127 results on '"Ong TK"'
Search Results
2. The Implementation of the Minimal Intervention Dentistry in the Undergraduate Dental Clinical Teaching: A Retrospective Audit
- Author
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Ab Ghani, SM, primary, Tengku Mohd Ariff, TF, additional, Ong, TK, additional, and Lim, TW, additional
- Published
- 2022
- Full Text
- View/download PDF
3. Thrombin and FXa plasma concentration levels in patients with atrial fibrillation on long term warfarin therapy
- Author
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Lim, MSH, Anchah, L, Tiong, WN, Hwang, SS, Ong, TK, Sim, KH, and Fong, AYY
- Published
- 2014
- Full Text
- View/download PDF
4. Thermal and mechanical properties of chemically treated oil palm fiber filled acrylonitrile butadiene styrene composites
- Author
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Ong, TK, Tshai, KY, Khiew, PS, and Yap, EH
- Subjects
Materials - Abstract
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim In this work, chemical surface treated oil palm fibers, including alkali, maleic and silane pre-treatments are melt blended and hot compression molded with acrylonitrile butadiene styrene into varying compositions of polymer composites. The effectiveness of the chemical pre-treatment and fiber dispersion are analyzed with the aid of Fourier-transform infrared spectrometry and scanning electron microscope while the influences on thermal degradation and mechanical properties of the resulting composites are analyzed through thermal gravimetric analysis and tensile test respectively. Differential thermogravimetric analysis result show that alkali, maleic and silane pre-treatments could lower the onset thermal degradation temperature of oil palm fiber filled acrylonitrile butadiene styrene composites. The tensile test results show that chemically treated oil palm fiber filled acrylonitrile butadiene styrene composites attained enhancement in tensile strength as compared to untreated counterpart. Scanning electron microscopy observations on fracture surfaces of oil palm fiber filled acrylonitrile butadiene styrene composites found that the reinforcing efficiency of chemically treated oil palm fiber could be further increased by improving interfacial bonding between oil palm fiber and acrylonitrile butadiene styrene.
- Published
- 2019
5. Effects of Alirocumab on Cardiovascular Events After Coronary Bypass Surgery
- Author
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Szarek, M, Bhatt, DL, Bittner, VA, Diaz, R, Edelberg, JM, Hanotin, C, Harrington, RA, Jukema, JW, Letierce, A, Moryusef, A, Pordy, R, Lopez, GAR, Roe, MT, White, HD, Zeiher, AM, Steg, PG, Schwartz, GG, Aylward, PE, Drexel, H, Sinnaeve, P, Dilic, M, Goodman, SG, Prieto, JC, Yong, H, Lopez-Jaramillo, P, Pecin, I, Reiner, Z, Ostadal, P, Poulsen, SH, Viigimaa, M, Nieminen, MS, Danchin, N, Chumburidze, V, Tse, HF, Xavier, D, Zahger, D, Valgimigli, M, Kimura, T, Kim, HS, Kim, SH, Erglis, A, Laucevicius, A, Kedev, S, Yusoff, K, Alings, M, Halvorsen, S, Flores, RMC, Sy, RG, Budaj, A, Morais, J, Dorobantu, M, Karpov, Y, Ristic, AD, Chua, T, Murin, J, Fras, Z, Tunon, J, de Silva, HA, Muller, C, Ray, KK, Vogel, R, Chaitman, B, Kelsey, SF, Olsson, AG, Rouleau, JL, Simoons, ML, Alexander, K, Meloni, C, Rosenson, R, Sijbrands, EJG, Alexander, JH, Armaganijan, L, Bagai, A, Bahit, MC, Brennan, JM, Clifton, S, DeVore, AD, Deloatch, S, Dickey, S, Dombrowski, K, Ducrocq, G, Eapen, Z, Endsley, P, Eppinger, A, Hess, CN, Hlatky, MA, Jordan, JD, Knowles, JW, Kolls, BJ, Kong, DF, Leonardi, S, Lillis, L, Maron, DJ, Marcus, J, Mathews, R, Mehta, RH, Mentz, RJ, Moreira, HG, Patel, CB, Pereira, SB, Perkins, L, Povsic, TJ, Puymirat, E, Jones, WS, Shah, BR, Sherwood, MW, Stringfellow, K, Sujjavanich, D, Toma, M, Trotter, C, van Diepen, SFP, Wilson, MD, Yan, ATK, Schiavi, LB, Garrido, M, Alvarisqueta, AF, Sassone, SA, Bordonava, AP, De Lima, AEA, Schmidberg, JM, Duronto, EA, Caruso, OC, Novaretto, LP, Hominal, MA, Montana, OR, Caccavo, A, Vilamajo, OAG, Lorenzatti, AJ, Cartasegna, LR, Paterlini, GA, Mackinnon, IJ, Caime, GD, Amuchastegui, M, Codutti, OR, Jure, HO, Bono, JOE, Hrabar, AD, Vallejos, JA, Rodolfo, AAG, Novoa, F, Patocchi, CA, Zaidman, CJ, Giuliano, ME, Dran, RD, Vico, ML, Carnero, GS, Guzman, PN, Allende, JCM, Brasca, DFG, Labarta, MHB, Nani, S, Blumberg, EDS, Colombo, HR, Liberman, A, Luciardi, HL, Waisman, GD, Berli, MA, Duran, ROG, Cestari, HG, Luquez, HA, Giordano, JA, Saavedra, SS, Waites, JH, Collins, N, Soward, A, Hii, CLS, Shaw, J, Arstall, MA, Horowitz, J, Rogers, JF, Colquhoun, D, Flores, REO, Roberts-Thomson, P, Raffel, O, Lehman, SJ, Coverdale, SGM, Garrahy, PJ, Starmer, G, Sader, M, Carroll, PA, Zweiker, R, Hoppe, U, Huber, K, Berger, R, Weidinger, F, Faes, D, Hermans, K, Pirenne, B, Leone, A, Hoffer, E, Vrolix, MCM, De Wolf, L, Wollaert, B, Castadot, M, Dujardin, K, Beauloye, C, Vervoort, G, Striekwold, H, Convens, C, Roosen, J, Barbato, E, Claeys, M, Cools, F, Terzic, I, Barakovic, F, Midzic, Z, Pojskic, B, Fazlibegovic, E, Durak-Nalbantic, A, Vulic, D, Muslibegovic, A, Reis, G, Sousa, L, Nicolau, JC, Giorgeto, FE, Silva, RP, Maia, LN, Rech, R, Rossi, PRF, Cerqueira, MJAG, Duda, N, Kalil, R, Kormann, A, Abrantes, JAM, Pimentel, P, Soggia, AP, de Santos, MON, Neuenschwander, F, Bodanese, LC, Michalaros, YL, Eliaschewitz, FG, Vidotti, MH, Leaes, PE, Botelho, RV, Kaiser, S, Manenti, ERFF, Precoma, DB, Jorge, JCM, Silva, PGMD, Silveira, JA, Saporito, W, Marin, JA, Feitosa, GS, Ritt, LEF, de Souza, JA, Costa, F, Souza, WKSB, Reis, HJL, Lopes, RD, Machado, L, Ayoub, JCA, Todorov, GV, Nikolov, FP, Velcheva, ES, Tzekova, ML, Benov, HO, Petranov, SL, Tumbev, HS, Shehova-Yankova, NS, Markov, DT, Raev, DH, Mollov, MN, Kichukov, KN, Ilieva-Pandeva, KA, Gotcheva, NN, Ivanova, R, Mincheva, VM, Lazov, PV, Dimov, BI, Senaratne, M, Stone, J, Kornder, J, Pearce, S, Dion, D, Savard, D, Pesant, Y, Pandey, A, Robinson, S, Gosselin, G, Vizel, S, Hoag, G, Bourgeois, R, Morisset, A, Sabbah, E, Sussex, B, Kouz, S, MacDonald, P, Diaz, A, Michaud, N, Fell, D, Leung, R, Vuurmans, T, Lai, C, Nigro, F, Davies, R, Nogareda, G, Vijayaraghavan, R, Ducas, J, Lepage, S, Mehta, S, Cha, J, Dupuis, R, Fong, P, Rodes-Cabau, J, Fadlallah, H, Cleveland, D, Huynh, T, Bata, I, Hameed, A, Pincetti, C, Potthoff, S, Acevedo, M, Aguirre, A, Vejar, M, Yanez, M, Araneda, G, Fernandez, M, Perez, L, Varleta, P, Florenzano, F, Huidobro, L, Raffo, CA, Olivares, C, Chen, JY, Dong, YG, Huang, WJ, Wang, JZ, Huang, SA, Yao, ZH, Cui, L, Lin, WH, Sun, YM, Wang, JF, Li, JP, Zhang, XL, Zhu, H, Chen, DD, Huang, L, Dong, SH, Su, GH, Xu, B, Su, X, Cheng, XS, Lin, JX, Zong, WX, Li, HM, Feng, Y, Xu, DL, Yang, XC, Ke, YN, Lin, XF, Zhang, Z, Zheng, ZQ, Luo, ZR, Chen, YD, Ding, CH, Zheng, Y, Li, XD, Peng, DQ, Li, Y, Wei, M, Liu, SW, Yu, YH, Qu, BM, Jiang, WH, Zhou, YJ, Zhao, XS, Yuan, ZY, Guo, Y, Xu, XP, Shi, XB, Ge, JB, Fu, GS, Bai, F, Fang, WY, Shou, XL, Yang, XJ, Wang, JA, Jaramillo, N, Vallejo, GS, Botia, DCL, Lopez, RB, De Salazar, DIM, Bonfanti, AJC, Higuera, JD, Silva, SIB, Lozada, HJG, Arroyo, JAC, Mendoza, JLA, Ruiz, RLF, Fernandez, AM, Jatin, FGM, Herazo, AS, Parada, JC, Triana, MAU, Spinar, J, Horak, D, Stasek, J, Alan, D, Machova, V, Linhart, A, Novotny, V, Kaucak, V, Rokyta, R, Naplava, R, Coufal, Z, Adamkova, V, Podpera, I, Zizka, J, Motovska, Z, Marusincova, I, Svab, P, Heinc, P, Kuchar, J, Povolny, P, Raungaard, B, Clemmensen, P, Bang, LE, May, O, Bottcher, M, Hove, JD, Frost, L, Gislason, G, Larsen, J, Johansen, PB, Hald, F, Jeppesen, J, Nielsen, T, Kristensen, KS, Walichiewicz, PM, Lomholdt, JD, Klausen, IC, Nielsen, PK, Davidsen, F, Videbaek, L, Soots, M, Vahula, V, Hedman, A, Soopold, U, Martsin, K, Taskinen, MR, Porthan, K, Airaksinen, JK, Juonala, M, Kiviniemi, T, Vikman, S, Posio, P, Taurio, J, Huikuri, H, Kaikkonen, K, Coste, P, Ferrari, E, Morel, O, Montalescot, G, Barone-Rochette, G, Mansourati, J, Cottin, Y, Leclercq, F, Belhassane, A, Delarche, N, Boccara, F, Paganelli, F, Clerc, J, Schiele, F, Aboyans, V, Probst, V, Berland, J, Lefevre, T, Khintibidze, I, Shaburishvili, T, Pagava, Z, Ghlonti, R, Lominadze, Z, Khabeishvili, G, Hemetsberger, R, Rauch-Krohnert, U, Stratmann, M, Appel, KF, Schmidt, E, Omran, H, Stellbrink, C, Dorsel, T, Lianopoulos, E, Marx, R, Zirlik, A, Schellenberg, D, Heitzer, T, Laufs, U, Marx, N, Gielen, S, Winkelmann, B, Behrens, S, Sydow, K, Simonis, G, Muenzel, T, Werner, N, Leggewie, S, Bocker, D, Braun-Dullaeus, R, Toursarkissian, N, Jeserich, M, Weissbrodt, M, Schaeufele, T, Weil, J, Voller, H, Waltenberger, J, Natour, M, Steiner, S, Heidenreich, L, Gremmler, U, Killat, H, Patsilinakos, S, Kartalis, A, Manolis, A, Sionis, D, Liberopoulos, E, Skoumas, I, Athyros, V, Parthenakis, PIF, Hahalis, PIG, Lekakis, J, Xatzitolios, A, Ovando, SRF, Valdovinos, PCM, Benecke, JLA, De Leon, ERR, Yan, BPY, Siu, DCW, Turi, T, Merkely, B, Kiss, RG, Ungi, I, Lupkovics, G, Nagy, L, Katona, A, Edes, I, Muller, G, Horvath, I, Kapin, T, Falukozy, J, Kumbla, M, Sandhu, M, Annam, S, Proddutur, NR, Premchand, RK, Mahajan, A, Abhyanakar, AD, Kerkar, P, Govinda, RA, Oomman, A, Sinha, D, Patil, SN, Kahali, D, Sawhney, J, Joshi, AB, Chaudhary, S, Harkut, P, Guha, S, Porwal, S, Jujjuru, S, Pothineni, RB, Monteiro, MR, Khan, A, Iyengar, SS, Grewal, JS, Chopda, M, Fulwani, MC, Patange, A, Chopra, VK, Goyal, NK, Shinde, R, Manakshe, GV, Patki, N, Sethi, S, Munusamy, V, Karna, S, Adhyapak, S, Pandurangi, U, Mathur, R, Kalashetti, S, Bhagwat, A, Raghuraman, B, Yerra, SK, Bhansali, P, Borse, R, Das, S, Abdullakutty, J, Saathe, S, Palimkar, P, Atar, S, Shechter, M, Mosseri, M, Arbel, Y, Lotan, C, Rosenschein, U, Katz, A, Henkin, Y, Francis, A, Klutstein, M, Nikolsky, E, Turgeman, Y, Halabi, M, Kornowski, R, Jonas, M, Amir, O, Rozenman, Y, Fuchs, S, Hussein, O, Gavish, D, Vered, Z, Caraco, Y, Elias, M, Tov, N, Piovaccari, G, De Pellegrin, A, Guardigli, G, Licciardello, G, Auguadro, C, Cuccia, C, Salvioni, A, Musumeci, G, Calabro, P, Novo, S, Faggiano, P, De Cesare, NB, Berti, S, Cavallini, C, Puccioni, E, Galvani, M, Tespili, M, Piatti, P, Palvarini, M, De Luca, G, Violini, R, De Leo, A, Filardi, PP, Ferratini, M, Dai, K, Kamiya, H, Ando, K, Takeda, Y, Morino, Y, Hata, Y, Kimura, K, Kishi, K, Michishita, I, Uehara, H, Higashikata, T, Hirayama, A, Hirooka, K, Sakagami, S, Taguchi, S, Koike, A, Fujinaga, H, Koba, S, Kozuma, K, Kawasaki, T, Ono, Y, Shimizu, M, Katsuda, Y, Wada, A, Shinke, T, Ako, J, Fujii, K, Takahashi, T, Sakamoto, T, Furukawa, Y, Sugino, H, Mano, T, Utsu, N, Ito, K, Haraguchi, T, Ueda, Y, Nishibe, A, Fujimoto, K, Yoon, JH, Park, HS, Chae, IH, Kim, MH, Jeong, MH, Rha, S, Kim, C, Hong, T, Busmane, A, Pontaga, N, Strelnieks, A, Mintale, I, Sime, I, Petrulioniene, Z, Kavaliauskiene, R, Jurgaitiene, R, Sakalyte, G, Slapikas, R, Norkiene, S, Misonis, N, Kibarskis, A, Kubilius, R, Bojovski, S, Lozance, N, Kjovkaroski, A, Doncovska, S, Ong, TK, Kasim, S, Maskon, O, Kandasamy, B, Liew, HB, Mohamed, WMIW, Castillo, AG, Calvillo, JC, Campos, PF, Fragoso, JCN, Llamas, EAB, Gamba, MAA, Madrigal, JC, Salas, LGG, Rosas, EL, Diaz, BG, Vazquez, ES, Ackar, AN, Esperon, GAL, Sanchez, CRM, De Leon, MG, Otero, RS, Salmon, GF, Rios, JAP, Ruiz, JAG, Breedveld, RW, Hoogslag, PAM, Suryapranata, H, Oomen, A, Wiersma, JJ, Van Der Wal, RMA, Van Huysduynen-Monraats, PSH, Karalis, I, Verdel, GJE, Brueren, BRG, Troquay, RPT, Viergever, EP, Al-Windy, NYY, Bartels, GL, Cornel, JH, Hermans, WRM, Herrman, JPR, Bos, RJ, Groutars, RGEJ, Van Der Zwaan, CC, Kaplan, R, Ronner, E, Groenemeijer, BE, Bronzwaer, PNA, Liem, AAH, Rensing, BJWM, Bokern, MJJA, Nijmeijer, R, Hersbach, FMRJ, Willems, FF, Gosselink, ATM, Elliott, J, Wilkins, G, Fisher, R, Scott, D, Hart, H, Stewart, R, Harding, S, Ternouth, I, Fisher, N, Aitken, D, Anscombe, R, Tomala, T, Nygard, O, Sparby, JA, Andersen, K, Gullestad, L, Jortveit, J, Munk, PS, Hurtig, U, Ticona, JRC, Velasquez, JRD, Miguel, SAN, Perez, ESS, Chambilla, JMC, Ayala, CAC, Leon, RPC, Gonzales, RJV, Zuniga, JDH, Cosavalente, LAC, Mannucci, JEB, Navarro, NCL, Concha, YMR, Chavez, VER, Hernandez, HAA, Nunez, CAZ, Ferrolino, A, Sy, RAG, Tirador, L, Matiga, G, Coching, RM, Bernan, A, Rogelio, G, Morales, DD, Tan, E, Wlodarczak, A, Jaworska, K, Skonieczny, G, Pawlowicz, L, Wojewoda, P, Busz-Papiez, B, Bednarski, J, Goch, A, Staneta, P, Dulak, E, Saminski, K, Krasowski, W, Sudnik, W, Zurakowski, A, Skorski, M, Lysek, R, Miklaszewicz, B, Kubica, J, Lipko, JA, Kostarska-Srokosz, E, Piepiorka, M, Drzewiecka, A, Sciborski, R, Stasiewski, A, Blicharski, T, Bystryk, L, Szpajer, M, Korol, M, Czerski, T, Mirek-Bryniarska, E, Gniot, J, Lubinski, A, Gorny, J, Franek, E, Monteiro, P, Bastos, JM, Pereira, HH, Martins, D, Seixo, F, Mendonca, C, Botelho, A, Minescu, B, Istratoaie, O, Tesloianu, DN, Cristian, G, Podoleanu, CGC, Constantinescu, MCA, Bengus, CM, Militaru, C, Rosu, D, Parepa, IR, Matei, AV, Alexandru, TM, Shvarts, Y, Orlikova, O, Kobalava, Z, Barbarash, OL, Markov, V, Lyamina, N, Gordienko, A, Zrazhevsky, K, Vishnevsky, AY, Gurevich, V, Stryuk, R, Lomakin, NV, Bokarev, I, Shalaev, S, Khaisheva, L, Chizhov, P, Viktorova, I, Osokina, N, Akatova, E, Chumakova, G, Libov, I, Voevoda, MI, Tretyakova, TV, Baranov, E, Shustov, S, Yakushin, S, Gordeev, I, Khasanov, N, Reshetko, O, Sotnikova, T, Molchanova, O, Nikolaev, K, Gapon, L, Baranova, E, Shogenov, Z, Kosmachova, E, Povzun, A, Egorova, L, Tyrenko, VV, Ivanov, IG, Simic, D, Ivanovic, N, Davidovic, G, Tasic, N, Asanin, MR, Stojic, S, Apostolovic, SR, Ilic, S, Putnikovic, B, Stankovic, A, Arandjelovic, A, Radovanovic, S, Balinovac, J, Dincic, DV, Seferovic, P, Dodic, S, Dimkovic, S, Poh, KK, Ong, HY, Micko, K, Nociar, J, Pella, D, Fulop, P, Hranai, M, Palka, J, Mazur, J, Majercak, I, Dzupina, A, Fazekas, F, Gonsorcik, J, Bugan, V, Selecky, J, Kamensky, G, Strbova, J, Smik, R, Dukat, A, Zuran, I, Oklukar, J, Suligoj, NC, Cevc, M, Lipar, L, Cyster, HP, Ranjith, N, Corbett, C, Bayat, J, Makotoko, EM, Kapp, IE, Basson, MMD, Lottering, H, Van Zyl, LJ, Sebastian, PJ, Pillay, T, Saaiman, JA, Commerford, PJ, Cassimjee, S, Ebrahim, IO, Sarvan, M, Mynhardt, JH, Dalby, AJ, Reuter, H, Moodley, R, Vida, M, Fillat, ARC, Peris, VB, Jimenez, FF, Marin, F, Fernandez, JMC, Gil-Extremera, B, Diz, FW, Garcia-Dorado, D, Iniguez, A, Fernandez, JT, Gonzalez-Juanatey, JR, Portales, JF, Murillo, FC, Pericas, LM, Zamorano, JL, Martin, MD, Cortada, JB, Martin, JJA, Fernandez, JRD, Fernandez, JFD, Lledo, JAG, Sales, JC, Rodriguez, JB, Tragant, GG, Benedicto, A, Gonzalez-Juanatey, C, Potau, MC, Perez, IP, De La Tassa, CM, Rincon, PLO, Recena, JB, Escudier, JM, Constantine, G, Haniffa, R, Tissera, N, Amarasekera, S, Fernando, N, Jayawardena, J, Santharaj, W, Ekanayaka, R, Mendis, S, Senaratne, V, Mayurathan, G, Sirisena, T, Rajapaksha, A, Herath, JI, Amarasena, N, Berglund, S, Rasmanis, G, Hagstrom, E, Witt, N, Mourtzinis, G, Nicol, P, Hansen, O, Romeo, S, Torstensson, I, Jensen, SA, Ahremark, U, Sundelin, T, Moccetti, T, Mach, F, Binder, R, Chiang, CE, Tsai, WC, Ueng, KC, Lai, WT, Liu, ME, Hwang, JJ, Yin, WH, Hsieh, IC, Kuo, JY, Huang, TY, Fang, CY, Kaewsuwanna, P, Soonfuang, W, Jintapakorn, W, Sukonthasarn, A, Sritara, P, Wongpraparut, N, Sastravaha, K, Sansanayudh, N, Kehasukcharoen, W, Piyayotai, D, Camsari, A, Kultursay, H, Guneri, S, Mutlu, B, Ersanli, M, Demirtas, M, Kirma, C, Ural, E, Koldas, L, Karpenko, O, Prokhorov, A, Vakaluyk, I, Myshanych, H, Reshotko, D, Batushkin, V, Rudenko, L, Kovalskyi, I, Kushnir, M, Tseluyko, V, Mostovoy, Y, Stanislavchuk, M, Kyiak, Y, Karpenko, Y, Malynovsky, Y, Klantsa, A, Kutniy, O, Amosova, E, Tashchuk, V, Leshchuk, O, Parkhomenko, A, Rishko, M, Kopytsya, M, Yagensky, A, Vatutin, M, Bagriy, A, Barna, OM, Ushakov, O, Dzyak, G, Goloborodko, B, Rudenko, A, Trevelyan, J, Zaman, A, Lee, K, Moriarty, A, Aggarwal, RK, Clifford, P, Wong, YK, Iqbal, SMR, Subkovas, E, Braganza, D, Sarkar, D, Storey, R, Griffiths, H, Mcclure, S, Muthusamy, R, Kurian, J, Levy, T, Barr, C, Kadr, H, Gerber, R, Simaitis, A, Soran, H, Mathur, A, Brodison, A, Oliver, R, Mudawi, T, Reynolds, T, Sharman, D, Butler, R, Wilkinson, P, Lip, GYH, Halcox, J, Vardi, G, Baldari, D, Brabham, D, Treasure, C, Dahl, C, Palmer, B, Wiseman, A, Puri, S, Mohart, AE, Ince, C, Flores, E, Wright, S, Cheng, SC, Rosenberg, M, Rogers, W, Kosinski, E, Forgosh, L, Waltman, J, Khan, M, Shoukfeh, M, Dagher, G, Lieber, I, Kumar, P, East, C, Krichmar, P, White, L, Knickelbine, T, Haldis, T, Gillespie, E, Suh, D, Arif, I, Akhter, F, Carlson, E, D'Urso, M, El-Ahdab, F, Nelson, W, Harris, B, Cohen, S, Carter, L, Sabatino, K, Haddad, T, Malik, A, Rao, S, Mulkay, A, Jovin, I, Klancke, K, Malhotra, V, Devarapalli, SK, Koren, M, Chandna, H, Dodds, G, Janik, M, Moran, J, Sumner, A, Kobayashi, J, Davis, W, Yazdani, S, Pasquini, J, Thakkar, M, Vedere, A, Leimbach, W, Rider, J, Singh, N, Shah, AV, Moriarty, PM, Janosik, D, Pepine, C, Berman, B, Gelormini, J, Daniels, C, Keating, F, Kondo, NI, Shetty, S, Waider, W, Takata, T, Abu-Fadel, M, Shah, V, Aggarwal, R, Izzo, M, Kumar, A, Hattler, B, Link, C, Bortnick, A, Kinzfogl, G, Ghitis, A, Larry, J, Teufel, E, Kuhlman, P, Mclaurin, B, Zhang, WW, Thew, S, Abbas, J, White, M, Ranadive, N, Gring, C, Henderson, D, Schuchard, T, Farhat, N, Kline, G, Mahal, S, Whitaker, J, Speirs, S, Andersen, R, Daboul, N, Horwitz, P, Jafar, Z, Mcgarvey, J, Panchal, V, Voyce, S, Blok, T, Sheldon, W, Azizad, MM, Schmalfuss, C, Picone, M, Herzog, W, Lindsey, J, Nowins, R, Lepor, N, El Shahawy, M, Weintraub, H, Irimpen, A, May, W, Galski, T, Chu, A, Mody, F, Hodes, Z, Fairlamb, J, Lambert, C, Raisinghani, A, Abbate, A, King, M, Carey, C, Gerber, J, Younis, L, Park, H, Vidovich, M, Knutson, T, Friedman, D, Chaleff, F, Loussararian, A, Kimmelstiel, C, Silver, K, Foster, M, Tonnessen, G, Amlani, M, Wali, A, Malozzi, C, Wattanakit, K, O'Donnell, PJ, Singal, D, Jaffrani, N, Banuru, S, Fisher, D, Xenakis, M, Perlmutter, N, Bhagwat, R, Strader, J, Akyea-Djamson, A, Labroo, A, Marais, HJ, Claxton, E, Berk, M, Rossi, P, Joshi, P, Khaira, AS, Kumkumian, G, Lupovitch, S, Purow, J, Welka, S, Hoffman, D, Fischer, S, Soroka, E, Eagerton, D, Pancholy, S, Ray, M, Farrar, M, Pollock, S, French, WJ, Diamantis, S, Gimple, L, Schwartz, S, Pereira, E, Spriggs, D, Strain, J, Vo, A, Chane, M, Hall, J, Vijay, N, Lotun, K, Lester, FM, Nahhas, A, Pope, T, Nager, P, Vohra, R, Bashir, R, Ahmed, H, Berlowitz, M, Fishberg, R, Barrucco, R, Yang, E, Radin, M, Sporn, D, Eisenberg, S, Landzberg, J, Mcgough, M, Turk, S, Schwartz, M, Sundram, PS, Jain, D, Zainea, M, Bayron, C, Karlsberg, R, Lui, H, Keen, W, Westerhausen, D, Khurana, S, Agarwal, H, Birchem, J, Penny, W, Chang, M, Gilbert, JM, Chalavarya, G, Eaton, C, Schmedtje, JF, Christenson, S, Denham, D, Macdonell, A, Gibson, P, Rahman, A, Al Joundi, T, Conrad, G, Kotha, P, Love, M, Giesler, G, Rubenstein, H, Akright, L, Schifferdecker, B, Krawczyk, J, Wells, T, Welker, J, Foster, R, Gilmore, R, Anderson, J, Jacoby, D, Gardner, G, Dandillaya, R, Vora, K, Kostis, J, Hunter, J, Laxson, D, Ball, E, İÜC, and Ege Üniversitesi
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Male ,medicine.medical_specialty ,Acute coronary syndrome ,alirocumab ,030204 cardiovascular system & hematology ,Antibodies, Monoclonal, Humanized ,lipids ,PCSK9 ,03 medical and health sciences ,0302 clinical medicine ,Postoperative Complications ,Double-Blind Method ,coronary artery bypass graft ,Internal medicine ,medicine ,Humans ,Cardiac and Cardiovascular Systems ,030212 general & internal medicine ,Myocardial infarction ,cardiovascular diseases ,Acute Coronary Syndrome ,Coronary Artery Bypass ,Alirocumab ,Aged ,Kardiologi ,business.industry ,Unstable angina ,Hazard ratio ,cholesterol ,Middle Aged ,medicine.disease ,surgical procedures, operative ,Bypass surgery ,Cardiovascular Diseases ,Cardiology ,Drug Therapy, Combination ,Female ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Cardiology and Cardiovascular Medicine ,business ,Mace - Abstract
Sherwood, Matthew/0000-0002-4305-5883; Taskinen, Marja-Riitta/0000-0002-6229-3588; Leonardi, Sergio/0000-0002-4800-6132; Raffel, Owen C/0000-0001-5470-7050; Muenzel, Thomas/0000-0001-5503-4150; Ersanli, Murat/0000-0003-1847-3087; Gislason, Gunnar H/0000-0002-0548-402X; bastos, jose/0000-0002-9526-3123; Abbate, Antonio/0000-0002-1930-785X; Chumakova, Galina A/0000-0002-2810-6531; Nikolaev, Konstantin/0000-0003-4601-6203; Tse, Hung Fat/0000-0002-9578-7808; Keskin, Kudret/0000-0002-9049-1530; Reshetko, Olga/0000-0003-3107-7636; Podoleanu, Cristian/0000-0001-9987-2519; Aylward, Philip/0000-0002-5358-8552; LETIERCE, Alexia/0000-0001-6679-5772, WOS: 000483334800002, PubMed: 31466614, BACKGROUND Patients with acute coronary syndrome (ACS) and history of coronary artery bypass grafting (CABG) are at high risk for recurrent cardiovascular events and death. OBJECTIVES This study sought to determine the clinical benefit of adding alirocumab to statins in ACS patients with prior CABG in a pre-specified analysis of ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab). METHODS Patients (n = 18,924) 1 to 12 months post-ACS with elevated atherogenic lipoprotein levels despite high-intensity statin therapy were randomized to alirocumab or placebo subcutaneously every 2 weeks. Median follow-up was 2.8 years. the primary composite endpoint of major adverse cardiovascular events (MACE) comprised coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or unstable angina requiring hospitalization. All-cause death was a secondary endpoint. Patients were categorized by CABG status: no CABG (n = 16,896); index CABG after qualifying ACS, but before randomization (n = 1,025); or CABG before the qualifying ACS (n = 1,003). RESULTS in each CABG category, hazard ratios (95% confidence intervals) for MACE (no CABG 0.86 [0.78 to 0.95], index CABG 0.85 [0.54 to 1.35], prior CABG 0.77 [0.61 to 0.98]) and death (0.88 [ 0.75 to 1.03], 0.85 [0.46 to 1.59], 0.67 [0.44 to 1.01], respectively) were consistent with the overall trial results (0.85 [ 0.78 to 0.93] and 0.85 [0.73 to 0.98], respectively). Absolute risk reductions (95% confidence intervals) differed across CABG categories for MACE (no CABG 1.3% [0.5% to 2.2%], index