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1. Pragmatic solutions to reduce the global burden of stroke: a World Stroke Organization–Lancet Neurology Commission

Author

Feigin, V, Owolabi, M, Abd-Allah, F, Akinyemi, R, Bhattacharjee, N, Brainin, M, Cao, J, Caso, V, Dalton, B, Davis, A, Dempsey, R, Duprey, J, Feng, W, Ford, G, Gall, S, Gandhi, D, Good, D, Hachinski, V, Hacke, W, Hankey, G, Ishida, M, Johnson, W, Kim, J, Lavados, P, Lindsay, P, Mahal, A, Martins, S, Murray, C, Nguyen, T, Norrving, B, Olaiya, M, Olalusi, O, Pandian, J, Phan, H, Platz, T, Ranta, A, Rehman, S, Roth, G, Sebastian, I, Smith, A, Suwanwela, N, Sylaja, P, Thapa, R, Thrift, A, Uvere, E, Vollset, S, Yavagal, D, Yaria, J, Abera, S, Ibrahim, N, Liu, L, Ovbiagele, B, Piradov, M, Abanto, C, Addissie, A, Adeleye, A, Adilbekov, Y, Adilbekova, B, Adoukonou, T, Aguiar de Sousa, D, Akhmetzhanova, Z, Akpalu, A, El Alaoui-Faris, M, Ameriso, S, Andonova, S, Arsovska, A, Awoniyi, F, Bakhiet, M, Barboza, M, Basri, H, Bath, P, Bereczki, D, Beretta, S, Berkowitz, A, Bernhardt, J, Berzina, G, Bhavsar, B, Bisharyan, M, Bohara, M, Bovet, P, Budincevic, H, Cadilhac, D, Cerimagic, D, Charway-Felli, A, Chen, C, Chin, J, Christensen, H, Chwojnicki, K, Conforto, A, Correia, M, Mora Cuervo, D, Czlonkowska, A, D'Amelio, M, Danielyan, K, Davis, S, Demarin, V, Demchuk, A, Dichgans, M, Dokova, K, Donnan, G, Duran, J, Ekeng, G, Elkind, M, Endres, M, Fischer, U, Flomin, Y, Gankpe, F, Gavidia, M, Gaye Saavedra, A, Gebreyohanns, M, George, M, Gierlotka, M, Giroud, M, Gnedovskaya, E, Goncalves, I, Gongora-Rivera, F, Gunaratne, P, Hamadeh, R, Hamzat, T, Heldner, M, Ibrahim, E, Ihle-Hansen, H, Jee, S, Jiann-Shing, J, Johnston, S, Jovanovic, D, Jurjans, K, Kalani, R, Kalkonde, Y, Kamenova, S, Karaszewski, B, Kelly, P, Kiechl, S, Kondybayeva, A, Korv, J, Kozera, G, Kravchenko, M, Krespi, Y, Krishnamurthi, R, Kruja, J, Kutluk, K, Langhorne, P, Law, Z, Lebedynets, D, Lee, T, Leung, T, Liebeskind, D, Lopez-Jaramillo, P, Lotufo, P, Machline-Carrion, M, Maia, L, Malojcic, B, Markus, H, Marquez-Romero, J, Medina, M, Medukhanova, S, Mehndiratta, M, Miglane, E, Mihejeva, I, Mikulik, R, Mirrakhimov, E, Mohl, S, Munakomi, S, Murphy, S, Musa, K, Nasreldein, A, Nogueira, R, Nolte, C, Noubiap, J, Novarro-Escudero, N, Ocampo, C, O'Donnell, M, Ogun, Y, Ogunniyi, A, Oraby, M, Orken, D, Ozdemir, A, Ozturk, S, Paccot, M, Pereira, T, Peeters, A, Potpara, T, Proios, H, Rathore, F, Sacco, R, Sahathevan, R, Sandset, E, Renato Santos, I, Saposnik, G, Sarfo, F, Sargento-Freitas, J, Sharma, M, Shaw, L, Sheth, K, Shin, Y, Shobhana, A, Silva, S, Tedim Cruz, V, Thakur, K, Thapa, L, Toni, D, Topcuoglu, M, Torales, J, Towfighi, A, Truelsen, T, Tsiskaridze, A, Tulloch-Reid, M, Useche, J, Vanacker, P, Vassilopoulou, S, Vukorepa, G, Vuletic, V, Wahab, K, Wang, W, Wijeratne, T, Wojtyniak, B, Wolfe, C, Yacouba, M, Yang, J, Yifru, Y, Yock-Corrales, A, Yonemoto, N, Yperzeele, L, Zagozdzon, P, Feigin V. L., Owolabi M. O., Abd-Allah F., Akinyemi R. O., Bhattacharjee N. V., Brainin M., Cao J., Caso V., Dalton B., Davis A., Dempsey R., Duprey J., Feng W., Ford G. A., Gall S., Gandhi D., Good D. C., Hachinski V., Hacke W., Hankey G. J., Ishida M., Johnson W., Kim J., Lavados P., Lindsay P., Mahal A., Martins S., Murray C., Nguyen T. P., Norrving B., Olaiya M. T., Olalusi O. V., Pandian J., Phan H., Platz T., Ranta A., Rehman S., Roth G., Sebastian I. A., Smith A. E., Suwanwela N. C., Sylaja P. N., Thapa R., Thrift A. G., Uvere E., Vollset S. E., Yavagal D., Yaria J., Abera S. F., Akinyemi R., Dempsey R. J., Ibrahim N. M., Liu L., Ovbiagele B., Piradov M., Suwanwela N., Abanto C., Addissie A., Adeleye A. O., Adilbekov Y., Adilbekova B., Adoukonou T. A., Aguiar de Sousa D., Akhmetzhanova Z., Akpalu A., El Alaoui-Faris M., Ameriso S. F., Andonova S., Arsovska A., Awoniyi F. E., Bakhiet M., Barboza M. A., Basri H., Bath P. M., Bereczki D., Beretta S., Berkowitz A. L., Bernhardt J., Berzina G., Bhavsar B., Bisharyan M. S., Bohara M., Bovet P., Budincevic H., Cadilhac D. A., Cerimagic D., Charway-Felli A., Chen C., Chin J. H., Christensen H., Chwojnicki K., Conforto A. B., Correia M., Mora Cuervo D. L., Czlonkowska A., D'Amelio M., Danielyan K. E., Davis S., Demarin V., Demchuk A. M., Dichgans M., Dokova K., Donnan G., Duran J. C., Ekeng G., Elkind M. S., Endres M., Fischer U., Flomin Y., Gankpe F., Gavidia M., Gaye Saavedra A., Gebreyohanns M., George M., Gierlotka M., Giroud M., Gnedovskaya E. V., Goncalves I. P., Gongora-Rivera F., Gunaratne P. S., Hamadeh R. R., Hamzat T. -H. K., Heldner M. R., Ibrahim E., Ihle-Hansen H., Jee S., Jiann-Shing J., Johnston S. C., Jovanovic D., Jurjans K., Kalani R., Kalkonde Y., Kamenova S., Karaszewski B., Kelly P., Kiechl S., Kondybayeva A., Korv J., Kozera G., Kravchenko M., Krespi Y., Krishnamurthi R., Kruja J., Kutluk K., Langhorne P., Law Z. K., Lebedynets D., Lee T. -H., Leung T. W., Liebeskind D. S., Lopez-Jaramillo P., Lotufo P. A., Machline-Carrion M. J., Maia L. F., Malojcic B., Markus H. S., Marquez-Romero J. M., Medina M. T., Medukhanova S., Mehndiratta M. M., Miglane E., Mihejeva I., Mikulik R., Mirrakhimov E., Mohl S., Munakomi S., Murphy S., Musa K. I., Nasreldein A., Nogueira R. G., Nolte C. H., Noubiap J. J., Novarro-Escudero N., Ocampo C., O'Donnell M., Ogun Y., Ogunniyi A., Oraby M. I., Orken D. N., Ozdemir A. O., Ozturk S., Paccot M., Pereira T., Peeters A., Potpara T., Proios H., Rathore F. A., Sacco R. L., Sahathevan R., Sandset E. S., Renato Santos I., Saposnik G., Sarfo F. S., Sargento-Freitas J., Sharma M., Shaw L., Sheth K. N., Shin Y. -I., Shobhana A., Silva S. N., Tedim Cruz V., Thakur K., Thapa L. J., Toni D., Topcuoglu M. A., Torales J., Towfighi A., Truelsen T., Tsiskaridze A., Tulloch-Reid M., Useche J. N., Vanacker P., Vassilopoulou S., Vukorepa G., Vuletic V., Wahab K. W., Wang W., Wijeratne T., Wojtyniak B., Wolfe C., Yacouba