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1. Arduino-Based Sensing Platform for Rapid, Low-Cost, and High-Sensitivity Detection and Quantification of Analytes in Fluidic Samples

Author

Derek Hayden, Sergio Anacleto, Daphne-Eleni Archonta, Nour Khalil, Antonia Pennella, Shadan Qureshi, Alexandre Séguin, and Nima Tabatabaei

Subjects
THC, lateral flow immunoassay, Arduino, point-of-need, photo-thermal radiometry, Engineering machinery, tools, and implements, TA213-215
Abstract

Lateral flow assays (LFAs; aka. rapid tests) are inexpensive paper-based devices for rapid and specific detection of analyte of interest (e.g., COVID virus) in fluidic samples. Areas of application of LFAs cover a broad spectrum, spanning from agriculture to food/water safety to point-of-care medical testing and, most recently, to detection of COVID-19 infection. While these low-cost and rapid tests are specific to the target analyte, their sensitivity and limit of detection are far inferior to their laboratory-based counterparts. In addition, rapid tests normally cannot quantify the concentration of target analyte and only provide qualitative/binary detection. We have developed a low-cost, end-user sensing platform that significantly improves the sensitivity of rapid tests. The developed platform is based on Arduino and utilizes low-cost far infrared, single-element detectors to offer sensitive and semi-quantitative results from commercially available rapid tests. The sensing paradigm integrated to the low-cost device is based on radiometric detection of photothermal responses of rapid tests in the frequency domain when exposed to modulated laser excitation. As a proof of principle, we studied commercially available rapid tests for detection of THC (the principal psychoactive constituent of cannabis) in oral fluid with different concentrations of control positive solutions and, subsequently, interpret them with the developed sensor. Results suggest that the developed end-user sensor is not only able to improve the detection limit of the rapid test by approximately an order of magnitude from 25 ng/mL to 5 ng/mL, but also offers the ability to obtain semi-quantitative insight into concentration of THC in the fluidic samples.

Published
2022
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2. Piloting a randomized, double-blind, placebo-controlled study design at a community hospital to evaluate prophylactic antibiotics in endoscopic carpal tunnel release: Clinical, logistic, and economic considerations

Author

Chelsea Bush, Richard Trevino, and Derek Hayden

Subjects
Orthopedic surgery, medicine.medical_specialty, business.industry, Placebo-controlled study, Hand surgery, Endoscopic carpal tunnel release, Prophylactic antibiotic administration, Evidence-based medicine, Placebo, Community hospital, Research in community hospitals, Emergency medicine, Medicine, Clinical significance, Antibiotic prophylaxis, business, Surgical site infection, RD701-811
Abstract

Introduction Surgical site infection is low following endoscopic carpal tunnel release (ECTR), yet antibiotic prophylaxis is still common in these procedures. This study piloted a randomized, double-blind, placebo-controlled study design at a community hospital to generate discourse in support of discontinuing antibiotic prophylaxis in ECTR procedures. Methods Patients undergoing dual-incision endoscopic carpal tunnel release at a single community hospital between May 1, 2018 and December 31, 2020 were enrolled in a pilot study. Subjects were randomized to prophylactic antibiotics or placebo saline solution arms. Infection rates and complications were compared. Study workflow processes were streamlined to facilitate eventual study duplication at additional sites. Results One hundred twenty-four subjects (140 hands) were included in the final analysis. No subjects in either study arm sustained an infection. The race and ethnic distributions of the study sample closely resembled those of the census-reported community distributions. Implementing a randomized, double-blind, placebo-controlled study at a community hospital presented numerous challenges. Discussion Although statistical nor clinical significance could be established in the absence of infection, these results validate what is presently known regarding the low likelihood of infection in clean hand surgery and demonstrated the feasibility of designing and implementing methodologically sound research in a community setting. Conclusion Duplicating this study design at additional research sites can provide the level of evidence necessary to discourage unnecessary prophylactic antibiotic administration in clean hand surgery.