CABG 0.9% [-2.3% to 4.0%], prior CABG 6.4% [0.9% to 12.0%]) and for death (0.4% [-0.1% to 1.0%], 0.5% [-1.9% to 2.9%], and 3.6% [0.0% to 7.2%]). CONCLUSIONS Among patients with recent ACS and elevated atherogenic lipoproteins despite intensive statin therapy, alirocumab was associated with large absolute reductions in MACE and death in those with CABG preceding the ACS event. (ODYSSEY OUTCOMES: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402) (C) 2019 by the American College of Cardiology Foundation., Fondation Assistance Publique-Hopitaux de Paris, Paris, France, The authors thank the patients, study coordinators, and investigators who participated in this trial. Sophie Rushton-Smith, PhD (MedLink Healthcare Communications, London) provided editorial assistance in the preparation of the manuscript (limited to editing for style, referencing, and figure and table editing) and was funded by Fondation Assistance Publique-Hopitaux de Paris, Paris, France.
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- 2019
6. Effect of Alirocumab on Mortality After Acute Coronary Syndromes An Analysis of the ODYSSEY OUTCOMES Randomized Clinical Trial
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Baranova, E, Shogenov, Z, Kosmachova, E, Povzun, A, Egorova, L, Tyrenko, VV, Ivanov, IG, Kanorsky, S, Simic, D, Ivanovic, N, Davidovic, G, Tasic, N, Asanin, MR, Stojic, S, Apostolovic, SR, Ilic, S, Putnikovic, B, Stankovic, A, Arandjelovic, A, Radovanovic, S, Balinovac, J, Dincic, DV, Seferovic, P, Dodic, S, Dimkovic, S, Poh, K-K, Ong, HY, Micko, K, Nociar, J, Pella, D, Fulop, P, Hranai, M, Palka, J, Mazur, J, Majercak, I, Dzupina, A, Fazekas, F, Gonsorcik, J, Bugan, V, Selecky, J, Kamensky, G, Strbova, J, Smik, R, Dukat, A, Olexa, P, Zuran, I, Poklukar, J, Suligoj, NC, Cevc, M, Cyster, HP, Ranjith, N, Corbett, C, Bayat, J, Makotoko, EM, Kapp, IE, Basson, MMDV, Lottering, H, Van Zyl, LJ, Sebastian, PJ, Pillay, T, Saaiman, JA, Commerford, PJ, Cassimjee, S, Ebrahim, IO, Sarvan, M, Mynhardt, JH, Reuter, H, Moodley, R, Vida, M, Cequier Fillat, AR, Peris, VB, Jimenez, FF, Marin, F, Cruz Fernandez, JM, Gil-Extremera, B, Diz, FW, Garcia-Dorado, D, Iniguez, A, Tunon Fernandez, J, Gonzalez-Juanatey, JR, Fernandez Portales, J, Civeira Murillo, F, Matas Pericas, L, Luis Zamorano, J, De Mora Martin, M, Bruguera Cortada, J, Alonso Martin, JJ, De Berrazueta Fernandez, JR, Diaz Fernandez, JF, Garcia Lledo, JA, Cosin Sales, J, Botas Rodriguez, J, Gusi Tragant, G, Benedicto, A, Gonzalez-Juanatey, C, Camprubi Potau, M, Plaza Perez, I, Moris De La Tassa, C, Loma-Osorio Rincon, P, Balaguer Recena, J, Escudier, JM, Coca Payeras, A, Alonso Orcajo, N, Valdivielso, P, Constantine, G, Haniffa, R, Tissera, N, Amarasekera, S, Fernando, N, Jayawardena, J, Santharaj, W, Ekanayaka, R, Mendis, S, Senaratne, V, Mayurathan, G, Sirisena, T, Rajapaksha, A, Herath, JI, Amarasena, N, Berglund, S, Rasmanis, G, Witt, N, Mourtzinis, G, Nicol, P, Hansen, O, Romeo, S, Jensen, SA, Torstensson, I, Ahremark, U, Sundelin, T, Moccetti, T, Mach, F, Binder, R, Tsai, W-C, Ueng, K-C, Lai, W-T, Liu, M-E, Hwang, J-J, Yin, W-H, Hsieh, I-C, Lin, WH, Kuo, J-Y, Huang, T-Y, Fang, C-Y, Kaewsuwanna, P, Soonfuang, W, Jintapakorn, W, Sukonthasarn, A, Wongpraparut, N, Sastravaha, K, Sansanayudh, N, Kehasukcharoen, W, Piyayotai, D, Chotnoparatpat, P, Camsari, A, Kultursay, H, Mutlu, B, Ersanli, M, Demirtas, M, Kirma, C, Ural, E, Koldas, L, Karpenko, O, Prokhorov, A, Vakaluyk, I, Myshanych, H, Reshotko, D, Batushkin, V, Rudenko, L, Kovalskyi, I, Kushnir, M, Tseluyko, V, Mostovoy, Y, Stanislavchuk, M, Kyiak, Y, Karpenko, Y, Malynovsky, Y, Klantsa, A, Kutniy, O, Amosova, E, Tashchuk, V, Leshchuk, O, Rishko, M, Kopytsya, M, Yagensky, A, Vatutin, M, Bagriy, A, Barna, OM, Ushakov, O, Dzyak, G, Goloborodko, B, Rudenko, A, Zheleznyy, V, Trevelyan, J, Zaman, A, Lee, K, Moriarty, A, Aggarwal, RK, Clifford, P, Wong, Y-K, Iqbal, SMR, Subkovas, E, Braganza, D, Sarkar, D, Storey, R, Griffiths, H, Mcclure, S, Muthusamy, R, Kurian, J, Levy, T, Barr, C, Kadr, H, Gerber, R, Simaitis, A, Soran, H, Mathur, A, Brodison, A, Oliver, R, Mudawi, T, Reynolds, T, Sharman, D, Butler, R, Wilkinson, P, Lip, GYH, Halcox, J, Vardi, G, Baldari, D, Brabham, D, Treasure, C, Dahl, C, Palmer, B, Wiseman, A, Puri, S, Mohart, AE, Ince, C, Flores, E, Wright, S, Cheng, S-C, Rosenberg, M, Rogers, W, Kosinski, E, Forgosh, L, Waltman, J, Khan, M, Shoukfeh, M, Dagher, G, Lieber, I, Kumar, P, East, C, Krichmar, P, White, L, Knickelbine, T, Haldis, T, Gillespie, E, Suh, D, Arif, I, Akhter, F, Carlson, E, D'Urso, M, El-Ahdab, F, Nelson, W, Harris, B, Cohen, S, Carter, L, Sabatino, K, Haddad, T, Malik, A, Rao, S, Mulkay, A, Jovin, I, Klancke, K, Malhotra, V, Devarapalli, SK, Koren, M, Chandna, H, Dodds, G, Janik, M, Moran, J, Sumner, A, Kobayashi, J, Davis, W, Yazdani, S, Pasquini, J, Thakkar, M, Vedere, A, Leimbach, W, Rider, J, Singh, N, Shah, AV, Janosik, D, Pepine, C, Berman, B, Gelormini, J, Daniels, C, Keating, F, Kondo, NI, Shetty, S, Waider, W, Takata, T, Abu-Fadel, M, Shah, V, Aggarwal, R, Izzo, M, Kumar, A, Hattler, B, Link, C, Bortnick, A, Kinzfogl, G, Ghitis, A, Larry, J, Teufel, E, Kuhlman, P, Mclaurin, B, Zhang, W, Thew, S, Abbas, J, White, M, Ranadive, N, Gring, C, Henderson, D, Schuchard, T, Farhat, N, Kline, G, Mahal, S, Whitaker, J, Speirs, S, Andersen, R, Daboul, N, Horwitz, P, Ponce, G, Jafar, Z, Mcgarvey, J, Panchal, V, Voyce, S, Blok, T, Sheldon, W, Azizad, MM, Schmalfuss, C, Picone, M, Herzog, W, Lindsey, J, Nowins, R, Lepor, N, El Shahawy, M, Weintraub, H, Irimpen, A, May, W, Galski, T, Chu, A, Mody, F, Hodes, Z, Rose, G, Fairlamb, J, Lambert, C, Raisinghani, A, Abbate, A, King, M, Carey, C, Gerber, J, Younis, L, Park, HT, Vidovich, M, Knutson, T, Friedman, D, Chaleff, F, Loussararian, A, Rozeman, P, Kimmelstiel, C, Silver, K, Foster, M, Tonnessen, G, Amlani, M, Wali, A, Malozzi, C, Wattanakit, K, O'Donnell, PJ, Singal, D, Jaffrani, N, Banuru, S, Fisher, D, Xenakis, M, Perlmutter, N, Bhagwat, R, Strader, J, Akyea-Djamson, A, Labroo, A, Marais, HJ, Claxton, E, Berk, M, Rossi, P, Joshi, P, Khaira, AS, Kumkumian, G, Lupovitch, S, Purow, J, Welka, S, Hoffman, D, Fischer, S, Soroka, E, Eagerton, D, Pancholy, S, Ray, M, Farrar, M, Pollock, S, French, WJ, Diamantis, S, Gimple, L, Neustel, M, Schwartz, S, Pereira, E, Spriggs, D, Strain, J, Vo, A, Chane, M, Hall, J, Vijay, N, Lotun, K, Lester, FM, Nahhas, A, Pope, T, Nager, P, Vohra, R, Bashir, R, Ahmed, H, Berlowitz, M, Fishberg, R, Barrucco, R, Yang, E, Radin, M, Sporn, D, Eisenberg, S, Landzberg, J, Mcgough, M, Turk, S, Schwartz, M, Sundram, PS, Jain, D, Zainea, M, Bayron, C, Karlsberg, R, Lui, H, Keen, W, Westerhausen, D, Khurana, S, Agarwal, H, Birchem, J, Penny, W, Chang, M, Murphy, S, Schifferdecker, B, Gilbert, JM, Chalavarya, G, Eaton, C, Schmedtje, JF, Christenson, S, Denham, D, Macdonell, A, Gibson, P, Rahman, A, Al Joundi, T, Conrad, G, Kotha, P, Love, M, Giesler, G, Rubenstein, H, Akright, L, Krawczyk, J, Wells, T, Welker, J, Foster, R, Gilmore, R, Anderson, J, Jacoby, D, Gardner, G, Dandillaya, R, Vora, K, Kostis, J, Hunter, J, Laxson, D, Ball, E, Camp, A, Lopes, R, Egydio, F, Kawakami, A, Oliveira, J, Wozniak, J, Matthews, A, Ratky, C, Valiris, J, Berdan, L, Hepditch, A, Quintero, K, Rorick, T, Westbrook, M, Pascual, A, Rovito, C, Bezault, M, Drouet, E, Simon, T, Alsweiler, C, Luyten, A, Aylward, P, Butters, J, Griffith, L, Shaw, M, Grunberg, L, Islam, S, Bougon, N, Faustino, D, Fontecave, S, Murphy, J, Verrier, M, Agnetti, V, Andersen, D, Badreddine, E, Bekkouche, M, Bouancheau, C, Brigui, I, Brocklehurst, M, Cianciarulo, J, Devaul, D, Domokos, S, Gache, C, Gobillot, C, Guillou, S, Healy, J, Heath, M, Jaiwal, G, Javierre, C, Labeirie, J, Monier, M, Morales, U, Mrabti, A, Mthombeni, B, Okan, B, Smith, L, Sheller, J, Sopena, S, Pellan, V, Benbernou, F, Bengrait, N, Lamoureux, M, Kralova, K, Scemama, M, Bejuit, R, Coulange, A, Berthou, C, Repincay, J, Lorenzato, C, Etienne, A, Gouet, V, Loizeau, V, Normand, M, Ourliac, A, Rondel, C, Adamo, A, Beltran, P, Barraud, P, Dubois-Gache, H, Halle, B, Metwally, L, Mourgues, M, Sotty, M, Vincendet, M, Cotruta, R, Zhu, C, Fournie-Lloret, D, Morrello, C, Perthuis, A, Picault, P, Zobouyan, I, ODYSSEY OUTCOMES Comm, İÜC, Ege Üniversitesi, Rushton-Smith, Sophie, and ODYSSEY OUTCOMES Committees and Investigators
- Subjects
Male ,Cardiac & Cardiovascular Systems ,MONOCLONAL-ANTIBODY ,alirocumab ,Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage ,law.invention ,PCSK9 ,chemistry.chemical_compound ,Randomized controlled trial ,law ,Cardiac and Cardiovascular Systems ,1102 Cardiorespiratory Medicine and Haematology ,Hypercholesterolemia/blood ,Kardiologi ,Hazard ratio ,Middle Aged ,Treatment Outcome ,SAFETY ,Cardiology ,Female ,Drug Therapy, Combination ,Cholesterol, LDL/antagonists & inhibitors ,Cardiology and Cardiovascular Medicine ,Life Sciences & Biomedicine ,REDUCING LIPIDS ,Akutes Koronarsyndrom ,acute coronary syndrome ,cholesterol ,mortality ,PCSK9 protein ,Antibodies, Monoclonal, Humanized/administration & dosage ,medicine.medical_specialty ,Acute coronary syndrome ,Injections, Subcutaneous ,Hypercholesterolemia ,Placebo ,Antibodies, Monoclonal, Humanized ,1117 Public Health and Health Services ,Sterblichkeit ,Double-Blind Method ,Physiology (medical) ,Internal medicine ,medicine ,Humans ,ddc:610 ,Alirocumab ,Aged ,Science & Technology ,Cholesterol ,business.industry ,EVOLOCUMAB ,1103 Clinical Sciences ,Cholesterol, LDL ,medicine.disease ,EFFICACY ,Increased risk ,chemistry ,Peripheral Vascular Disease ,Cardiovascular System & Hematology ,Cardiovascular System & Cardiology ,Acute Coronary Syndrome/blood ,Cholesterin ,Human medicine ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,business ,Follow-Up Studies - Abstract
bastos, jose/0000-0002-9526-3123; Manakshe, Gajendra/0000-0002-4983-4271; Tse, Hung Fat/0000-0002-9578-7808; Gislason, Gunnar H/0000-0002-0548-402X; Taskinen, Marja-Riitta/0000-0002-6229-3588; Racca, Vittorio/0000-0002-4465-3789; Keskin, Kudret/0000-0002-9049-1530; Sherwood, Matthew/0000-0002-4305-5883; Sandhu, Manjinder/0000-0003-2538-2079; Nikolaev, Konstantin/0000-0003-4601-6203; Ersanli, Murat/0000-0003-1847-3087; Raffel, Owen C/0000-0001-5470-7050; Abbate, Antonio/0000-0002-1930-785X; Muenzel, Thomas/0000-0001-5503-4150; Leonardi, Sergio/0000-0002-4800-6132; Chumakova, Galina A/0000-0002-2810-6531; Podoleanu, Cristian/0000-0001-9987-2519; Pereira, Helder/0000-0001-8656-4883; Reshetko, Olga/0000-0003-3107-7636, WOS: 000476768100007, PubMed: 31117810, Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. in a prespecified analysis of 8242 patients eligible for >= 3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P= 100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; P-interaction=0.007). in the alirocumab group, all-cause death declined with achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for >= 3 years, if baseline LDL-C is >= 100 mg/dL, or if achieved LDL-C is low., Sanofi; Regeneron Pharmaceuticals, Inc., The trial was funded by Sanofi and Regeneron Pharmaceuticals, Inc.
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- 2019
7. Alirocumab Reduces Total Hospitalizations and Increases Days Alive and Out of Hospital in the ODYSSEY OUTCOMES Trial
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DiCenso, D, Gotcheva, N, Sourdille, T, White, HD, Schwartz, GG, Steg, PG, Bhatt, DL, Bittner, VA, Diaz, R, Harrington, RA, Jukema, JW, Szarek, M, Zeiher, AM, Tricoci, P, Mahaffey, KW, Edelberg, JM, Hanotin, C, Lecorps, G, Moryusef, A, Pordy, R, Sasiela, WJ, Drexel, H, Sinnaeve, P, Dilic, M, Gotcheva, NN, Goodman, SG, Prieto, JC, Yong, H, Lopez-Jaramillo, P, Pecin, I, Reiner, Z, Poulsen, SH, Viigimaa, M, Nieminen, MS, Danchin, N, Chumburidze, V, Tse, HF, Xavier, D, Zahger, D, Valgimigli, M, Kim, HS, Erglis, A, Laucevicius, A, Lopez, R, Lopez, GAR, Alings, M, Chua, T, Murin, J, Fras, Z, Dalby, AJ, Tunon, J, De Silva, HA, Chiang, CE, Sritara, P, Guneri, S, Parkhomenko, A, Ray, KK, Moriarty, PM, Roe, MT, Chaitman, B, Kelsey, SF, Olsson, AG, Rouleau, JL, Simoons, ML, Alexander, K, Meloni, C, Rosenson, R, Sijbrands, EJG, Alexander, JH, Armaganijan, L, Bagai, A, Bahit, MC, Brennan, JM, Clifton, S, DeVore, AD, Deloatch, S, Dickey, S, Dombrowski, K, Ducrocq, G, Eapen, Z, Endsley, P, Eppinger, A, Harrison, RW, Hess, CN, Hlatky, MA, Jordan, JD, Knowles, JW, Kolls, BJ, Kong, DF, Leonardi, S, Lillis, L, Maron, DJ, Marcus, J, Mathews, R, Mehta, RH, Mentz, RJ, Moreira, HG, Patel, CB, Pereira, SB, Perkins, L, Povsic, TJ, Puymirat, E, Jones, WS, Shah, BR, Sherwood, MW, Stringfellow, K, Sujjavanich, D, Toma, M, Van Diepen, SFP, Wilson, MD, Yan, ATK, Lopes, RD, Trotter, C, Schiavi, LB, Garrido, M, Alvarisqueta, AF, Sassone, SA, Bordonava, AP, De Lima, AEA, Schmidberg, JM, Duronto, EA, Caruso, OC, Novaretto, LP, Hominal, MA, Montana, OR, Caccavo, A, Vilamajo, OAG, Lorenzatti, AJ, Cartasegna, LR, Paterlini, GA, Mackinnon, IJ, Caime, GD, Amuchastegui, M, Salomone, R, Codutti, OR, Jure, HO, Bono, JOE, Hrabar, AD, Vallejos, JA, Guerrero, RAA, Novoa, F, Patocchi, CA, Zaidman, CJ, Giuliano, ME, Dran, RD, Vico, ML, Carnero, GS, Guzman, PN, Allende, JCM, Brasca, DFG, Labarta, MHB, Nani, S, Blumberg, EDS, Colombo, HR, Liberman, A, Luciardi, HL, Waisman, GD, Berli, MA, Duran, ROG, Cestari, HG, 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MH, Leaes, PE, Botelho, RV, Kaiser, S, Manenti, ERFF, Precoma, DB, Jorge, JCM, Silva, PGMD, Silveira, JA, Saporito, W, Marin, JA, Feitosa, GS, Ritt, LEF, de Souza, JA, Costa, F, Souza, WKSB, Reis, HJL, Machado, L, Ayoub, JCA, Todorov, GV, Nikolov, FP, Velcheva, ES, Tzekova, ML, Benov, HO, Petranov, SL, Tumbev, HS, Shehova-Yankova, NS, Markov, DT, Raev, DH, Mollov, MN, Kichukov, KN, Ilieva-Pandeva, KA, Ivanova, R, Mincheva, VM, Lazov, PV, Dimov, BI, Senaratne, M, Stone, J, Kornder, J, Pearce, S, Dion, D, Savard, D, Pesant, Y, Pandey, A, Robinson, S, Gosselin, G, Vizel, S, Hoag, G, Bourgeois, R, Morisset, A, Sabbah, E, Sussex, B, Kouz, S, MacDonald, P, Diaz, A, Michaud, N, Fell, D, Leung, R, Vuurmans, T, Lai, C, Nigro, F, Davies, R, Nogareda, G, Vijayaraghavan, R, Ducas, J, Lepage, S, Mehta, S, Cha, J, Dupuis, R, Fong, P, Rodes-Cabau, J, Fadlallah, H, Cleveland, D, Huynh, T, Bata, I, Hameed, A, Pincetti, C, Potthoff, S, Acevedo, M, Aguirre, A, Vejar, M, Yanez, M, Araneda, G, Fernandez, 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Dimkovic, S, Poh, KK, Ong, HY, Micko, K, Nociar, J, Pella, D, Fulop, P, Hranai, M, Palka, J, Mazur, J, Majercak, I, Dzupina, A, Fazekas, F, Gonsorcik, J, Bugan, V, Selecky, J, Kamensky, G, Strbova, J, Smik, R, Dukat, A, Olexa, P, Zuran, I, Poklukar, J, Suligoj, NC, Cevc, M, Cyster, HP, Ranjith, N, Corbett, C, Bayat, J, Makotoko, EM, Kapp, IE, Basson, MMD, Lottering, H, Van Zyl, LJ, Sebastian, PJ, Pillay, T, Saaiman, JA, Commerford, PJ, Cassimjee, S, Ebrahim, IO, Sarvan, M, Mynhardt, JH, Reuter, H, Moodley, R, Vida, M, Fillat, ARC, Peris, VB, Jimenez, FF, Marin, F, Fernandez, JMC, Gil-Extremera, B, Diz, FW, Garcia-Dorado, D, Iniguez, A, Fernandez, JT, Gonzalez-Juanatey, JR, Portales, JF, Murillo, FC, Pericas, LM, Zamorano, JL, Martin, MD, Cortada, JB, Martin, JJA, Fernandez, JRD, Fernandez, JFD, Lledo, JAG, Sales, JC, Rodriguez, JB, Tragant, GG, Benedicto, A, Gonzalez-Juanatey, C, Potau, MC, Perez, IP, De La Tassa, CM, Rincon, PLO, Recena, JB, Escudier, JM, Payeras, AC, Orcajo, NA, Valdivielso, P, Constantine, G, Haniffa, R, Tissera, N, Amarasekera, S, Fernando, N, Jayawardena, J, Santharaj, W, Ekanayaka, R, Mendis, S, Senaratne, V, Mayurathan, G, Sirisena, T, Rajapaksha, A, Herath, JI, Amarasena, N, Berglund, S, Rasmanis, G, Witt, N, Mourtzinis, G, Nicol, P, Hansen, O, Romeo, S, Jensen, SA, Torstensson, I, Ahremark, U, Sundelin, T, Moccetti, T, Muller, C, Mach, F, Binder, R, Tsai, WC, Ueng, KC, Lai, WT, Liu, ME, Hwang, JJ, Yin, WH, Hsieh, IC, Kuo, JY, Huang, TY, Fang, CY, Kaewsuwanna, P, Soonfuang, W, Jintapakorn, W, Sukonthasarn, A, Wongpraparut, N, Sastravaha, K, Sansanayudh, N, Kehasukcharoen, W, Piyayotai, D, Chotnoparatpat, P, Camsari, A, Kultursay, H, Mutlu, B, Ersanli, M, Demirtas, M, Kirma, C, Ural, E, Koldas, L, Karpenko, O, Prokhorov, A, Vakaluyk, I, Myshanych, H, Reshotko, D, Batushkin, V, Rudenko, L, Kovalskyi, I, Kushnir, M, Tseluyko, V, Mostovoy, Y, Stanislavchuk, M, Kyiak, Y, Karpenko, Y, Malynovsky, Y, Klantsa, A, Kutniy, O, Amosova, E, Tashchuk, V, Leshchuk, O, Rishko, M, Kopytsya, M, Yagensky, A, Vatutin, M, Bagriy, A, Barna, OM, Ushakov, O, Dzyak, G, Goloborodko, B, Rudenko, A, Zheleznyy, V, Trevelyan, J, Zaman, A, Lee, K, Moriarty, A, Aggarwal, RK, Clifford, P, Wong, YK, Iqbal, SM, Subkovas, E, Braganza, D, Sarkar, D, Storey, R, Griffiths, H, Mcclure, S, Muthusamy, R, Kurian, J, Levy, T, Barr, C, Kadr, H, Gerber, R, Simaitis, A, Soran, H, Mathur, A, Brodison, A, Oliver, R, Mudawi, T, Reynolds, T, Sharman, D, Butler, R, Wilkinson, P, Lip, GYH, Halcox, J, Vardi, G, Baldari, D, Brabham, D, Treasure, C, Dahl, C, Palmer, B, Wiseman, A, Puri, S, Mohart, AE, Ince, C, Flores, E, Wright, S, Cheng, SC, Rosenberg, M, Rogers, W, Kosinski, E, Forgosh, L, Waltman, J, Khan, M, Shoukfeh, M, Dagher, G, Lieber, I, Kumar, P, East, C, Krichmar, P, White, L, Knickelbine, T, Haldis, T, Gillespie, E, Suh, D, Arif, I, Akhter, F, Carlson, E, D'Urso, M, El-Ahdab, F, Nelson, W, Harris, B, Cohen, S, Carter, L, Sabatino, K, Haddad, T, Malik, A, Rao, S, Mulkay, A, Jovin, I, Klancke, K, Malhotra, V, Devarapalli, SK, Koren, M, Chandna, H, Dodds, G, Janik, M, Moran, J, Sumner, A, Kobayashi, J, Davis, W, Yazdani, S, Pasquini, J, Thakkar, M, Vedere, A, Leimbach, W, Rider, J, Singh, N, Shah, AV, Janosik, D, Pepine, C, Berman, B, Gelormini, J, Daniels, C, Keating, F, Kondo, NI, Shetty, S, Waider, W, Takata, T, Abu-Fadel, M, Shah, V, Aggarwal, R, Izzo, M, Kumar, A, Hattler, B, Link, C, Bortnick, A, Kinzfogl, G, Ghitis, A, Larry, J, Teufel, E, Kuhlman, P, Mclaurin, B, Zhang, WW, Thew, S, Abbas, J, White, M, Ranadive, N, Gring, C, Henderson, D, Schuchard, T, Farhat, N, Kline, G, Mahal, S, Whitaker, J, Speirs, S, Andersen, R, Daboul, N, Horwitz, P, Ponce, G, Jafar, Z, Mcgarvey, J, Panchal, V, Voyce, S, Blok, T, Sheldon, W, Azizad, MM, Schmalfuss, C, Picone, M, Herzog, W, Lindsey, J, Nowins, R, Lepor, N, El Shahawy, M, Weintraub, H, Irimpen, A, May, W, Galski, T, Chu, A, Mody, F, Hodes, Z, Rose, G, Fairlamb, J, Lambert, C, Raisinghani, A, Abbate, A, King, M, Carey, C, Gerber, J, Younis, L, Park, H, Vidovich, M, Knutson, T, Friedman, D, Chaleff, F, Loussararian, A, Rozeman, P, Kimmelstiel, C, Silver, K, Foster, M, Tonnessen, G, Amlani, M, Wali, A, Malozzi, C, Wattanakit, K, O'Donnell, PJ, Singal, D, Jaffrani, N, Banuru, S, Fisher, D, Xenakis, M, Perlmutter, N, Bhagwat, R, Strader, J, Akyea-Djamson, A, Labroo, A, Marais, HJ, Claxton, E, Berk, M, Rossi, P, Joshi, P, Khaira, AS, Kumkumian, G, Lupovitch, S, Purow, J, Welka, S, Hoffman, D, Fischer, S, Soroka, E, Eagerton, D, Pancholy, S, Ray, M, Farrar, M, Pollock, S, French, WJ, Diamantis, S, Gimple, L, Neustel, M, Schwartz, S, Pereira, E, Spriggs, D, Strain, J, Vo, A, Chane, M, Hall, J, Vijay, N, Lotun, K, Lester, FM, Nahhas, A, Pope, T, Nager, P, Vohra, R, Bashir, R, Ahmed, H, Berlowitz, M, Fishberg, R, Barrucco, R, Yang, E, Radin, M, Sporn, D, Eisenberg, S, Landzberg, J, Mcgough, M, Turk, S, Schwartz, M, Sundram, PS, Jain, D, Zainea, M, Bayron, C, Karlsberg, R, Lui, H, