones, Pascal P. Gratz, Siu Hung Li, Stephen Makin, Arumug Nallasivam, Jane Sword, Mauro S.B. Silva, Ping Wing Ng, Layan Akijian, Krishna A Dani, Sebastian Thilemann, Marie Dominique Fratacci, Gareth Ambler, Nagaendran Kandiah, Lee-Anne Slater, Ilse Burger, Kath Pasco, Paul J. Nederkoorn, Suk Fung Tsang, Tae Jin Song, Henry Ma, Kaori Miwa, Keith W. Muir, Susana Muñoz-Maniega, Jihoon Kang, Nicolas Christ, Beom Joon Kim, Noortje A.M. Maaijwee, Kwok Kui Wong, Jon Scott, Leonidas Panos, Oi Ling Chan, Shigeru Inamura, Prasanna Aghoram, David Hargroves, Lino Ramos, Ying Zhou, Chung Yan Chan, Masayuki Shiozawa, Eleni Sakka, Michelle Davis, Matthew Smith, Leo H. Bonati, Dilek Necioglu Orken, Toshihiro Ide, Jaap Kappelle, Ale Algra, Charlotte Zerna, Laurence Legrand, Eric Jouvent, Roland Veltkamp, Simon Jung, Zeynep Tanriverdi, Shahoo Singhal, Sarah Caine, Natan M. Bornstein, Régis Bordet, Anil M. Tuladhar, Maarten Schrooten, John F. Corrigan, Alexander P. Leff, Kazunori Toyoda, Mathuri Prabhakaran, Kim Wiegertjes, Eunbin Ko, Wouter Schoonewille, Sebastian Köhler, Yvo B.W.E.M. Roos, Wing Chi Fong, Jun Tanaka, Abduelbaset Elmarim, Syed Mansoor, Peter J. Koudstaal, Kari Saastamoinen, Eric E. Smith, Paul O'Mahony, Hugues Chabriat, Duncan Wilson, Appu Suman, Dianne H.K. van Dam-Nolen, Parashkev Nachev, Ahamad Hassan, Maria del C. Valdés Hernández, Clare Shakeshaft, Stefan T. Engelter, James Okwera, Aad van der Lugt, Els De Schryver, Stef Bakker, Azlisham Mohd Nor, Yusuke Yakushiji, Robert J. van Oostenbrugge, Claire Cullen, Man Yu Tse, Sebastian Eppinger, Gregory Y.H. Lip, Kotaro Iida, Efrat Kliper, Bibek Gyanwali, Elizabeth A. Warburton, Hee-Joon Bae, Thanh G. Phan, Tarek A. Yousry, Henrik Gensicke, Christine Delmaire, Jean-Louis Mas, Jill Abrigo, Fiona Carty, Jan C. Purrucker, Masashi Nishihara, Leopold Hertzberger, Joachim Fladt, Einor Ben Assayag, Simon Leach, Winnie C.W. Chu, Edward S. Hui, Bonnie Y.K. Lam, Moon Ku Han, Francesca M Chappell, David Williams, Robin Lemmens, Philippe Lyrer, Hiroyuki Irie, Raquel Delgado-Mederos, Ronil V. Chandra, Nigel Smyth, Henry K.F. Mak, Young Dae Kim, Ryan Hoi Kit Cheung, Beatriz Gómez-Ansón, Fidel Nuñez, Anna K. Heye, Adrian Barry, Janet Putterill, Mark White, Alejandro Martínez-Domeño, Vincent Mok, Rachel Marsh, Mahmud Sajid, Timothy J. England, SL Ho, Christopher Patterson, Daniel Guisado-Alonso, Peter J. Kelly, Lawrence K.S. Wong, Anthea Parry, Enrico Flossman, Chao Xu, Marwan El-Koussy, Karim Mahawish, Sissi Ispoglou, Franz Fazekas, Toshio Imaizumi, David J. Seiffge, Wenyan Liu, Chahin Pachai, Adrian Wong, Khaled Darawil, Jeremy Molad, Sanjeevikumar Meenakishundaram, Enrico Flossmann, Harald Proschel, Caroline E. Lovelock, Christine Roffe, Kui Kai Lau, Michael McCormick, Peter M. Rothwell, Paul A. Armitage, Sarah Gunkel, Myung Suk Jang, Martin Cooper, Pol Camps-Renom, Martin M. Brown, David Cohen, David J. Werring, Koon-Ho Chan, Deborah Kelly, Neurology, ACS - Atherosclerosis & ischemic syndromes, ANS - Neurovascular Disorders, Division 2, Radiology & Nuclear Medicine, RS: Carim - B06 Imaging, Beeldvorming, MUMC+: DA BV Klinisch Fysicus (9), RS: NUTRIM - R1 - Obesity, diabetes and cardiovascular health, RS: CARIM - R3.11 - Imaging, MUMC+: MA Neurologie (3), Klinische Neurowetenschappen, RS: Carim - B05 Cerebral small vessel disease, RS: CARIM - R3.03 - Cerebral small vessel disease, and MUMC+: MA Med Staf Spec Neurologie (9)
Subjects: INTRACEREBRAL HEMORRHAGE, 030204 cardiovascular system & hematology, AMYLOID ANGIOPATHY, PREDICT, Brain Ischemia, 0302 clinical medicine, SMALL VESSEL DISEASE, Medicine, CHINESE PATIENTS, 10. No inequality, Stroke, medicine.diagnostic_test, DEMENTIA, Hazard ratio, Absolute risk reduction, Brain, Atrial fibrillation, ASSOCIATION, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], Magnetic Resonance Imaging, 3. Good health, Ischemic Attack, Transient, Cardiology, Life Sciences & Biomedicine, Intracranial Hemorrhages, medicine.drug, Cohort study, medicine.medical_specialty, RECURRENT STROKE, Clinical Neurology, 610 Medicine & health, Neuroimaging, Article, WARFARIN, 03 medical and health sciences, Internal medicine, Journal Article, Humans, Intracerebral hemorrhage, Science & Technology, business.industry, Warfarin, Magnetic resonance imaging, T2-ASTERISK-WEIGHTED MR-IMAGES, medicine.disease, ATRIAL-FIBRILLATION, Neurosciences & Neurology, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: Contains fulltext : 208975.pdf (Publisher’s version ) (Open Access) BACKGROUND: Cerebral microbleeds are a neuroimaging biomarker of stroke risk. A crucial clinical question is whether cerebral microbleeds indicate patients with recent ischaemic stroke or transient ischaemic attack in whom the rate of future intracranial haemorrhage is likely to exceed that of recurrent ischaemic stroke when treated with antithrombotic drugs. We therefore aimed to establish whether a large burden of cerebral microbleeds or particular anatomical patterns of cerebral microbleeds can identify ischaemic stroke or transient ischaemic attack patients at higher absolute risk of intracranial haemorrhage than ischaemic stroke. METHODS: We did a pooled analysis of individual patient data from cohort studies in adults with recent ischaemic stroke or transient ischaemic attack. Cohorts were eligible for inclusion if they prospectively recruited adult participants with ischaemic stroke or transient ischaemic attack; included at least 50 participants; collected data on stroke events over at least 3 months follow-up; used an appropriate MRI sequence that is sensitive to magnetic susceptibility; and documented the number and anatomical distribution of cerebral microbleeds reliably using consensus criteria and validated scales. Our prespecified primary outcomes were a composite of any symptomatic intracranial haemorrhage or ischaemic stroke, symptomatic intracranial haemorrhage, and symptomatic ischaemic stroke. We registered this study with the PROSPERO international prospective register of systematic reviews, number CRD42016036602. FINDINGS: Between Jan 1, 1996, and Dec 1, 2018, we identified 344 studies. After exclusions for ineligibility or declined requests for inclusion, 20 322 patients from 38 cohorts (over 35 225 patient-years of follow-up; median 1.34 years [IQR 0.19-2.44]) were included in our analyses. The adjusted hazard ratio [aHR] comparing patients with cerebral microbleeds to those without was 1.35 (95% CI 1.20-1.50) for the composite outcome of intracranial haemorrhage and ischaemic stroke; 2.45 (1.82-3.29) for intracranial haemorrhage and 1.23 (1.08-1.40) for ischaemic stroke. The aHR increased with increasing cerebral microbleed burden for intracranial haemorrhage but this effect was less marked for ischaemic stroke (for five or more cerebral microbleeds, aHR 4.55 [95% CI 3.08-6.72] for intracranial haemorrhage vs 1.47 [1.19-1.80] for ischaemic stroke; for ten or more cerebral microbleeds, aHR 5.52 [3.36-9.05] vs 1.43 [1.07-1.91]; and for >/=20 cerebral microbleeds, aHR 8.61 [4.69-15.81] vs 1.86 [1.23-1.82]). However, irrespective of cerebral microbleed anatomical distribution or burden, the rate of ischaemic stroke exceeded that of intracranial haemorrhage (for ten or more cerebral microbleeds, 64 ischaemic strokes [95% CI 48-84] per 1000 patient-years vs 27 intracranial haemorrhages [17-41] per 1000 patient-years; and for >/=20 cerebral microbleeds, 73 ischaemic strokes [46-108] per 1000 patient-years vs 39 intracranial haemorrhages [21-67] per 1000 patient-years). INTERPRETATION: In patients with recent ischaemic stroke or transient ischaemic attack, cerebral microbleeds are associated with a greater relative hazard (aHR) for subsequent intracranial haemorrhage than for ischaemic stroke, but the absolute risk of ischaemic stroke is higher than that of intracranial haemorrhage, regardless of cerebral microbleed presence, antomical distribution, or burden. FUNDING: British Heart Foundation and UK Stroke Association.
Published: 2019
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13. Effects of fluoxetine on functional outcomes after acute stroke (FOCUS) : a pragmatic, double-blind, randomised, controlled trial