Published
2021

3. 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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4. 218 Swallowing/Communication Screening in Older Adults Attending the Emergency Department and Association with Clinical Frailty Scale Scores

Author

Orla Boyle, Maeve Ryan, Louise Kelly, Orlaith Doherty, Catriona Whelan, Maeve Murphy, Sarah Mello, Deirdre Brady, Paul McElwaine, James Gray, Derek Hayden, Sean Kennelly, and Ruth Wade

Subjects
Aging, medicine.medical_specialty, business.industry, General Medicine, Emergency department, Speech therapy, Patient referral, Chronic disease, Swallowing, Scale (social sciences), Physical therapy, Medicine, Frail elderly, Geriatrics and Gerontology, business, Association (psychology)
Abstract

Background Dysphagia, frailty and negative patient outcomes are interlinked1. Changes in communication may result from the ageing process, chronic conditions, and/or neurologic conditions presenting in later years2. However, unlike other cohorts, including stroke, frail older patients are not routinely screened for swallowing/communication difficulties in acute settings. We investigated the proportion of Speech and Language Therapy (SLT) referrals generated for older patients attending our Emergency Department (ED) following use of a swallowing/communication screening tool and their association with Clinical Frailty Scale (CFS) scores. Methods A retrospective analysis of data collected over a four week period was completed. Older patients presenting to ED were screened by the interdisciplinary gerontological ED team using a screening tool, including a locally developed swallow/communication screen. Statistical analyses were performed using STATA Version 12. Results Of 176 patients screened (mean age 81.8 years, SD 5.9 years), median CFS score was 5 (IQR 3-6). Thirty-seven percent (66/176) of patients were referred for SLT assessment following initial screen. SLT referrals were more commonly required in patients with a CFS score of ≥4 (46.2% vs. 19.3%, P=0.001) and likelihood of requiring SLT referral increased with greater CFS score (P Conclusion Results suggest that screening for swallowing and communication difficulties in older patients yields a high level of SLT referrals, with a higher frequency of SLT referrals observed with increasing frailty scores. Further research is required to determine the optimum swallowing/communication screening tool in the acute setting. Future research will focus on evaluating outcomes of SLT assessments completed and determining the prevalence of swallowing and/or communication difficulties in this cohort.

Published
2019
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5. 172 Sarcopenia, Frailty and Malnutrition in the Older Adults in the Emergency Department Setting

Author

Derek Hayden, Louise Kelly, Orlaith Doherty, Sarah Mello, Sean Kennelly, Ruth Wade, Deirdre Brady, Paul McElwaine, Caitriona Whelan, James Gray, Orla Boyle, Maeve Ryan, and Maeve Murphy

Subjects
Aging, medicine.medical_specialty, business.industry, General Medicine, Emergency department, medicine.disease, Malnutrition, Grip strength, Sarcopenia, Physical therapy, Medicine, Posterior crural muscle, Geriatrics and Gerontology, business
Abstract

Background The physical phenotype of frailty shows significant overlap with sarcopenia, and sarcopenia phenotype is associated with malnutrition. Integrating screening of these interrelated conditions, could help identify those most vulnerable in the Emergency Department (ED) setting. Methods Patients ≥75 were screened in the Emergency department (ED) by an interdisciplinary Gerontological ED team using a standardised assessment tool, incorporating the Clinical Frailty Scale (CFS) and the mini-nutritional assessment short form (MNA-SF). Patients at risk of malnutrition ( MNA-SF Results In a convenience sample of patients referred to dietetics following initial screen in ED, 57% were female (25/44) and the mean age was 83 years (range 75-94). Eighty-eight percent (39/44) were at risk of malnutrition/malnourished and 25% (11/44) were diagnosed with malnutrition (MNA-SF score 0-7). Seventy-three percent (32/44) scored ≥4 on the CFS. Fifty-two percent of all patients (23/44) had a Sarc-F ≥ 4, suggestive of sarcopenia, while 45% (20/44) had a probable diagnosis of sarcopenia and 39% (17/44) met diagnostic criteria for sarcopenia. Risk of malnutrition was more commonly observed in those patients with a CFS score ≥4 (94% vs. 75%), as was risk of sarcopenia (81% vs. 17%). Fifty percent (22/44) of all patients screened positive for suspicion of both frailty and sarcopenia (frailty score≥4 and Sarc-F score≥4). Patients with a probable diagnosis of sarcopenia and concomitant frailty had more ED attendances, falls and longer lengths of stay. Conclusion Frailty, malnutrition and sarcopenia are frequently observed in older patients in the acute setting. The integration of screening measures for malnutrition, frailty and sarcopenia in clinical practice can facilitate the identification of patients for multi-component targeted interventions.

