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1. Factors Associated with Ophthalmology Referral and Adherence in a Teleretinal Screening Program: Insights from a Federally Qualified Health Center

Author

Song A, Johnson NA, Mirzania D, Ayala AM, Muir KW, and Thompson AC

Subjects
teleretinal screening, teleophthalmology, uninsured, underinsured, adherence, ophthalmology referral, Ophthalmology, RE1-994
Abstract

Ailin Song,1 Nicholas A Johnson,1 Delaram Mirzania,1,2 Alexandria M Ayala,1 Kelly W Muir,3,4 Atalie C Thompson3,5 1Duke University School of Medicine, Durham, NC, USA; 2Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan Health, Ann Arbor, MI, USA; 3Department of Ophthalmology, Duke University, Durham, NC, USA; 4Durham Center of Innovation to Accelerate Discovery and Practice Transformation, Durham Veterans Affairs Health Care System, Durham, NC, USA; 5Wake Forest Baptist Health, Winston Salem, NC, USACorrespondence: Atalie C Thompson, Wake Forest Baptist Health, Janeway Tower, 6 th Floor, 1 Medical Center Blvd, Winston Salem, NC, 27103, USA, Tel +1 650-868-8050, Email ataliethompson@gmail.comBackground: Early detection of ophthalmic conditions such as diabetic retinopathy (DR) and glaucoma is crucial to preventing vision loss. Previous studies have evaluated teleretinal screening programs for DR in well-insured populations. The purpose of this retrospective study was to evaluate a teleretinal screening program in a population of uninsured and underinsured patients seen in a Federally Qualified Health Center (FQHC).Methods: We conducted a retrospective chart review of patients (age ≥ 18) who underwent teleretinal imaging (TRI) at a FQHC between January 2015 and September 2019. TRI gradings and patient demographic and clinical information were abstracted. Factors associated with referral for a dilated eye exam by an ophthalmologist, adherence to recommended follow-up dilated eye exam, and ophthalmology visit attendance were examined.Results: 3130 TRIs were graded in 2216 eyes (1107 patients). 65.2% (N = 722) self-identified as Hispanic and 56.3% (N = 623) required interpreter services. Follow-up dilated fundus examination (DFE) was recommended for 388 TRIs, 49% (N = 190) of which were completed within 1 year. Adherence to the recommended ophthalmology exam was not associated with any baseline clinical or demographic characteristics (p > 0.05). Older age, male sex, hypertension, proteinuria, and higher A1c were significantly associated with greater odds of ophthalmology referral based on TRI (all p < 0.05), after adjusting for covariates. Less severe diabetic retinopathy, no insurance coverage, and Hispanic ethnicity were associated with lower odds of attending an ophthalmology visit, regardless of follow-up recommendations based on TRI (all p < 0.05).Conclusion: In an FQHC serving predominantly uninsured and underinsured patients, only 49% of recommended DFE were completed within one year. Less severe diabetic retinopathy, lack of insurance coverage, and Hispanic ethnicity were associated with a lower likelihood of having a DFE regardless of recommendation. These results suggest that greater system-level efforts are needed to increase adherence to follow-up eye exams after TRI to ensure sight-saving care for underserved populations.Keywords: teleretinal screening, teleophthalmology, uninsured, underinsured, adherence, ophthalmology referral

Published
2022

2. Awareness and attitudes toward corneal donation: challenges and opportunities

Author

Williams AM and Muir KW

Subjects
Eye donation, corneal transplantation, attitudes, eye bank, organ donation, Ophthalmology, RE1-994
Abstract

Andrew M Williams,1 Kelly W Muir2,3 1Department of Ophthalmology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA; 2Department of Ophthalmology, Duke University Medical Center, Durham, NC, USA; 3Durham VA Medical Center, Health Services Research and Development, Durham, NC, USA Abstract: There is a severe shortage of donor corneas available worldwide for transplantation, with the number of patients in need of transplant greatly exceeding the number of cornea tissues available. Understanding awareness and attitudes about corneal donation worldwide is a critical step toward addressing this shortage. In this review, awareness of corneal donation and reported willingness to donate are summarized from 55 published studies across 13 countries. In general, many more respondents indicated positive attitudes toward eye donation and willingness to donate their eyes than the number of respondents who have pledged their eyes for donation, suggesting an unrealized potential of additional donors. Specifically, of 38,851 respondents across all included studies, 52% endorsed a willingness to donate their eyes after death, yet only 5% reported being a pledged donor. The most commonly cited reason for not being a registered eye donor was lack of awareness about eye donation. The disconnection between the large number of people who expressed willingness to donate and the scarcity of individuals who have pledged their eyes for donation could be addressed through educational media campaigns, collaborations with medical personnel, partnerships with grief counselors and religious leaders, use of social media, and educational sessions with medical students and staff. Keywords: eye donation, corneal transplantation, attitudes, eye bank, organ donation

Published
2018

3. Identifying risk factors for blindness from primary open-angle glaucoma by race: a case–control study

Author

Williams AM, Huang W, Muir KW, Stinnett SS, Stone JS, and Rosdahl JA

Subjects
glaucoma, blindness, POAG, race, disparity, Ophthalmology, RE1-994
Abstract

Andrew M Williams,1 Wei Huang,2 Kelly W Muir,3,4 Sandra S Stinnett,3 Jordan S Stone,5 Jullia A Rosdahl3 1Department of Ophthalmology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA; 2Charlotte Eye Ear Nose & Throat Associates, Charlotte, NC, USA; 3Department of Ophthalmology, Duke University Medical Center, Durham, NC, USA; 4Health Services Research and Development, Durham Veterans Affairs Medical Center, Durham, NC, USA; 5School of Medicine, University of California San Diego, La Jolla, CA, USA Purpose: To examine the factors associated with blindness from primary open-angle glaucoma (POAG) among black and white patients at our institution.Patients and methods: For this retrospective, case–control study, patients legally blind from POAG (“cases”) were matched on age, race, and gender with non-blind POAG patients (“controls”). Thirty-seven black case–control pairs and 19 white case–control pairs were included in this study. Clinical variables were compared at initial presentation and over the course of follow-up.Results: Black case–control pairs and white case–control pairs had similar characteristics at presentation, including cup-to-disc ratio and number of glaucoma medications. However, over the course of follow-up, black cases underwent significantly more glaucoma surgeries than matched controls (2.4 versus 1.2, p=0.001), whereas white cases and controls had no significant difference in glaucoma operations (0.9 versus 0.6, p=0.139). Our analysis found that glaucoma surgery is associated with blindness in black patients (odds ratio [OR] 1.6, 95% CI 1.1–2.2) but not in white patients (OR 1.5, 95% CI 0.7–3.2).Conclusion: Black and white case–control pairs with POAG shared similar risk factors for blindness at presentation. However, over the follow-up period, black cases required significantly more glaucoma surgeries compared to black controls, whereas there was no significant difference in surgery between white cases and controls. There was no difference in medication changes in either case–control set. Keywords: health disparities, glaucoma surgery, glaucoma treatment, glaucoma medications

Published
2018

4. An upright eyedrop bottle: accuracy, usage of excess drops, and contamination compared to a conventional bottle

Author

Davies IJ, Brown NH, Wen JC, Stinnett SS, Kubelick K, Patel RP, Benokraitis KL, Greene L, Cheek C, and Muir KW

Subjects
glaucoma, children, adherence, Ophthalmology, RE1-994
Abstract

Isaiah J Davies,1 Ninita H Brown,2 Joanne C Wen,3 Sandra S Stinnett,1 Kelsey Kubelick,4,5 Roma P Patel,6 Kristin L Benokraitis,7 Latoya Greene,1 Curry Cheek,1 Kelly W Muir1,8 1Department of Ophthalmology, Duke University School of Medicine, Durham, NC, USA; 2Metrolina Eye Associates, Charlotte, NC, USA; 3Department of Ophthalmology, University of Washington, Seattle, WA, USA; 4Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology, 5Wallace H Coulter Department of Biomedical Engineering, Emory University School of Medicine, Atlanta, Georgia, USA; 6University of California Davis Health System Eye Center, Sacramento, CA, USA; 7EG-GILERO, Durham, NC, USA; 8Health Services Research & Development, Durham VA Medical Center, Durham, NC, USA Purpose: This study tested the feasibility of using an upright eyedrop bottle (UEB), a device designed to assist patients with eyedrop placement without reclining their head. Patients and methods: Experienced eyedrop users were enrolled who answered “yes” to the question, “Do you ever have trouble getting your eyedrops in?” After being shown a multimedia presentation and answering a questionnaire regarding eyedrop usage, participants were observed instilling eyedrops. Participants were instructed to instill a single eyedrop in each eye with both a standard bottle and the UEB. They repeated this process three times. With each trial, the amount of time taken to instill drops was recorded, as well as whether a drop landed in the eye (accuracy), if excess drops were used, and if the bottle tip was contaminated. Results: Forty participants were enrolled, with an average age of 72.4±8.9 years; the majority were females (24 females). Thirty-four participants had been using eyedrops for at least 1 year. The time required to instill eyedrops was significantly less with the UEB in the second and third trials. There was no difference in accuracy between the conventional bottle and the UEB in the left or right eye in any trials. Significantly more participants used excess number of drops while using the conventional bottle in both the left and right eyes in all three trials. The bottle tip was never contaminated with the UEB. Depending on the trial and the eye, the conventional bottle was contaminated by between 42% and 53% of participants. Conclusion: The UEB has the potential to assist patients with eyedrop placement. Although there was no difference in accuracy between the UEB and the conventional bottle, the UEB was associated with less use of excess drops and less contamination of the bottle tip, compared to the conventional bottle. Keywords: glaucoma, compliance, medical devices