Author: Martin Dennis, Gillian Mead, John Forbes, Catriona Graham, Maree Hackett, Graeme J Hankey, Allan House, Stephanie Lewis, Erik Lundström, Peter Sandercock, Karen Innes, Carol Williams, Jonathan Drever, Aileen Mcgrath, Ann Deary, Ruth Fraser, Rosemary Anderson, Pauli Walker, David Perry, Connor Mcgill, David Buchanan, Yvonne Chun, Lynn Dinsmore, Emma Maschauer, Amanda Barugh, Shadia Mikhail, Gordon Blair, Ingrid Hoeritzauer, Maggie Scott, Greig Fraser, Katherine Lawrence, Alison Shaw, Judith Williamson, David Burgess, Malcolm Macleod, Dan Morales, Frank Sullivan, Marian Brady, Ray French, Frederike Van Wijck, Caroline Watkins, Fiona Proudfoot, Joanna Skwarski, Diane Mcgowan, Rachael Murphy, Seona Burgess, William Rutherford, Katrina Mccormick, Ruaridh Buchan, Allan Macraild, Ruth Paulton, Adnan Fazal, Pat Taylor, Ruwan Parakramawansha, Neil Hunter, Jack Perry, John Bamford, Dean Waugh, Emelda Veraque, Caroline Bedford, Mary Kambafwile, Luis Idrovo, Linetty Makawa, Paula Smalley, Marc Randall, Tharani Thirugnana-Chandran, Ahamad Hassan, Richard Vowden, Joanne Jackson, Ajay Bhalla, Anthony Rudd, Chi Kai Tam, Jonathan Birns, Charlotte Gibbs, Leonie Lee Carbon, Elizabeth Cattermole, Katherine Marks, Angela Cape, Lisa Hurley, Sagal Kullane, Nigel Smyth, Charlotte Eglinton, Jennifer Wilson, Elio Giallombardo, Angela Frith, Paul Reidy, Matthew Pitt, Lucy Sykes, Deborah Dellafera, Victoria Croome, Lauriane Kerwood, Mirea Hancevic, Christina Narh, Carley Merritt, John Duffy, Duncan Cooke, Juliet Willson, Ali Ali, Aaizza Naqvi, Christine Kamara, Helen Bowler, Simon Bell, Tracy Jackson, Kirsty Harkness, Kathy Stocks, Suzanna Duty, Clare Doyle, Geoffrey Dunn, Keith Endean, Fiona Claydon, Emma Richards, Jo Howe, Ralf Lindert, Arshad Majid, Katy Dakin, Ahmad Maatouk, Luke Barron, Madana Meegada, Pratap Rana, Anand Nair, Christine Brighouse-Johnson, Jill Greig, Myint Kyu, Sanjeev Prasad, Matthew Robinson, Irfan Alam, Belinda Mclean, Lindsay Greenhalgh, Zenab Ahmed, Christine Roffe, Susan Brammer, Carole Beardmore, Kay Finney, Adrian Barry, Paul Hollinshead, Jeanette Grocott, Holly Maguire, Indira Natarajan, Jayan Chembala, Ranjan Sanyal, Sue Lijko, Nenette Abano, Alda Remegoso, Phillip Ferdinand, Stephanie Stevens, Resti Varquez, Chelsea Causley, Adrian Butler, Philip Whitmore, Caroline Stephen, Racquel Carpio, Joanne Hiden, Girish Muddegowda, Hayley Denic, Jane Sword, Ross Curwen, Martin James, Paul Mudd, Fiona Hall, Julie Cageao, Samantha Keenan, Caroline Roughan, Hayley Kingwell, Anthony Hemsley, Christoph Lohan, Sue Davenport, Angela Bowring, Tamika Chapter, Max Hough, David Strain, Karin Gupwell, Keniesha Miller, Anita Goff, Ellie Cusack, Shirley Todd, Rebecca Partridge, Georgiana Jennings, Kevin Thorpe, Jacquelyn Stephenson, Kelly Littlewood, Mark Barber, Fiona Brodie, Steven Marshall, Derek Esson, Irene Coburn, Caroline Mcinnes, Fiona Ross, Emma Bowie, Heather Barcroft, Victoria Withers, Laura Miller, Paul Willcoxson, Michelle Donninson, Richard Evans, Di Daniel, John Coyle, Michael Keeling, Peter Wanklyn, Mark Elliott, John Wightman, Elizabeth Iveson, Natasha Dyer, Anne-Marie Porteous, Monica Haritakis, Mandy Ward, Lucy Doughty, Lisa Carr, Mark O Neill, Cosmas Anazodo, Paul Wood, Poppy Cottrell, Cheryl Donne, Romina Rodriguez, Ruhail Mir, Jax Westmoreland, Judith Bell, Christopher Emms, Lorraine Wright, Pearl Clark Brown, Elizabeth Bamford, Andrew Stanners, Mike Carpenter, Prabal Datta, Richard Davey, Ann Needle, Marjorie Jane Eastwood, Fathima Zeena Razik, Imran Ghouri, Gavin Bateman, Judy Archer, Venkatesh Balasubramanian, Richard Bowers, Julie Ball, Louise Benton, Linda Jackson, Julie Ellam, Kate Norton, Paul Guyler, Terry Dowling, Sharon Tysoe, Paula Harman, Ashish Kundu, Ololade Omodunbi, Thayalini Loganathan, Stuart Chandler, Shanas Noor, Anwer Siddiqui, Amber Siddiqui, Swapna Kunhunny, Devesh Sinha, Martin Sheppard, Sindhu Rashmi, Elena France, Rajalakshmi Orath Prabakaran, Laura Wilson, Amiirah Ropun, Shyam Kelavkar, Kheng Xiong Ng, Lucy Kamuriwo, Sweni Shah, David Mangion, Camen Constantin, Luigi De Michele Hock, Anne Hardwick, Jayne Borley, Skarlet Markova, Kimberley Netherton, Tara Lawrence, Jo Fletcher, Rebecca Spencer, Helen Palmer, Claire Cullen, Dolores Hamill, Ramesh Durairaj, Zoe Mellor, Tanya Fluskey, Diane Wood, Alison Keeling, Victoria Hankin, Jennifer Peters, Daniela Shackcloth, Thant Hlaing, Rebecca Tangney, Jordan Ewing, Melanie Harrison, Sarah Stevenson, Victoria Sutton, Mohamed Soliman, Julia Hindle, Elizabeth Watson, Claire Hewitt, Susie Butler, Ibrahim Wahishi, Sarwat Arif, Amy Fields, Jagdish Sharma, Rose Brown, Caroline Taylor, Sarah Bell, Simon Leach, Chris Patterson, Sophia Khan, Helen Wilson, Joanne Price, Hawraman Ramadan, Stuart Maguire, Ruth Bellfield, Michaela Hooley, Umair Hamid, Waqar Gaba, Robina Ghulam, Leslie Masters, Outi Quinn, Lakshmanan Sekaran, Margaret Tate, Niaz Mohammed, Kiranjit Bharaj, Frances Justin, Rajan Pattni, Lanka Alwis, Sakthivel Sethuraman, Rianne Robinson, Lianne Eldridge, Susan Mintias, Meena Chauhan, Chi-Kai Tam, Jeremias Palmones, Clare Holmes, Lucy Belle Guthrie, Mairead Osborn, Lindsay Ball, Sarah Caine, Amy Steele, Peter Murphy, Nikki Devitt, Jayne Leonard, Ronak Patel, Ian Penwarden, Emily Dodd, Amy Holloway, Pauline Baker, Samantha Clarke, Sandra Williams, Lindsey Dow, Roland Wynn-Williams, James Kennedy, Rachel Teal, Ursula Schulz, Gary Ford, Philip Mathieson, Ian Reckless, Ana Deveciana, Paige Mccann, Gillian Cluckie, Geoffrey Howell, Jonathan Ayer, Barry Moynihan, Rita Ghatala, Brian Clarke, Geoffrey Cloud, Bhavini Patel, Usman Khan, Nia Al-Samarrai, Sarah Trippier, Neha Chopra, Temi Adedoyin, Fran Watson, Val Jones, Liqun Zhang, Lillian Choy, Rebecca Williams, Natasha Clarke, Adrian