Published
2019
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6. 221 Delirium Detection in the ED Utilizing the 4AT Delirium Screening Tool

Author

Orla Boyle, Deirdre Brady, Paul McElwaine, Louise Kelly, Orlaith Doherty, Derek Hayden, James Gray, Ruth Wade, Maeve Murphy, Caitriona Whelan, Sarah Mello, Maeve Ryan, and Sean Kennelly

Subjects
Aging, medicine.medical_specialty, business.industry, General Medicine, medicine.disease, Patient referral, Malnutrition, mental disorders, Medicine, Delirium, Screening tool, Frail elderly, Geriatrics and Gerontology, medicine.symptom, business, Intensive care medicine
Abstract

Background Delirium is a medical emergency and is associated with increased risk of mortality, in-hospital complications, length of stay and institutionalisation. Delirium screening is recommended for patients at risk on admission. Despite this, delirium screening is frequently not undertaken in the acute setting leading to undiagnosed delirium and sub-optimal clinical care. We aim to investigate the prevalence of delirium in patients aged ≥75 years attending the Emergency Department (ED) of a tertiary referral centre. Methods Patients aged ≥75yrs presenting to the ED between 08.30 and 18.30, Monday- Friday were assessed by an interdisplinary gerontological service using a standardised assessment tool including the 4AT to screen for delirium. Data was collected and analysed via Excel. Results Of 163 patients screened over a 4 week period 47.9% (78/163) were male with a mean age of 81.8 years (SD 2.7). Twenty three percent (34/148) scored ≥4 indicating a possible delirium. Patients with delirium were older (85 yrs vs. 80 yrs, P Conclusion Routine screening of patients in the acute setting detected a high rate of delirium at a level which is consistent with previous studies. Patients with delirium were older, more frequently frail and at risk of malnutrition. Our results support the evidence for routine screening for delirium in the acute setting.

Published
2019
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7. 190 Who is ‘Fit to Sit’ in Our Emergency Department?

Author

Orla Boyle, Caitriona Whelan, Derek Hayden, Ruth Wade, Aileen McCabe, Deirdre Brady, Paul McElwaine, Louise Kelly, Orlaith Doherty, Sarah Mello, Brendan Malone, James Gray, Maeve Murphy, and Maeve Ryan

Subjects
Aging, Nursing staff, Dishonesty, business.industry, media_common.quotation_subject, General Medicine, Emergency department, Health outcomes, medicine.disease, Impaired mobility, Medicine, Medical emergency, Geriatrics and Gerontology, business, media_common
Abstract

Background Older admitted patients are at risk of deconditioning related to immobility. “Fit to Sit” is a simple change in the Emergency Department (ED) culture and attitude, promoting independence, maximizing well-being and improving health outcomes. We aim to describe the prevalence of patients deemed “Fit to Sit” who were in hospital gowns and lying on trolleys in our ED prior to the commencement of the “Fit to Sit” pilot. Methods An observational study was conducted prospectively, over five working days, to determine the proportion of patients present who were dressed and sitting out on a chair, opposed to wearing pyjamas (PJs) and lying on a trolley. Nursing staff familiar with each patient were asked whether or not the patient was fit to sit out in a chair. Statistical analysis was conducted with Microsoft Excel using the chi squared test to calculate differences between the two groups. Results Data was collected on 147 patients, median age 66 years (IQR 47-74). 82% were on a trolley and 18% in a chair. 33% were in their clothes, the remaining 67% were in PJs or hospital gowns. 45% of those deemed “Fit to Sit” were on a trolley. Patients 65 and older were more likely to be wearing PJs (p= 0.03), but not more likely to be on a trolley (p= 0.23). Patients in ED for greater than 12 hours were also more likely to be in PJs (p= 0.001) and on a trolley (p= 0.057). Conclusion Our study suggests that a significant proportion of ED patients are lying on trolleys despite being deemed to be “Fit to Sit”. Introduction of an ED “Fit to Sit” programme may alleviate deconditioning and promote patient independence.