M. N., Yang J., Yifru Y. M., Yock-Corrales A., Yonemoto N., Yperzeele L., Zagozdzon P., Feigin, V, Owolabi, M, Abd-Allah, F, Akinyemi, R, Bhattacharjee, N, Brainin, M, Cao, J, Caso, V, Dalton, B, Davis, A, Dempsey, R, Duprey, J, Feng, W, Ford, G, Gall, S, Gandhi, D, Good, D, Hachinski, V, Hacke, W, Hankey, G, Ishida, M, Johnson, W, Kim, J, Lavados, P, Lindsay, P, Mahal, A, Martins, S, Murray, C, Nguyen, T, Norrving, B, Olaiya, M, Olalusi, O, Pandian, J, Phan, H, Platz, T, Ranta, A, Rehman, S, Roth, G, Sebastian, I, Smith, A, Suwanwela, N, Sylaja, P, Thapa, R, Thrift, A, Uvere, E, Vollset, S, Yavagal, D, Yaria, J, Abera, S, Ibrahim, N, Liu, L, Ovbiagele, B, Piradov, M, Abanto, C, Addissie, A, Adeleye, A, Adilbekov, Y, Adilbekova, B, Adoukonou, T, Aguiar de Sousa, D, Akhmetzhanova, Z, Akpalu, A, El Alaoui-Faris, M, Ameriso, S, Andonova, S, Arsovska, A, Awoniyi, F, Bakhiet, M, Barboza, M, Basri, H, Bath, P, Bereczki, D, Beretta, S, Berkowitz, A, Bernhardt, J, Berzina, G, Bhavsar, B, Bisharyan, M, Bohara, M, Bovet, P, Budincevic, H, Cadilhac, D, Cerimagic, D, Charway-Felli, A, Chen, C, Chin, J, Christensen, H, Chwojnicki, K, Conforto, A, Correia, M, Mora Cuervo, D, Czlonkowska, A, D'Amelio, M, Danielyan, K, Davis, S, Demarin, V, Demchuk, A, Dichgans, M, Dokova, K, Donnan, G, Duran, J, Ekeng, G, Elkind, M, Endres, M, Fischer, U, Flomin, Y, Gankpe, F, Gavidia, M, Gaye Saavedra, A, Gebreyohanns, M, George, M, Gierlotka, M, Giroud, M, Gnedovskaya, E, Goncalves, I, Gongora-Rivera, F, Gunaratne, P, Hamadeh, R, Hamzat, T, Heldner, M, Ibrahim, E, Ihle-Hansen, H, Jee, S, Jiann-Shing, J, Johnston, S, Jovanovic, D, Jurjans, K, Kalani, R, Kalkonde, Y, Kamenova, S, Karaszewski, B, Kelly, P, Kiechl, S, Kondybayeva, A, Korv, J, Kozera, G, Kravchenko, M, Krespi, Y, Krishnamurthi, R, Kruja, J, Kutluk, K, Langhorne, P, Law, Z, Lebedynets, D, Lee, T, Leung, T, Liebeskind, D, Lopez-Jaramillo, P, Lotufo, P, Machline-Carrion, M, Maia, L, Malojcic, B, Markus, H, Marquez-Romero, J, Medina, M, Medukhanova, S, Mehndiratta, M, Miglane, E, Mihejeva, I, Mikulik, R, Mirrakhimov, E, Mohl, S, Munakomi, S, Murphy, S, Musa, K, Nasreldein, A, Nogueira, R, Nolte, C, Noubiap, J, Novarro-Escudero, N, Ocampo, C, O'Donnell, M, Ogun, Y, Ogunniyi, A, Oraby, M, Orken, D, Ozdemir, A, Ozturk, S, Paccot, M, Pereira, T, Peeters, A, Potpara, T, Proios, H, Rathore, F, Sacco, R, Sahathevan, R, Sandset, E, Renato Santos, I, Saposnik, G, Sarfo, F, Sargento-Freitas, J, Sharma, M, Shaw, L, Sheth, K, Shin, Y, Shobhana, A, Silva, S, Tedim Cruz, V, Thakur, K, Thapa, L, Toni, D, Topcuoglu, M, Torales, J, Towfighi, A, Truelsen, T, Tsiskaridze, A, Tulloch-Reid, M, Useche, J, Vanacker, P, Vassilopoulou, S, Vukorepa, G, Vuletic, V, Wahab, K, Wang, W, Wijeratne, T, Wojtyniak, B, Wolfe, C, Yacouba, M, Yang, J, Yifru, Y, Yock-Corrales, A, Yonemoto, N, Yperzeele, L, Zagozdzon, P, Feigin V. L., Owolabi M. O., Abd-Allah F., Akinyemi R. O., Bhattacharjee N. V., Brainin M., Cao J., Caso V., Dalton B., Davis A., Dempsey R., Duprey J., Feng W., Ford G. A., Gall S., Gandhi D., Good D. C., Hachinski V., Hacke W., Hankey G. J., Ishida M., Johnson W., Kim J., Lavados P., Lindsay P., Mahal A., Martins S., Murray C., Nguyen T. P., Norrving B., Olaiya M. T., Olalusi O. V., Pandian J., Phan H., Platz T., Ranta A., Rehman S., Roth G., Sebastian I. A., Smith A. E., Suwanwela N. C., Sylaja P. N., Thapa R., Thrift A. G., Uvere E., Vollset S. E., Yavagal D., Yaria J., Abera S. F., Akinyemi R., Dempsey R. J., Ibrahim N. M., Liu L., Ovbiagele B., Piradov M., Suwanwela N., Abanto C., Addissie A., Adeleye A. O., Adilbekov Y., Adilbekova B., Adoukonou T. A., Aguiar de Sousa D., Akhmetzhanova Z., Akpalu A., El Alaoui-Faris M., Ameriso S. F., Andonova S., Arsovska A., Awoniyi F. E., Bakhiet M., Barboza M. A., Basri H., Bath P. M., Bereczki D., Beretta S., Berkowitz A. L., Bernhardt J., Berzina G., Bhavsar B., Bisharyan M. S., Bohara M., Bovet P., Budincevic H., Cadilhac D. A., Cerimagic D., Charway-Felli A., Chen C., Chin J. H., Christensen H., Chwojnicki K., Conforto A. B., Correia M., Mora Cuervo D. L., Czlonkowska A., D'Amelio M., Danielyan K. E., Davis S., Demarin V., Demchuk A. M., Dichgans M., Dokova K., Donnan G., Duran J. C., Ekeng G., Elkind M. S., Endres M., Fischer U., Flomin Y., Gankpe F., Gavidia M., Gaye Saavedra A., Gebreyohanns M., George M., Gierlotka M., Giroud M., Gnedovskaya E. V., Goncalves I. P., Gongora-Rivera F., Gunaratne P. S., Hamadeh R. R., Hamzat T. -H. K., Heldner M. R., Ibrahim E., Ihle-Hansen H., Jee S., Jiann-Shing J., Johnston S. C., Jovanovic D., Jurjans K., Kalani R., Kalkonde Y., Kamenova S., Karaszewski B., Kelly P., Kiechl S., Kondybayeva A., Korv J., Kozera G., Kravchenko M., Krespi Y., Krishnamurthi R., Kruja J., Kutluk K., Langhorne P., Law Z. K., Lebedynets D., Lee T. -H., Leung T. W., Liebeskind D. S., Lopez-Jaramillo P., Lotufo P. A., Machline-Carrion M. J., Maia L. F., Malojcic B., Markus H. S., Marquez-Romero J. M., Medina M. T., Medukhanova S., Mehndiratta M. M., Miglane E., Mihejeva I., Mikulik R., Mirrakhimov E., Mohl S., Munakomi S., Murphy S., Musa K. I., Nasreldein A., Nogueira R. G., Nolte C. H., Noubiap J. J., Novarro-Escudero N., Ocampo C., O'Donnell M., Ogun Y., Ogunniyi A., Oraby M. I., Orken D. N., Ozdemir A. O., Ozturk S., Paccot M., Pereira T., Peeters A., Potpara T., Proios H., Rathore F. A., Sacco R. L., Sahathevan R., Sandset E. S., Renato Santos I., Saposnik G., Sarfo F. S., Sargento-Freitas J., Sharma M., Shaw L., Sheth K. N., Shin Y. -I., Shobhana A., Silva S. N., Tedim Cruz V., Thakur K., Thapa L. J., Toni D., Topcuoglu M. A., Torales J., Towfighi A., Truelsen T., Tsiskaridze A., Tulloch-Reid M., Useche J. N., Vanacker P., Vassilopoulou S., Vukorepa G., Vuletic V., Wahab K. W., Wang W., Wijeratne T., Wojtyniak B., Wolfe C., Yacouba M. N., Yang J., Yifru Y. M., Yock-Corrales A., Yonemoto N., Yperzeele L., and Zagozdzon P.

