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55. Longitudinal Impact of Temporary Mechanical Circulatory Support on Durable Left Ventricular Assist Device Outcomes: An IMACS Registry Analysis

Author

Hernandez-Montfort, J.A., primary, Ton, V. Khue, additional, Xie, R., additional, Fisher, A., additional, Meyns, B., additional, Nakatani, T., additional, Netuka, I., additional, Pettit, S., additional, Shaw, S., additional, Yanase, M., additional, Kirklin, J.K., additional, Rowe, A., additional, Goldstein, D.J., additional, and Cowger, J., additional

Published
2019
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56. First to 50: Early Outcomes Following Heart Transplantation at Royal Papworth Hospital from Donation after Circulatory Determined Death (DCD) Donors

Author

Messer, S., primary, Page, A., additional, Berman, M., additional, Colah, S., additional, Dunning, J., additional, Pavlushkov, E., additional, Kaul, P., additional, Parameshwar, J., additional, Abu-Omar, Y., additional, Pettit, S., additional, Lewis, C., additional, Kydd, A., additional, Bhagra, S., additional, Cockell, A., additional, Quigley, R., additional, Baxter, J., additional, Ellis, C., additional, Jenkins, D., additional, Sudarshan, C., additional, Ali, A., additional, Tsui, S., additional, Catarino, P., additional, and Large, S., additional

Published
2019
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57. Vasoplegia in Patients Undergoing Heart Transplantation Bridged with an LVAD is Not Associated with Inferior Long-Term Outcomes

Author

Ali, J., primary, Patel, S., additional, Catarino, P., additional, Abu-Omar, Y., additional, Messer, S., additional, Page, A., additional, Pettit, S., additional, Bhagra, S., additional, Parameshwar, J., additional, Lewis, C., additional, Kydd, A., additional, Large, S., additional, Sudarshan, C., additional, Jenkins, D., additional, Tsui, S., additional, and Berman, M., additional

Published
2019
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62. Non-specific inflammatory bowel disease

Author

Pettit, S. and Irving, M.H.

Subjects
Ulcerative colitis -- Care and treatment, Inflammatory bowel diseases -- Care and treatment, Crohn's disease -- Care and treatment, Health, Care and treatment
Abstract

Non-specific inflammatory bowel diseases are those for which there is no discernible aetiological agent. The two most important of these diseases affecting the large bowel are ulcerative colitis and Crohn's [...]

Published
1992

63. Outcome of CentriMag BiVAD Support for Cariogenic Shock

Author

Schibilsky, D., primary, Page, A., additional, Zho, M., additional, Kaul, P., additional, Messer, S., additional, Bhagra, S., additional, Kydd, A., additional, Pettit, S., additional, Lewis, C., additional, Bermann, M., additional, Ali, A., additional, Abu-Omar, Y., additional, Catarino, P., additional, Sudarshan, C., additional, Jenkins, D., additional, Dunning, J., additional, Parameshwar, J., additional, and Tsui, S., additional

Published
2018
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64. One Year- Outcomes Following Heart Transplantation from Donation After Circulatory Determined Death (DCD) Donors

Author

Hudson, V., primary, Messer, S., additional, Page, A., additional, Berman, M., additional, Dunning, J., additional, Pavlushkov, E., additional, Tweed, K., additional, Parameshwar, J., additional, Abu Omar, Y., additional, Goddard, M., additional, Pettit, S., additional, Lewis, C., additional, Kydd, A., additional, Jenkins, D., additional, Sudarshan, C., additional, Catarino, P., additional, Ali, A., additional, Tsui, S., additional, Large, S.R., additional, and Bhagra, S., additional

Published
2018
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65. Early Outcomes from DCD Heart Transplantation: A Single Centre Experience