Published
2016

5. Pediatric glaucoma medical therapy: who more accurately reports medication adherence, the caregiver or the child?

Author

Moore DB, Neustein RF, Jones SK, Robin AL, and Muir KW

Subjects
Ophthalmology, RE1-994
Abstract

Daniel B Moore,1 Rebecca F Neustein,2 Sarah K Jones,1 Alan L Robin,3 Kelly W Muir1,4 1Duke Eye Center, Duke University Medical Center, Durham, NC, 2Emory School of Medicine, Atlanta, GA, 3Department of Ophthalmology, Johns Hopkins School of Medicine and International Health, Bloomberg School of Public Health, Baltimore, MD, 4Health Services Research & Development, Durham VA Medical Center, Durham, NC, USA Abstract: As they grow older, most children with glaucoma must eventually face the transition to self-administering medications. We previously reported factors associated with better or worse medication adherence in children with glaucoma, using an objective, electronic monitor. Utilizing the same data set, the purpose of the current study was to determine whose report (the caregiver’s or the child’s) corresponded better with electronically monitored adherence. Of the 46 participants (22 girls), the mean age of children primarily responsible, and caregiver primarily responsible for medication administration was 15±2 and 10±2 years, respectively. For the children whose caregiver regularly administered the eyedrops, the caregiver’s assessment of drop adherence was associated with measured adherence (P=0.012), but the child’s was not (P=0.476). For the children who self-administered eyedrops, neither the child’s (P=0.218) nor the caregiver’s (P=0.395) assessment was associated with measured percent adherence. This study highlights potential errors when relying on self-reporting of compliance in patients and caregivers with pediatric glaucoma, particularly when the child is responsible for administering their own eyedrops. Frank discussions about the importance of medication adherence and how to improve compliance may help both the child and caregiver better communicate with the treating provider. Keywords: glaucoma, children, adherence

Published
2015

6. Health coaching for glaucoma care: a pilot study using mixed methods

Author

Vin A, Schneider S, Muir KW, and Rosdahl JA

Subjects
Ophthalmology, RE1-994
Abstract

Anita Vin,1 Suzanne Schneider,2 Kelly W Muir,1,3 Jullia A Rosdahl11Department of Ophthalmology, Duke University, Durham, NC, 2Department of Health Philosophy and Promotion, Maryland University of Integrative Health, Laurel, MD, 3Durham VA Medical Center, Durham, NC, USAIntroduction: Adherence to glaucoma medications is essential for successful treatment of the disease but is complex and difficult for many of our patients. Health coaching has been used successfully in the treatment of other chronic diseases. This pilot study explores the use of health coaching for glaucoma care.Methods: A mixed methods study design was used to assess the health coaching intervention for glaucoma patients. The health coaching intervention consisted of four to six health coaching sessions with a certified health coach via telephone. Quantitative measures included demographic and health information, adherence to glaucoma medications (using the visual analog adherence scale and medication event monitoring system), and an exit survey rating the experience. Qualitative measures included a precoaching health questionnaire, notes made by the coach during the intervention, and an exit interview with the subjects at the end of the study.Results: Four glaucoma patients participated in the study; all derived benefits from the health coaching. Study subjects demonstrated increased glaucoma drop adherence in response to the coaching intervention, in both visual analog scale and medication event monitoring system. Study subjects’ qualitative feedback reflected a perceived improvement in both eye and general health self-care. The subjects stated that they would recommend health coaching to friends or family members.Conclusion: Health coaching was helpful to the glaucoma patients in this study; it has the potential to improve glaucoma care and overall health.Keywords: motivation, behavior change, adherence, medication, health

Published
2015

7. Finding the best glaucoma questionnaire: a qualitative and quantitative evaluation of glaucoma knowledge assessments

Author

Rosdahl JA and Muir KW

Subjects
Ophthalmology, RE1-994
Abstract

Jullia A Rosdahl,1 Kelly W Muir1,2 1Department of Ophthalmology, Duke University, Durham, NC, USA; 2Health Services Research and Development, Durham Veterans Affairs Medical Center, Durham, NC, USA Objective: The goal of the study was to determine which glaucoma quiz provides the best information about patient glaucoma knowledge to clinicians in clinical practice settings. Methods: Four glaucoma quizzes were identified from the literature and national eye education programs and were qualitatively analyzed to categorize questions by topic. Quizzes were assessed by 64 glaucoma specialists using an online survey, with descriptive statistics. Comments about the quizzes were analyzed qualitatively using themes and representative quotations. Results: Quizzes covered content that was important for glaucoma diagnosis and management. The National Eye Health Education Program (NEHEP) and Prevent Blindness America quizzes covered primarily diagnosis, screening, and risk factors, and the quizzes from the literature primarily covered causes of glaucoma, vision loss, eye drops, and systemic disease. Overall, the NEHEP quiz was ranked best for clinical practice, ranked first by 38%. Ranked second overall, the Gray quiz was ranked first by 34% and last by 34%. Conclusion: The NEHEP quiz was rated most useful for assessing baseline general glaucoma knowledge for a busy clinical practice. The Gray quiz appears to be more useful as part of a comprehensive education program, perhaps in combination with an ophthalmic educator. Keywords: patient education, quiz, clinical practice

Published
2015

8. Patient education preferences in ophthalmic care

Author

Rosdahl JA, Swamy L, Stinnett S, and Muir KW

Subjects
Medicine (General), R5-920
Abstract

Jullia A Rosdahl, Lakshmi Swamy, Sandra Stinnett, Kelly W MuirDepartment of Ophthalmology, Duke Eye Center, Duke University, Durham, NC, USABackground: The learning preferences of ophthalmology patients were examined.Methods: Results from a voluntary survey of ophthalmology patients were analyzed for education preferences and for correlation with race, age, and ophthalmic topic.Results: To learn about eye disease, patients preferred one-on-one sessions with providers as well as printed materials and websites recommended by providers. Patients currently learning from the provider were older (average age 59 years), and patients learning from the Internet (average age 49 years) and family and friends (average age 51 years) were younger. Patients interested in cataracts, glaucoma, macular degeneration, and dry eye were older; patients interested in double vision and glasses were younger. There were racial differences regarding topic preferences, with Black patients most interested in glaucoma (46%), diabetic retinopathy (31%), and cataracts (28%) and White patients most interested in cataracts (22%), glaucoma (22%), and macular degeneration (19%).Conclusion: Most ophthalmology patients preferred personalized education: one-on-one with their provider or a health educator and materials (printed and electronic) recommended by their provider. Age-related topics were more popular with older patients, and diseases with racial risk factors were more popular with high risk racial groups.Keywords: patient education, eye disease, cataracts, macular degeneration, glaucoma, diabetic retinopathy

Published
2014

9. Brain repair: cell therapy in stroke

Author

Kalladka D and Muir KW

Subjects
Cytology, QH573-671
Abstract

Dheeraj Kalladka, Keith W Muir Institute of Neuroscience and Psychology, University of Glasgow, Southern General Hospital, Glasgow, United Kingdom Abstract: Stroke affects one in every six people worldwide, and is the leading cause of adult disability. Some spontaneous recovery is usual but of limited extent, and the mechanisms of late recovery are not completely understood. Endogenous neurogenesis in humans is thought to contribute to repair, but its extent is unknown. Exogenous cell therapy is promising as a means of augmenting brain repair, with evidence in animal stroke models of cell migration, survival, and differentiation, enhanced endogenous angiogenesis and neurogenesis, immunomodulation, and the secretion of trophic factors by stem cells from a variety of sources, but the potential mechanisms of action are incompletely understood. In the animal models of stroke, both mesenchymal stem cells (MSCs) and neural stem cells (NSCs) improve functional recovery, and MSCs reduce the infarct volume when administered acutely, but the heterogeneity in the choice of assessment scales, publication bias, and the possible confounding effects of immunosuppressants make the comparison of effects across cell types difficult. The use of adult-derived cells avoids the ethical issues around embryonic cells but may have more restricted differentiation potential. The use of autologous cells avoids rejection risk, but the sources are restricted, and culture expansion may be necessary, delaying treatment. Allogeneic cells offer controlled cell numbers and immediate availability, which may have advantages for acute treatment. Early clinical trials of both NSCs and MSCs are ongoing, and clinical safety data are emerging from limited numbers of selected patients. Ongoing research to identify prognostic imaging markers may help to improve patient selection, and the novel imaging techniques may identify biomarkers of recovery and the mechanism of action for cell therapies. Keywords: stroke, cerebrovascular disease, cell therapy, neurological disease

Published
2014

10. Rivaroxaban or aspirin for patent foramen ovale and embolic stroke of undetermined source: a prespecified subgroup analysis from the NAVIGATE ESUS trial