Published
2019
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8. Renal dysfunction and chronic kidney disease in ischemic stroke and transient ischemic attack: A population-based study

Author

David Williams, Layan Akijian, Lorraine Kyne, Eamon Dolan, Derek Hayden, Killian O' Rourke, Yvonne M. O'Meara, Sean Murphy, Gillian Horgan, Joseph Duggan, Elizabeth Callaly, Danielle Ní Chróinín, Christine McCarthy, and Peter J. Kelly

Subjects
Male, medicine.medical_specialty, Renal function, 030204 cardiovascular system & hematology, Kidney, 03 medical and health sciences, 0302 clinical medicine, Population Groups, Internal medicine, Prevalence, Humans, Medicine, Renal Insufficiency, Chronic, Stroke, Aged, Aged, 80 and over, business.industry, Middle Aged, medicine.disease, Survival Analysis, Population based study, Neurology, Ischemic Attack, Transient, Ischemic stroke, Cardiology, Female, business, Ireland, 030217 neurology & neurosurgery, Glomerular Filtration Rate, Kidney disease
Abstract

Background and purpose The prevalence of chronic kidney disease (estimated glomerular filtration rate (eGFR) 2 for ≥3 months, chronic kidney disease (CKD)) in ischemic stroke and transient ischemic attack (TIA) is unknown, as estimates have been based on single-point estimates of renal function. Studies investigating the effect of renal dysfunction (eGFR 2, renal dysfunction) on post-stroke outcomes are limited to hospitalized cohorts and have provided conflicting results. Methods We investigated rates, determinants and outcomes of renal dysfunction in ischemic stroke and TIA in the North Dublin Population Stroke Study. We also investigate the persistence of renal dysfunction in 90-day survivors to determine the prevalence of CKD. Ascertainment included hot and cold pursuit using multiple overlapping sources. Survival analysis was performed using Kaplan–Meier survival curves and Cox proportional hazards modeling. Results In 547 patients (ischemic stroke in 76.4%, TIA in 23.6%), the mean eGFR at presentation was 63.7 mL/min/1.73 m2 (SD 22.1). Renal dysfunction was observed in 44.6% (244/547). Among 90-day survivors, 31.2% (139/446) met criteria for CKD. After adjusting for age and stroke severity, eGFR 2 (hazard ratio 2.53, p = 0.01) independently predicted 28-day fatality but not at two years. Poor post-stroke functional outcome (Modified Rankin Scale 3–5) at two years was more common in those with renal dysfunction (52.5% vs. 20.6%, p Conclusion Renal dysfunction and CKD are common in ischemic stroke and TIA. Renal dysfunction is associated with considerable post-stroke morbidity and mortality. Further studies are needed to investigate if modifiable mechanisms underlie these associations.

Published
2017
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9. 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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10. 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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11. Why do transient ischemic attack patients have higher early stroke recurrence risk than those with ischemic stroke? Influence of patient behavior and other risk factors in the North Dublin Population Stroke Study

Author

Niamh Hannon, Gillian Horgan, Eamon Dolan, Aine Merwick, Orla Sheehan, Derek Hayden, Killian O'Rourke, Michael Marnane, Peter J. Kelly, Joseph Duggan, Danielle Ní Chróinín, Lorraine Kyne, Layan Akijian, Sean Murphy, Elizabeth Callaly, and David Williams

Subjects
Male, medicine.medical_specialty, Time Factors, Early Recurrence, Stroke recurrence, Health Behavior, Population, 030204 cardiovascular system & hematology, Time-to-Treatment, 03 medical and health sciences, 0302 clinical medicine, Recurrence, Internal medicine, Odds Ratio, medicine, Humans, Prospective Studies, education, Stroke, Aged, education.field_of_study, business.industry, medicine.disease, Surgery, Logistic Models, Neurology, Ischemic Attack, Transient, Multivariate Analysis, Ischemic stroke, Cardiology, Female, Patient behavior, business, Ireland, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract

Background Few studies have directly compared stroke recurrence rates after stroke and transient ischemic attack, and the risk factors underlying early recurrence are poorly understood. We aimed to investigate risk factors for recurrent stroke after first stroke and transient ischemic attack in a population-based study. Methods The North Dublin Population Stroke Study applied multiple overlapping hot and cold pursuit methods, to ascertain hospital- and community-treated stroke and transient ischemic attack patients over a 12-month period. Inclusion criteria were: (1) Stroke-physician confirmed transient ischemic attack/ischemic stroke; (2) first-stroke/transient ischemic attack event within the ascertainment period. Patients were prospectively followed at 72 h, 7, 28 and 90 days. Results A total of 584 patients met eligibility criteria (172 transient ischemic attack, 412 stroke). More transient ischemic attack than stroke patients presented to medical attention with recurrent stroke (8.24% vs. 0.24%, p = 0.0002). Recurrent stroke was more common after transient ischemic attack than index stroke at each time-interval (at 72 h, 4.07% vs. 1.23%, p = 0.03; at 90 days, 13.45% vs. 5.72%, p = 0.002). Stroke recurrence at 90 days was also associated with delay seeking medical attention after the index event (OR 3.2, p = 0.001), delayed anti-platelet (OR 2.8, p = 0.001) and statin (OR 2.4, p = 0.009) treatment, carotid stenosis/occlusion (OR 2.4, p = 0.008). On multivariable analysis, transient ischemic attack as index event (adjusted OR 2.3, p = 0.02), delayed statin treatment (OR 2.5, p = 0.02), and carotid stenosis/occlusion (OR 2.4, p = 0.02) were independent predictors of 90-day recurrent stroke. Conclusion A combination of pathophysiological and behavioral factors was associated with early stroke recurrence risk. Improved public awareness to reduce delays to self-referral for transient ischemic attack symptoms is needed.

Published
2016
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12. Rates, Predictors, and Outcomes of Early and Late Recurrence After Stroke

Author

Niamh Hannon, Eamon Dolan, Danielle Ní Chróinín, Layan Akijian, Aine Merwick, Lorraine Kyne, Joseph Duggan, Orla Sheehan, Elizabeth Callaly, Derek Hayden, Michael Marnane, Sean Murphy, Peter J. Kelly, Gillian Horgan, Killian O'Rourke, and David Williams

Subjects
Male, medicine.medical_specialty, Pediatrics, Stroke recurrence, Population, 030204 cardiovascular system & hematology, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Predictive Value of Tests, Recurrence, Late Recurrence, medicine, Humans, Prospective Studies, education, Stroke, Aged, Aged, 80 and over, Advanced and Specialized Nursing, education.field_of_study, business.industry, Middle Aged, medicine.disease, Surgery, Treatment Outcome, Ischemic Attack, Transient, Population Surveillance, Female, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, Ireland, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract

Background and Purpose— Few recent studies have investigated the rates and predictors of early and late stroke recurrence using prospective population–based methodology. We investigated recurrent stroke at 2 years in the North Dublin Population Stroke Study (NDPSS). Methods— Patients were ascertained from December 2005 to 2006 from overlapping community and hospital sources using hot and cold pursuit. Stroke recurrence, survival, and functional outcome were ascertained at 72 hours, 7 days, 28 days, 90 days, 1 year, and 2 years. Results— Of 567 patients, cumulative 2-year stroke recurrence rate was 10.8% and case fatality was 38.6%. Recurrence subtype was associated with initial stroke subtype ( P P =0.005) and prior stroke (adjusted hazard ratio, 2.92; P =0.01) were independent predictors of 2-year recurrence in 28-day survivors. Conclusions— Despite rigorous ascertainment, recurrent stroke rates were lower in current study than in earlier studies. Our data suggest that large sample sizes may be needed for future secondary prevention trials in patients treated with modern preventive medications.

Published
2016
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13. Rates and Determinants of 5-Year Outcomes After Atrial Fibrillation-Related Stroke: A Population Study

Author

Gillian Horgan, Danielle Ní Chróinín, Sean Murphy, Niamh Hannon, Joseph Duggan, Killian O'Rourke, Peter J. Kelly, Derek Hayden, Lorraine Kyne, Elizabeth Callaly, David Williams, and Eamon Dolan

Subjects
Male, medicine.medical_specialty, Time Factors, Population, Risk Factors, Atrial Fibrillation, medicine, Humans, Prospective Studies, education, Prospective cohort study, Survival rate, Stroke, Survival analysis, Aged, Advanced and Specialized Nursing, Aged, 80 and over, education.field_of_study, business.industry, Incidence (epidemiology), Atrial fibrillation, medicine.disease, Confidence interval, Survival Rate, Treatment Outcome, Population Surveillance, Emergency medicine, Physical therapy, Female, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, Ireland, Follow-Up Studies
Abstract

Background and Purpose— Demographic trends in atrial fibrillation (AF) incidence may yield a substantial rise in the societal burden of AF-related stroke (AF-stroke). Accurate population-wide outcome data are essential to inform health service planning to improve AF-stroke prevention, and provision of rehabilitation, nursing home, and community supports for AF-stroke survivors. Methods— We investigated rates and determinants of 5-year fatality, stroke recurrence, functional outcomes, and prescribing of secondary prevention medications in AF-stroke in the North Dublin Population Stroke Study. Ascertainment included hot and cold pursuit using multiple overlapping sources. Survival analysis was performed using lifetables and Kaplan–Meier survival curves, and Cox proportional hazard modeling was performed to identify predictors of death and recurrent stroke. Results— Five hundred sixty-eight patients with new stroke were identified, including 177 (31.2%) AF-stroke. At 5 years, 39.2% (confidence interval, 31.5–46.8) of ischemic AF-stroke patients were alive. Congestive heart failure, hypertension, age 2 DS 2 -VASc) score (hazard ratio [HR], 1.34; P 2 score (HR 1.42, P =0.004), National Institute of Health Stroke Scale (HR, 1.09; P P =0.003) were independently associated with 5-year fatality, whereas warfarin (HR, 0.40; P =0.001) and statin use after index stroke (HR, 0.52; P =0.005) were associated with improved survival. The 5-year recurrence rate after ischemic AF-stroke was 21.5% (confidence interval, 14.5–31.3). Trends toward greater risk of recurrence were observed for persistent AF (HR, 3.09; P =0.07) and CHA 2 DS 2 -VASc score (HR, 1.34; P =0.07). Nursing home care was needed for 25.9% of patients. Conclusions— AF-stroke is associated with considerable long-term morbidity, fatality, stroke recurrence, and nursing home requirement. Adequately resourced national AF strategies to improve AF detection and prevention are needed.

Published
2015

14. Recurrent stroke in symptomatic carotid stenosis awaiting revascularization: A pooled analysis

Author

Angel Ois, Elisa Cuadrado-Godia, Per Wester, Elias Johansson, Jaume Roquer, Jakob Bjellerup, Peter J. Kelly, and Derek Hayden

Subjects
Adult, Male, medicine.medical_specialty, Neurology, Time Factors, medicine.medical_treatment, Cerebral Revascularization, Carotid endarterectomy, 030204 cardiovascular system & hematology, Revascularization, 03 medical and health sciences, 0302 clinical medicine, Recurrence, Risk Factors, Internal medicine, medicine, Humans, Carotid Stenosis, cardiovascular diseases, Prospective Studies, Prospective cohort study, Stroke, Endarterectomy, Aged, Aged, 80 and over, Endarterectomy, Carotid, business.industry, Middle Aged, medicine.disease, Surgery, Stenosis, Carotid Arteries, Treatment Outcome, Ischemic Attack, Transient, cardiovascular system, Cardiology, Female, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