Author

Page, A., primary, Messer, S., additional, Hudson, V., additional, Pavlushkov, E., additional, Berman, M., additional, Dunning, J., additional, Parameshwar, J., additional, Abu-Omar, Y., additional, Goddard, M., additional, Bhagra, S., additional, Pettit, S., additional, Lewis, C., additional, Kydd, A., additional, Valchanov, K., additional, Parizkova, B., additional, Colah, S., additional, Jenkins, D., additional, Sudarshan, C., additional, Catarino, P., additional, Ali, A., additional, Tsui, S., additional, and Large, S., additional

Published
2018
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66. Post-Transplant Assessment of Donation after Circulatory Death (DCD) Cardic Allografts with MRI - An Update

Author

Pavlushkov, E., primary, Page, A., additional, Messer, S., additional, Kydd, A., additional, Abu-Omar, Y., additional, Ali, A., additional, Berman, M., additional, Catarino, P., additional, Dunning, J., additional, Jenkins, D., additional, Bhagra, S., additional, Lewis, C., additional, Parameshwar, J., additional, Pettit, S., additional, Sudarshan, C., additional, Tsui, S., additional, Large, S., additional, and Tweed, K., additional

Published
2018
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67. Association of postoperative high-sensitivity troponin levels with myocardial injury and 30-day mortality among patients undergoing noncardiac surgery

Author

Chan, MTV, Writing Committee for the VISION Study Investigators, Devereaux, PJ, Biccard BM, Sigamani, A, Xavier, D, Srinathan, SK, Walsh, M, Abraham, V, Pearse, R, Wang, CY, Sessler, DI, Kurz, A, Szczeklik, W, Berwanger, O, Villar, JC, Malaga, G, Garg, AX, Chow, CK, Ackland, G, Patel, A, Borges, FK, Belley-Cote, EP, Duceppe, E, Spence, J, Tandon, V, Williams, C, Sapsford, RJ, Polanczyk, CA, Tiboni, M, Alonso-Coello, P, Faruqui, A, Heels-Ansdell, D, Lamy, A, Whitlock, R, LeManach, Y, Roshanov, PS, McGillion, M, Kavsak, P, McQueen, MJ, Thabane, L, Rodseth, RN, Buse, GAL, Bhandari, M, Garutti, I, Jacka, MJ, Schünemann, HJ, Cortes, OL, Coriat, P, Dvirnik, N, Botto, F, Pettit, S, Jaffe, AS, Guyatt, GH, Chan, MTV, Writing Committee for the VISION Study Investigators, Devereaux, PJ, Biccard BM, Sigamani, A, Xavier, D, Srinathan, SK, Walsh, M, Abraham, V, Pearse, R, Wang, CY, Sessler, DI, Kurz, A, Szczeklik, W, Berwanger, O, Villar, JC, Malaga, G, Garg, AX, Chow, CK, Ackland, G, Patel, A, Borges, FK, Belley-Cote, EP, Duceppe, E, Spence, J, Tandon, V, Williams, C, Sapsford, RJ, Polanczyk, CA, Tiboni, M, Alonso-Coello, P, Faruqui, A, Heels-Ansdell, D, Lamy, A, Whitlock, R, LeManach, Y, Roshanov, PS, McGillion, M, Kavsak, P, McQueen, MJ, Thabane, L, Rodseth, RN, Buse, GAL, Bhandari, M, Garutti, I, Jacka, MJ, Schünemann, HJ, Cortes, OL, Coriat, P, Dvirnik, N, Botto, F, Pettit, S, Jaffe, AS, and Guyatt, GH