Author

Abdelhamid, N, Abdul Rahman, D, Abdul-Saheb, M, Abreu, P, Abroskina, M, Abu Ahmad, F, Accassat, S, Acciaresi, M, Adami, A, Ahmad, N, Ahmed, F, Alberto Hawkes, M, Alemseged, F, Ali, A, Altavilla, R, Alwis, L, Amarenco, P, Amaro, S, Amaya Sanchez, LE, Amelia Pinto, A, Ameriso, SF, Amin, H, Amino, T, Amjad, AK, Anagnostou, E, Andersen, G, Anderson, C, Anderson, DC, Andrea Falco, M, Andres Mackinnon, F, Andreu, D, Androulakis, M, Angel Gamero, M, Angel Saredo, G, Angeles Diaz, R, Angels Font, M, Anticoli, S, Arauz, A, Arauz Gongora, AA, Araya, P, Arenillas Lara, JF, Arias Rivas, S, Arnold, M, Augustin, S, Avelar, W, Azevedo, E, Babikian, V, Bacellar, A, Badalyan, K, Bae, HJ, Baez Martinez, EM, Bagelmann, H, Bailey, P, Bak, Z, Baker, M, Balazs, A, Baldaranov, D, Balogun, I, Balueva, T, Bankuti, Z, Bar, M, Baranowska, A, Bardutzky, J, Barker Trejo, S, Barlinn, J, Baronnet, F, Barroso, C, Barteys, M, Bartolottiova, T, Barulin, A, Bas, M, Bashir, S, Basile, V, Bathe-Peters, R, Bathula, R, Batista, C, Batur Caglayan, H, Baumgartner, P, Bazan, R, Bazhenova, O, Beaudry, M, Beer, J, Behnam, Y, Beilei, C, Beinlich, A, Bejot, Y, Belkin, A, Benavente, OR, Benjamin, A, Berardi, V, Bereczki, D, Berkowitz, SD, Berlingieri, J, Berrios, W, Berrouschot, J, Bhandari, M, Bhargavah, M, Bicker, H, Bicsak, T, Bilik, M, Bindila, D, Birchenall, J, Birnbaum, L, Black, T, Blacker, D, Blacquiere, D, Blanc-Labarre, C, Blank, C, Blazejewska-Hyzorek, B, Bloch, S, Bodiguel, E, Bogdanov, E, Boos, L, Borcsik, L, Bornstein, N, Bouly, S, Braga, G, Bragado, I, Bravi, MC, Brokalaki, C, Brola, W, Brouns, R, Bruce, D, Brzoska-Mizgalska, J, Buck, B, Buksinska-Lisik, M, Burke, J, Burn, M, Bustamante, G, Cabrejo, L, Cai, K, Cajaraville, S, Calejo, M, Calvet, D, Campillo, J, Campos Costa, E, Camps, P, Can Alaydin, H, Candeloro, E, Canepa, C, Cantu Brito, CG, Cappellari, M, Carcel, C, Cardona Portela, P, Cardoso, F, Carek, M, Carletti, M, Carlos Portilla, J, Caruso, P, Casado-Naranjo, I, Castellini, P, Castro, D, Castro Meira, F, Cavallini, A, Cayuela Caudevilla, N, Cenciarelli, S, Cereda, C, Cerrone, P, Chakrabarti, A, Chaloulos-Iakovidis, P, Chamorro, A, Chandrasena, D, Chang, DI, Che, C, Chembala, J, Chen, J, Chen, Z, Chen, T, Chen, H, Chen, X, Chen, G, Chen, L, Chen, S, Cheripelli, B, Chin, M, Chiquete Anaya, E, Chorazy, M, Christensen, H, Christensen, T, Christian, L, Chu, F, Chung, CS, Clark, W, Clarke, R, Claverie, S, Clemente Agostoni, E, Clissold, B, Coelho, J, Cohen, D, Colakoglu, S, Collas, D, Condurso, R, Connolly, SJ, Consoli, D, Constantin, C, Constantino Silva, AB, Contardo, L, Corlobe, A, Correia, M, Correia, C, Cortijo Garcia, E, Coull, B, Coutts, S, Coveney, S, Cras, P, Crols, R, Crozier, S, Csanyi, A, Csiba, L, Csontos, K, Csuha, R, Cui, L, Cunha, L, Curtze, S, Czerska, M, Czlonkowska, A, Czurko, M, Czuryszkiewicz, M, Dagnino, M, Dai, C, Daineko, A, Dalek, G, Damgaard, D, Danese, A, Dani, K, Danku, V, Dario Toledo, W, Dávalos, A, De Havenon, A, De Keyser, J, De Klippel, N, De La Torre, J, De Pauw, A, De Smedt, A, De Torres, R, De Vries Basson, MM, Dearborn, J, Deganutto, R, Degeorgia, M, Deguchi, I, Del Giudice, A, Delcourt, C, Delgado-Mederos, R, Della Marca, G, Delpont, B, Deltour, S, Demets, DL, Dennis, M, Desai, J, Devine, J, Dhollander, I, Di Mascio, MT, Diaconu, M, Diaz Otero, F, Dietzel, J, Diez-Tejedor, E, Ding, N, Ding, J, Diomedi, M, Dioszeghy, P, Distefano, M, Domigo, V, Dorodnicov, E, Dossi, D, Doubal, F, Druzenko, I, Du, P, Du, J, Duman, T, Duodu, Y, Dutta, D, Dylewicz, L, Eckstein, J, Ehrensperger, E, Ehrlich, S, Einer Allende, G, Elena Halac, B, Elyas, S, Endres, M, Engelbrecht, JM, Engelter, S, Epinat, M, Eren, F, Esbjornsson, M, Escribano, B, Escudero, I, Esisi, B, Essa, B, Esterbauer, M, Evans, N, Eveson, D, Fabio, S, Fang, L, Fanta, S, Fares, M, Fatar, M, Faust, K, Favate, A, Fazekas, F, Federica Denaro, M, Fedin, A, Felipe Amaya, P, Feng, J, Ferencova, K, Fernanda Gilli, M, Fernandez, MD, Fernandez Pirrone, PN, Fernandez Vera, J, Ferrari, J, Ferreira, A, Ferreira Junior, G, Fidler, M, Field, D, Field, T, Figueroa, C, Fiksa, J, Filipov, A, Firstenfeld, A, Fisch, L, Fischer, U, Fisselier, M, Fiszer, U, Fluri, F, Fortea, G, Fotherby, K, Fraczek, A, France, E, Freitas, G, Frey, S, Frick, M, Friedman, A, Friedrich, M, Frisullo, G, Fryze, W, Fuentes Gimeno, B, Fujigasaki, H, Fukuyama, K, Furlan, A, Furlanis, G, Furnace, J, Gabriel, M, Gabriel Reich, E, Gagliardi, RJ, Galati, F, Galli Giqueauk, E, Gallina, A, Gallinella, E, Gallo, J, Gangadharan, S, Gao, Y, Garcia Lopez, R, Garcia Pastor, A, Garcia Sanchez, SM, Garnauf, M, Garnier, P, Gasecki, D, Gasic, K, Gasiorek, K, Gasser, S, Gaugg, M, Gebreyohanns, M, Gebura, K, Geng, J, Geniz Clavijo, M, Georg Haeusler, K, Geran, R, Geremek, M, Gerocs, Z, Ghia, D, Giannandrea, D, Giatsidis, F, Gien Lopez, JA, Gil Nunez, A, Gimenez, L, Giralt, E, Glabinski, A, Gladstone, D, Gliem, M, Gluszkiewicz, M, Goddeau, R, Gogoleva, E, Gokce, M, Goldemund, D, Golikov, K, Gomes Neto, A, Gomez Schneider, M, Gomez-Choco, M, Gomis, M, Gongora-Rivera, JF, Gonysheva, Y, Gonzalez, L, Gonzalez Toledo, ME, Gottschal, M, Gozdzik, I, Grabowski, S, Graf, S, Green, D, Greer, D, Gregorio, T, Greisenegger, S, Greshnova, I, Griebe, M, Grzesik, M, Guan, J, Guarda, S, Gueguen, A, Guidoux, C, Guillermo Povedano, P, Guillon, B, Guiraudg, V, Gunathilagan, G, Guryanova, N, Gusev, V, Gustavo Persi, G, Gutiérrez, R, Guyler, P, Gyuker, N, Hachinski, V, Hajas, A, Hallevi, H, Hankey, G, Hankey, GJ, Hanouskova, L, Hao, L, Haraguchi, K, Haralur Sreekantaiah, Y, Haratz, S, Hargroves, D, Harkness, K, Harmel, P, Harrasser, M, Hart, RG, Harvey, M, Hasan, R, Hasegawa, Y, Hassan, A, Hattori, M, Hatzitolios, A, Hauk, M, Hayashi, T, Hayhoe, H, Hedna, VS, Heine, M, Held, V, Hellwig, S, Henkner, J, Henninger, N, Hermans, S, Hernandez, J, Herrero, D, Hervieu-Begue, M, Herzig, R, Hicken, L, Hieber, M, Hill, M, Hirose, M, Hobeanu, MC, Hobson, B, Hochstetter, M, Hoe Heo, J, Hoffmann, M, Holmstedt, C, Hon, P, Hong, KS, Honma, Y, Horev, A, Horgan, G, Horvath, L, Horvath, M, Hoyer, C, Huang, D, Huang, H, Huber, B, Huhtakangas, J, Hussain, M, Igarashi, S, Iglesias Mohedano, AM, Ignacio Tembl, J, Impellizzeri, M, Inanc, Y, Ioli, P, Irina Aniculaesei, A, Ishida, K, Itabashi, R, Iversen, H, Jagolino, A, Jakab, K, Jander, S, Janka, H, Jankovych, J, Jansen, J, Jasek, L, Javier Alet, M, Javor, L, Jin, X, Jing, P, Joachim, B, Joan Macleod, M, Johnson, M, Jose Martin, J, Joyner, C, Judit Szabo, K, Jun-Oconnell, A, Jura, R, Kaczorowska, B, Kadlcikova, J, Kahles, T, Kakaletsis, N, Kakuk, I, Kalinowska, K, Kaminska, K, Kaneko, C, Kanellos, I, Kapeller, P, Kapica-Topczewska, K, Karasz, O, Karlinski, M, Karlsson, JE, Kasa, K, Kashaeva, E, Kasner, SE, Kaste, M, Kasza, J, Katalin Iljicsov, A, Katsurayama, M, Kaur, S, Kawanishi, M, Kaygorodtseva, S, Ke, K, Kei, A, Keilitz, J, Kellner, J, Kelly, P, Kelly, S, Kemlink, D, Kerekgyarto, M, Keskinarkaus, I, Khairutdinova, D, Khanna, A, Khaw, A, Kholopov, M, Khoumri, C, Kirpicheva, S, Kirshner, H, Kitagawa, K, Kittner, S, Kivioja, R, Klein, F, Kleindorfer, D, Kleinig, T, Klivenyi, P, Knecht, S, Kobayashi, Y, Kobayashi, A, Koch, M, Koehler, L, Koivu, M, Kolianov, V, Koltsov, I, Kondo, T, Konkov, I, Kopecky, S, Korompoki, E, Korpela, J, Kosarz-Lanczek, K, Koutroubi, A, Kovacs, K, Kovacs, T, Kovacs, H, Kowalczyk, K, Kowalska, M, Krajickova, D, Kral, M, Krarup Hansen, C, Kraska, J, Krebs, S, Krejci, V, Kremer, C, Kreuzpointer, R, Krzyzanowska, M, Kucken, D, Kulakowska, A, Kunzmann, J, Kurenkova, N, Kuris, A, Kurkowska-Jastrzebska, I, Kurtenkova, N, Kurushina, O, Kusnick, G, Kustova, M, Kuwashiro, T, Kwan Cha, J, Lago, A, Lagutenko, M, Lajos, B, Lambeck, J, Lamy, C, Landolfi, A, Lanfranconi, S, Lang, W, Lara Lezama, LB, Lara Rodriguez, B, Largo, T, Lasek-Bal, A, Latte, L, Lauer, V, Lavados, P, Le Bouc, R, Leal Cantu, R, Lechner, H, Lecouturier, K, Leder, S, Lee, J, Lee, BC, Leger, A, Leira, E, Leisse, I, Leker, R, Lembo, G, Lenskaya, L, Leyden, 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Stiehm, M, Stocker, R, Stoinski, J, Stoll, A, Stotts, G, Stumpp, A, Sucapane, P, Suenaga, T, Sun, X, Sundararajan, S, Sung Kim, J, Suzuki, H, Svaneborg, N, Szasz, G, Szczuchniak, W, Szczyrba, S, Szegedi, N, Szekely, A, Szewczyk, Z, Szilagyi, G, Szlufik, S, Szoboszlai, K, Szpisjak, L, Sztajzel, R, Sztriha, L, Ta Wil, SE, Taggeselle, J, Takamatsu, K, Takao, M, Taki, W, Takizawa, S, Talahma, M, Tamayo, A, Tan, J, Tanne, D, Tapanainen, A, Tapiola, T, Tarasiuk, J, Tatlisumak, T, Tayal, A, Tcvetkova, S, Teal, P, Tejada Garcia, J, Tejada Meza, H, Tenora, D, Terceno, M, Terentiou, A, Tezcan, S, Thaler, D, Thomson, A, Thouvenot, E, Tiainen, M, Timberg, I, Timsit, S, Tinchon, A, Tirschwell, D, Togay Isikay, C, Tokunaga, K, Tolino, M, Toloza, C, Tomelleri, G, Tomoyuki, K, Tomppo, LM, Tong, Z, Tong, L, Toni, D, Torres, J, Tossavainen, C, Toth, G, Tountopoulou, A, Touze, E, Tovar, M, Toyoda, K, Trillo, S, Trommer, A, Tropepi, D, Tryambake, D, Tu, H, Tuetuencue, S, Tumova, R, Tumpula, O, Turc, G, 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Windt, J, Winkler, A, Winska-Tereszkiewicz, A, Wisniewska, A, Wittayer, M, Wlodek, A, Wojnarowska-Arendt, A, Wolf, M, Wolff, V, Wolter, C, Wong, A, Wook Nah, H, Worthmann, H, Wu, W, Wu, S, Wunderlich, S, Wurzinger, H, Wyse, DG, Xiao, B, Xiaopeng, W, Ximenez-Carrillo, A, Xiong, L, Xiong, Y, Xiong, W, Xu, Y, Xu, J, Xu, Z, Yalo, B, Yamada, T, Yamasaki, M, Yang, L, Yang, Y, Yang, X, Yang, Q, Yang, B, Yang, J, Yasuhiro, I, Yee Lam, M, Yegappan, C, Yip, S, Ylikallio, E, Ylikotila, P, Yongwon Jin, A, Yoon, BW, Yoshida, Y, Yperzeele, L, Yuan, H, Yuasa, H, Zalewska, J, Zanferrari, C, Zapata, E, Zboznovits, D, Zelenka, I, Zhang, C, Zhang, B, Zhang, S, Zhang, M, Zhang, X, Zhang, J, Zhao, L, Zhirnova, O, Zhou, L, Zielinska-Turek, J, Zinchenko, I, Ziomek, M, Zitzmann, A, Zweifler, R, Zwiernik, J, Kasner, Scott E, Swaminathan, Balakumar, Lavados, Pablo, Sharma, Mukul, Muir, Keith, Veltkamp, Roland, Ameriso, Sebastian F, Endres, Matthias, Lutsep, Helmi, Messé, Steven R, Spence, J David, Nedeltechev, Krassen, Perera, Kanjana, Santo, Gustavo, Olavarria, Veronica, Lindgren, Arne, Bangdiwala, Shrikant, Shoamanesh, Ashkan, Berkowitz, Scott D, Mundl, Hardi, Connolly, Stuart J, and Hart, Robert G