Published
2023

2. A quantum field theoretical model of neutrino oscillation without external wave packets

Author

Law, Z. Y., Chan, A. H., and Oh, C. H.

Subjects
High Energy Physics - Phenomenology
Abstract

We develop a general and consistent model of neutrino oscillation based on the quantum field theoretical description of the neutrino production and detection processes. Emphasis is placed on the locality of the interactions of these processes, where on top of the usual application of the four fermion local Hamiltonian, we assume that weak interactions switched on only when the wave functions of the particles involved are overlapping and switched off upon their separation. A key assumption in our treatment is that the wave packet sizes of the particles, in particular, the neutrino producing source particles and the neutrino absorbing detector particles, are taken to be negligible compared with their mean free path in their respective medium. With this assumption, and taking into considerations of the finite time of neutrino production, neutrino wave packets with well-defined edges are generated. This fact, together with the locality of weak interactions, enable us to relate the propagation time to the propagation distance, thus doing away with the ad hoc time averaging procedure normally employing in derivations of neutrino oscillation formula. No assumptions on the particular forms of particle wave functions; for example, Gaussians, need to be made. A good feature of our approach is that the neutrino oscillation formula is automatically normalised if the in-going states of the production and detection processes are normalised. We also show that causality and unitarity cannot both be satisfied in virtual neutrino models., Comment: 32 pages, 10 figures