Abstract

IMPORTANCE: Little is known about the relationship between perioperative high-sensitivity troponin T (hsTnT) measurements and 30-day mortality and myocardial injury after noncardiac surgery (MINS). OBJECTIVE: To determine the association between perioperative hsTnT measurements and 30-day mortality and potential diagnostic criteria for MINS (ie, myocardial injury due to ischemia associated with 30-day mortality). DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of patients aged 45 years or older who underwent inpatient noncardiac surgery and had a postoperative hsTnT measurement. Starting in October 2008, participants were recruited at 23 centers in 13 countries; follow-up finished in December 2013. EXPOSURES: Patients had hsTnT measurements 6 to 12 hours after surgery and daily for 3 days; 40.4% had a preoperative hsTnT measurement. MAIN OUTCOMES AND MEASURES: A modified Mazumdar approach (an iterative process) was used to determine if there were hsTnT thresholds associated with risk of death and had an adjusted hazard ratio (HR) of 3.0 or higher and a risk of 30-day mortality of 3% or higher. To determine potential diagnostic criteria for MINS, regression analyses ascertained if postoperative hsTnT elevations required an ischemic feature (eg, ischemic symptom or electrocardiography finding) to be associated with 30-day mortality. RESULTS: Among 21 842 participants, the mean age was 63.1 (SD, 10.7) years and 49.1% were female. Death within 30 days after surgery occurred in 266 patients (1.2%; 95% CI, 1.1%-1.4%). Multivariable analysis demonstrated that compared with the reference group (peak hsTnT <5 ng/L), peak postoperative hsTnT levels of 20 to less than 65 ng/L, 65 to less than 1000 ng/L, and 1000 ng/L or higher had 30-day mortality rates of 3.0% (123/4049; 95% CI, 2.6%-3.6%), 9.1% (102/1118; 95% CI, 7.6%-11.0%), and 29.6% (16/54; 95% CI, 19.1%-42.8%), with corresponding adjusted HRs of 23.63 (95% CI, 10.32-54.09), 70.34 (95% CI, 30.60-161.71), and 2

Published
2017

68. Jejunal Adenocarcinoma: An Unusual Cause of Small Bowel Obstruction

Author

Varia H, Pettit S, Patankar A, and Boyle J

Subjects
Bowel obstruction, medicine.medical_specialty, Jejunal adenocarcinoma, business.industry, Open access publishing, Internal medicine, medicine, medicine.disease, business, Gastroenterology
Published
2016