Published
2018
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12. Clinical outcome of patients with mild pre-stroke morbidity following endovascular treatment: a HERMES substudy

Author

McDonough, RV, Ospel, JM, Majoie, CBLM, Saver, JL, White, P, Dippel, DWJ, Brown, SB, Demchuk, AM, Jovin, TG, Mitchell, PJ, Bracard, S, Campbell, BCV, Muir, KW, Hill, MD, Guillemin, F, Goyal, M, Martí-Fàbregas J., and HERMES Collaborators

Subjects
thrombectomy, stroke
Abstract

Background Analyses of the effect of pre-stroke functional levels on the outcome of endovascular therapy (EVT) have focused on the course of patients with moderate to substantial pre-stroke disability. The effect of complete freedom from pre-existing disability (modified Rankin Scale (mRS) 0) versus predominantly mild pre-existing disability/symptoms (mRS 1-2) has not been well delineated. Methods The HERMES meta-analysis pooled data from seven randomized trials that tested the efficacy of EVT. We tested for a multiplicative interaction effect of pre-stroke mRS on the relationship between treatment and outcomes. Ordinal regression was used to assess the association between EVT and 90-day mRS (primary outcome) in the subgroup of patients with pre-stroke mRS 1-2. Multivariable regression modeling was then used to test the effect of mild pre-stroke disability/symptoms on the primary and secondary outcomes (delta-mRS, mRS 0-2/5-6) compared with patients with pre-stroke mRS 0. Results We included 1764 patients, of whom 199 (11.3%) had pre-stroke mRS 1-2. No interaction effect of pre-stroke mRS on the relationship between treatment and outcome was observed. Patients with pre-stroke mRS 1-2 had worse outcomes than those with pre-stroke mRS 0 (adjusted common OR (acOR) 0.53, 95% CI 0.40 to 0.70). Nonetheless, a significant benefit of EVT was observed within the mRS 1-2 subgroup (cOR 2.08, 95% CI 1.22 to 3.55). Conclusions Patients asymptomatic/without disability prior to onset have better outcomes following EVT than patients with mild disability/symptoms. Patients with pre-stroke mRS 1-2, however, more often achieve good outcomes with EVT compared with conservative management. These findings indicate that mild pre-existing disability/symptoms influence patient prognosis after EVT but do not diminish the EVT treatment effect.

Published
2022

14. Baseline factors associated with early and late death in intracerebral haemorrhage survivors

Author

Banerjee, G, Ambler, G, Wilson, D, Hostettler, IC, Shakeshaft, C, Lunawat, S, Cohen, H, Yousry, T, Salman, R Al-Shahi, Lip, GYH, Houlden, H, Muir, KW, Brown, MM, Jager, HR, Werring, DJ, and Collaborators, CROMIS-2

Subjects
Male, Change over time, medicine.medical_specialty, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Modified Rankin Scale, Internal medicine, Humans, Medicine, Glasgow Coma Scale, Anticoagulant use, Survivors, 030212 general & internal medicine, Aged, Cerebral Hemorrhage, Aged, 80 and over, business.industry, Hazard ratio, intracerebral haemorrhage, Middle Aged, Prognosis, mortality, Confidence interval, Stroke, Neurology, Cohort, Original Article, Female, Observational study, prognosis, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

Background and purpose: \ud \ud The aim of this study was to determine whether early and late death are associated with different baseline factors in intracerebral haemorrhage (ICH) survivors.\ud \ud Methods: \ud \ud This was a secondary analysis of the multicentre prospective observational CROMIS‐2 ICH study. Death was defined as ‘early’ if occurring within 6 months of study entry and ‘late’ if occurring after this time point.\ud \ud Results: \ud \ud In our cohort (n = 1094), there were 306 deaths (per 100 patient‐years: absolute event rate, 11.7; 95% confidence intervals, 10.5–13.1); 156 were ‘early’ and 150 ‘late’. In multivariable analyses, early death was independently associated with age [per year increase; hazard ratio (HR), 1.05, P = 0.003], history of hypertension (HR, 1.89, P = 0.038), pre‐event modified Rankin scale score (per point increase; HR, 1.41, P < 0.0001), admission National Institutes of Health Stroke Scale score (per point increase; HR, 1.11, P < 0.0001) and haemorrhage volume >60 mL (HR, 4.08, P < 0.0001). Late death showed independent associations with age (per year increase; HR, 1.04, P = 0.003), pre‐event modified Rankin scale score (per point increase; HR, 1.42, P = 0.001), prior anticoagulant use (HR, 2.13, P = 0.028) and the presence of intraventricular extension (HR, 1.73, P = 0.033) in multivariable analyses. In further analyses where time was treated as continuous (rather than dichotomized), the HR of previous cerebral ischaemic events increased with time, whereas HRs for Glasgow Coma Scale score, National Institutes of Health Stroke Scale score and ICH volume decreased over time.\ud \ud Conclusions: \ud \ud We provide new evidence that not all baseline factors associated with early mortality after ICH are associated with mortality after 6 months and that the effects of baseline variables change over time. Our findings could help design better prognostic scores for later death after ICH.