Blight, Kate Kennedy, Alice Dainty, Johann Selvarajah, Dheeraj Kalladka, Bharath Cheripelli, Wilma Smith, Fiona Moreton, Angela Welch, Xuya Huang, Elizabeth Douglas, Audrey Lush, Nicola Day, Salwa El Tawil, Karen Montgomery, Helen Hamilton, Doreen Ritchie, Sankaranarayanan Ramachandra, Kirsty Mcleish, Kamy Thavanesan, Sathyabama Loganathan, Josh Roberts, Chantel Cox, Sarah Orr, Alison Hogan, Divya Tiwari, Gail Hann, Barbara Longland, Owen David, Jo Bell, Catherine Ovington, Emily Rogers, Rachel Bower, Marketa Keltos, David Cohen, Joseph Devine, Lankantha Alwis, Lucy Southworth, Laura Burgess, Matilda Lang, Bhavna Badiani, Fenglin Guo, Anne Oshodi, Emmanuelle Owoyele, Norah Epie, Anette David, Mushiya Mpelembue, Rajaram Bathula, Mudhar Abdul-Saheb, Angela Chamberlain, Varthi Sudkeo, Khalid Rashed, Barbara Williams-Yesson, Joanne Board, Sarah De Bruijn, Clare Buckley, Sarah Board, Joanna Allison, Elizabeth Keeling, Tracey Duckett, Dave Donaldson, Carinna Vickers, Claire Barron, Linda Balian, Jodhi Wilson, Adam Edwards, Timothy England, Amanda Hedstrom, Elizabeth Bedford, Margaret Harper, Elina Melikyan, Wendy Abbott, Kashmira Subramanian, Marie Goldsworthy, Meena Srinivasan, Angela Yeomans, Denise Donaldson, Frances Hurford, Riquella Chapman, Sana Shahzad, Nicki Motherwell, Louise Tonks, Rachel Young, Usman Ghani, Indranil Mukherjee, Dipankar Dutta, Mudhar Obaid, Pauline Brown, Fiona Davis, Deborah Ward, Jennifer Turfrey, Bethan Cartwright, Bilal Topia, Judith Spurway, Kayleigh Collins, Rehana Bakawala, Chloe Hughes, Susan Oconnell, Linda Hill, Kausik Chatterjee, Tim Webster, Syed Haider, Pamela Rushworth, Fiona Macleod, Arumugam Nallasivan, Charlotte Perkins, Edel Burns, Sandra Leason, Tom Carter, Samantha Seagrave, Eman Sami, Lisa Armstrong, Syed Naseem Naqvi, Muhammad Hassan, Sharron Parkinson, Samantha Mawer, Gillian Darnbrook, Carl Booth, Brigid Hairsine, Matthew Smith, Sue Williamson, Fiona Farquhar, Bernard Esisi, Tim Cassidy, Gavin Mankin, Beverley Mcclelland, Maria Bokhari, David Sproates, Elliot Epstein, Steve Hurdowar, Ruth Blackburn, Nazran Sukhdeep, Saika Razak, Khalid Osman, Amina Hashmi, Natasha Upton, Frances Harrington, Gillian Courtauld, Christine Schofield, Linda Lucas, Katja Adie, Kirsty Bond, Abhijit Mate, Jo Skewes, Ali James, Carolyn Brodie, Matthew Johnson, Linda Allsop, Emma Driver, Karina Harris, Mark Drake, Sam Ellis, Bev Maund, Emma Thomas, Kimberley Moore, Matthew Burn, Adam Hamilton, Shageetha Mahalingam, Amulya Misra, Farrah Reid, Adrienne Benford, Derek Hilton, Lorraine Hazell, Keziah Ofori, Anne Louise Thomas, Moncy Mathew, Sonia Dayal, Iona Burn, Kenneth Fotherby, Karla Jennings-Preece, Angela Willberry, Debbie Morgan, Donna Butler, Gurminder Sahota, Kelly Kauldhar, Nasar Ahmad, Angela Stevens, Saugata Das, David Bruce, Yogish Pai, Khin Nyo, Lynsey Stephenson, Richard Nendick, Gill Rogers, Mahesh Dhakal, Sofia Dima, Ellen Brown, Susan Clayton, Penny Gamble, Muhammad Naeem, Rachel Hayman, Rachel Burnip, Philip Earnshaw, David Hargroves, Barbara Ransom, Hannah Rudenko, Ibrahim Balogun, Kirsty Griffiths, Kim Mears, Tom Webb, Linda Cowie, Tessa Hammond, Audrey Thomson, Daniela Ceccarelli, Navraj Chattha, Eva Beranova, Anna Verrion, Andrew Gillian, Natasha Schumacher, Anna Bahk, Susannah Walker, Vera Cvoro, Nicola Chapman, Susan Pound, Rebecca Cain, Sean Mcauley, Mandy Couser, Maria Simpson, Athan Tachtatzis, Khalil Ullah, Don Sims, Rachael Jones, Jonathan Smith, Rebecca Tongue, Mark Willmot, Claire Sutton, Edward Littleton, Jattinder Khaira, Susan Maiden, James Cunningham, Carole Green, Yin-May Chin, Michelle Bates, Katherine Ahlquist, Ingrid Kane, Joanna Breeds, Tenesa Sargent, Laura Latter, Alexandra Pitt Ford, Nicola Gainsborough, Tom Levett, Philip Thompson, Emma Barbon, Angela Dunne, Simon Hervey, Suzanne Ragab, Tracy Sandell, Christine Dickson, Judith Dube, Sharon Power, Nick Evans, Beverley Wadams, Savina Elitova, Beth Aubrey, Tatiana Garcia, James Mcilmoyle, Carol Jeffs, Christina Dickinson, Anis Ahmed, Sanjeev Kumar, Julie Frudd, Charlotte Armer, Andrew Potter, Stacey Donaldson, Joanne Howard, Kirsty Jones, Saikat Dhar, David Collas, Saul Sundayi, Lynn Denham, Deepali Oza, Elaine Walker, Mohit Bhandari, Sissy Ispoglou, Rachel Evans, Kamel Sharobeem, Elaine Walton, Steven Shanu, Anne Hayes, Jennifer Howard-Brown, Steven Billingham, Nic Weir, Vanessa Pressly, Emma Wood, Gabriella Howard, Holly Burton, Pam Crawford, Shuna Egerton, Sue Evans, Jasmine Hakkak, Janet Andrews, Rebecca Lampard, Christopher Allen, Ashleigh Walters, Rasha Said, James Richard Marigold, Sau-Mon Tsang, Robyn Creeden, Chloe Cox, Simon Smith, Imogen Gartrell, Fiona Smith, Colin Jenkins, Joanna Pryor, Andrew Hedges, Fiona Price, Linda Moseley, Lily Mercer, Claire Hughes, Abul Azim, Julie White, Milena Krasinska-Chavez, Shaun Chaplin, James Curtis, Deepwant Singh, Javed Imam, Anne Nicolson, Sajid Alam, Simon Whitworth, Lisa Wood, Elizabeth Warburton, Siobhan Kelly, Joanne Mcgee, Hugh Markus, Denish Chandrasena, Derek Hayden, Juliana Sesay, Helen Hayhoe, Mark Bolton, Jane Macdonald, Jenny Mitchell, Charlotte Farron, Elaine Amis, Diana Day, Ainsley Culbert, Ailene Espanol, Niamh Hannon, Dominic Handley, Sarah Finlay, Sarah Crisp, Lynne Whitehead, Jobbin Francis, Janice Oconnell, Emily Osborne, Rod Beard, Ramesh Krishnamurthy, Langanani Mokoena, Naweed Sattar, Min Myint, Michelle Edwards, Andrew Smith, Paul Corrigan, Anthony Byrne, Joanne Blackburn, Caroline Mcghee, Amanda Smart, Fiona Donaldson, Claire Copeland, Jill Wilson, Rhona Scott, Paul Fitzsimmons, Paula Lopez, Mark Wilkinson, Aravindakshan Manoj, Penelope Cox, Leona Trainor, Glyn Fletcher, Lisa Denny, Karen Kavanagh, Hannah Allsop, Hedley Emsley, Sulaiman Sultan, Alison Mcloughlin, Benjamin