69. Aspirin in Patients Undergoing Noncardiac Surgery

Author

Devereaux, Pj, Mrkobrada, M, Sessler, Di, Leslie, K, Alonso Coello, P, Kurz, A, Villar, Jc, Sigamani, A, Biccard, Bm, Meyhoff, Cs, Parlow, Jl, Guyatt, G, Robinson, A, Garg, Ax, Rodseth, Rn, Botto, F, Lurati Buse, G, Xavier, D, Chan, Mt, Tiboni, M, Cook, D, Kumar, Pa, Forget, P, Malaga, G, Fleischmann, E, Amir, M, Eikelboom, J, Mizera, R, Torres, D, Wang, Cy, Vanhelder, T, Paniagua, P, Berwanger, O, Srinathan, S, Graham, M, Pasin, L, Le Manach, Y, Gao, P, Pogue, J, Whitlock, R, Lamy, A, Kearon, C, Baigent, C, Chow, C, Pettit, S, Chrolavicius, S, Yusuf, S, DeBeer J, POISE 2 I. n. v. e. s. t. i. g. a. t. o. r. s., Patel, A, Dechert, W, Jackson, P, Allard, R, Dumerton Shore, D, Mccourt, J, Jones, Pm, Lavi, R, Lavi, S, Moor, R, Dresser, Gk, Gros, Ml, Schumann, Vc, Baur, M, Macdonald, C, Wirzba, B, Regalado, O, Srinathan, Sk, Ong, Dd, Todd, A, Abbas, S, Beattie, Ws, Chan, Vw, Chin, Kj, Wijeysundera, Dn, Graham, Mm, Irwin, M, Jacka, M, El Beheiry, H, Mcmullen, Sm, Macdonald, P, Akhtar, Z, Ayad, S, Buttar, M, Deroee, A, Eshraghi, Y, Fergany, A, Finnigan, P, Fu, A, Grady, M, Helper, S, Hesler, B, Honar, H, Hutcherson, M, Krebs, V, Lee, J, Malik, M, Podolyak, A, Salmasi, V, Arora, H, Coombs, Rf, Martinelli, Sm, Bergese, Sd, Melibary, Sb, Uribe, Aa, Jordan, M, Miller, Sa, Cata, Jp, Nemergut, Ec, Candiotti, Ka, Memtsoudis, Sg, Mckay, Re, Montes, Fr, Parra, Ga, Rojas, Mf, Plata, R, Vásquez, Sm, Sarquis, T, Haider, Z, Jane, Nb, Lanjewar, Pp, Rahate, Pv, Mehra, Br, Premendaran, B, Abraham, V, George, P, Kumar, P, Gaikwad, Sb, Mohan, Nv, Sidhu, G, Alvarez, J, Gonzalez, R, Maestre, M, Popova, E, Urrutia, G, de Nadal, M, González Suárez, S, González Tallada, A, Plou, P, Mena, E, Riveira, C, del Valle, S, Tena, B, Lang, Sa, Ludbrook, Gl, Painter, Tw, Terblanche, Nc, Osborne, C, Mahood, Jr, Myles, Ps, Sivalingam, P, Riedel, B, Elhalawani, I, Drummond, L, Mugabi, A, Naidoo, P, Myburgh, Al, Porrill, Os, Diedericks, Bj, Turton, Ew, Bøgeskov, M, Dahl, Rm, Madsen, Mv, Søndergaard, Es, Bauer, Ne, Martinsen, Kr, Choi, Gy, Gin, T, Ng, Ss, Bidgoli, Sj, Van der Linden PJ, De Kock, M, Kabon, B, Luf, F, Radonic, M, Ishtiaq, O, Safdar, J, Acuna Villaorduna, A, Barrionuevo, P, Castaneda Guarderas, A, Caballero, Ja, Lau, Ve, Aphang Lam MR, Lembo, R, Gossetti, Bruno, Jara, X, Leon, P, Ong, Gs, Lee, Hs, Seeberger, Ee, Seeberger, Md, Alfonsi, P, Coriat, P, Piriou, V, Vizcaychipi, Mp, Rech, Rl, Bergo, Rr, Walker, S, Rodseth, R, Lemanach, Y, Díaz, R, Cortés, Ol, Wetterslev, J, Hoeft, A, Wittmann, M, Chan, M, Landoni, G, Conen, D, Balaji, P, Sovereign, T, Blake, L, Sephton, J, Serra, A, Agrippa, C, Lawrence, M, Biccard, B, Gluud, C, Karthikeyan, G, Auerbach, A, Beattie, S, Buckley, N, Douketis, J, Gerstein, H, Ghali, W, Hart, R, Hill, M, Mcalister, F, Mcauley, D, Miller, S, O'Donnell, M, Pais, P, Parlow, J, Schricker, T, Sessler, D, Simunovic, M, Teoh, K, Walsh, M, Wijeysundera, D, Yang, H, Alshalash, S, Bessissow, A, Duceppe, E, Khalid, Z, Khan, J, Lauw, M, Martinsen, K, Neary, J, Oczkowski, W, Papina, M, Seeberger, M, Tandon, V, Thomas, S, Friedman, L, Cheng, D, Johnstone, D, Lowenstein, E, Roberts, R., Devereaux, Pj, Mrkobrada, M, Sessler, Di, Leslie, K, Alonso Coello, P, Kurz, A, Villar, Jc, Sigamani, A, Biccard, Bm, Meyhoff, C, Parlow, Jl, Guyatt, G, Robinson, A, Garg, Ax, Rodseth, Rn, Botto, F, Lurati Buse, G, Xavier, D, Chan, Mt, Tiboni, M, Cook, D, Kumar, Pa, Forget, P, Malaga, G, Fleischmann, E, Amir M, Eikelboom J, Mizera, R, Torres, D, Wang, Cy, Vanhelder, T, Paniagua, P, Berwanger, O, Srinathan, S, Graham, M, Pasin, L, Le Manach, Y, Gao, P, Pogue, J, Whitlock, R, Lamy, A, Kearon, C, Baigent, C, Chow, C, Pettit, S, Chrolavicius, S, Yusuf, S, and Landoni, Giovanni

Subjects
Male, Myocardial Infarction, Kaplan-Meier Estimate, noncardiac surgery, postoperative period, law.invention, low drug dose, hazard ratio, Postoperative Complications, Randomized controlled trial, law, Myocardial infarction, Treatment Failure, Aspirin, Medicine (all), Hazard ratio, drug effect, article, risk assessment, General Medicine, Middle Aged, female, priority journal, Anesthesia, drug withdrawal, factorial design, Surgical Procedures, Operative, Platelet aggregation inhibitor, Female, medicine.drug, hospitalization, heart infarction, perioperative period, preoperative treatment, Postoperative Hemorrhage, Perioperative Care, length of stay, death, medicine, Humans, follow up, controlled study, human, clonidine, outcome assessment, Aged, treatment duration, Vascular disease, business.industry, Platelet Aggregation Inhibitor, patient care, acetylsalicylic acid, medicine.disease, bleeding, major clinical study, Confidence interval, purl.org/pe-repo/ocde/ford#3.02.00 [https], Clinical research, multicenter study, randomized controlled trial, placebo, Postoperative Complication, business, Platelet Aggregation Inhibitors
Abstract

BACKGROUND: There is substantial variability in the perioperative administration of aspirin in patients undergoing noncardiac surgery, both among patients who are already on an aspirin regimen and among those who are not. METHODS: Using a 2-by-2 factorial trial design, we randomly assigned 10,010 patients who were preparing to undergo noncardiac surgery and were at risk for vascular complications to receive aspirin or placebo and clonidine or placebo. The results of the aspirin trial are reported here. The patients were stratified according to whether they had not been taking aspirin before the study (initiation stratum, with 5628 patients) or they were already on an aspirin regimen (continuation stratum, with 4382 patients). Patients started taking aspirin (at a dose of 200 mg) or placebo just before surgery and continued it daily (at a dose of 100 mg) for 30 days in the initiation stratum and for 7 days in the continuation stratum, after which patients resumed their regular aspirin regimen. The primary outcome was a composite of death or nonfatal myocardial infarction at 30 days. RESULTS: The primary outcome occurred in 351 of 4998 patients (7.0%) in the aspirin group and in 355 of 5012 patients (7.1%) in the placebo group (hazard ratio in the aspirin group, 0.99; 95% confidence interval [CI], 0.86 to 1.15; P = 0.92). Major bleeding was more common in the aspirin group than in the placebo group (230 patients [4.6%] vs. 188 patients [3.8%]; hazard ratio, 1.23; 95% CI, 1.01, to 1.49; P = 0.04). The primary and secondary outcome results were similar in the two aspirin strata. CONCLUSIONS: Administration of aspirin before surgery and throughout the early postsurgical period had no significant effect on the rate of a composite of death or nonfatal myocardial infarction but increased the risk of major bleeding. (Funded by the Canadian Institutes of Health Research and others; POISE-2 ClinicalTrials.gov number, NCT01082874.) Copyright © 2014 Massachusetts Medical Society.

Published
2014

71. Post-Transplant Assessment of DCD Cardiac Allografts with MRI

Author

Pavlushkov, E., primary, Page, A., additional, Messer, S., additional, Kydd, A., additional, Tweed, K., additional, Abu-Omar, Y., additional, Ali, A., additional, Berman, M., additional, Catarino, P., additional, Dunning, J., additional, Jenkins, D., additional, Lewis, C., additional, Parameshwar, J., additional, Pettit, S., additional, Sudarshan, C., additional, Tsui, S., additional, and Large, S., additional

Published
2017
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74. Excellent Early Outcomes Following Heart Transplantation from Circulatory Dead Donors

Author

Messer, S., primary, Page, A., additional, Axell, R., additional, Colah, S., additional, Hernandez-Sanchez, J., additional, Parizkova, B., additional, Valchanov, K., additional, Dunning, J., additional, Parameshwar, J., additional, Lewis, C., additional, Omar, Y.Abu, additional, Pettit, S., additional, Kydd, A., additional, Jenkins, D., additional, Sudarshan, C., additional, Catarino, P., additional, Berman, M., additional, Findlay, M., additional, Ali, A., additional, Tsui, S., additional, and Large, S.R., additional

Published
2017
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80. Clonidine in patients undergoing noncardiac surgery

Author

Devereaux, Pj, Sessler, Di, Leslie, K, Kurz, A, Mrkobrada, M, Alonso Coello, P, Villar, Jc, Sigamani, A, Biccard, Bm, Meyhoff, Cs, Parlow, Jl, Guyatt, G, Robinson, A, Garg, Ax, Rodseth, Rn, Botto, F, Lurati Buse, G, Xavier, D, Chan, Mt, Tiboni, M, Cook, D, Kumar, Pa, Forget, P, Malaga, G, Fleischmann, E, Amir, M, Eikelboom, J, Mizera, R, Torres, D, Wang, Cy, Vanhelder, T, Paniagua, P, Berwanger, O, Srinathan, S, Graham, M, Pasin, L, Le Manach, Y, Gao, P, Pogue, J, Whitlock, R, Lamy, A, Kearon, C, Chow, C, Pettit, S, Chrolavicius, S, Yusuf, S, Debeer, J, Patel, A, Dechert, W, Jackson, P, Allard, R, Dumerton Shore, D, Mccourt, J, Jones, Pm, Lavi, R, Lavi, S, Moor, R, Dresser, Gk, Gros, Ml, Schumann, Vc, Baur, M, Macdonald, C, Wirzba, B, Regalado, O, Srinathan, Sk, Ong, Dd, Todd, A, Abbas, S, Beattie, Ws, Chan, Vw, Chin, Kj, Wijeysundera, Dn, Graham, Mm, Irwin, M, Jacka, M, El Beheiry, H, Mcmullen, Sm, Macdonald, P, Akhtar, Z, Ayad, S, Buttar, M, Deroee, A, Eshraghi, Y, Fergany, A, Finnigan, P, Fu, A, Grady, M, Helper, S, Hesler, B, Honar, H, Hutcherson, M, Krebs, V, Lee, J, Malik, M, Podolyak, A, Salmasi, V, Arora, H, Coombs, Rf, Martinelli, Sm, Bergese, Sd, Melibary, Sb, Uribe, Aa, Jordan, M, Miller, Sa, Cata, Jp, Nemergut, Ec, Candiotti, Ka, Memtsoudis, Sg, Mckay, Re, Montes, Fr, Parra, Ga, Rojas, Mf, Plata, R, Vásquez, Sm, Sarquis, T, Haider, Z, Jane, Nb, Lanjewar, Pp, Rahate, Pv, Mehra, Br, Premendaran, B, Abraham, V, George, P, Kumar, P, Gaikwad, Sb, Mohan, Nv, Sidhu, G, Alvarez, J, Gonzalez, R, Maestre, M, Popova, E, Urrutia, G, de Nadal, M, González Suárez, S, González Tallada, A, Plou, P, Mena, E, Riveira, C, del Valle, S, Tena, B, Lang, Sa, Ludbrook, Gl, Painter, Tw, Terblanche, Nc, Osborne, C, Mahood, Jr, Myles, Ps, Sivalingam, P, Riedel, B, Elhalawani, I, Drummond, L, Mugabi, A, Naidoo, P, Myburgh, Al, Porrill, Os, Diedericks, Bj, Turton, Ew, Bøgeskov, M, Dahl, Rm, Madsen, Mv, Søndergaard, Es, Bauer, Ne, Martinsen, Kr, Choi, Gy, Gin, T, Ng, Ss, Bidgoli, Sj, Van der Linden PJ, De Kock, M, Kabon, B, Luf, F, Radonic, M, Ishtiaq, O, Safdar, J, Acuna Villaorduna, A, Barrionuevo, P, Castaneda Guarderas, A, Caballero, Ja, Lau, Ve, Aphang Lam MR, Lembo, R, Gossetti, Bruno, Jara, X, Leon, P, Ong, G, Lee, Hs, Seeberger, Ee, Seeberger, Md, Alfonsi, P, Coriat, P, Piriou, V, Vizcaychipi, Mp, Rech, Rl, Bergo, Rr, Walker, S, Rodseth, R, Lemanach, Y, Díaz, R, Cortés, Ol, Wetterslev, J, Hoeft, A, Wittmann, M, Chan, M, Landoni, G, Conen, D, Balaji, P, Sovereign, T, Blake, L, Sephton, J, Serra, A, Agrippa, C, Lawrence, M, Biccard, B, Gluud, C, Baigent, C, Karthikeyan, G, Auerbach, A, Beattie, S, Buckley, N, Douketis, J, Gerstein, H, Ghali, W, Hart, R, Hill, M, Mcalister, F, Mcauley, D, Miller, S, O'Donnell, M, Pais, P, Parlow, J, Schricker, T, Sessler, D, Simunovic, M, Teoh, K, Walsh, M, Wijeysundera, D, Yang, H, Alshalash, S, Bessissow, A, Duceppe, E, Khalid, Z, Khan, J, Lauw, M, Martinsen, K, Neary, J, Oczkowski, W, Papina, M, Seeberger, M, Tandon, V, Thomas, S, Friedman, L, Cheng, D, Johnstone, D, Lowenstein, E, and Roberts, R.

Subjects
Male, hypotension, drug safety, Heart disease, Myocardial Infarction, Kaplan-Meier Estimate, high risk patient, noncardiac surgery, surgery, low drug dose, hazard ratio, Postoperative Complications, dose response, Adrenergic alpha-2 Receptor Agonists, Myocardial infarction, Treatment Failure, risk reduction, Aspirin, Hazard ratio, drug effect, article, risk assessment, General Medicine, Middle Aged, Clonidine, aged, female, priority journal, Anesthesia, factorial design, Surgical Procedures, Operative, Female, Hypotension, medicine.drug, medicine.medical_specialty, heart infarction, perioperative period, preoperative treatment, Placebo, bradycardia, Perioperative Care, length of stay, death, medicine, Humans, controlled study, human, Aged, treatment duration, business.industry, Perioperative, Vascular surgery, acetylsalicylic acid, medicine.disease, major clinical study, purl.org/pe-repo/ocde/ford#3.02.00 [https], drug efficacy, multicenter study, randomized controlled trial, incidence, treatment outcome, placebo, business, heart arrest
Abstract

Background: Marked activation of the sympathetic nervous system occurs during and after noncardiac surgery. Low-dose clonidine, which blunts central sympathetic outflow, may prevent perioperative myocardial infarction and death without inducing hemodynamic instability. Methods: We performed a blinded, randomized trial with a 2-by-2 factorial design to allow separate evaluation of low-dose clonidine versus placebo and low-dose aspirin versus placebo in patients with, or at risk for, atherosclerotic disease who were undergoing noncardiac surgery. A total of 10,010 patients at 135 centers in 23 countries were enrolled. For the comparison of clonidine with placebo, patients were randomly assigned to receive clonidine (0.2 mg per day) or placebo just before surgery, with the study drug continued until 72 hours after surgery. The primary outcome was a composite of death or nonfatal myocardial infarction at 30 days. Results: Clonidine, as compared with placebo, did not reduce the number of primary-outcome events (367 and 339, respectively; hazard ratio with clonidine, 1.08; 95% confidence interval [CI], 0.93 to 1.26; P=0.29). Myocardial infarction occurred in 329 patients (6.6%) assigned to clonidine and in 295 patients (5.9%) assigned to placebo (hazard ratio, 1.11; 95% CI, 0.95 to 1.30; P=0.18). Significantly more patients in the clonidine group than in the placebo group had clinically important hypotension (2385 patients [47.6%] vs. 1854 patients [37.1%]; hazard ratio 1.32; 95% CI, 1.24 to 1.40; P

Published
2014

84. Covert stroke after non-cardiac surgery: a prospective cohort study

Author

Mrkobrada, M., primary, Hill, M.D., additional, Chan, M.T.V., additional, Sigamani, A., additional, Cowan, D., additional, Kurz, A., additional, Sessler, D.I., additional, Jacka, M., additional, Graham, M., additional, Dasgupta, M., additional, Dunlop, V., additional, Emery, D.J., additional, Gulka, I., additional, Guyatt, G., additional, Heels-Ansdell, D., additional, Murkin, J., additional, Pettit, S., additional, Sahlas, D.J., additional, Sharma, M., additional, Srinathan, S., additional, St John, P., additional, Tsai, S., additional, Gelb, A.W., additional, O’Donnell, M., additional, Siu, D., additional, Chiu, P.W.Y., additional, Sharath, V., additional, George, A., additional, and Devereaux, P.J., additional

Published
2016
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97. Ordered Processing of the Human Immunodeficiency Virus Type 1 GagPol Precursor Is Influenced by the Context of the Embedded Viral Protease

Author

Jeung, J. A., Clemente, J. C., Dunn, B. M., Kaplan, A. H., and Pettit, S. C.

Abstract

Ordered and accurate processing of the human immunodeficiency virus type 1 (HIV-1) GagPol polyprotein precursor by a virally encoded protease is an indispensable step in the appropriate assembly of infectious viral particles. The HIV-1 protease (PR) is a 99-amino-acid enzyme that is translated as part of the GagPol precursor. Previously, we have demonstrated that the initial events in precursor processing are accomplished by the PR domain within GagPol in cis, before it is released from the polyprotein. Despite the critical role that ordered processing of the precursor plays in viral replication, the forces that define the order of cleavage remain poorly understood. Using an in vitro assay in which the full-length HIV-1 GagPol is processed by the embedded PR, we examined the effect of PR context (embedded within GagPol versus the mature 99-amino-acid enzyme) on precursor processing. Our data demonstrate that the PR domain within GagPol is constrained in its ability to cleave some of the processing sites in the precursor. Further, we find that this constraint is dependent upon the presence of a proline as the initial amino acid in the embedded PR; substitution of an alanine at this position produces enhanced cleavage at additional sites when the precursor is processed by the embedded, but not the mature, PR. Overall, our data support a model in which the selection of processing sites and the order of precursor processing are defined, at least in part, by the structure of GagPol itself.

Published
2005
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98. Initial Cleavage of the Human Immunodeficiency Virus Type 1 GagPol Precursor by Its Activated Protease Occurs by an Intramolecular Mechanism

Author

Everitt, L. E., Choudhury, S., Kaplan, A. H., Dunn, B. M., and Pettit, S. C.

Abstract

Processing of the GagPol polyprotein precursor of human immunodeficiency virus type 1 (HIV-1) is a critical step in viral assembly and replication. The HIV-1 protease (PR) is translated as part of GagPol and is both necessary and sufficient for precursor processing. The PR is active only as a dimer; enzyme activation is initiated when the PR domains in two GagPol precursors dimerize. The precise mechanism by which the PR becomes activated and the subsequent initial steps in precursor processing are not well understood. However, it is clear that processing is initiated by the PR domain that is embedded within the precursor itself. We have examined the earliest events in precursor processing using an in vitro assay in which full-length GagPol is cleaved by its embedded PR. We demonstrate that the embedded, immature PR is as much as 10,000-fold less sensitive to inhibition by an active-site PR inhibitor than is the mature, free enzyme. Further, we find that different concentrations of the active-site inhibitor are required to inhibit the processing of different cleavage sites within GagPol. Finally, our results indicate that the first cleavages carried out by the activated PR within GagPol are intramolecular. Overall, our data support a model of virus assembly in which the first cleavages occur in GagPol upstream of the PR. These intramolecular cleavages produce an extended form of PR that completes the final processing steps accompanying the final stages of particle assembly by an intermolecular mechanism.

Published
2004
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