Published
2020

15. Germline selection shapes human mitochondrial DNA diversity

Author

Wei, W, Tuna, S, Keogh, MJ, Smith, KR, Aitman, TJ, Beales, PL, Bennett, DL, Gale, DP, Bitner-Glindzicz, MAK, Black, GC, Brennan, P, Elliott, P, Flinter, FA, Floto, RA, Houlden, H, Irving, M, Koziell, A, Maher, ER, Markus, HS, Morrell, NW, Newman, WG, Roberts, I, Sayer, JA, Smith, KGC, Taylor, JC, Watkins, H, Webster, AR, Wilkie, AOM, Williamson, C, Attwood, A, Brown, M, Brod, NC, Crisp-Hihn, A, Davis, J, Deevi, SVV, Dewhurst, EF, Edwards, K, Erwood, M, Fox, J, Frary, AJ, Hu, F, Jolley, J, Kingston, N, Linger, R, Mapeta, R, Martin, J, Meacham, S, Papadia, S, Rayner-Matthews, PJ, Samarghitean, C, Shamardina, O, Simeoni, I, Staines, S, Staples, E, Stark, H, Stephens, J, Titterton, C, Von Ziegenweidt, J, Watt, C, Whitehorn, D, Wood, Y, Yates, K, Yu, P, James, R, Ashford, S, Penkett, CJ, Stirrups, KE, Bariana, T, Lentaigne, C, Sivapalaratnam, S, Westbury, SK, Allsup, DJ, Bakchoul, T, Biss, T, Boyce, S, Collins, J, Collins, PW, Curry, NS, Downes, K, Dutt, T, Erber, WN, Evans, G, Everington, T, Favier, R, Gomez, K, Greene, D, Gresele, P, Hart, D, Kazmi, R, Kelly, AM, Lambert, M, Madan, B, Mangles, S, Mathias, M, Millar, C, Obaji, S, Peerlinck, K, Roughley, C, Schulman, S, Scully, M, Shapiro, SE, Sibson, K, Sims, MC, Tait, RC, Talks, K, Thys, C, Toh, C-H, Van Geet, C, Westwood, J-P, Mumford, AD, Ouwehand, WH, Freson, K, Laffan, MA, Tan, RYY, Harkness, K, Mehta, S, Muir, KW, Hassan, A, Traylor, M, Drazyk, AM, Parry, D, Ahmed, M, Kazkaz, H, Vandersteen, AM, Ormondroyd, E, Thomson, K, Dent, T, Buchan, RJ, Bueser, T, Carr-White, G, Cook, S, Daniels, MJ, Harper, AR, Ware, JS, Dixon, PH, Chambers, J, Cheng, F, Estiu, MC, Hague, WM, Marschall, H-U, Vazquez-Lopez, M, Arno, G, French, CE, Michaelides, M, Moore, AT, Sanchis-Juan, A, Carss, K, Raymond, FL, Chinnery, PF, Griffiths, P, Horvath, R, Hudson, G, Jurkute, N, Pyle, A, Yu-Wai-Man, P, Whitworth, J, Adlard, J, Armstrong, R, Brewer, C, Casey, R, Cole, TRP, Evans, DG, Greenhalgh, L, Hanson, HL, Hoffman, J, Izatt, L, Kumar, A, Lalloo, F, Ong, KR, Park, S-M, Searle, C, Side, L, Snape, K, Woodward, E, Tischkowitz, M, Grozeva, D, Kurian, MA, Themistocleous, AC, Gosal, D, Marshall, A, Matthews, E, McCarthy, MI, Renton, T, Rice, ASC, Vale, T, Walker, SM, Woods, CG, Thaventhiran, JE, Allen, HL, Savic, S, Alachkar, H, Antrobus, R, Baxendale, HE, Browning, MJ, Buckland, MS, Cooper, N, Edgar, JDM, Egner, W, Gilmour, KC, Goddard, S, Gordins, P, Grigoriadou, S, Hackett, S, Hague, R, Hayman, G, Herwadkar, A, Huissoon, AP, Jolles, S, Kelleher, P, Kumararatne, D, Longhurst, H, Lorenzo, LE, Lyons, PA, Maimaris, J, Noorani, S, Richter, A, Sargur, RB, Sewell, WAC, Thomas, D, Thomas, MJ, Worth, A, Yong, PFK, Kuijpers, TW, Thrasher, AJ, Levine, AP, Sadeghi-Alavijeh, O, Wong, EKS, Cook, HT, Chan, MMY, Hall, M, Harris, C, McAlinden, P, Marchbank, KJ, Marks, S, Maxwell, H, Mozere, M, Wessels, J, Johnson, SA, Bleda, M, Hadinnapola, C, Haimel, M, Swietlik, E, Bogaard, H, Church, C, Coghlan, G, Condliffe, R, Corris, P, Danesino, C, Eyries, M, Gall, H, Ghofrani, H-A, Gibbs, JSR, Girerd, B, Holden, S, Houweling, A, Howard, LS, Humbert, M, Kiely, DG, Kovacs, G, Lawrie, A, Ross, RVM, Moledina, S, Montani, D, Newnham, M, Olschewski, A, Olschewski, H, Peacock, A, Pepke-Zaba, J, Scelsi, L, Seeger, W, Soubrier, F, Suntharalingam, J, Toshner, M, Treacy, C, Trembath, R, Noordegraaf, AV, Waisfisz, Q, Wharton, J, Wilkins, MR, Wort, SJ, Graf, S, Louka, E, Roy, NB, Rao, A, Ancliff, P, Babbs, C, Layton, DM, Mead, AJ, O'Sullivan, J, Okoli, S, Saleem, M, Bierzynska, A, Diz, CB, Colby, E, Ekani, MN, Satchell, S, Fowler, T, Rendon, A, Scott, R, Smedley, D, Thomas, E, Caulfield, M, Abbs, S, Burrows, N, Chitre, M, Gattens, M, Gurnell, M, Kelsall, W, Poole, KES, Ross-Russell, R, Spasic-Boskovic, O, Twiss, P, Wagner, A, Banka, S, Clayton-Smith, J, Douzgou, S, Abulhoul, L, Aurora, P, Bockenhauer, D, Cleary, M, Dattani, M, Ganesan, V, Pilkington, C, Rahman, S, Shah, N, Wedderburn, L, Compton, CJ, Deshpande, C, Fassihi, H, Haque, E, Josifova, D, Mohammed, SN, Robert, L, Rose, SJ, Ruddy, DM, Sarkany, RN, Sayer, G, Shaw, AC, Campbell, C, Gibson, K, Koelling, N, Lester, T, Nemeth, AH, Palles, C, Patel, S, Sen, A, Taylor, J, Tomlinson, IP, Malka, S, Browning, AC, Burn, J, De Soyza, A, Graham, J, Pearce, S, Quinton, R, Schaefer, AM, Wilson, BT, Wright, M, Simpson, M, Syrris, P, Bradley, JR, Turro, E, ARD - Amsterdam Reproduction and Development, AII - Inflammatory diseases, Paediatric Infectious Diseases / Rheumatology / Immunology, Medical Research Council (MRC), Wellcome Trust, Wei, Wei [0000-0002-2945-3543], Tuna, Salih [0000-0003-3606-4367], Smith, Katherine R [0000-0002-0329-5938], Beales, Phil L [0000-0002-9164-9782], Bennett, David L [0000-0002-7996-2696], Gale, Daniel P [0000-0002-9170-1579], Brennan, Paul [0000-0003-1128-6254], Elliott, Perry [0000-0003-3383-3984], Floto, R Andres [0000-0002-2188-5659], Houlden, Henry [0000-0002-2866-7777], Koziell, Ania [0000-0003-4882-0246], Maher, Eamonn R [0000-0002-6226-6918], Markus, Hugh S [0000-0002-9794-5996], Morrell, Nicholas W [0000-0001-5700-9792], Newman, William G [0000-0002-6382-4678], Sayer, John A [0000-0003-1881-3782], Smith, Kenneth GC [0000-0003-3829-4326], Taylor, Jenny C [0000-0003-3602-5704], Watkins, Hugh [0000-0002-5287-9016], Webster, Andrew R [0000-0001-6915-9560], Wilkie, Andrew OM [0000-0002-2972-5481], Penkett, Christopher J [0000-0003-4006-7261], Stirrups, Kathleen E [0000-0002-6823-3252], Rendon, Augusto [0000-0001-8994-0039], Bradley, John R [0000-0002-7774-8805], Turro, Ernest [0000-0002-1820-6563], Chinnery, Patrick F [0000-0002-7065-6617], and Apollo - University of Cambridge Repository

Subjects
0301 basic medicine, Non-Mendelian inheritance, Genome, Mitochondrial/genetics, DNA, Mitochondrial/genetics, 0302 clinical medicine, Ovum/growth & development, MTDNA, TRANSCRIPTION, Genetics, education.field_of_study, Multidisciplinary, NIHR BioResource–Rare Diseases, ASSOCIATION, Heteroplasmy, Mitochondrial, Multidisciplinary Sciences, GENOME, REPLACEMENT, Science & Technology - Other Topics, Female, Maternal Inheritance, Mitochondrial DNA, General Science & Technology, Genetic genealogy, Population, Biology, Human mitochondrial genetics, SEQUENCE, DNA, Mitochondrial, 03 medical and health sciences, Genetic, 100,000 Genomes Project–Rare Diseases Pilot, Genetic variation, MD Multidisciplinary, Humans, Selection, Genetic, education, Selection, Ovum, Science & Technology, MUTATIONS, Genetic Variation, DNA, LEIGH-DISEASE, 030104 developmental biology, REPLICATION, Genome, Mitochondrial, HETEROPLASMY, 030217 neurology & neurosurgery
Abstract

INTRODUCTION Only 2.4% of the 16.5-kb mitochondrial DNA (mtDNA) genome shows homoplasmic variation at >1% frequency in humans. Migration patterns have contributed to geographic differences in the frequency of common genetic variants, but population genetic evidence indicates that selection shapes the evolving mtDNA phylogeny. The mechanism and timing of this process are not clear. Unlike the nuclear genome, mtDNA is maternally transmitted and there are many copies in each cell. Initially, a new genetic variant affects only a proportion of the mtDNA (heteroplasmy). During female germ cell development, a reduction in the amount of mtDNA per cell causes a “genetic bottleneck,” which leads to rapid segregation of mtDNA molecules and different levels of heteroplasmy between siblings. Although heteroplasmy is primarily governed by random genetic drift, there is evidence of selection occurring during this process in animals. Yet it has been difficult to demonstrate this convincingly in humans. RATIONALE To determine whether there is selection for or against heteroplasmic mtDNA variants during transmission, we studied 12,975 whole-genome sequences, including 1526 mother–offspring pairs of which 45.1% had heteroplasmy affecting >1% of mtDNA molecules. Harnessing both the mtDNA and nuclear genome sequences, we then determined whether the nuclear genetic background influenced mtDNA heteroplasmy, validating our findings in another 40,325 individuals. RESULTS Previously unknown mtDNA variants were less likely to be inherited than known variants, in which the level of heteroplasmy tended to increase on transmission. Variants in the ribosomal RNA genes were less likely to be transmitted, whereas variants in the noncoding displacement (D)–loop were more likely to be transmitted. MtDNA variants predicted to affect the protein sequence tended to have lower heteroplasmy levels than synonymous variants. In 12,975 individuals, we identified a correlation between the location of heteroplasmic sites and known D-loop polymorphisms, including the absence of variants in critical sites required for mtDNA transcription and replication. We defined 206 unrelated individuals for which the nuclear and mitochondrial genomes were from different human populations. In these individuals, new population-specific heteroplasmies were more likely to match the nuclear genetic ancestry than the mitochondrial genome on which the mutations occurred. These findings were independently replicated in 654 additional unrelated individuals. CONCLUSION The characteristics of mtDNA in the human population are shaped by selective forces acting on heteroplasmy within the female germ line and are influenced by the nuclear genetic background. The signature of selection can be seen over one generation, ensuring consistency between these two independent genetic systems.

