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16. Understanding the neuroprotective effect of tranexamic acid: an exploratory analysis of the CRASH-3 randomised trial

Author

Brenner, A., Belli, A., Chaudhri, R., Coats, T., Frimley, L., Jamaluddin, S. F., Jooma, R., Mansukhani, R., Sandercock, P., Shakur-Still, H., Shokunbi, T., Roberts, I., Aeron-Thomas, A., Chaudary, M. A., Jamaluddin, S. F. B., Javaid, K., Kayani, A., Leech, C., Mahmood, K., Noor, J. M., Mejia-Mantilla, J., Moss, P., Pott, J., Vallecilla, L., Hartzenberg, H. B., Joshipura, M., Perel, P., Clarke, M. J., Ohaegbulam, S. C., Rodgers, A., Brady, T., Dewan, Y., Edwards, P., Komolafe, E. O., Arribas, M., Austin, E., Balogun, E., Barneston, L., Barrow, C., Beaumont, D., Benyahia, M., Brooks, I., Cargill, M., Carrington, L., Cook, L., Cornu-Hewitt, B., Geer, A., Gilbert, D., Gilliam, C., Gil-Onandia, J., Hetherington, D., Howe, C., Hughes, C., I'Anson, D., Jackson, R., Joshi, M., Kansagra, S., Kawahara, T., Ker, K., Kostrov, S., Mahmood, A., Miah, H., Ndungu, B., Needham, K., Okusi, C., Outtandy, A., Pardinaz-Solis, R., Pearson, D., Pepple, T., Pisani, C., Prieto-Merino, D., Prowse, D., Quashi, N., Quinn, A., Ramos, M., Reid, M., Roukas, C., Scrapa, G., Squires, C., Tanner, J., Thayne, A., Vidaurre, L., Woods, E., Fawole, B., Adetayo, O., Okunade, O., Gogichaishvili, T., de los Angeles Munoz-Sanchez, M., Olldashi, F., Krishnan, S., Djientcheu, V., Castellanos, J. L., Rasulo, F., Hama, Q., Mulla, Y., Florian, I. S., Tobar, J., Khamis, H., Deasy, C., Wellsh, B., Williams-Johnson, J., Chandra, S., Mutiso, V., Butt, R., Nasir, M. H., Ahmad, S., Aslam, F., Ishaque, K., Usmani, F., Rizvi, S., Ali, F., Sajjad, O., Zunair, A., Rehman, L., Rizvi, R., Javeed, F., Ahmed, S., Abbas, A., Afzal, A., Mikdad, A., Bashir, A., Chaudary, A., Salahuddin, T., Ahemed, B., Aziz, A., Ashraf, N., Hussain, S., Ahmad, U., Asif, M., Adil, M., Rauf, A., Khan, R., Ahmad, B., Afzal, U., Raza, H., Ain, Q., Yaqoob, S., Waseem, Q., Nishat, M., Semvel, S., Iqbal, J., Majeed, S., Zulfiqar, S., Iqbal, M., Majeed, N., Ahmed, M., Akhtar, N., Malik, M., Shehzad, Y., Yousaf, M., Wahid, A., Samad, A., Shah, S., Ali, M., Zeb, J., Khan, A. S., Irfan, A., Sharif, S., Memon, R., Bloom, B., Harris, T., Skene, I., Bellhouse, G., Boulton, O., Ward, G., Jarvis, C., Swann, C., Ratnam, S., Carrera, R., Yakoub, K., Davies, D., Fellows, E., Jarman, H., Rounding, S., Johnson, E., Loughran, C., Lecky, F., Clayton, K., Michael, A., Coumbarides, A., Kendall, J., Faulkner, B., Worner, R., Gendall, E., Hopkins, P., Riozzi, P., Cotton, H., Astin-Chamberlain, R., Wilson, M., Bodnar, J., Williams, R., Rigoni, A., Sattout, A., Fletcher, J., Edge, C., Maryanji, N., Boyle, A., Hardwick, S., Nichols, E., Hayhurst, C., Coffey, F., Gough, C., Miller, P., Ryan, L., Darwent, M., Espinosa, A., Beer, S., Norton, J., Maguire, H., Finney, K., Kehoe, A., Squire, R., Jeffery, A., Vorwerk, C., Foord, D., Wilkinson, E., Kuhrt, A., Ramlakhan, S., Reid, S., Curran, A., Mcmullan, S., Hassan, T., Nuttall, S., Haig, S., Al-Nahhas, S., Bulters, D., Zolnourian, A., Ribbons, T., Mew, I., de