Walmsley, Louise Hough, Shakeel Ahmed, Donna Doyle, Bindu Gregary, Sonia Raj, Kirubananthan Nagaratnam, Neelima Mannava, Nyla Haque, Norma Shields, Kate Preston, Geraldine Mason, Kirsty Short, Gemma Lumsdale, Giulia Uitenbosch, Ugnius Sukys, Stacey Valentine, David Jarrett, Kerry Dodsworth, Mary Wands, Nisa Khan, Jane Tandy, Catrin Watkinson, Wendy Golding, Rebecca Butler, Max Williams, Yasmin Davies, Keith Yip, Claire James, Anne Suttling, Aditya Maney, Giles Edward Gamble, Adam Hague, Bethan Charles, Sujata Blane, Beatriz Duran, Caroline Lambert, Katherine Stagg, Robert Whiting, Jane E Homan, Sarah Brown, Malik Hussain, Miriam Harvey, Libby Graham, Leanne Foote, Catherine Lane, Liz (Joan) Kemp, Joy Rowe, Helen Durman, Jayne Foot, Lucy Brotherton, Nicholas Hunt, Corinne Pawley, Alison Whitcher, Patrick Sutton, Susan Mcdonald, Denys Pak, Alison Wiltshire, Jennifer Jagger, Anthony K Metcalf, Gail Louise Healey, Joyce Balami, Clare Marie Self, Melissa Crofts, Annie Chakrabarti, Chit Hmu, Garth Ravenhill, Charmaine Grimmer, Thandar Soe, Jocelyn Keshet-Price, Margaret Langley, Ian Potter, Pui-Lin Tam, Mary Joan Macleod, Patricia Cooper, Michael Christie, Janice Irvine, Faye Annison, David Christie, Celia Meneses, Amber Johnson, Anu Joyson, Sandra Nelson, Vicky Taylor, John Reid, Rebecca Clarke, Jacqueline Furnace, Heather Gow, Youssif Abousleiman, Tania Beadling, Sally Collins, Stuart Jones, Jessica Purcell, Samantha Bloom, Shelly Goshawk, Marcial Landicho, Sivatharshini Sangaralingham, Yasmin Begum, Sherree Mutton, Elangovan Munuswamy Vaiyapuri, Jane Allen, Jemma Lowe, Martin Hughes, Ivan Wiggam, Sarah Cuddy, Suzanne Tauro, Brian Wells, Azlisham Mohd Nor, Nicola Persad, Maggie Kalita, Stuart Weatherby, Claire Brown, Adrian Pace, Daniel Lashley, Mike Marner, Marie Weinling, Natasha Wilmshurst, Darren Waugh, Anna Mucha, Alex Shah, John Baker, Jacqueline Westcott, Richard Cowan, Evangelos Vasileiadis, Samira Mumani, Anthea Parry, Cathy Mason, Melinda Holden, Katerina Petrides, Tomoko Nishiyama, Hina Mehta, Manju Krishnan, Dacey Lynne, Lisa Thomas, Connor Lynda, Catherine Hughes, Clare Clements, Rhys Williams, Tal Anjum, Storton Sharon, Susan Tucker, Paul Jones, Deanne Colwill, Helen Thompson Jones, Dinesh Chadha, Mark Fairweather, Deborah Walstow, Rosanna Fong, Stuart Johnston, Christine Almadenboyle, Sarah Ross, Shona Carson, Priya Nair, Emily Tenbruck, Mairi Stirling, Aparna Pusalkar, Hannah Beadle, Kelly Chan, Puneet Dangri, Asaipillai Asokanathan, Anita Rana, Sunita Gohil, Mark Massyn, Prabhu Aruldoss, Angela Cook, Karen Crabtree, Sura Dabbagh, Toby Black, Caroline Clarke, Denise Mead, Ruth Fennelly, Alpha Anthony, Linda Nardone, Victoria Dimartino, Michele Tribbeck, David Broughton, Dinesh Tryambake, Lynn Dixon, Agnieszka Skotnicka, Jane Thompson, Sarah Whitehouse, Andrew Sigsworth, Jason Wong, Arunkumar Annamalai, Julie Pagan, Brendan Affley, Caroline Sunderland, Lynda Goldenberg, Atif Khan, Peter Wilkinson, Raad Nari, Lucy Abbott, Emma Young, Amritpal Shakhon, Sally Lock, Jack Stewart, Rita Pereira, Margaret Dsouza, Sally Dunn, Anne-Marie Mckenna, Nina Cron, Michelle Kidd, Grace Hull, Kerry Bunworth, Graham Drummond, Karim Mahawish, Nicola Hayes, Lynne Connell, Jennifer Simpson, Helen Penney, Shuja Punekar, Joanne Nevinson, William Wareing, Jacqueline Ward, Richard Greenwood, Duncan Austin, Azra Banaras, Carolin Hogan, Thomas Corbett, Nnebuife Oji, Emma Elliott, Maria Brezitski, Nathalie Passeron, Laura Howaniec, Caroline Watchurst, Krishna Patel, Renuka Erande, Rahi Shah, Nabarun Sengupta, Maria Metiu, Celia Gonzalez, Sarah Funnell, Jordi Margalef, Gillian Peters, Indra Chadbourn, Ramachandran Sivakumar, Rajesh Saksena, Jane Ketley-O'donel, Richard Needle, Elaine Chinery, Alison Wright, Sue Cook, Joseph Ngeh, Harald Proeschel, Paige Cook, Pauline Ashcroft, Simon Sharpe, Stephanie Jones, Damian Jenkinson, Deborah Kelly, Holly Bray, Gunaratnam Gunathilagan, Sally Jones, Sorrell Tilbey, Saidu Abubakar, Joseph Vassallo, Dee Leonard, Lucy Orrell, Aziz Hasan, Asif Khan, Sulmaaz Qamar, Susan Graham, Emma Hewitt, Jennifer Awolesi, Muhammad Haque, Alissa Kent, Elizabeth Bradshaw, Martin Cooper, Inez Wynter, Anoja Rajapakse, Joumana Janbieh, Abu M Nasar, Lynne Wade, Linda Otter, Steve Haigh, Jamie-Rae Burgoyne, Rebecca Boulton, Andrew Boulton, Rayessa Rayessa, Emma Clarkson, Horne Rhian, Amy Fleming, Kim Mitchelson, Vicki Lowthorpe, Ahmed Abdul-Hamid, Phil Jones, Claire Duggan, Abigail Hynes, Emma Nurse, Syed Abid Raza, Sarah Jones, Udaya Pallikona, Bleddyn Edwards, Geraint Morgan, Kirsty Dennett, Helen Tench, Ronda Loosley, Toby Trugeon-Smith, Rhian Jones, Richard Williams, Donna Robson, Sunanda Mavinamane, Sanjeevi Meenakshisundaram, Lalitha Ranga, Sharon Dealing, Andrew Hill, Margaret Hargreaves, Tom Smith, Julie Bate, Linda Harrison, Ramanathan Kirthivasan, Emma Cannon, Joanne Topliffe, Rebecca Keskeys, Sarah Williams, Fiona Mcneela, Frances Cairns, Thomas James, Amanda Lyle, Sheela Shah, George Zachariah, Lauren Fergey, Susan Smolen, Lucy Cooper, Elizabeth Bohannan, Siddiq Omer, Sageet Amlani, Nadia Hunter, Melissa Hawkes-Blackburn, Giosue Gulli, Alice Peacocke, Justine Amero, Maria Burova, Ottilia Speirs, Steph Levy, Lynda Francis, Susan Holland, Sean Brotheridge, Helen Lyon, Christine Hare, Samantha Jackson, Lorraine Stephenson, Samer Al Hussayni, James Featherstone, Agness Bwalya, Arun Singh, M N Goorah, Jamie Walford, Angela Bell, Christine Kelly, Darren Rusk, Deborah Sutton, Farzana Patel, Stephen Duberley, Kathryn Hayes, Lorraine Hunt, Ahmed El Nour, Sacha Honour, Chloe Box, Simon Dyer, Lynne Brown, Kerry Elliott, Emma Temlett, John Paterson, Rosie Furness, Shelli Young, Enoch Orugun, Chris Brewer, Sarah Thornthwaite, Hannah Crowther, Rachel