We aimed to quantify the risk and predictors of ipsilateral ischemic stroke in patients with symptomatic carotid stenosis awaiting revascularization (carotid endarterectomy [CEA] or carotid artery stenting) by pooling individual patient data from recent prospective studies with high rates of treatment with modern stroke prevention medications.Data were included from 2 prospective hospital-based registries (Umeå, Barcelona) and one prospective population-based study (Dublin). Patients with symptomatic 50%-99% carotid stenosis eligible for carotid revascularization were included and followed for early recurrent ipsilateral stroke or retinal artery occlusion (RAO).Of 607 patients with symptomatic 50%-99% carotid stenosis, 377 met prespecified inclusion criteria. Ipsilateral recurrent ischemic stroke/RAO risk pre-revascularization was 2.7% (1 day), 5.3% (3 days), 11.5% (14 days), and 18.8% (90 days). On bivariate analysis, presentation with a cerebral vs ocular event was associated with higher recurrent stroke risk (log-rank p = 0.04). On multivariable Cox regression, recurrence was associated with older age (adjusted hazard ratio [HR] per 10-year increase 1.5, p = 0.02) with a strong trend for association with cerebral (stroke/TIA) vs ocular symptoms (adjusted HR 2.7, p = 0.06), but not degree of stenosis, smoking, vascular risk factors, or medications.We found high risk of recurrent ipsilateral ischemic events within the 14-day time period currently recommended for CEA. Randomized trials are needed to determine the benefits and safety of urgent vs subacute carotid revascularization within 14 days after symptom onset.

Published
2015

15. 117SINGLE HOSPITAL THROMBOLYSIS RATES IN CONSECUTIVE ISCHAEMIC STROKE PATIENTS

Author

Ronan O'Toole, Patrick O'Donoghue, Derek Hayden, Killian O'Rourke, Peter J. Kelly, Timothy Lynch, Brian Drumm, Shane Smyth, and Sean M. Murphy

Subjects
Aging, medicine.medical_specialty, business.industry, Internal medicine, medicine.medical_treatment, Ischaemic stroke, medicine, Cardiology, General Medicine, Thrombolysis, Geriatrics and Gerontology, business
Published
2016
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16. Human Stem Cells for Modeling Amyotrophic Lateral Sclerosis Disease Mechanisms and Modifiers

Author

Oakley, Derek Hayden

Subjects
FOS: Clinical medicine, Developmental biology, Neurosciences
Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of the motor system. Although ALS has been extensively studied in post-mortem patient samples and animal models, there are currently no very effective treatments and there is no cure. One reason for the lack of treatment options in ALS may stem from the inaccessibility of living human motor neurons for use in disease research and subsequent therapeutic target validation. Recent developments in the field of stem cell biology can potentially provide access to living human motor neurons from individual ALS patients. It is now possible to derive induced pluripotent stem cells (iPS cells) from the somatic tissues of ALS patients and then to differentiate these iPS cells into motor neurons with the precise genetic makeup of the donor patient (iPS-MNs). Before iPS-MNs can be put to productive use, however, the iPS system as a whole must be validated as a reliable source of motor neurons with characteristics that closely resemble their endogenous or hES-derived counterparts. This thesis will first address a series of issues relating to the validation of iPS cells as a reliable source of motor neurons a then move on to expression profiling studies aimed at identifying a transcriptional signature of ALS in iPS-MNs. I will first describe a collaborative study aimed at determining whether or not iPS cells are as useful as ES cells for the production of motor neurons. By comparing motor neuron differentiation efficiency across a panel of 6 ES lines and 16 iPS lines, we demonstrated that iPS cells are equally capable of producing electrophysiologically active motor neurons as ES cells. Moreover, both ALS and control iPS lines produce motor neurons with equal efficiency, suggesting that iPS cells will be useful in the production of ALS iPS-MNs for disease research. In addition, our results identify some of the variables that contribute to differentiation efficiency, including donor identity and individual iPS/ES line identity. The following section will serve to provide a deeper molecular and electrophysiological understanding of human stem cell-derived motor neurons. I first generated expression profiles from purified hES-MNs to identify potential motor neuron-specific surface markers as well as maturational changes occurring in motor neurons in vitro. Using calcium imaging techniques, I then demonstrated that iPS-MNs behave functionally similarly to ES-MNs and described culture-wide rhythmic depolarizations that are likely influencing multiple properties of iPS-MNs. After characterizing the iPS-MN culture system, I made a first attempt at defining the transcriptional phenotypes of ALS in iPS-MNs. This work relied on the use of a motor neuron-specific lentiviral reporter that I developed to isolate and transcriptionally profile iPS-MNs from two control iPS lines and four ALS iPS lines. I show evidence of significant transcriptional differences between motor neurons isolated from ALS lines and those from control patients. These differences may in the future help to define ALS-specific phenotypes. Lastly, I conducted a meta-analysis comparing transcriptional changes in ALS iPS-MNs to those in existing models of ALS and identified some common stress-related features of ALS in iPS-MNs. In order to form new hypotheses about what sorts of individual patient-specific phenotypes may be present in iPS-MNs, I will then utilize published expression profiles from post-mortem ALS patient motor neurons to identify a previously-overlooked class of genes that exhibit expression levels highly correlated with individual age at ALS onset. This group of 43 onset-correlated genes contains many members with known or hypothesized relationships to neurodegenerative disease. I discuss how onset-correlated genes may function as disease-modifiers or biomarkers and design experiments to investigate these possibilities. Taken together, the work in this thesis will lay the foundations for developing a human iPS-based model of ALS and point toward numerous avenues of future investigation.