Published
2019
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16. Rivaroxaban for Stroke Prevention after Embolic Stroke of Undetermined Source

Author

Hart, RG, Sharma, M, Mundl, H, Kasner, SE, Bangdiwala, SI, Berkowitz, SD, Swaminathan, B, Lavados, P, Wang, Y, Davalos, A, Shamalov, N, Mikulik, R, Cunha, L, Lindgren, A, Arauz, A, Lang, W, Czlonkowska, A, Eckstein, J, Gagliardi, RJ, Amarenco, P, Ameriso, SF, Tatlisumak, T, Veltkamp, R, Hankey, GJ, Toni, D, Bereczki, D, Uchiyama, S, Ntaios, G, Yoon, BW, Brouns, R, Endres, M, Muir, KW, Bornstein, N, Ozturk, S, O'Donnell, MJ, Basson, MMD, Pare, G, Pater, C, Kirsch, B, Sheridan, P, Peters, G, Weitz, JI, Peacock, WF, Shoamanesh, A, Benavente, OR, Joyner, C, Themeles, E, and Connolly, SJ

Abstract

BACKGROUND Embolic strokes of undetermined source represent 20% of ischemic strokes and are associated with a high rate of recurrence. Anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, may result in a lower risk of recurrent stroke than aspirin. METHODS We compared the efficacy and safety of rivaroxaban (at a daily dose of 15 mg) with aspirin (at a daily dose of 100 mg) for the prevention of recurrent stroke in patients with recent ischemic stroke that was presumed to be from cerebral embolism but without arterial stenosis, lacune, or an identified cardioembolic source. The primary efficacy outcome was the first recurrence of ischemic or hemorrhagic stroke or systemic embolism in a time-to-event analysis; the primary safety outcome was the rate of major bleeding. RESULTS A total of 7213 participants were enrolled at 459 sites; 3609 patients were randomly assigned to receive rivaroxaban and 3604 to receive aspirin. Patients had been followed for a median of 11 months when the trial was terminated early because of a lack of benefit with regard to stroke risk and because of bleeding associated with rivaroxaban. The primary efficacy outcome occurred in 172 patients in the rivaroxaban group (annualized rate, 5.1%) and in 160 in the aspirin group (annualized rate, 4.8%) (hazard ratio, 1.07; 95% confidence interval [CI], 0.87 to 1.33; P=0.52). Recurrent ischemic stroke occurred in 158 patients in the rivaroxaban group (annualized rate, 4.7%) and in 156 in the aspirin group (annualized rate, 4.7%). Major bleeding occurred in 62 patients in the rivaroxaban group (annualized rate, 1.8%) and in 23 in the aspirin group (annualized rate, 0.7%) (hazard ratio, 2.72; 95% CI, 1.68 to 4.39; P

Published
2018

17. Rivaroxaban or aspirin for patent foramen ovale and embolic stroke of undetermined source: a prespecified subgroup analysis from the NAVIGATE ESUS trial

