5 results on '"Jill Gallagher"'
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2. Large Animal Models of Huntington’s Disease: What We Have Learned and Where We Need to Go Next
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Deborah Fernau, Heather L. Gray-Edwards, Jill Gallagher, Zdenka Ellederova, Neil Aronin, David Howland, Jodi L. McBride, Amanda Taylor, Alison Weiss, and Jon D. Hennebold
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0301 basic medicine ,Primates ,sheep ,Swine ,nonhuman primates ,Disease ,Biology ,Article ,Animals, Genetically Modified ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Huntington's disease ,Single species ,medicine ,Htt gene ,therapeutics ,Animals ,medicine.disease ,Response to treatment ,Minipigs ,Biomarker (cell) ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,Huntington Disease ,Swine, Miniature ,Neurology (clinical) ,Neuroscience ,030217 neurology & neurosurgery ,Neuroanatomy ,Large animal - Abstract
Genetically modified rodent models of Huntington’s disease (HD) have been especially valuable to our understanding of HD pathology and the mechanisms by which the mutant HTT gene alters physiology. However, due to inherent differences in genetics, neuroanatomy, neurocircuitry and neurophysiology, animal models do not always faithfully or fully recapitulate human disease features or adequately predict a clinical response to treatment. Therefore, conducting translational studies of candidate HD therapeutics only in a single species (i.e. mouse disease models) may not be sufficient. Large animal models of HD have been shown to be valuable to the HD research community and the expectation is that the need for translational studies that span rodent and large animal models will grow. Here, we review the large animal models of HD that have been created to date, with specific commentary on differences between the models, the strengths and disadvantages of each, and how we can advance useful models to study disease pathophysiology, biomarker development and evaluation of promising therapeutics.
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- 2020
3. Development of a Disease Progression Model for Leucine‐Rich Repeat Kinase 2 in Parkinson's Disease to Inform Clinical Trial Designs
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Romeo Maciuca, Rachael A Lawson, Timothy Nicholas, David T. Dexter, Malidi Ahamadi, Chao Chen, David J. Burn, Kenneth Marek, Minhua Yang, Klaus Romero, Bob Stafford, Sreeraj Macha, Julie A. Stone, Diane Stephenson, Jackson Burton, Daniela J. Conrado, Vikram Sinha, Hans Smit, Massimo Bani, Mussie Akalu, Jill Gallagher, Babak Boroojerdi, Jonas Weidemann, and Charles S. Venuto
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Adult ,Male ,Research design ,Oncology ,medicine.medical_specialty ,Parkinson's disease ,Disease ,Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 ,030226 pharmacology & pharmacy ,Article ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Humans ,Medicine ,Pharmacology (medical) ,Aged ,Aged, 80 and over ,Pharmacology ,Clinical Trials as Topic ,business.industry ,Incidence (epidemiology) ,Parkinson Disease ,Middle Aged ,Models, Theoretical ,medicine.disease ,LRRK2 ,Clinical trial ,Research Design ,030220 oncology & carcinogenesis ,Concomitant ,Mutation ,Disease Progression ,Female ,business ,Cohort study - Abstract
A quantitative assessment of Parkinson’s disease (PD) progression is critical for optimizing clinical trials design. Disease progression model was developed using pooled data from the Progression Marker Initiative study and the Incidence of Cognitive Impairment in Cohorts with Longitudinal Evaluation in Parkinson’s Disease study. Age, gender, concomitant medication, and study arms were predictors of baseline. A mutation in the leucine-rich repeat kinase 2 (LRRK2) encoding gene was associated with the disease progression rate. The progression rate in subjects with PD who carried LRRK2 mutation was slightly slower (~0.170 points/month) than that in PD subjects without the mutation (~0.222 points/month). For a non-enriched placebo-controlled clinical trial, approximately 70 subjects/arm would be required to detect a drug effect of 50% reduction in the progression rate with 80% probability. Whereas, 85, 93 and 100 subjects/arm would be required for an enriched clinical trial with 30%, 50% and 70% subjects with LRRK2 mutations, respectively.
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- 2019
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4. The Qualification of an Enrichment Biomarker for Clinical Trials Targeting Early Stages of Parkinson’s Disease
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Arthur Roach, Ed Somer, Klaus Romero, Glenn T. Stebbins, John Seibyl, Daniela J. Conrado, Maria B. Tome, Timothy Nicholas, Donald G. Grosset, Peter Basseches, Paul Maguire, Kenneth Marek, David T Dexter, David S. Russell, Diane Stephenson, Syed Z. Imam, Derek L. G. Hill, Dawn Matthews, Jill Gallagher, Zhiyong Xie, Danna Jennings, Mark Forrest Gordon, Jesse M. Cedarbaum, and Spiros Vamvakas
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0301 basic medicine ,medicine.medical_specialty ,Parkinson's disease ,enrichment biomarker ,Review ,Disease ,01 natural sciences ,Motor symptoms ,SWEDD ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,PPMI ,0302 clinical medicine ,Physical medicine and rehabilitation ,Neuroimaging ,EMA ,medicine ,Humans ,030212 general & internal medicine ,0101 mathematics ,PRECEPT ,Societies, Medical ,Tomography, Emission-Computed, Single-Photon ,Clinical Trials as Topic ,Dopamine Plasma Membrane Transport Proteins ,business.industry ,Clinical Studies as Topic ,010102 general mathematics ,Dopaminergic ,Parkinson Disease ,medicine.disease ,Corpus Striatum ,3. Good health ,Clinical trial ,Observational Studies as Topic ,030104 developmental biology ,Dopamine transporter ,Biomarker (medicine) ,Observational study ,Neurology (clinical) ,Erratum ,business ,Biomarkers ,030217 neurology & neurosurgery - Abstract
As therapeutic trials target early stages of Parkinson's disease (PD), appropriate patient selection based purely on clinical criteria poses significant challenges. Members of the Critical Path for Parkinson's Consortium formally submitted documentation to the European Medicines Agency (EMA) supporting the use of Dopamine Transporter (DAT) neuroimaging in early PD. Regulatory documents included a comprehensive literature review, a proposed analysis plan of both observational and clinical trial data, and an assessment of biomarker reproducibility and reliability. The research plan included longitudinal analysis of the Parkinson Research Examination of CEP-1347 Trial (PRECEPT) and the Parkinson's Progression Markers Initiative (PPMI) study to estimate the degree of enrichment achieved and impact on future trials in subjects with early motor PD. The presence of reduced striatal DAT binding based on visual reads of single photon emission tomography (SPECT) scans in early motor PD subjects was an independent predictor of faster decline in UPDRS Parts II and III as compared to subjects with scans without evidence of dopaminergic deficit (SWEDD) over 24 months. The EMA issued in 2018 a full Qualification Opinion for the use of DAT as an enrichment biomarker in PD trials targeting subjects with early motor symptoms. Exclusion of SWEDD subjects in future clinical trials targeting early motor PD subjects aims to enrich clinical trial populations with idiopathic PD patients, improve statistical power, and exclude subjects who are unlikely to progress clinically from being exposed to novel test therapeutics.
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- 2019
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5. 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
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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
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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
- Full Text
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