Glover, Moe Sein, Kashif Haque, Elspeth Gibson, Sam Wong, Karen Rotchell, Karen Burton, Lisa Brookes, Linda Bailey, Chris Lindley, Abbi Murray, Karen Waltho, Maureen Holland, Pradeep Kumar, Purnima Harlekar, Laura Booth, Charlotte Culmsee, Jade Drew, Mohammad Khan, Nicola Mackenzie, Carmel Thomas, Jane Ritchie, James Barker, Michael Haley, Donna Cotterill, Lynne Lane, Christine Little, Dawn Simmons, Glenn Saunders, Harvey Dymond, Sarah Kidd, Rachel Warinton, Yara Neves-Silva, Branimir Nevajda, Michael Villaruel, Udayaraj Umasankar, Seema Patel, Anna Man, Natasha Christmas, Ravi Rangasamy, Richard Ladner, Georgina Butt, Wilson Alvares, Narasimha Gadi, Michael Power, Belinda Wroath, Kevin Dynan, David Wilson, Sarah Crothers, Catherine Leonard, Samantha Hagan, Geraldine Douris, Djamil Vahidassr, Alastair Thompson, Brian Gallen, Shirley Mckenna, Collette Edwards, Clare Mcgoldrick, Murdi Bhattad, Khalil Kawafi, Deborah Morse, Patricia Jacob, Lisa Turner, Narayanamoorti Saravanan, Linda Johnson, Sadie Humphrey, Robert Namushi, Ramesh Patel, Jemma Mclaughlin, Paul Omahony, Esther Osikominu, Chukwuka Orefo, Chisha Mcdonald, Esther Makanju, Tabindah Khan, Grace Appiatse, Helena Stone, Martia Augustin, Alicia Wardale, Maqsud Salehin, Duncan Bailey, Luciano Garcia-Alen, Latheef Kalathil, Sarah Tinsley, Taya Jones, Kelly Amor, Andrew Ritchings, Emma Margerum, Jane Horton, Richard Miller, Nireekshana Gautam, Julie Meir, Amaryl Jones, Janet Putteril, Mirella Lepore, Rachel Gallifent, Laura-Louise Arundell, Catherine Mcredmond, Alicia Goulding, Vivek Nadarajan, Julia Laurence, Su Fung Lo, Sabina Melander, Paul Nicholas, Elizabeth Woodford, Gillian Mckenzie, Vietland Le, Jacolene Crause, Robert Luder, Maneesh Bhargava, Girish Bhome, Venetia V Johnson, Dara Chesser, Hayley Bridger, Elodie Murali, Jon Scott, Susan Morrison, Amy Burns, Julie Graham, Madeline Duffy, Khalid Ali, Emma Pitcher, Jane Gaylard, Julie Newman, Sunil Punnoose, Sarah Besley, Kirtan Purohit, Amy Rees, Mark Davy, Osman Chohan, Muhammad Fozan Khan, Rachel Walker, Vicky Murray, Charlotte Bent, Susan Oakley, Cassilda Peixoto, Suzanne Jones, Gaybrielle Livingstone, Fiona Butler, Sally Bradfield, Laura Gordon, Jenneke Schmit, Anika Wijewardane, Tineke Edmunds, Rebecca Wills, Catherine Medcalf, Lucia Argandona, Larissa Cuenoud, Hanna Hassan, Esther Erumere, Aidan Ocallaghan, Patrick Gompertz, Ozlem Redjep, Grace Auld, Anna Song, Tillana Tarkas, Hashim Kabash, Rumbi Hungwe, University of St Andrews. Sir James Mackenzie Institute for Early Diagnosis, University of St Andrews. Population and Behavioural Science Division, and University of St Andrews. School of Medicine
Subjects: RM, medicine.medical_specialty, Neurology, Neurologi, NDAS, 030204 cardiovascular system & hematology, Placebo, Minimisation (clinical trials), Article, B700, law.invention, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, Randomized controlled trial, Modified Rankin Scale, law, Fluoxetine, Internal medicine, Humans, Medicine, 030212 general & internal medicine, R2C, Acute stroke, business.industry, ~DC~, General Medicine, Odds ratio, RM Therapeutics. Pharmacology, Stroke, RC Internal medicine, BDC, business, Selective Serotonin Reuptake Inhibitors, RC, medicine.drug
Abstract: Background: Results of small trials indicate that fluoxetine might improve functional outcomes after stroke. The FOCUS trial aimed to provide a precise estimate of these effects.Methods: FOCUS was a pragmatic, multicentre, parallel group, double-blind, randomised, placebo-controlled trial done at 103 hospitals in the UK. Patients were eligible if they were aged 18 years or older, had a clinical stroke diagnosis, were enrolled and randomly assigned between 2 days and 15 days after onset, and had focal neurological deficits. Patients were randomly allocated fluoxetine 20 mg or matching placebo orally once daily for 6 months via a web-based system by use of a minimisation algorithm. The primary outcome was functional status, measured with the modified Rankin Scale (mRS), at 6 months. Patients, carers, health-care staff, and the trial team were masked to treatment allocation. Functional status was assessed at 6 months and 12 months after randomisation. Patients were analysed according to their treatment allocation. This trial is registered with the ISRCTN registry, number ISRCTN83290762.Findings: Between Sept 10, 2012, and March 31, 2017, 3127 patients were recruited. 1564 patients were allocated fluoxetine and 1563 allocated placebo. mRS data at 6 months were available for 1553 (99·3%) patients in each treatment group. The distribution across mRS categories at 6 months was similar in the fluoxetine and placebo groups (common odds ratio adjusted for minimisation variables 0·951 [95% CI 0·839–1·079]; p=0·439). Patients allocated fluoxetine were less likely than those allocated placebo to develop new depression by 6 months (210 [13·43%] patients vs 269 [17·21%]; difference 3·78% [95% CI 1·26–6·30]; p=0·0033), but they had more bone fractures (45 [2·88%] vs 23 [1·47%]; difference 1·41% [95% CI 0·38–2·43]; p=0·0070). There were no significant differences in any other event at 6 or 12 months.Interpretation: Fluoxetine 20 mg given daily for 6 months after acute stroke does not seem to improve functional outcomes. Although the treatment reduced the occurrence of depression, it increased the frequency of bone fractures. These results do not support the routine use of fluoxetine either for the prevention of post-stroke depression or to promote recovery of function.Funding: UK Stroke Association and NIHR Health Technology Assessment Programme.
Published: 2019
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14. Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial

Author: Ruth Graham, Charlotte Eglinton, Swapna Kunhunny, J Banns, Alison K Wright, Sunil Munshi, C Khuoge, Beverley McClelland, A Benford, Jean Buxton, Maia Beridze, K Deighton, Neha Chopra, Nichola Motherwell, Emily C. O'Brien, Sonia S. Anand, Anand Dixit, Una Poultney, N Beridze, Jessica Beavan, K Dizayee, Thompson G. Robinson, Deborah Howcroft, Alison Sarah rachel Mcloughlin, A Kenton, Derek Esson, A Tittle, L Matter, Kerstin Knops, C Hubbuck, Kath Chapman, R Rangasamay, Ranjan Sanyal, Sarah Lewis, Alpha Anthony, Sarah Board, Janice Irvine, Anna Verrion, Katherine Whittamore, N Khizanishvili, L O'Shea, Lisa Shaw, K Ayes, Tracey Dobson, N Akiashvili, Gill Rogers, Jenny Peters, Alda Remegoso, S S Hansen, James A. White, T Attygalle, Rosalind Brown, Irene Martin, Manesh R. Patel, D O'Kane, Stuart J. Pocock, Khalid Rashed, G Spurling, Sharon Tysoe, Frances Harrington, Margo Henry, Rowilson Jarapa, Julia Hindle, K A Kay, Carinna Vickers, S Duty, Angela Bowring, David Eveson, Saul Sundayi, Mary Kambafwile, Rashmi Kumar, Jack Roffe, Marilyn James, Natalie Temple, R Oliver, Christine Kelly, M Niemierko, J Chembala, S Jones, M Dent, K Chatterjee, S Atkinson, J Tomlinson, S Norman, E Cattermole, P Daboo, Nicola Gilzeane, Anne Hardwick, Pietro Cariga, C Rankin, David A. Wood, Lelia Duley, John Bamford, L Holford, J Good, C Ambulo, S Gomm, Girish Muddegowda, Fiona Wright, M Alao, L Sztriha, Maite D. Rodriguez, Christine Dickson, S Merotra, Helen Bearne, Ann Needle, Emma Mckenzie, Olga Balazikova, Emily Osborne, A Lankester, Rod S Taylor, Pauline Fitzell, Bernard Esisi, E Young, Richard Donnelly, Anu Joyson, Debbie Morgan, Fran Watson, Caroline Mcinnes, C Padilla-Harris, Stephanie McCann, T Ajao, Suzanne Lucas, Inez Wynter, Barbara Longland, Don Sims, Gavin Bateman, Anthony Hemsley, Vera Cvoro, Fiona Kennedy, Peter Langhorne, Adrian Butler, P Jacob, Barry Moynihan, Amit K. Mistri, W Sunman, Hannah Beadle, Polly Scutt, M Garside, Glyn Fletcher, Deborah Walstow, L Ryan, Michelle Fawcett, D Wilkinson, E Gibson, O Orugun, Malcolm R. Macleod, Philip M.W. Bath, Elio Giallombardo, T Kherkheulidze, Lourda Kerin, Clare Doyle, Brigid Hairsine, N Kakabadze, B Wadams, Enas Lawrence, Dinesh Chadha, I Memon, Cheryl L. Perkins, Victoria Sutton, C.B. Patel, A Ravindrane, K Javaid, Mahmud Sajid, T Tsanava, Y Duodu, Timothy J. England, Geoffrey A. Rose, Sheila Nyabadza, Louisa M. Christensen, M Bajoriene, F Faola, J Kok, C Vernon, Aravindakshan Manoj, E Horsley, T Gordon, Linda Cowie, S Hurdowar, D Sandler, Temi Adedoyin, Mandy Couser, C Jenkins, C Pringle, Paula Lopez, Vicky Taylor, James Cunningham, Gillian Courtauld, S Maheswaran, H Rehman, Christine Roffe, M Sein, Carla Richardson, John B. Davis, Nenette Abano, Racquel Carpio, Sheila Mashate, P Christian, Lynn Dixon, Dulka Manawadu, Jeanette Grocott, Peter Owusu-Agyei, P Farren, F K Chan, Komal Ali, Annemarei Ranta, Judith Clarke, Dean Waugh, Stan Heptinstall, M Reader, Nikola Sprigg, John F. Corrigan, Caroline Roughan, F Brodie, Paula Harman, P Webster, Kenneth Smith, Julie Reddan, Angela Willberry, Peter Howard, Kay Finney, S Buddha, C Hewitt, M Zaidi, Tracy Marsden, Heather Gow, Robert A. Dineen, Kimberley Netherton, Kashif Musarrat, Emma Barbon, V Riddell, G Storey, Ahamad Hassan, O Adegbaju, S Wong, Bethan Charles, Bindu Gregary, Rhys Williams, M G Metiu, Nilofer Dayal, C Lawlor, Kirsten E Anderson, R Icart Palau, N Khanom, C Stevenson, Prabel Datta, Betty Mokoena, Kelly Chan, Amanda Hedstrom, Sonia Raj, Y Gruenbeck, D Dellafera, Georgina Butt, A Peacocke, James Okwera, L Mokoena, Holly Maguire, Mohana Maddula, C Bailey, Ian Shread, LáShauntá M. Glover, Elizabeth Keeling, Mari Smith, Jane Powell, A Tevdoradze, Christopher Price, Hannah Rudenko, K Gill, Laura Howaniec, P Lingwood, Katherine Marks, Ivan Iniesta, F Barrett, Barbara Madigan, Emery N. Brown, Katie Flaherty, Gail Hann, Mark Barber, Kelley Storey, Aparna Pusalkar, Jason P. Appleton, Joanne Hiden, R Jolly, Hedley C. A. Emsley, J Chambers, Christina Kruuse, Mairead Osborn, P Lai, Tracy Fuller, David G. Bruce, Robert Namushi, Martin Cooper, Peter Murphy, Naomi Jeyaraj, Hayley Kingwell, A Nair, Robert S.M. Davies, Katrina McCormick, Rachel L. Lakey, Sharon Dealing, F Leslie, Peter Wilkinson, Amitava Banerjee, Penelope Cox, Janice E. O’Connell, N Sikondari, Sandra Leason, Lisa J Woodhouse, Judith Bell, Puneet Dangri, Donna Butler, Judith Dube, Rachel Gascoyne, Amberly Brigden, Debs Kelly, Renuka Erande, Kirsty Harkness, Sarah Trippier, Kirsten Harvey, Georgina Ayres, R Rowland-Axe, E Campbell, Sue Lyjko, Sylvia Szabo, David Mangion, Suzanne Ragab, C Hilaire, Alan A Montgomery, Dawn Tomlin, John Paterson, K Muhidden, Grace Auld, C Keaveney, Hannah Crowther, Lisa Hyatt, Louise E. Jackson, K Castro, Khaled Elfandi, H Russell, S Tennant, Ozlem Redjep, Tim Cassidy, Linda Y Johnson, Amulya Misra, E Khoromana, Catherine Ovington, Stuart Maguire, S Khan, Zoe Mellor, Michael Funnell, Hugh S. Markus, Emma Richards, I Toidze, Colin Smith, R Sivakumar, Janet Wilson, Amina Ahmed, A Mohd Nor, A Barkat, Line Bentsen, K Whysall, Carol L Clarke, N Sengupta, Meena Srinivasan, Balakrishna Kumar, Mgg Soliman, A Thomson, Adrian Barry, Abul Azim, Ed Gamble, H Eccleson, Kelly Marie Shaw, Christine Schofield, Linetty Makawa, Carole Hays, David Hargroves, Jordi Margalef, S Butler, H Webb, Carol Denniss, Samantha Stafford, Faye Shelton, D Forrest, Amanda Buck, Tarn Nozedar, Indira Natarajan, Jane Perez, Susanna R. Stevens, Denise Button, Mary Johnes, Samantha Keenan, Olivia C. Geraghty, Eva Beranova, Emma Jinks, S Hassan, Caroline McGhee, Nicola Persad, Gunaratnam Gunathilagan, Clare Buckley, Jennifer Mitchell, Mike Clarke, Mathew Burn, B Bhaskaran, D Hayward, Lucy Belle Guthrie, S Meenakshisundaram, Anushka Warusevitane, O Speirs, J O'Callaghan, Sudipto Ghosh, Peter Wilding, Helen Cochrane, Susan Clayton, Mandy Doherty, Fiona Price, L Montague, Valerie Hogg, S Arif, Beth Hazel, Margaret Ball, S Johnson-Holland, S Booth, N Rands, Dionne Hove, Teresa Thompson, C Krarup Hansen, Lisa Manning, Andrew Smith, Jo Howe, Jill Greig, Kailash Krishnan, Caroline Watchurst, L Finlay, Sandra Nelson, Toby Black, S Tilby, Zin Naing, D Morse, David Broughton, K Preece, M Platton, M Siddiqui, Angela Dodd, Catrin Blank, Maria Bokhari, Jacqueline Furnace, F Hammonds, Helen Guy, A Lehman, J Hunt, S Windebank, Becky Jupp, K Fotherby, Ruth Bellfield, P Wanklyn, D Hilton, Amy Steele, S Mahmood, N Lobjanidze, Sarah Finlay, L Hunt, M Krasinska-Chavez, Gemma Grimwood, H H Jensen, J. Duignan, Jane Gaylard, Asaipillai Asokanathan, Joanna O'Reilly, J Kessell, Diane Havard, T Fluskey, L Lee-Carbon, Graham Venables, Margi Godfrey, L Boxall, C Douglass, Emelda Veraque, Elaine Amis, M Chowdhury, Rekha Keshvara, Adrian Blight, G Thomas, Marc Randall, S Stoddart, Paul Guyler, Rita Ghatala, Janet T Scott, Kathy J. Jenkins, Sarah Ross, John Aeron-Thomas, C Allcock, J Goodsell, Ifan Jones, D Kakabadze, T T Thomsen, V Petrovic, I. Watson, C Athulathmudali, Hanne Christensen, Susan Crawford, Christine Kamara, James McIlmoyle, Stephen Woodward, Christine McAlpine, Emma Temlett, Gwendoline Wilkes, Benjamin Hyams, L Mills, S Brixey, Raj Shekhar, P Findlay, Markus, Hugh [0000-0002-9794-5996], and Apollo - University of Cambridge Repository
Subjects: Male, medicine.medical_specialty, Georgia, Ticlopidine, Denmark, Hemorrhage, 030204 cardiovascular system & hematology, Risk Assessment, Brain Ischemia, 03 medical and health sciences, 0302 clinical medicine, Ischemia, Recurrence, Modified Rankin Scale, Internal medicine, medicine, Humans, Thrombolytic Therapy, Prospective Studies, cardiovascular diseases, Stroke, Aged, Aspirin, business.industry, Dipyridamole, General Medicine, Guideline, Middle Aged, Clopidogrel, medicine.disease, United Kingdom, Treatment Outcome, Ischemic Attack, Transient, Research Design, Acute Disease, Platelet aggregation inhibitor, Drug Therapy, Combination, Female, business, Platelet Aggregation Inhibitors, 030217 neurology & neurosurgery, New Zealand, medicine.drug
Abstract: Summary Background Intensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel, and dipyridamole) with that of guideline-based antiplatelet therapy. Methods We did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using computer randomisation to receive loading doses and then 30 days of intensive antiplatelet therapy (combined aspirin 75 mg, clopidogrel 75 mg, and dipyridamole 200 mg twice daily) or guideline-based therapy (comprising either clopidogrel alone or combined aspirin and dipyridamole). Randomisation was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days, as assessed by central telephone follow-up with masking to treatment assignment, and analysed by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN47823388. Findings 3096 participants (1556 in the intensive antiplatelet therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy (93 [6%] participants vs 105 [7%]; adjusted common odds ratio [cOR] 0·90, 95% CI 0·67–1·20, p=0·47). By contrast, intensive antiplatelet therapy was associated with more, and more severe, bleeding (adjusted cOR 2·54, 95% CI 2·05–3·16, p Interpretation Among patients with recent cerebral ischaemia, intensive antiplatelet therapy did not reduce the incidence and severity of recurrent stroke or TIA, but did significantly increase the risk of major bleeding. Triple antiplatelet therapy should not be used in routine clinical practice. Funding National Institutes of Health Research Health Technology Assessment Programme, British Heart Foundation.
Published: 2017