Published
2014

3. Primary stroke prevention worldwide: translating evidence into action

Author

Owolabi, M, Thrift, A, Mahal, A, Ishida, M, Martins, S, Johnson, W, Pandian, J, Abd-Allah, F, Yaria, J, Phan, H, Roth, G, Gall, S, Beare, R, Phan, T, Mikulik, R, Akinyemi, R, Norrving, B, Brainin, M, Feigin, V, Abanto, C, Abera, S, Addissie, A, Adebayo, O, Adeleye, A, Adilbekov, Y, Adilbekova, B, Adoukonou, T, Aguiar de Sousa, D, Ajagbe, T, Akhmetzhanova, Z, Akpalu, A, Alvarez Ahlgren, J, Ameriso, S, Andonova, S, Awoniyi, F, Bakhiet, M, Barboza, M, Basri, H, Bath, P, Bello, O, Bereczki, D, Beretta, S, Berkowitz, A, Bernabe-Ortiz, A, Bernhardt, J, Berzina, G, Bisharyan, M, Bovet, P, Budincevic, H, Cadilhac, D, Caso, V, Chen, C, Chin, J, Chwojnicki, K, Conforto, A, Cruz, V, D'Amelio, M, Danielyan, K, Davis, S, Demarin, V, Dempsey, R, Dichgans, M, Dokova, K, Donnan, G, Elkind, M, Endres, M, Fischer, U, Gankpe, F, Gaye Saavedra, A, Gil, A, Giroud, M, Gnedovskaya, E, Hachinski, V, Hafdi, M, Hamadeh, R, Hamzat, T, Hankey, G, Heldner, M, Ibrahim, E, Ibrahim, N, Inoue, M, Jee, S, Jeng, J, Kalkonde, Y, Kamenova, S, Karaszewski, B, Kelly, P, Khan, T, Kiechl, S, Kondybayeva, A, Korv, J, Kravchenko, M, Krishnamurthi, R, Kruja, J, Lakkhanaloet, M, Langhorne, P, Lavados, P, Law, Z, Lawal, A, Lazo-Porras, M, Lebedynets, D, Lee, T, Leung, T, Liebeskind, D, Lindsay, P, Lopez-Jaramillo, P, Lotufo, P, Machline-Carrion, J, Makanjuola, A, Markus, H, Marquez-Romero, J, Medina, M, Medukhanova, S, Mehndiratta, M, Merkin, A, Mirrakhimov, E, Mohl, S, Moscoso-Porras, M, Muller-Stierlin, A, Murphy, S, Musa, K, Nasreldein, A, Nogueira, R, Nolte, C, Noubiap, J, Novarro-Escudero, N, Ogun, Y, Oguntoye, R, Oraby, M, Osundina, M, Ovbiagele, B, Orken, D, Ozdemir, A, Ozturk, S, Paccot, M, Phromjai, J, Piradov, P, Platz, T, Potpara, T, Ranta, A, Rathore, F, Richard, E, Sacco, R, Sahathevan, R, Santos Carquin, I, Saposnik, G, Sarfo, F, Sharma, M, Sheth, K, Shobhana, A, Suwanwela, N, Svyato, I, Sylaja, P, Tao, X, Thakur, K, Toni, D, Topcuoglu, M, Torales, J, Towfighi, A, Truelsen, T, Tsiskaridze, A, Tulloch-Reid, M, Useche, N, Vanacker, P, Vassilopoulou, S, Vukorepa, G, Vuletic, V, Wahab, K, Wang, W, Wijeratne, T, Wolfe, C, Yifru, Y, Yock-Corrales, A, Yonemoto, N, Yperzeele, L, Zhang, P, Owolabi M. O., Thrift A. G., Mahal A., Ishida M., Martins S., Johnson W. D., Pandian J., Abd-Allah F., Yaria J., Phan H. T., Roth G., Gall S. L., Beare R., Phan T. G., Mikulik R., Akinyemi R. O., Norrving B., Brainin M., Feigin V. L., Abanto C., Abera S. F., Addissie A., Adebayo O., Adeleye A. O., Adilbekov Y., Adilbekova B., Adoukonou T. A., Aguiar de Sousa D., Ajagbe T., Akhmetzhanova Z., Akpalu A., Alvarez Ahlgren J., Ameriso S., Andonova S., Awoniyi F. E., Bakhiet M., Barboza M., Basri H., Bath P., Bello O., Bereczki D., Beretta S., Berkowitz A., Bernabe-Ortiz A., Bernhardt J., Berzina G., Bisharyan M., Bovet P., Budincevic H., Cadilhac D., Caso V., Chen C., Chin J., Chwojnicki K., Conforto A., Cruz V. T., D'Amelio M., Danielyan K., Davis S., Demarin V., Dempsey R., Dichgans M., Dokova K., Donnan G., Elkind M. S., Endres M., Fischer U., Gankpe F., Gaye Saavedra A., Gil A., Giroud M., Gnedovskaya E., Hachinski V., Hafdi M., Hamadeh R., Hamzat T. K., Hankey G., Heldner M., Ibrahim E. A., Ibrahim N. M., Inoue M., Jee S., Jeng J. -S., Kalkonde Y., Kamenova S., Karaszewski B., Kelly P., Khan T., Kiechl S., Kondybayeva A., Korv J., Kravchenko M., Krishnamurthi R. V., Kruja J., Lakkhanaloet M., Langhorne P., Lavados P. M., Law Z. K., Lawal A., Lazo-Porras M., Lebedynets D., Lee T. -H., Leung T., Liebeskind D. S., Lindsay P., Lopez-Jaramillo P., Lotufo P. A., Machline-Carrion J., Makanjuola A., Markus H. S., Marquez-Romero J. M., Medina M., Medukhanova S., Mehndiratta M. M., Merkin A., Mirrakhimov E., Mohl S., Moscoso-Porras M., Muller-Stierlin A., Murphy S., Musa K. I., Nasreldein A., Nogueira R. G., Nolte C., Noubiap J. J., Novarro-Escudero N., Ogun Y., Oguntoye R. A., Oraby M. I., Osundina M., Ovbiagele B., Orken D. N., Ozdemir A. O., Ozturk S., Paccot M., Phromjai J., Piradov P., Platz T., Potpara T., Ranta A., Rathore F., Richard E., Sacco R. L., Sahathevan R., Santos Carquin I., Saposnik G., Sarfo F. S., Sharma M., Sheth K., Shobhana A., Suwanwela N., Svyato I., Sylaja P. N., Tao X., Thakur K. T., Toni D., Topcuoglu M. A., Torales J., Towfighi A., Truelsen T. C., Tsiskaridze A., Tulloch-Reid M., Useche N., Vanacker P., Vassilopoulou S., Vukorepa G., Vuletic V., Wahab K. W., Wang W., Wijeratne T., Wolfe C., Yifru Y. M., Yock-Corrales A., Yonemoto N., Yperzeele L., Zhang P., Owolabi, M, Thrift, A, Mahal, A, Ishida, M, Martins, S, Johnson, W, Pandian, J, Abd-Allah, F, Yaria, J, Phan, H, Roth, G, Gall, S, Beare, R, Phan, T, Mikulik, R, Akinyemi, R, Norrving, B, Brainin, M, Feigin, V, Abanto, C, Abera, S, Addissie, A, Adebayo, O, Adeleye, A, Adilbekov, Y, Adilbekova, B, Adoukonou, T, Aguiar de Sousa, D, Ajagbe, T, Akhmetzhanova, Z, Akpalu, A, Alvarez Ahlgren, J, Ameriso, S, Andonova, S, Awoniyi, F, Bakhiet, M, Barboza, M, Basri, H, Bath, P, Bello, O, Bereczki, D, Beretta, S, Berkowitz, A, Bernabe-Ortiz, A, Bernhardt, J, Berzina, G, Bisharyan, M, Bovet, P, Budincevic, H, Cadilhac, D, Caso, V, Chen, C, Chin, J, Chwojnicki, K, Conforto, A, Cruz, V, D'Amelio, M, Danielyan, K, Davis, S, Demarin, V, Dempsey, R, Dichgans, M, Dokova, K, Donnan, G, Elkind, M, Endres, M, Fischer, U, Gankpe, F, Gaye Saavedra, A, Gil, A, Giroud, M, Gnedovskaya, E, Hachinski, V, Hafdi, M, Hamadeh, R, Hamzat, T, Hankey, G, Heldner, M, Ibrahim, E, Ibrahim, N, Inoue, M, Jee, S, Jeng, J, Kalkonde, Y, Kamenova, S, Karaszewski, B, Kelly, P, Khan, T, Kiechl, S, Kondybayeva, A, Korv, J, Kravchenko, M, Krishnamurthi, R, Kruja, J, Lakkhanaloet, M, Langhorne, P, Lavados, P, Law, Z, Lawal, A, Lazo-Porras, M, Lebedynets, D, Lee, T, Leung, T, Liebeskind, D, Lindsay, P, Lopez-Jaramillo, P, Lotufo, P, Machline-Carrion, J, Makanjuola, A, Markus, H, Marquez-Romero, J, Medina, M, Medukhanova, S, Mehndiratta, M, Merkin, A, Mirrakhimov, E, Mohl, S, Moscoso-Porras, M, Muller-Stierlin, A, Murphy, S, Musa, K, Nasreldein, A, Nogueira, R, Nolte, C, Noubiap, J, Novarro-Escudero, N, Ogun, Y, Oguntoye, R, Oraby, M, Osundina, M, Ovbiagele, B, Orken, D, Ozdemir, A, Ozturk, S, Paccot, M, Phromjai, J, Piradov, P, Platz, T, Potpara, T, Ranta, A, Rathore, F, Richard, E, Sacco, R, Sahathevan, R, Santos Carquin, I, Saposnik, G, Sarfo, F, Sharma, M, Sheth, K, Shobhana, A, Suwanwela, N, Svyato, I, Sylaja, P, Tao, X, Thakur, K, Toni, D, Topcuoglu, M, Torales, J, Towfighi, A, Truelsen, T, Tsiskaridze, A, Tulloch-Reid, M, Useche, N, Vanacker, P, Vassilopoulou, S, Vukorepa, G, Vuletic, V, Wahab, K, Wang, W, Wijeratne, T, Wolfe, C, Yifru, Y, Yock-Corrales, A, Yonemoto, N, Yperzeele, L, Zhang, P, Owolabi M. O., Thrift A. G., Mahal A., Ishida M., Martins S., Johnson W. D., Pandian J., Abd-Allah F., Yaria J., Phan H. T., Roth G., Gall S. L., Beare R., Phan T. G., Mikulik R., Akinyemi R. O., Norrving B., Brainin M., Feigin V. L., Abanto C., Abera S. F., Addissie A., Adebayo O., Adeleye A. O., Adilbekov Y., Adilbekova B., Adoukonou T. A., Aguiar de Sousa D., Ajagbe T., Akhmetzhanova Z., Akpalu A., Alvarez Ahlgren J., Ameriso S., Andonova S., Awoniyi F. E., Bakhiet M., Barboza M., Basri H., Bath P., Bello O., Bereczki D., Beretta S., Berkowitz A., Bernabe-Ortiz A., Bernhardt J., Berzina G., Bisharyan M., Bovet P., Budincevic H., Cadilhac D., Caso V., Chen C., Chin J., Chwojnicki K., Conforto A., Cruz V. T., D'Amelio M., Danielyan K., Davis S., Demarin V., Dempsey R., Dichgans M., Dokova K., Donnan G., Elkind M. S., Endres M., Fischer U., Gankpe F., Gaye Saavedra A., Gil A., Giroud M., Gnedovskaya E., Hachinski V., Hafdi M., Hamadeh R., Hamzat T. K., Hankey G., Heldner M., Ibrahim E. A., Ibrahim N. M., Inoue M., Jee S., Jeng J. -S., Kalkonde Y., Kamenova S., Karaszewski B., Kelly P., Khan T., Kiechl S., Kondybayeva A., Korv J., Kravchenko M., Krishnamurthi R. V., Kruja J., Lakkhanaloet M., Langhorne P., Lavados P. M., Law Z. K., Lawal A., Lazo-Porras M., Lebedynets D., Lee T. -H., Leung T., Liebeskind D. S., Lindsay P., Lopez-Jaramillo P., Lotufo P. A., Machline-Carrion J., Makanjuola A., Markus H. S., Marquez-Romero J. M., Medina M., Medukhanova S., Mehndiratta M. M., Merkin A., Mirrakhimov E., Mohl S., Moscoso-Porras M., Muller-Stierlin A., Murphy S., Musa K. I., Nasreldein A., Nogueira R. G., Nolte C., Noubiap J. J., Novarro-Escudero N., Ogun Y., Oguntoye R. A., Oraby M. I., Osundina M., Ovbiagele B., Orken D. N., Ozdemir A. O., Ozturk S., Paccot M., Phromjai J., Piradov P., Platz T., Potpara T., Ranta A., Rathore F., Richard E., Sacco R. L., Sahathevan R., Santos Carquin I., Saposnik G., Sarfo F. S., Sharma M., Sheth K., Shobhana A., Suwanwela N., Svyato I., Sylaja P. N., Tao X., Thakur K. T., Toni D., Topcuoglu M. A., Torales J., Towfighi A., Truelsen T. C., Tsiskaridze A., Tulloch-Reid M., Useche N., Vanacker P., Vassilopoulou S., Vukorepa G., Vuletic V., Wahab K. W., Wang W., Wijeratne T., Wolfe C., Yifru Y. M., Yock-Corrales A., Yonemoto N., Yperzeele L., and Zhang P.