Weymarn, T., Hughes, V., Mcvicar, J., Mckiernan, C., Keating, L., Reschreiter, H., Wright, J., Chan, L., Kataria, H., Ireland, A., Body, R., Corfield, A., Francis, S., Townend, W., Gagg, J., Wilson, S., Cottingham, R., Tucker, S., Sutherland, F., Mitchell, L., Parker, L., Afolabi, O., Hunter, F., Jadav, M., Adeboye, K., Grocutt, M., May, G., Watson, D., Wootten, A., Robertshaw, S., Dorrian, S., Perry, R., Choi, H., Mcgroarty, C., Shone, P., Maritz, D., Jamaluddin, S., Noor, J., Rosli, N., Xian, L. L. S., De Jun, Y., Mohamed, F., Song, C. H., Hawari, A., Chin, L. Y., Hussein, H. M., Lotfi, M., Hamid, H., Udin, N., Lian, P., Choo, S., Wong, K., Gani, F., Jusoh, M., Rajakumar, D., Yang, C. B., Dzulkiflee, N. S. B., W. C., Ky, Azman, M. A. B. M., Osman, A. B., Ahmad, A. H., Ismail, R., Lai, S. Q., Mohidin, M. A. B., Deraman, N. B., Selamat, S. B., Abidin, I., Halim, N., Bakar, Z., Ismail, Z. M., Hisham, B., Kamal, R., Effendy, Z., Ismail, M., Azleen, N., Seng, L. Y., Baharuddin, K. A., Kandasamy, R., Kamalludin, A., Asmee, S., Fadzil, M., Basitz, A., Abdullah, N., Ingorokva, G., Ingorokva, S., Agdgomelashvili, I., Mumladze, K., Maisuradze, I., Kugusheva, I., Shalamberidze, B., Tomadze, G., Fernandez-Ortega, J., Seara-Valero, R., Ibanez-Botella, G., Garcia-Martinez, V., Martul, M. G., Ramos, S. F., Preciado, G. L., Garcia-Alfaro, C., Munoz-Sanchez, A., Bellido-Alba, R., Corcobado, C., Bueno, A., Ambros, A., Jimenez, J. T., Ramirez, J. R., Martin, J., Rodriguez, L. I., Fontanals, J., Jimenez-Moragas, J. M., Berbegal, J. P., Oluwole, O., Mahmud, R., Ukwu, N., Bankole, F., Oseni, A., Adebayo, B., Malomo, A., Tiamiyu, L., Adekanmbi, A., Thanni, L., Olubodun, A., Ojeblenu, F., Uwaezuoke, M., Komolafe, E., Owagbemi, O., Ishola, F., Durodola, A., Udoffa, U., James, A., Tella, A., Dongo, A., Ekpemiro, U., Anyanwu, S., Aigoro, N., Mezue, W., Shilong, D., Azeez, A., Babalola, O., Ibrahim, M., Obande, J., Franco, A. C., Salazar, E. V., Londono, S. B., Cardona, V. M., Morales, C., Naranjo, S., Agudelo, J., Carvajal, S., Fajardo-Gaviria, Y., Roka, Y., Ghising, U., Roka, N., Shrestha, M., Devkota, U., Vaidya, B., Nepal, P., Thapa, A., Kc, B., Shrestha, A., Jha, R., Shrestha, P., Hodaj, I., Spaho, E., Selaj, A., Bendo, N., Shoko, T., Endo, H., Senda, A., Hagihara, Y., Fuse, T., Masunaga, N., Otomo, Y., Egashira, R., Ohnuki, T., Almazmi, A., Saha, S., Suvarov, A., Aung, T. L., Tun, K. M., Khaing, T. T., Maw, T., Ndome, O., Moumi, M., Mbida, A., Fondop, J., Sebastien, M., Azim, A., Adil, J., Amiry, Z., Loria-Castellanos, J., Rubio, N. G., Leon, P. O., Estrada, F., de Oca-Garcia, E. M., Sanchez, H., Soria, A., Bonucci, P., Franchi, F., Girardini, A., Hameed, H., Basim, M., Stock, S., Hourt, E., Ilunga, A., Mulenga, J., Ples, H., Danil, A., Gorgan, M., Florian, I., Vlahovic, D., French, J., East, J., Kurniawan, A., and Kiboi, J.

Subjects
medicine.medical_specialty, Tranexamic acid, Traumatic brain injury, Epidemiology, Critical Care and Intensive Care Medicine, Placebo, CRASH-3 trial, Neuroprotection, Intracranial haemorrhage, law.invention, Emergence care, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Medicine, Humans, 030212 general & internal medicine, Randomised controlled trial, business.industry, Multiple Trauma, Research, lcsh:Medical emergencies. Critical care. Intensive care. First aid, 030208 emergency & critical care medicine, lcsh:RC86-88.9, Protective Factors, medicine.disease, Polytrauma, Antifibrinolytic Agents, 3. Good health, Neuroprotective Agents, Relative risk, Brain Injuries, business, medicine.drug
Abstract

Background The CRASH-3 trial hypothesised that timely tranexamic acid (TXA) treatment might reduce deaths from intracranial bleeding after traumatic brain injury (TBI). To explore the mechanism of action of TXA in TBI, we examined the timing of its effect on death. Methods The CRASH-3 trial randomised 9202 patients within 3 h of injury with a GCS score ≤ 12 or intracranial bleeding on CT scan and no significant extracranial bleeding to receive TXA or placebo. We conducted an exploratory analysis of the effects of TXA on all-cause mortality within 24 h of injury and within 28 days, excluding patients with a GCS score of 3 or bilateral unreactive pupils, stratified by severity and country income. We pool data from the CRASH-2 and CRASH-3 trials in a one-step fixed effects individual patient data meta-analysis. Results There were 7637 patients for analysis after excluding patients with a GCS score of 3 or bilateral unreactive pupils. Of 1112 deaths, 23.3% were within 24 h of injury (early deaths). The risk of early death was reduced with TXA (112 (2.9%) TXA group vs 147 (3.9%) placebo group; risk ratio [RR] RR 0.74, 95% CI 0.58–0.94). There was no evidence of heterogeneity by severity (p = 0.64) or country income (p = 0.68). The risk of death beyond 24 h of injury was similar in the TXA and placebo groups (432 (11.5%) TXA group vs 421 (11.7%) placebo group; RR 0.98, 95% CI 0.69–1.12). The risk of death at 28 days was 14.0% in the TXA group versus 15.1% in the placebo group (544 vs 568 events; RR 0.93, 95% CI 0.83–1.03). When the CRASH-2 and CRASH-3 trial data were pooled, TXA reduced early death (RR 0.78, 95% CI 0.70–0.87) and death within 28 days (RR 0.88, 95% CI 0.82–0.94). Conclusions Tranexamic acid reduces early deaths in non-moribund TBI patients regardless of TBI severity or country income. The effect of tranexamic acid in patients with isolated TBI is similar to that in polytrauma. Treatment is safe and even severely injured patients appear to benefit when treated soon after injury. Trial registration ISRCTN15088122, registered on 19 July 2011; NCT01402882, registered on 26 July 2011.

Published
2020

17. Australian sapphires and rubies

Author

Sutherland, F. Lin and Webb, Gayle B.

Subjects
Sapphires -- Discovery and exploration, Sapphires -- Natural history, Sapphires -- Composition, Rubies -- Discovery and exploration, Rubies -- Natural history, Rubies -- Composition, Australia -- Natural resources
Published
2007

48. Triassic to Neogene tectono-magmatic events within Lorne Basin evolution, coastal New South Wales, eastern Australia.

Author

Sutherland, F. L., Graham, I. T., Zwingmann, H., Och, D. J., Gardner, C. J., Pogson, R. E., Griffiths, R. J., and Lay, A.

Subjects
*IGNEOUS intrusions, *DIKES (Geology), *NEOGENE Period, *PETROLOGY, *RADIAL flow, *SEDIMENTARY basins, *ANALYTICAL geochemistry
Abstract

Within the Lorne Basin, Mesozoic granitoid plutons and dacitic to rhyolitic extrusions form extensive components in a faulted, eroded Triassic sedimentary basin. Late Cenozoic plugs and flows of evolved basalts represent easterly extensions of the eroded Comboyne Volcano. The basin marks a terminal outpost of the New England Orogen, much modified by later alkaline felsic intrusions and flow remnants. Many origins are invoked for its tectonic genesis and magmatic evolution including plate tectonic, caldera and even meteoritic impact events. This review uses extended field study, zircon fission track, K–Ar and Ar–Ar age-dating, petrography and geochemical analyses on igneous suites. These results are combined with previously published and unpublished studies to clarify relationships between volcanic and plutonic suites, structural features and paleotopographic developments, allowing for an enlarged synthesis of Lorne Basin magmatism and its tectonic contexts. Dating reveals rhyodacitic volcanism began at ca 221 Ma (Milligans Road) and culminated in emplacements of I- and A-type dioritic to granitic suites (North Brother, Middle Brother) at ca 217–212 Ma (MAGMATIC EPISODE 1, late Triassic). Voluminous alkaline rhyolitic feeders and flows (Bago Range, Batar Creek) erupted between ca 187 and 160 Ma (MAGMATIC EPISODE 2, early–mid-Jurassic). Lavas infilled extended drainages cut into a dissected, faulted terrain and disrupted former drainage patterns. An alkaline monzodioritic to granitic pluton and late-stage rhyolitic dyke swarm (South Brother) were emplaced at ca 126 and 119 Ma (MAGMATIC EPISODE 3, early Cretaceous). This chemically distinct magmatism coincided with thermal coastal faulting along eastern Australia. A large eroded plug and dyke complex (Mount Lorne) shows steep flow banding and lies within dissected radial flow infillings. This prominent eruptive conduit tapped a significant ring fault system. Although undated, its petrography resembles features related to MAGMATIC EPISODE 3. The study revealed a far greater profusion of rhyolitic feeders and flows than previously thought, making likely volcanic volumes within episodes difficult to estimate. The youngest volcanic remnants infill later drainages, are dated between ca 17 and 13 Ma (MAGMATIC EPISODE 4, mid-Neogene), and are evolved derivatives related to the adjacent Comboyne central volcano. Some evolved basalts contain feldspathic and mafic crystallisations indicating mid-crustal melt processes. These bimodal suites represent a traverse over an asthenospheric plume during northward lithospheric migration of eastern Australia. Minor vitrophyric bodies recorded across the Lorne Basin only intrude Carboniferous basement beds. Their origin and age are enigmatic and represent a final puzzle to solve in the evolution of Lorne Basin magmatism. [ABSTRACT FROM AUTHOR]

Published
2020
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