Published
2012
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17. A 44-year-old man with eye, kidney, and brain dysfunction

Author

Vodopivec, Ivana, Oakley, Derek Hayden, Perugino, Cory Adam, Venna, Nagagopal, Hedley-Whyte, E. Tessa, and Stone, John H

Abstract

Retinal vasculopathy with cerebral leukodystrophy (RVCL) is a rare, autosomal dominant condition caused by mutations of the three-prime repair exonuclease-1 (TREX1). The phenotypic expressions range from isolated retinal involvement to varying degrees of retinopathy, cerebral infarction with calcium depositions, nephropathy, and hepatopathy. We report a case of RVCL caused by a novel TREX1 mutation. This patient’s multisystem presentation, retinal involvement interpreted as “retinal vasculitis”, and improvement of neuroimaging abnormalities with dexamethasone led to the accepted diagnosis of a rheumatologic disorder resembling Behçet’s disease. Clinicians should consider RVCL in any patient with retinal capillary obliterations associated with tumefactive brain lesions or nephropathy.

Published
2016
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18. Pathways Disrupted in Human ALS Motor Neurons Identified through Genetic Correction of Mutant SOD1

Author

Kiskinis, Evangelos, Sandoe, Jackson L, Williams, Lauren N., Boulting, Gabriella Lutz, Moccia, Robert, Wainger, Brian Jason, Han, Steve Sang-woo, Peng, Theodore, Thams, Sebastian, Mikkilineni, Shravani, Mellin, Cassidy, Merkle, Florian Tobias, Davis-Dusenbery, B, Ziller, Michael Johannes, Oakley, Derek Hayden, Ichida, Justin, Di Costanzo, Stefania, Atwater, Nick, Maeder, M, Goodwin, Marcus, Nemesh, James, Handsaker, Robert E, Paull, Daniel, Noggle, Scott, McCarroll, Steven A., Joung, Jae Keith, Woolf, Carl, Brown, Robert H, and Eggan, Kevin Carl

Abstract

Direct electrical recording and stimulation of neural activity using micro-fabricated silicon and metal micro-wire probes have contributed extensively to basic neuroscience and therapeutic applications; however, the dimensional and mechanical mismatch of these probes with the brain tissue limits their stability in chronic implants and decreases the neuron–device contact. Here, we demonstrate the realization of a three-dimensional macroporous nanoelectronic brain probe that combines ultra-flexibility and subcellular feature sizes to overcome these limitations. Built-in strains controlling the local geometry of the macroporous devices are designed to optimize the neuron/probe interface and to promote integration with the brain tissue while introducing minimal mechanical perturbation. The ultra-flexible probes were implanted frozen into rodent brains and used to record multiplexed local field potentials and single-unit action potentials from the somatosensory cortex. Significantly, histology analysis revealed filling-in of neural tissue through the macroporous network and attractive neuron–probe interactions, consistent with long-term biocompatibility of the device., Stem Cell and Regenerative Biology

Published
2014
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