Abstract

Stroke is the second leading cause of death and the third leading cause of disability worldwide and its burden is increasing rapidly in low-income and middle-income countries, many of which are unable to face the challenges it imposes. In this Health Policy paper on primary stroke prevention, we provide an overview of the current situation regarding primary prevention services, estimate the cost of stroke and stroke prevention, and identify deficiencies in existing guidelines and gaps in primary prevention. We also offer a set of pragmatic solutions for implementation of primary stroke prevention, with an emphasis on the role of governments and population-wide strategies, including task-shifting and sharing and health system re-engineering. Implementation of primary stroke prevention involves patients, health professionals, funders, policy makers, implementation partners, and the entire population along the life course.

Published
2022

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

Author

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

Abstract

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

Published
2021

6. Volumes and types of unused Certified Emission Reductions (CERs): lessons learned from CDM transactions under the Kyoto Protocol, transparency gaps and implications for post-2020 international carbon markets

Author

perspectives Climate Group, Freiburg, School of Management and Law, ZHAW, perspectives Climate Group, F ( Freiburg ), School of Management and Law, Z ( ZHAW ), Michaelowa, Axel; https://orcid.org/0000-0001-5053-3700, Censkowsky, Philipp, Espelage, Aglaja, Singh, Aayushi, Betz, Regina, Kotsch, Raphaela, Dzukowski, Tim, perspectives Climate Group, Freiburg, School of Management and Law, ZHAW, perspectives Climate Group, F ( Freiburg ), School of Management and Law, Z ( ZHAW ), Michaelowa, Axel; https://orcid.org/0000-0001-5053-3700, Censkowsky, Philipp, Espelage, Aglaja, Singh, Aayushi, Betz, Regina, Kotsch, Raphaela, and Dzukowski, Tim

Abstract

Commissioned by the Swedish Energy Agency, Z Perspectives and Zurich University of Applied Sciences studied the volume and origin of CERs that are still on the market, looking into information in the various national registries and the CDM registry. The study also draws lessons from the Kyoto Protocol on supply and demand in international carbon markets, as well as transparency and accounting (or the lack thereof). This analysis complements earlier studies on which CDM activities are still active and the potential additional supply of CERs in the instance of a renewed carbon price signal.

Published
2021

22. TICH-2 Trial – Tranexamic Acid for Intracerebral Haemorrhage 2

Author

Sprigg, Nikola, Bath, Philip M.W., Appleton, J., Law, Z., Flaherty, Katie, Scutt, Polly, Hyman-Taylor, Pauline, Adrian, M., Stringer, M., Longmate, J., Gray, R., Gregory, H., Lysons, C., Ali, A., Sprigg, Nikola, Bath, Philip M.W., Appleton, J., Law, Z., Flaherty, Katie, Scutt, Polly, Hyman-Taylor, Pauline, Adrian, M., Stringer, M., Longmate, J., Gray, R., Gregory, H., Lysons, C., and Ali, A.

Abstract

Rationale: To assess in a pragmatic phase III prospective double blind randomised placebo-controlled trial whether tranexamic acid is safe and reduces death or dependency after spontaneous intracerebral haemorrhage (SICH). The results will determine whether tranexamic acid should be used to treat ICH. Design: Patients will be randomised (1:1) to receive either tranexamic acid or placebo (0.9 % saline) within 8 hours of acute SICH. Randomisation will be computerised and minimised on key prognostics age; sex; time since onset; systolic blood pressure; stroke severity (NIHSS); presence of intraventricular haemorrhage and known history of antiplatelet treatment. Patients, investigators and outcome assessors will be blind to treatment allocation. The primary outcome is death or dependency (modified Rankin Scale) and telephone follow-up is at day 90. Trial status: The start-up phase of the trial commenced on 1st March 2013, the main phase commenced 1st April 2014. The recruitment target was 300 participants in the startup phase and 2,000 in the main phase. As of 30th May 2017, 2191 patients have been recruited from 123 centres (UK, Georgia, Italy, Malaysia, Switzerland, Republic of Ireland, Turkey, Sweden, Denmark, Hungary, Spain and Poland). The objective was to have 80 UK centres and 40 international centres.

23. TICH-2 Trial – Tranexamic Acid for Intracerebral Haemorrhage 2

Author

Sprigg, Nikola, Bath, Philip M.W., Appleton, J., Law, Z., Flaherty, Katie, Scutt, Polly, Hyman-Taylor, Pauline, Adrian, M., Stringer, M., Longmate, J., Gray, R., Gregory, H., Lysons, C., Ali, A., Sprigg, Nikola, Bath, Philip M.W., Appleton, J., Law, Z., Flaherty, Katie, Scutt, Polly, Hyman-Taylor, Pauline, Adrian, M., Stringer, M., Longmate, J., Gray, R., Gregory, H., Lysons, C., and Ali, A.

Abstract

Rationale: To assess in a pragmatic phase III prospective double blind randomised placebo-controlled trial whether tranexamic acid is safe and reduces death or dependency after spontaneous intracerebral haemorrhage (SICH). The results will determine whether tranexamic acid should be used to treat ICH. Design: Patients will be randomised (1:1) to receive either tranexamic acid or placebo (0.9 % saline) within 8 hours of acute SICH. Randomisation will be computerised and minimised on key prognostics age; sex; time since onset; systolic blood pressure; stroke severity (NIHSS); presence of intraventricular haemorrhage and known history of antiplatelet treatment. Patients, investigators and outcome assessors will be blind to treatment allocation. The primary outcome is death or dependency (modified Rankin Scale) and telephone follow-up is at day 90. Trial status: The start-up phase of the trial commenced on 1st March 2013, the main phase commenced 1st April 2014. The recruitment target was 300 participants in the startup phase and 2,000 in the main phase. As of 30th May 2017, 2191 patients have been recruited from 123 centres (UK, Georgia, Italy, Malaysia, Switzerland, Republic of Ireland, Turkey, Sweden, Denmark, Hungary, Spain and Poland). The objective was to have 80 UK centres and 40 international centres.

24. TICH-2 Trial – Tranexamic Acid for Intracerebral Haemorrhage 2

Author

Sprigg, Nikola, Bath, Philip M.W., Appleton, J., Law, Z., Flaherty, Katie, Scutt, Polly, Hyman-Taylor, Pauline, Adrian, M., Stringer, M., Longmate, J., Gray, R., Gregory, H., Lysons, C., Ali, A., Sprigg, Nikola, Bath, Philip M.W., Appleton, J., Law, Z., Flaherty, Katie, Scutt, Polly, Hyman-Taylor, Pauline, Adrian, M., Stringer, M., Longmate, J., Gray, R., Gregory, H., Lysons, C., and Ali, A.

Abstract

Rationale: To assess in a pragmatic phase III prospective double blind randomised placebo-controlled trial whether tranexamic acid is safe and reduces death or dependency after spontaneous intracerebral haemorrhage (SICH). The results will determine whether tranexamic acid should be used to treat ICH. Design: Patients will be randomised (1:1) to receive either tranexamic acid or placebo (0.9 % saline) within 8 hours of acute SICH. Randomisation will be computerised and minimised on key prognostics age; sex; time since onset; systolic blood pressure; stroke severity (NIHSS); presence of intraventricular haemorrhage and known history of antiplatelet treatment. Patients, investigators and outcome assessors will be blind to treatment allocation. The primary outcome is death or dependency (modified Rankin Scale) and telephone follow-up is at day 90. Trial status: The start-up phase of the trial commenced on 1st March 2013, the main phase commenced 1st April 2014. The recruitment target was 300 participants in the startup phase and 2,000 in the main phase. As of 30th May 2017, 2191 patients have been recruited from 123 centres (UK, Georgia, Italy, Malaysia, Switzerland, Republic of Ireland, Turkey, Sweden, Denmark, Hungary, Spain and Poland). The objective was to have 80 UK centres and 40 international centres.

25. TICH-2 Trial – Tranexamic Acid for Intracerebral Haemorrhage 2

Author

Sprigg, Nikola, Bath, Philip M.W., Appleton, J., Law, Z., Flaherty, Katie, Scutt, Polly, Hyman-Taylor, Pauline, Adrian, M., Stringer, M., Longmate, J., Gray, R., Gregory, H., Lysons, C., Ali, A., Sprigg, Nikola, Bath, Philip M.W., Appleton, J., Law, Z., Flaherty, Katie, Scutt, Polly, Hyman-Taylor, Pauline, Adrian, M., Stringer, M., Longmate, J., Gray, R., Gregory, H., Lysons, C., and Ali, A.