15. An Interactional Profile to Assist the Differential Diagnosis of Neurodegenerative and Functional Memory Disorders

Author: Kerry Ardern, Annalena Venneri, Markus Reuber, Sarah Wakefield, Daniel Blackburn, Kirsty Harkness, Danielle Jones, Chloe Shaw, Christopher Elsey, and Paul Drew
Subjects: Male, MEDLINE, Medical information, Neuropsychological Tests, Article, Diagnosis, Differential, 03 medical and health sciences, 0302 clinical medicine, Surveys and Questionnaires, medicine, Dementia, Humans, Memory disorder, 030212 general & internal medicine, Medical diagnosis, functional memory disorder, Memory Disorders, business.industry, screening, Memory clinic, Middle Aged, medicine.disease, Memory problems, body regions, Psychiatry and Mental health, Clinical Psychology, Female, Geriatrics and Gerontology, Differential diagnosis, Nervous System Diseases, business, Gerontology, 030217 neurology & neurosurgery, Clinical psychology, dementia
Abstract: The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. Objective: Specialist services for dementia are seeing an increasing number of patients. We investigated whether interactional and linguistic features in the communication behaviour of patients with memory problems could help distinguish between those with problems secondary to neurological disorders (ND) and those with Functional Memory Disorder (FMD). Methods: In Part 1 of this study, a Diagnostic Scoring Aid (DSA) was developed encouraging linguists to provide quantitative ratings for 14 interactional features. An optimal cut-off differentiating ND and FMD was established by applying the DSA to 30 initial patient–doctor memory clinic encounters. In Part 2, the DSA was tested prospectively in ten additional cases analysed independently by two Conversation Analysts blinded to medical information. Results: In part one, the median score of the DSA was +5 in ND and -5 in FMD (p
Published: 2017
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16. Conversational assessment in memory clinic encounters: interactional profiling for differentiating dementia from functional memory disorders

Author: Kirsty Harkness, Markus Reuber, Sarah Wakefield, Paul Drew, Daniel Blackburn, Christopher Elsey, and Danielle Jones
Subjects: Male, medicine.medical_specialty, Video Recording, Timely diagnosis, Limited access, Diagnosis, Differential, 03 medical and health sciences, 0302 clinical medicine, Memory, Physicians, medicine, Dementia, Profiling (information science), Humans, 030212 general & internal medicine, Psychiatry, Medical History Taking, Referral and Consultation, Aged, Video recording, Memory Disorders, Physician-Patient Relations, business.industry, Communication, Memory clinic, Middle Aged, medicine.disease, Psychiatry and Mental health, Conversation analysis, Tape Recording, Female, Geriatrics and Gerontology, Pshychiatric Mental Health, business, Gerontology, 030217 neurology & neurosurgery
Abstract: Objectives: In the UK dementia is under-diagnosed, there is limited access to specialist memory clinics, and many of the patients referred to such clinics are ultimately found to have functional (non-progressive) memory disorders (FMD), rather than a neurodegenerative disorder. Government initiatives on ‘timely diagnosis’ aim to improve the rate and quality of diagnosis for those with dementia. This study seeks to improve the screening and diagnostic process by analysing communication between clinicians and patients during initial specialist clinic visits. Establishing differential conversational profiles could help the timely differential diagnosis of memory complaints.\ud \ud Method: This study is based on video- and audio recordings of 25 initial consultations between neurologists and patients referred to a UK memory clinic. Conversation analysis was used to explore recurrent communicative practices associated with each diagnostic group.\ud \ud Results: Two discrete conversational profiles began to emerge, to help differentiate between patients with dementia and functional memory complaints, based on (1) whether the patient is able to answer questions about personal information; (2) whether they can display working memory in interaction; (3) whether they are able to respond to compound questions; (4) the time taken to respond to questions; and (5) the level of detail they offer when providing an account of their memory failure experiences.\ud \ud Conclusion: The distinctive conversational profiles observed in patients with functional memory complaints on the one hand and neurodegenerative memory conditions on the other suggest that conversational profiling can support the differential diagnosis of functional and neurodegenerative memory disorders.
Published: 2016

17. Journeying through Dementia, a community-based self-management intervention for people aged 65 years and over: a feasibility study to inform a future trial

Author: Kirsty Harkness, Claire Craig, Kirsty Sprange, Daniel Blackburn, Peter Bowie, Gail Mountain, Katy Shortland, and Maggie Spencer
Subjects: Quality of life, medicine.medical_specialty, Manualised intervention, Population, Staffing, Medicine (miscellaneous), Community, 03 medical and health sciences, 0302 clinical medicine, Quality of life (healthcare), Intervention (counseling), medicine, Self-management, Dementia, 030212 general & internal medicine, Psychiatry, education, education.field_of_study, business.industry, Research, 030503 health policy & services, Usability, 16. Peace & justice, medicine.disease, Tailored Intervention, 3. Good health, Family medicine, 0305 other medical science, business
Abstract: Background: A study to determine the feasibility of conducting a future population-based trial into a selfmanagement\ud intervention for community-living adults with early stage dementia included evaluation of\ud intervention content and modes of delivery, staffing requirements, recruitment methods and the utility and usability\ud of patient reported outcomes.\ud Methods: Participants identified through memory clinics in one city took part in an intervention called ‘Journeying\ud through Dementia’. The 12-week programme incorporating four individual sessions with one of the facilitators\ud encourages participants to engage in discussion and activities related to health and well-being positioning them as\ud the expert enabling long-term behavioural change. Participants (n = 10) and their nominated carers (n = 7) were all\ud asked to complete selected outcomes at baseline, 8 weeks (participants only) and post intervention and invited to\ud comment on their usability. All participants and carers were qualitatively interviewed before intervention delivery\ud about their expectations and participants; nominated carers and facilitators were all interviewed after cessation\ud about their experiences.\ud Results: The manualised intervention and modes of delivery proved acceptable to participants and carers. Reported\ud benefits included increased confidence and self-efficacy, engagement in new or lapsed activities and reengagement\ud in fun and friendships. People with dementia and carers were able to self-complete all outcome\ud measures, but time required to complete the measures is a key factor. Strategies for recruitment need to include\ud direct contact within 24–48 h post invitation to the study. Analysis of data on the primary outcome did not reveal\ud any trends. Facilitators found the training and support to be appropriate and helpful.\ud Conclusions: The tailored intervention reportedly met the needs of all participants. The study confirmed the need\ud for careful identification and application of patient-reported outcome measures. Outcomes to measure some\ud dimensions of reported benefit are not available.\ud Trial registration: Current Controlled Trials ISRCTN67209155.
Published: 2015

18. Towards diagnostic conversational profiles of patients presenting with dementia or functional memory disorders to memory clinics

Author: Sarah Wakefield, Annalena Venneri, Kirsty Harkness, Christopher Elsey, Danielle Jones, Markus Reuber, Paul Drew, and Daniel Blackburn
Subjects: Male, medicine.medical_specialty, Video Recording, Ambulatory Care Facilities, Secondary care, Diagnosis, Differential, Neuroimaging, Memory, medicine, Dementia, Humans, Neurologists, Medical diagnosis, Psychiatry, Conversation Analysis, Aged, Aged, 80 and over, Memory Disorders, Physician-Patient Relations, business.industry, Communication, Gold standard, Memory clinic, Functional memory disorders, General Medicine, Middle Aged, medicine.disease, Conversation analysis, Female, Differential diagnosis, business, Clinical psychology
Abstract: The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. Objective: This study explores whether the profile of patients’ interactional behaviour in memory clinic conversations with a doctor can contribute to the clinical differentiation between functional memory disorders (FMD) and memory problems related to neurodegenerative diseases. Methods: Conversation Analysis of video recordings of neurologists’ interactions with patients attending a specialist memory clinic. “Gold standard” diagnoses were made independently of CA findings by a multi-disciplinary team based on clinical assessment, neuropsychological testing and brain imaging. Results: Two discrete conversational profiles for patients with memory complaints emerged, including (i) who attends the clinic (i.e., whether or not patients are accompanied), and (ii) patients’ responses to neurologists’ questions about memory problems, such as difficulties with compound questions and providing specific and elaborated examples and frequent “I don’t know” responses. Conclusion: Specific communicative difficulties are characteristic of the interaction patterns of patients with a neurodegenerative pathology. Those difficulties are manifest in memory clinic interactions with neurologists, thereby helping to differentiate patients with dementia from those with FMD. Practical implications: Our findings demonstrate that conversational profiles based on patients’ contributions to memory clinic encounters have diagnostic potential to assist the screening and referral process from primary care, and the diagnostic service in secondary care.
Published: 2015
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19. Medical management with or without interventional therapy for unruptured brain arteriovenous malformations (ARUBA): a multicentre, non-blinded, randomised trial

Author: Richard B. Libman, Kirsty Harkness, Andreas Hartmann, Alessandra Biondi, Michael K. Parides, Rüdiger von Kummer, Jessica Overbey, Eric Vicaut, Joachim Berkefeld, Ellen Moquete, Jay P. Mohr, Marco Antonio Stefani, Catharina J.M. Klijn, Xavier Barreau, Alan J. Moskowitz, Rustam Al-Shahi Salman, Emmanuel Houdart, Christian Stapf, Charlotte Cordonnier, William L. Young, Claudia S. Moy, Wanke, Isabel (Beitragende*r), Sandalcioglu, Ibrahim Esol (Beitragende*r), and Sure, Ulrich (Beitragende*r)
Subjects: Adult, Intracranial Arteriovenous Malformations, Male, Pediatrics, medicine.medical_specialty, Population, Medizin, Radiosurgery, Neurosurgical Procedures, Article, law.invention, Embolization, Young Adult, Randomized controlled trial, law, Cause of Death, Clinical endpoint, Medicine, Humans, Prospective Studies, education, Stroke, Cause of death, Aged, education.field_of_study, Intention-to-treat analysis, business.industry, Hazard ratio, General Medicine, Middle Aged, medicine.disease, Combined Modality Therapy, Embolization, Therapeutic, Treatment Outcome, Female, Neurosurgery, Therapeutic, business
Abstract: BACKGROUND: The clinical benefit of preventive eradication of unruptured brain arteriovenous malformations remains uncertain. A Randomised trial of Unruptured Brain Arteriovenous malformations (ARUBA) aims to compare the risk of death and symptomatic stroke in patients with an unruptured brain arteriovenous malformation who are allocated to either medical management alone or medical management with interventional therapy.METHODS: Adult patients (≥18 years) with an unruptured brain arteriovenous malformation were enrolled into this trial at 39 clinical sites in nine countries. Patients were randomised (by web-based system, in a 1:1 ratio, with random permuted block design [block size 2, 4, or 6], stratified by clinical site) to medical management with interventional therapy (ie, neurosurgery, embolisation, or stereotactic radiotherapy, alone or in combination) or medical management alone (ie, pharmacological therapy for neurological symptoms as needed). Patients, clinicians, and investigators are aware of treatment assignment. The primary outcome is time to the composite endpoint of death or symptomatic stroke; the primary analysis is by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00389181.FINDINGS: Randomisation was started on April 4, 2007, and was stopped on April 15, 2013, when a data and safety monitoring board appointed by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health recommended halting randomisation because of superiority of the medical management group (log-rank Z statistic of 4·10, exceeding the prespecified stopping boundary value of 2·87). At this point, outcome data were available for 223 patients (mean follow-up 33·3 months [SD 19·7]), 114 assigned to interventional therapy and 109 to medical management. The primary endpoint had been reached by 11 (10·1%) patients in the medical management group compared with 35 (30·7%) in the interventional therapy group. The risk of death or stroke was significantly lower in the medical management group than in the interventional therapy group (hazard ratio 0·27, 95% CI 0·14-0·54). No harms were identified, other than a higher number of strokes (45 vs 12, pINTERPRETATION: The ARUBA trial showed that medical management alone is superior to medical management with interventional therapy for the prevention of death or stroke in patients with unruptured brain arteriovenous malformations followed up for 33 months. The trial is continuing its observational phase to establish whether the disparities will persist over an additional 5 years of follow-up.FUNDING: National Institutes of Health, National Institute of Neurological Disorders and Stroke.
Published: 2013

20. Utility of an ultrafast magnetic resonance imaging protocol in recent and semi-recent strokes

Author: Martin J. Graves, Kirsty Harkness, Elizabeth A. Warburton, Nagui M. Antoun, Jean-Claude Baron, Ilse Joubert, Jean-Marie U-King-Im, Rikin A. Trivedi, H. Eales, Koo B, and Jonathan H. Gillard
Subjects: Adult, Male, medicine.medical_specialty, Technology Assessment, Biomedical, Quality Assurance, Health Care, Short Report, Fluid-attenuated inversion recovery, Sensitivity and Specificity, Magnetic resonance angiography, Brain Ischemia, medicine, Image Processing, Computer-Assisted, Humans, In patient, cardiovascular diseases, Stroke, Aged, Protocol (science), Aged, 80 and over, medicine.diagnostic_test, Cerebral infarction, business.industry, Brain, Magnetic resonance imaging, Cerebral Infarction, Middle Aged, medicine.disease, Image Enhancement, Magnetic Resonance Imaging, Psychiatry and Mental health, Editorial Commentary, Ischemic Attack, Transient, Feasibility Studies, Surgery, Female, Neurology (clinical), Radiology, business, Magnetic Resonance Angiography, Diffusion MRI
Abstract: To evaluate the technical feasibility of an integrated ultrafast head magnetic resonance (MR) protocol using a sensitivity encoding (SENSE) technique for depicting parenchymal ischaemia and vascular compromise in patients with suspected recent stroke.23 patients were evaluated with the ultrafast MR protocol using T2, T1, fluid attenuated inversion recovery (FLAIR), 3D time of flight magnetic resonance angiography (MRA), and diffusion weighted imaging (DWI) sequences. These were compared with routine conventional MR sequences.One patient could not tolerate conventional imaging, although imaging using the three minute head SENSE protocol was diagnostic. Both conventional and ultrafast protocols were of similar diagnostic yield in the remaining patients. There were no significant differences in clinical diagnostic quality for the T1, T2, FLAIR, and DWI sequences. One MRA examination was of better quality when SENSE was used, owing to reduced motion artefacts and shorter imaging time.It is possible to undertake a comprehensive MR examination in stroke patients in approximately three to five minutes. Ultrafast imaging may become a useful triage tool before thrombolytic therapy. It may be of particular benefit in patients unable to tolerate longer sequences. Further work is necessary to confirm these findings in hyperacute stroke.
Published: 2005

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20 results on '"Kirsty Harkness"'

1. Feasibility of comparing medical management and surgery (with neurosurgery or stereotactic radiosurgery) with medical management alone in people with symptomatic brain cavernoma – protocol for the Cavernomas: A Randomised Effectiveness (CARE) pilot trial

2. Prognostic indicators and outcomes of hospitalised COVID-19 patients with neurological disease: An individual patient data meta-analysis

3. Potential missed opportunities to prevent ischaemic stroke: prospective multicentre cohort study of atrial fibrillation-associated ischaemic stroke and TIA

4. 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

5. Safety and efficacy of losartan for the reduction of brain atrophy in clinically diagnosed Alzheimer's disease (the RADAR trial): a double-blind, randomised, placebo-controlled, phase 2 trial

6. Effects of oral anticoagulation for atrial fibrillation after spontaneous intracranial haemorrhage: a randomised, open-label, assessor-blinded, pilot phase, non-inferiority trial

7. Fully automated cognitive screening tool based on assessment of speech and language

8. Bayesian Inference Associates Rare KDR Variants with Specific Phenotypes in Pulmonary Arterial Hypertension

9. Medical management with interventional therapy versus medical management alone for unruptured brain arteriovenous malformations (ARUBA):final follow-up of a multicentre, non-blinded, randomised controlled trial

10. Cognitive Impairment Before Atrial Fibrillation-Related Ischemic Events:Neuroimaging and Prognostic Associations

11. Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

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

13. Effects of fluoxetine on functional outcomes after acute stroke (FOCUS) : a pragmatic, double-blind, randomised, controlled trial

14. Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial

15. An Interactional Profile to Assist the Differential Diagnosis of Neurodegenerative and Functional Memory Disorders

16. Conversational assessment in memory clinic encounters: interactional profiling for differentiating dementia from functional memory disorders

17. Journeying through Dementia, a community-based self-management intervention for people aged 65 years and over: a feasibility study to inform a future trial

18. Towards diagnostic conversational profiles of patients presenting with dementia or functional memory disorders to memory clinics

19. Medical management with or without interventional therapy for unruptured brain arteriovenous malformations (ARUBA): a multicentre, non-blinded, randomised trial

20. Utility of an ultrafast magnetic resonance imaging protocol in recent and semi-recent strokes

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