Author

Kasner, Scott E, primary, Swaminathan, Balakumar, additional, Lavados, Pablo, additional, Sharma, Mukul, additional, Muir, Keith, additional, Veltkamp, Roland, additional, Ameriso, Sebastian F, additional, Endres, Matthias, additional, Lutsep, Helmi, additional, Messé, Steven R, additional, Spence, J David, additional, Nedeltechev, Krassen, additional, Perera, Kanjana, additional, Santo, Gustavo, additional, Olavarria, Veronica, additional, Lindgren, Arne, additional, Bangdiwala, Shrikant, additional, Shoamanesh, Ashkan, additional, Berkowitz, Scott D, additional, Mundl, Hardi, additional, Connolly, Stuart J, additional, Hart, Robert G, additional, Abdelhamid, N, additional, Abdul Rahman, D, additional, Abdul-Saheb, M, additional, Abreu, P, additional, Abroskina, M, additional, Abu Ahmad, F, additional, Accassat, S, additional, Acciaresi, M, additional, Adami, A, additional, Ahmad, N, additional, Ahmed, F, additional, Alberto Hawkes, M, additional, Alemseged, F, additional, Ali, A, additional, Altavilla, R, additional, Alwis, L, additional, Amarenco, P, additional, Amaro, S, additional, Amaya Sanchez, LE, additional, Amelia Pinto, A, additional, Ameriso, SF, additional, Amin, H, additional, Amino, T, additional, Amjad, AK, additional, Anagnostou, E, additional, Andersen, G, additional, Anderson, C, additional, Anderson, DC, additional, Andrea Falco, M, additional, Andres Mackinnon, F, additional, Andreu, D, additional, Androulakis, M, additional, Angel Gamero, M, additional, Angel Saredo, G, additional, Angeles Diaz, R, additional, Angels Font, M, additional, Anticoli, S, additional, Arauz, A, additional, Arauz Gongora, AA, additional, Araya, P, additional, Arenillas Lara, JF, additional, Arias Rivas, S, additional, Arnold, M, additional, Augustin, S, additional, Avelar, W, additional, Azevedo, E, additional, Babikian, V, additional, Bacellar, A, additional, Badalyan, K, additional, Bae, HJ, additional, Baez Martinez, EM, additional, Bagelmann, H, additional, Bailey, P, additional, Bak, Z, additional, Baker, M, additional, Balazs, A, additional, Baldaranov, D, additional, Balogun, I, additional, Balueva, T, additional, Bankuti, Z, additional, Bar, M, additional, Baranowska, A, additional, Bardutzky, J, additional, Barker Trejo, S, additional, Barlinn, J, additional, Baronnet, F, additional, Barroso, C, additional, Barteys, M, additional, Bartolottiova, T, additional, Barulin, A, additional, Bas, M, additional, Bashir, S, additional, Basile, V, additional, Bathe-Peters, R, additional, Bathula, R, additional, Batista, C, additional, Batur Caglayan, H, additional, Baumgartner, P, additional, Bazan, R, additional, Bazhenova, O, additional, Beaudry, M, additional, Beer, J, additional, Behnam, Y, additional, Beilei, C, additional, Beinlich, A, additional, Bejot, Y, additional, Belkin, A, additional, Benavente, OR, additional, Benjamin, A, additional, Berardi, V, additional, Bereczki, D, additional, Berkowitz, SD, additional, Berlingieri, J, additional, Berrios, W, additional, Berrouschot, J, additional, Bhandari, M, additional, Bhargavah, M, additional, Bicker, H, additional, Bicsak, T, additional, Bilik, M, additional, Bindila, D, additional, Birchenall, J, additional, Birnbaum, L, additional, Black, T, additional, Blacker, D, additional, Blacquiere, D, additional, Blanc-Labarre, C, additional, Blank, C, additional, Blazejewska-Hyzorek, B, additional, Bloch, S, additional, Bodiguel, E, additional, Bogdanov, E, additional, Boos, L, additional, Borcsik, L, additional, Bornstein, N, additional, Bouly, S, additional, Braga, G, additional, Bragado, I, additional, Bravi, MC, additional, Brokalaki, C, additional, Brola, W, additional, Brouns, R, additional, Bruce, D, additional, Brzoska-Mizgalska, J, additional, Buck, B, additional, Buksinska-Lisik, M, additional, Burke, J, additional, Burn, M, additional, Bustamante, G, additional, Cabrejo, L, additional, Cai, K, additional, Cajaraville, S, additional, Calejo, M, additional, Calvet, D, additional, Campillo, J, additional, Campos Costa, E, additional, Camps, P, additional, Can Alaydin, H, additional, Candeloro, E, additional, Canepa, C, additional, Cantu Brito, CG, additional, Cappellari, M, additional, Carcel, C, additional, Cardona Portela, P, additional, Cardoso, F, additional, Carek, M, additional, Carletti, M, additional, Carlos Portilla, J, additional, Caruso, P, additional, Casado-Naranjo, I, additional, Castellini, P, additional, Castro, D, additional, Castro Meira, F, additional, Cavallini, A, additional, Cayuela Caudevilla, N, additional, Cenciarelli, S, additional, Cereda, C, additional, Cerrone, P, additional, Chakrabarti, A, additional, Chaloulos-Iakovidis, P, additional, Chamorro, A, additional, Chandrasena, D, additional, Chang, DI, additional, Che, C, additional, Chembala, J, additional, Chen, J, additional, Chen, Z, additional, Chen, T, additional, Chen, H, additional, Chen, X, additional, Chen, G, additional, Chen, L, additional, Chen, S, additional, Cheripelli, B, additional, Chin, M, additional, Chiquete Anaya, E, additional, Chorazy, M, additional, Christensen, H, additional, Christensen, T, additional, Christian, L, additional, Chu, F, additional, Chung, CS, additional, Clark, W, additional, Clarke, R, additional, Claverie, S, additional, Clemente Agostoni, E, additional, Clissold, B, additional, Coelho, J, additional, Cohen, D, additional, Colakoglu, S, additional, Collas, D, additional, Condurso, R, additional, Connolly, SJ, additional, Consoli, D, additional, Constantin, C, additional, Constantino Silva, AB, additional, Contardo, L, additional, Corlobe, A, additional, Correia, M, additional, Correia, C, additional, Cortijo Garcia, E, additional, Coull, B, additional, Coutts, S, additional, Coveney, S, additional, Cras, P, additional, Crols, R, additional, Crozier, S, additional, Csanyi, A, additional, Csiba, L, additional, Csontos, K, additional, Csuha, R, additional, Cui, L, additional, Cunha, L, additional, Curtze, S, additional, Czerska, M, additional, Czlonkowska, A, additional, Czurko, M, additional, Czuryszkiewicz, M, additional, Dagnino, M, additional, Dai, C, additional, Daineko, A, additional, Dalek, G, additional, Damgaard, D, additional, Danese, A, additional, Dani, K, additional, Danku, V, additional, Dario Toledo, W, additional, Dávalos, A, additional, De Havenon, A, additional, De Keyser, J, additional, De Klippel, N, additional, De La Torre, J, additional, De Pauw, A, additional, De Smedt, A, additional, De Torres, R, additional, De Vries Basson, MM, additional, Dearborn, J, additional, Deganutto, R, additional, Degeorgia, M, additional, Deguchi, I, additional, Del Giudice, A, additional, Delcourt, C, additional, Delgado-Mederos, R, additional, Della Marca, G, additional, Delpont, B, additional, Deltour, S, additional, Demets, DL, additional, Dennis, M, additional, Desai, J, additional, Devine, J, additional, Dhollander, I, additional, Di Mascio, MT, additional, Diaconu, M, additional, Diaz Otero, F, additional, Dietzel, J, additional, Diez-Tejedor, E, additional, Ding, N, additional, Ding, J, additional, Diomedi, M, additional, Dioszeghy, P, additional, Distefano, M, additional, Domigo, V, additional, Dorodnicov, E, additional, Dossi, D, additional, Doubal, F, additional, Druzenko, I, additional, Du, P, additional, Du, J, additional, Duman, T, additional, Duodu, Y, additional, Dutta, D, additional, Dylewicz, L, additional, Eckstein, J, additional, Ehrensperger, E, additional, Ehrlich, S, additional, Einer Allende, G, additional, Elena Halac, B, additional, Elyas, S, additional, Endres, M, additional, Engelbrecht, JM, additional, Engelter, S, additional, Epinat, M, additional, Eren, F, additional, Esbjornsson, M, additional, Escribano, B, additional, Escudero, I, additional, Esisi, B, additional, Essa, B, additional, Esterbauer, M, additional, Evans, N, additional, Eveson, D, additional, Fabio, S, additional, Fang, L, additional, Fanta, S, additional, Fares, M, additional, Fatar, M, additional, Faust, K, additional, Favate, A, additional, Fazekas, F, additional, Federica Denaro, M, additional, Fedin, A, additional, Felipe Amaya, P, additional, Feng, J, additional, Ferencova, K, additional, Fernanda Gilli, M, additional, Fernandez, MD, additional, Fernandez Pirrone, PN, additional, Fernandez Vera, J, additional, Ferrari, J, additional, Ferreira, A, additional, Ferreira Junior, G, additional, Fidler, M, additional, Field, D, additional, Field, T, additional, Figueroa, C, additional, Fiksa, J, additional, Filipov, A, additional, Firstenfeld, A, additional, Fisch, L, additional, Fischer, U, additional, Fisselier, M, additional, Fiszer, U, additional, Fluri, F, additional, Fortea, G, additional, Fotherby, K, additional, Fraczek, A, additional, France, E, additional, Freitas, G, additional, Frey, S, additional, Frick, M, additional, Friedman, A, additional, Friedrich, M, additional, Frisullo, G, additional, Fryze, W, additional, Fuentes Gimeno, B, additional, Fujigasaki, H, additional, Fukuyama, K, additional, Furlan, A, additional, Furlanis, G, additional, Furnace, J, additional, Gabriel, M, additional, Gabriel Reich, E, additional, Gagliardi, RJ, additional, Galati, F, additional, Galli Giqueauk, E, additional, Gallina, A, additional, Gallinella, E, additional, Gallo, J, additional, Gangadharan, S, additional, Gao, Y, additional, Garcia Lopez, R, additional, Garcia Pastor, A, additional, Garcia Sanchez, SM, additional, Garnauf, M, additional, Garnier, P, additional, Gasecki, D, additional, Gasic, K, additional, Gasiorek, K, additional, Gasser, S, additional, Gaugg, M, additional, Gebreyohanns, M, additional, Gebura, K, additional, Geng, J, additional, Geniz Clavijo, M, additional, Georg Haeusler, K, additional, Geran, R, additional, Geremek, M, additional, Gerocs, Z, additional, Ghia, D, additional, Giannandrea, D, additional, Giatsidis, F, additional, Gien Lopez, JA, additional, Gil Nunez, A, additional, Gimenez, L, additional, Giralt, E, additional, Glabinski, A, additional, Gladstone, D, additional, Gliem, M, additional, Gluszkiewicz, M, additional, Goddeau, R, additional, Gogoleva, E, additional, Gokce, M, additional, Goldemund, D, additional, Golikov, K, additional, Gomes Neto, A, additional, Gomez Schneider, M, additional, Gomez-Choco, M, additional, Gomis, M, additional, Gongora-Rivera, JF, additional, Gonysheva, Y, additional, Gonzalez, L, additional, Gonzalez Toledo, ME, additional, Gottschal, M, additional, Gozdzik, I, additional, Grabowski, S, additional, Graf, S, additional, Green, D, additional, Greer, D, additional, Gregorio, T, additional, Greisenegger, S, additional, Greshnova, I, additional, Griebe, M, additional, Grzesik, M, additional, Guan, J, additional, Guarda, S, additional, Gueguen, A, additional, Guidoux, C, additional, Guillermo Povedano, P, additional, Guillon, B, additional, Guiraudg, V, additional, Gunathilagan, G, additional, Guryanova, N, additional, Gusev, V, additional, Gustavo Persi, G, additional, Gutiérrez, R, additional, Guyler, P, additional, Gyuker, N, additional, Hachinski, V, additional, Hajas, A, additional, Hallevi, H, additional, Hankey, G, additional, Hankey, GJ, additional, Hanouskova, L, additional, Hao, L, additional, Haraguchi, K, additional, Haralur Sreekantaiah, Y, additional, Haratz, S, additional, Hargroves, D, additional, Harkness, K, additional, Harmel, P, additional, Harrasser, M, additional, Hart, RG, additional, Harvey, M, additional, Hasan, R, additional, Hasegawa, Y, additional, Hassan, A, additional, Hattori, M, additional, Hatzitolios, A, additional, Hauk, M, additional, Hayashi, T, additional, Hayhoe, H, additional, Hedna, VS, additional, Heine, M, additional, Held, V, additional, Hellwig, S, additional, Henkner, J, additional, Henninger, N, additional, Hermans, S, additional, Hernandez, J, additional, Herrero, D, additional, Hervieu-Begue, M, additional, Herzig, R, additional, Hicken, L, additional, Hieber, M, additional, Hill, M, additional, Hirose, M, additional, Hobeanu, MC, additional, Hobson, B, additional, Hochstetter, M, additional, Hoe Heo, J, additional, Hoffmann, M, additional, Holmstedt, C, additional, Hon, P, additional, Hong, KS, additional, Honma, Y, additional, Horev, A, additional, Horgan, G, additional, Horvath, L, additional, Horvath, M, additional, Hoyer, C, additional, Huang, D, additional, Huang, H, additional, Huber, B, additional, Huhtakangas, J, additional, Hussain, M, additional, Igarashi, S, additional, Iglesias Mohedano, AM, additional, Ignacio Tembl, J, additional, Impellizzeri, M, additional, Inanc, Y, additional, Ioli, P, additional, Irina Aniculaesei, A, additional, Ishida, K, additional, Itabashi, R, additional, Iversen, H, additional, Jagolino, A, additional, Jakab, K, additional, Jander, S, additional, Janka, H, additional, Jankovych, J, additional, Jansen, J, additional, Jasek, L, additional, Javier Alet, M, additional, Javor, L, additional, Jin, X, 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Zalewska, J, additional, Zanferrari, C, additional, Zapata, E, additional, Zboznovits, D, additional, Zelenka, I, additional, Zhang, C, additional, Zhang, B, additional, Zhang, S, additional, Zhang, M, additional, Zhang, X, additional, Zhang, J, additional, Zhao, L, additional, Zhirnova, O, additional, Zhou, L, additional, Zielinska-Turek, J, additional, Zinchenko, I, additional, Ziomek, M, additional, Zitzmann, A, additional, Zweifler, R, additional, and Zwiernik, J, additional

Published
2018
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18. Endovascular therapy for acute ischaemic stroke: the Pragmatic Ischaemic Stroke Thrombectomy Evaluation (PISTE) randomised, controlled trial

Author

Muir, KW, Ford, GA, Messow, C-M, Ford, I, Murray, A, Clifton, A, Brown, MM, Madigan, J, Lenthall, R, Robertson, F, Dixit, A, Cloud, GC, Wardlaw, J, Freeman, J, White, P, and PISTE Investigators

Abstract

OBJECTIVE: The Pragmatic Ischaemic Thrombectomy Evaluation (PISTE) trial was a multicentre, randomised, controlled clinical trial comparing intravenous thrombolysis (IVT) alone with IVT and adjunctive intra-arterial mechanical thrombectomy (MT) in patients who had acute ischaemic stroke with large artery occlusive anterior circulation stroke confirmed on CT angiography (CTA). DESIGN: Eligible patients had IVT started within 4.5 hours of stroke symptom onset. Those randomised to additional MT underwent thrombectomy using any Conformité Européene (CE)-marked device, with target interval times for IVT start to arterial puncture of

Published
2017

19. Effect of atrial fibrillation on endovascular thrombectomy for acute ischemic stroke. A meta-analysis of individual patient data from six randomised trials: Results from the HERMES collaboration.

Author

Smaal, JA, de Ridder, IR, Heshmatollah, A, van Zwam, WH, Dippel, DWJ, Majoie, CB, Brown, S, Goyal, M, Campbell, BCV, Muir, KW, Demchuck, AM, Davalos, A, Jovin, TG, Mitchell, PJ, White, P, Saver, JL, Hill, MD, Roos, YB, van der Lugt, A, and van Oostenbrugge, RJ

Published
2020
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20. Validity of a structured interview for the Modified Rankin Scale: Comparison with other stroke assessment scales

Author

Schulz, U., Baird, T., Grant, M., Bone, I., Muir, Kw, Hareendran, A., and Lindsay Wilson

Subjects
Advanced and Specialized Nursing, nervous system, cardiovascular diseases, Neurology (clinical), Cardiology and Cardiovascular Medicine
Abstract

98 Background & aims: We have recently developed a structured interview for the Modified Rankin Scale (MRS-SI) to improve the inter-rater reliability of this measure of outcome. The purpose of the current study was to investigate the relationship between the MRS-SI and other measures commonly used to assess functional state after stroke. Methods: 119 patients (60 males) were recruited to the study 3 to 24 months after stroke. The median age of patients was 67, and the median interval since stroke was 13 months. Patients were assessed on the Modified Rankin Scale using the structured interview. In addition patients were assessed on the same occasion using the Scandinavian Stroke Scale, the National Institutes of Health Stroke Scales, the Barthel Index, the extended Glasgow Outcome Scale (GOSE) and the Short Form 36 (SF-36). Results: Spearman correlations were computed between ratings on the MRS-SI and other assessments. The MRS-SI was most strongly related to the GOSE. There were also strong correlations with the Barthel Index, the Scandinavian Stroke Scale, and the National Institutes of Health Stroke Scales. However, there was evidence of substantial ceiling effects on all three of these assessments. The MRS-SI correlated significantly with individual subscales of the SF-36, and was particularly strongly related to Physical Function and Social Functioning. However, not all stroke patients were able to complete the SF-36. Conclusions: Systematic relationships observed between the MRS-SI and other established measurement are evidence of the validity of the structured interview. The stroke scales and the Barthel Index discriminate the more disabled groups (Rankin 3 to 5), but are insensitive to functional differences among less severely disabled patients (Rankin 0 to 2). Self-report measures such as the SF-36 indicate differences in health outcome in the less severely disabled groups, but not all stroke patients are able to complete this assessment. A particular strength of the Modified Rankin Scale is the ability to chart the complete spectrum of disability and handicap after stroke.

Published
2016

21. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke

Author

Hacke, Werner, Kaste, Markku, Bluhmki, Erich, Brozman, Miroslav, Dávalos, Antoni, Guidetti, Donata, Larrue, Vincent, Lees, Kennedy R., Medeghri, Zakaria, Machnig, Thomas, Schneider, Dietmar, Von Kummer, Rüdiger, Wahlgren, Nils, Toni, Danilo, Hacke, W, Dávalos, A, Kaste, M, von Kummer, R, Larrue, V, Toni, D, Wahlgren, N, Lees, Kr, Heiss, Wd, Lesaffre, E, Orgogozo, Jm, Bastianello, S, Wardlaw, Jm, Peyrieux, Jc, Sauce, C, Medeghri, Z, Mazenc, R, Machnig, T, Bluhmki, E, Aichner, F, Alf, C, Baumhackl, U, Brainin, M, Eggers, C, Gruber, F, Ladurner, G, Niederkorn, K, Noistering, G, Willeit, J, Vanhooren, G, Blecic, S, Bruneel, B, Caekebeke, J, Laloux, P, Simons, Pj, Thijs, V, Bar, M, Dvorakova, H, Vaclavik, D, Boysen, G, Andersen, G, Iversen, Hk, Traberg-Kristensen, B, Marttila, R, Sivenius, J, Trouillas, P, Amarenco, P, Bouillat, J, Ducrocq, X, Giroud, M, Jaillard, A, Larrieu, Jm, Leys, D, Magne, C, Mahagne, Mh, Milhaud, D, Sablot, D, Saudeau, D, Busse, O, Berrouschot, J, Faiss, Jh, Glahn, J, Görtler, M, Grau, A, Grond, M, Haberl, R, Hamann, G, Hennerici, M, Koch, H, Krauseneck, P, Marx, J, Meves, S, Meyding-Lamadé, U, Ringleb, P, Schneider, D, Schwarz, A, Sobesky, J, Urban, P, Karageorgiou, K, Komnos, A, Csányi, A, Csiba, L, Valikovics, A, Agnelli, G, Billo, G, Bovi, P, Comi, G, Gigli, G, Guidetti, D, Inzitari, D, Marcello, N, Marini, C, Orlandi, G, Pratesi, M, Rasura, M, Semplicini, A, Serrati, C, Tassinari, T, Brouwers, Pj, Stam, J, Naess, H, Indredavik, B, Kloster, R, Czlonkowska, A, Kuczyńska-Zardzewialy, A, Nyka, W, Opala, G, Romanowicz, S, Cunha, L, Correia, C, Cruz, V, Pinho e Melo, T, Brozman, M, Dvorak, M, Garay, R, Krastev, G, Kurca, E, Alvarez-Sabin, J, Chamorro, A, del Mar Freijo Guerrero, M, Herrero, Ja, Gil-Peralta, A, Leira, R, Martí-Vilalta, Jl, Masjuan Vallejo, J, Millán, M, Molina, C, Mostacero, E, Segura, T, Serena, J, Vivancos Mora, J, Danielsson, E, Cederin, B, Von, Zweigberg, Wahlgren, Ng, Welin, L, Lyrer, P, Bogousslavsky, J, Hungerbühler, Hj, Weder, B, Ford, Ga, Jenkinson, D, Macleod, Mj, Macwalter, Rs, Markus, Hs, Muir, Kw, Sharma, Ak, Walters, Mr, Warburton, Ea, ACS - Amsterdam Cardiovascular Sciences, ANS - Amsterdam Neuroscience, and Neurology

Subjects
Adult, Male, Time Factors, medicine.medical_treatment, Placebo, Drug Administration Schedule, Brain Ischemia, Brain ischemia, Double-Blind Method, Fibrinolytic Agents, Modified Rankin Scale, medicine, Odds Ratio, Desmoteplase, Humans, Infusions, Intravenous, Stroke, Aged, business.industry, Cerebral infarction, Medicine (all), General Medicine, Thrombolysis, Middle Aged, medicine.disease, Logistic Models, Treatment Outcome, Anesthesia, Tissue Plasminogen Activator, Acute Disease, Female, business, Intracranial Hemorrhages, Fibrinolytic agent
Abstract

Background Intravenous thrombolysis with alteplase is the only approved treatment for acute ischemic stroke, but its efficacy and safety when administered more than 3 hours after the onset of symptoms have not been established. We tested the efficacy and safety of alteplase administered between 3 and 4.5 hours after the onset of a stroke. Methods After exclusion of patients with a brain hemorrhage or major infarction, as detected on a computed tomographic scan, we randomly assigned patients with acute ischemic stroke in a 1:1 double-blind fashion to receive treatment with intravenous alteplase (0.9 mg per kilogram of body weight) or placebo. The primary end point was disability at 90 days, dichotomized as a favorable outcome (a score of 0 or 1 on the modified Rankin scale, which has a range of 0 to 6, with 0 indicating no symptoms at all and 6 indicating death) or an unfavorable outcome (a score of 2 to 6 on the modified Rankin scale). The secondary end point was a global outcome analysis of four neurologic and disability scores combined. Safety end points included death, symptomatic intracranial hemorrhage, and other serious adverse events. Results We enrolled a total of 821 patients in the study and randomly assigned 418 to the alteplase group and 403 to the placebo group. The median time for the administration of alteplase was 3 hours 59 minutes. More patients had a favorable outcome with alte plase than with placebo (52.4% vs. 45.2%; odds ratio, 1.34; 95% confidence interval [CI], 1.02 to 1.76; P = 0.04). In the global analysis, the outcome was also improved with alteplase as compared with placebo (odds ratio, 1.28; 95% CI, 1.00 to 1.65; P

Published
2008

22. Thrombolysis for stroke: pushed out of the window?

Author

Muir Kw

Subjects
Pharmacology, medicine.medical_specialty, business.industry, medicine.medical_treatment, Window (computing), Thrombolysis, Original Articles, medicine.disease, Cerebrovascular Disorders, Fibrinolytic Agents, Emergency medicine, medicine, Humans, Pharmacology (medical), Thrombolytic Therapy, Medical emergency, business, Stroke, Fibrinolytic agent
Published
1996

39. Visual evaluation of perfusion computed tomography in acute stroke accurately estimates infarct volume and tissue viability.

Author

Muir KW, Halbert HM, Baird TA, McCormick M, Teasdale E, Muir, K W, Halbert, H M, Baird, T A, McCormick, M, and Teasdale, E

Abstract

Objective: To establish the validity of visual interpretation of immediately processed perfusion computed tomography (CT) maps in acute stroke for prediction of final infarction.Methods: Perfusion CT studies acquired prospectively were reprocessed within six hours of stroke onset using standard CT console software. Four contiguous 5 mm thick images were obtained and maps of time to peak (TTP) and cerebral blood volume (CBV) generated. Volumes of lesions identified only by visual inspection were measured from manually drawn regions of interest. Volumes of tissue with prolonged TTP or reduced CBV were compared with independently calculated volume of infarction on non-contrast CT (NCCT) at 24-48 hours, and with clinical severity using the NIHSS score. Arterial patency at 24-48 h was included in analyses.Results: Studies were analysed from 17 patients 150 minutes (median) after stroke onset. Volume of tissue with prolonged TTP correlated with initial NIHSS (r = 0.62, p = 0.009), and with NCCT final infarct volume when arterial occlusion persisted (r = 0.953, p = 0.012). Volume of tissue with reduced CBV correlated with final infarct volume if recanalisation occurred (r = 0.835, p = 0.001). Recanalisation was associated with lower 24 h NIHSS score (6 (IQR, 5 to 9.5) v 19 (18 to 26), p = 0.027), and in 10 patients given rtPA for MCA M1 occlusion, with lower infarct volume (73 v 431 ml, p = 0.002).Conclusions: Visual evaluation of TTP and CBV maps generated by standard perfusion CT software correlated with 24-48 hour CT infarct volumes. Comparison of TTP and CBV maps yields information on tissue viability. Perfusion CT represents a practical technique to aid acute clinical decision making. Recanalisation was a crucial determinant of clinical and radiological outcome. [ABSTRACT FROM AUTHOR]

Published
2006

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