Abstract

Rationale: To assess in a pragmatic phase III prospective double blind randomised placebo-controlled trial whether tranexamic acid is safe and reduces death or dependency after spontaneous intracerebral haemorrhage (SICH). The results will determine whether tranexamic acid should be used to treat ICH. Design: Patients will be randomised (1:1) to receive either tranexamic acid or placebo (0.9 % saline) within 8 hours of acute SICH. Randomisation will be computerised and minimised on key prognostics age; sex; time since onset; systolic blood pressure; stroke severity (NIHSS); presence of intraventricular haemorrhage and known history of antiplatelet treatment. Patients, investigators and outcome assessors will be blind to treatment allocation. The primary outcome is death or dependency (modified Rankin Scale) and telephone follow-up is at day 90. Trial status: The start-up phase of the trial commenced on 1st March 2013, the main phase commenced 1st April 2014. The recruitment target was 300 participants in the startup phase and 2,000 in the main phase. As of 30th May 2017, 2191 patients have been recruited from 123 centres (UK, Georgia, Italy, Malaysia, Switzerland, Republic of Ireland, Turkey, Sweden, Denmark, Hungary, Spain and Poland). The objective was to have 80 UK centres and 40 international centres.

26. Tranexamic Acid for Prevention of Hematoma Expansion in Intracerebral Hemorrhage Patients With or Without Spot Sign.

Author

Ovesen C, Jakobsen JC, Gluud C, Steiner T, Law Z, Flaherty K, Dineen RA, Christensen LM, Overgaard K, Rasmussen RS, Bath PM, Sprigg N, and Christensen H

Subjects
Aged, Aged, 80 and over, Cerebral Angiography, Cerebral Hemorrhage diagnostic imaging, Cerebral Hemorrhage physiopathology, Computed Tomography Angiography, Disease Progression, Female, Hematoma diagnostic imaging, Hematoma physiopathology, Humans, Male, Middle Aged, Tomography, X-Ray Computed, Treatment Outcome, Antifibrinolytic Agents therapeutic use, Cerebral Hemorrhage drug therapy, Hematoma drug therapy, Tranexamic Acid therapeutic use
Abstract

Background and Purpose: The computed tomography angiography or contrast-enhanced computed tomography based spot sign has been proposed as a biomarker for identifying on-going hematoma expansion in patients with acute intracerebral hemorrhage. We investigated, if spot-sign positive participants benefit more from tranexamic acid versus placebo as compared to spot-sign negative participants., Methods: TICH-2 trial (Tranexamic Acid for Hyperacute Primary Intracerebral Haemorrhage) was a randomized, placebo-controlled clinical trial recruiting acutely hospitalized participants with intracerebral hemorrhage within 8 hours after symptom onset. Local investigators randomized participants to 2 grams of intravenous tranexamic acid or matching placebo (1:1). All participants underwent computed tomography scan on admission and on day 2 (24±12 hours) after randomization. In this sub group analysis, we included all participants from the main trial population with imaging allowing adjudication of spot sign status., Results: Of the 2325 TICH-2 participants, 254 (10.9%) had imaging allowing for spot-sign adjudication. Of these participants, 64 (25.2%) were spot-sign positive. Median (interquartile range) time from symptom onset to administration of the intervention was 225.0 (169.0 to 310.0) minutes. The adjusted percent difference in absolute day-2 hematoma volume between participants allocated to tranexamic versus placebo was 3.7% (95% CI, -12.8% to 23.4%) for spot-sign positive and 1.7% (95% CI, -8.4% to 12.8%) for spot-sign negative participants ( P heterogenity =0.85). No difference was observed in significant hematoma progression (dichotomous composite outcome) between participants allocated to tranexamic versus placebo among spot-sign positive (odds ratio, 0.85 [95% CI, 0.29 to 2.46]) and negative (odds ratio, 0.77 [95% CI, 0.41 to 1.45]) participants ( P heterogenity =0.88)., Conclusions: Data from the TICH-2 trial do not support that admission spot sign status modifies the treatment effect of tranexamic acid versus placebo in patients with acute intracerebral hemorrhage. The results might have been affected by low statistical power as well as treatment delay. Registration: URL: http://www.controlled-trials.com; Unique identifier: ISRCTN93732214.

Published
2021
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27. The effectiveness and safety of anti-fibrinolytics in patients with acute intracranial haemorrhage: statistical analysis plan for an individual patient data meta-analysis.

Author

Ker K, Prieto-Merino D, Sprigg N, Mahmood A, Bath P, Kang Law Z, Flaherty K, and Roberts I

Abstract

Introduction: The Anti-fibrinolytics Trialists Collaboration aims to increase knowledge about the effectiveness and safety of anti-fibrinolytic treatment by conducting individual patient data (IPD) meta-analyses of randomised trials. This article presents the statistical analysis plan for an IPD meta-analysis of the effects of anti-fibrinolytics for acute intracranial haemorrhage., Methods: The protocol for the IPD meta-analysis has been registered with PROSPERO (CRD42019128260). We will conduct an individual patient data meta-analysis of randomised controlled trials with 500 patients or more assessing the effects of anti-fibrinolytics in acute intracranial haemorrhage. The primary outcomes will be 1) death from stroke or head injury within 30 days of randomisation, and 2) death from stroke or head injury, or dependency within 90 days of randomisation. The primary outcomes will be limited to patients treated within three hours of injury or stroke onset. We will report treatment effects using odds ratios and 95% confidence intervals. We use logistic regression models to examine how the effect of anti-fibrinolytics vary by time to treatment, severity of intracranial bleeding, and age. We will also examine the effect of anti-fibrinolytics on secondary outcomes including death, dependency, vascular occlusive events, seizures, and neurological outcomes. Secondary outcomes will be assessed in all patients irrespective of time of treatment. All analyses will be conducted on an intention-to-treat basis., Conclusions: This IPD meta-analysis will examine important clinical questions about the effects of anti-fibrinolytic treatment in patients with intracranial haemorrhage that cannot be answered using aggregate data. With IPD we can examine how effects vary by time to treatment, bleeding severity, and age, to gain better understanding of the balance of benefit and harms on which to base recommendations for practice., Competing Interests: No competing interests were disclosed.

Published
2019
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28. Prevention of haematoma progression by tranexamic acid in intracerebral haemorrhage patients with and without spot sign on admission scan: a statistical analysis plan of a pre-specified sub-study of the TICH-2 trial.

Author

Ovesen C, Jakobsen JC, Gluud C, Steiner T, Law Z, Flaherty K, Dineen RA, Bath PM, Sprigg N, and Christensen H

Subjects
Antifibrinolytic Agents administration & dosage, Disease Progression, Humans, Tranexamic Acid administration & dosage, Antifibrinolytic Agents pharmacology, Cerebral Hemorrhage diagnostic imaging, Cerebral Hemorrhage drug therapy, Data Interpretation, Statistical, Hematoma diagnostic imaging, Hematoma drug therapy, Outcome Assessment, Health Care statistics & numerical data, Tranexamic Acid pharmacology
Abstract

Objective: We present the statistical analysis plan of a prespecified Tranexamic Acid for Hyperacute Primary Intracerebral Haemorrhage (TICH)-2 sub-study aiming to investigate, if tranexamic acid has a different effect in intracerebral haemorrhage patients with the spot sign on admission compared to spot sign negative patients. The TICH-2 trial recruited above 2000 participants with intracerebral haemorrhage arriving in hospital within 8 h after symptom onset. They were included irrespective of radiological signs of on-going haematoma expansion. Participants were randomised to tranexamic acid versus matching placebo. In this subgroup analysis, we will include all participants in TICH-2 with a computed tomography angiography on admission allowing adjudication of the participants' spot sign status., Results: Primary outcome will be the ability of tranexamic acid to limit absolute haematoma volume on computed tomography at 24 h (± 12 h) after randomisation among spot sign positive and spot sign negative participants, respectively. Within all outcome measures, the effect of tranexamic acid in spot sign positive/negative participants will be compared using tests of interaction. This sub-study will investigate the important clinical hypothesis that spot sign positive patients might benefit more from administration of tranexamic acid compared to spot sign negative patients. Trial registration ISRCTN93732214 ( http://www.isrctn.com ).

Published
2018
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29. The effectiveness and safety of antifibrinolytics in patients with acute intracranial haemorrhage: statistical analysis plan for an individual patient data meta-analysis.

Author

Ker K, Prieto-Merino D, Sprigg N, Mahmood A, Bath P, Kang Law Z, Flaherty K, and Roberts I

Abstract

Introduction : The Antifibrinolytic Trialists Collaboration aims to increase knowledge about the effectiveness and safety of antifibrinolytic treatment by conducting individual patient data (IPD) meta-analyses of randomised trials. This article presents the statistical analysis plan for an IPD meta-analysis of the effects of antifibrinolytics for acute intracranial haemorrhage. Methods : The protocol for the IPD meta-analysis has been registered with PROSPERO (CRD42016052155). We will conduct an individual patient data meta-analysis of randomised controlled trials with 1000 patients or more assessing the effects of antifibrinolytics in acute intracranial haemorrhage. We will assess the effect on two co-primary outcomes: 1) death in hospital at end of trial follow-up, and 2) death in hospital or dependency at end of trial follow-up. The co-primary outcomes will be limited to patients treated within three hours of injury or stroke onset. We will report treatment effects using odds ratios and 95% confidence intervals. We use logistic regression models to examine how the effect of antifibrinolytics vary by time to treatment, severity of intracranial bleeding, and age. We will also examine the effect of antifibrinolytics on secondary outcomes including death, dependency, vascular occlusive events, seizures, and neurological outcomes. Secondary outcomes will be assessed in all patients irrespective of time of treatment. All analyses will be conducted on an intention-to-treat basis. Conclusions : This IPD meta-analysis will examine important clinical questions about the effects of antifibrinolytic treatment in patients with intracranial haemorrhage that cannot be answered using aggregate data. With IPD we can examine how effects vary by time to treatment, bleeding severity, and age, to gain better understanding of the balance of benefit and harms on which to base recommendations for practice., Competing Interests: No competing interests were disclosed.

Published
2017
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30. Statistical analysis plan for the 'Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage' (TICH-2) trial.

Author

Flaherty K, Bath PM, Dineen R, Law Z, Scutt P, Pocock S, and Sprigg N

Subjects
Antifibrinolytic Agents adverse effects, Cerebral Hemorrhage diagnosis, Clinical Protocols, Data Interpretation, Statistical, Disability Evaluation, Double-Blind Method, Humans, Intention to Treat Analysis, Logistic Models, Prospective Studies, Research Design, Time Factors, Tranexamic Acid adverse effects, Treatment Outcome, Antifibrinolytic Agents therapeutic use, Cerebral Hemorrhage drug therapy, Tranexamic Acid therapeutic use
Abstract

Rationale: Aside from blood pressure lowering, treatment options for intracerebral haemorrhage remain limited and a proportion of patients will undergo early haematoma expansion with resultant significant morbidity and mortality. Tranexamic acid (TXA), an anti-fibrinolytic drug, has been shown to significantly reduce mortality in patients, who are bleeding following trauma, when given rapidly. TICH-2 is testing whether TXA is effective at improving outcome in spontaneous intracerebral haemorrhage (SICH)., Methods and Design: TICH-2 is a pragmatic, phase III, prospective, double-blind, randomised placebo-controlled trial. Two thousand adult (aged ≥ 18 years) patients with an acute SICH, within 8 h of stroke onset, will be randomised to receive TXA or the placebo control. The primary outcome is ordinal shift of modified Rankin Scale score at day 90. Analyses will be performed using intention-to-treat., Results: This paper and its attached appendices describe the statistical analysis plan (SAP) for the trial and were developed and published prior to database lock and unblinding to treatment allocation. The SAP includes details of analyses to be undertaken and unpopulated tables which will be reported in the primary and key secondary publications. The database will be locked in early 2018, ready for publication of the results later in the same year., Discussion: The SAP details the analyses that will be done to avoid bias arising from prior knowledge of the study findings. The trial will determine whether TXA can improve outcome after SICH, which currently has no definitive therapy., Trial Registration: ISRCTN registry, ID: ISRCTN93732214 . Registered on 17 January 2013.

Published
2017
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31. Re: A prospective randomized trial of povidone-iodine prophylactic cleansing of the rectum before transrectal ultrasound guided prostate biopsy: Z. AbuGhosh, J. Margolick, S. L. Goldenberg, S. A. Taylor, K. Afshar, R. Bell, D. Lange, W. R. Bowie, D. Roscoe, L. Machan and P. C. Black J Urol 2013; 189: 1326-1331.

Author

Goh YS, Law ZW, and Tiong HY

Subjects
Humans, Male, Anti-Infective Agents, Local therapeutic use, Bacterial Infections prevention & control, Image-Guided Biopsy adverse effects, Povidone-Iodine therapeutic use, Preoperative Care methods, Prostate pathology
Published
2013
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32. Effect of solvents on obligately anaerobic bacteria.

Author

Rodriguez Martinez MF, Kelessidou N, Law Z, Gardiner J, and Stephens G

Subjects
Acetobacterium growth & development, Bioreactors, Clostridium growth & development, Oxygen metabolism, Acetobacterium drug effects, Alkanes toxicity, Clostridium drug effects, Solvents toxicity
Abstract

Growth of Acetobacterium woodii and Clostridium sporogenes was studied in the presence of water-immiscible solvents. Nitrogen purging, vacuum distillation or distillation under nitrogen were all suitable as methods to remove oxygen from the solvents, since growth rates and yields of A. woodii were unaffected in the presence of tetradecane which had been degassed by these methods. Varying the solvent volume from 20% to 80% of the culture volume had little effect on growth rate of A. woodii. A.woodii was relatively sensitive to organic solvents since growth was inhibited by alkanes with logP(octanol/water) values below 7.1. C. sporogenes was less solvent sensitive, since it grew without inhibition when the logP of the solvent was > or = 6.6. Nevertheless, both A. woodii and C. sporogenes were more sensitive to solvent polarity than aerobic bacteria.

Published
2008
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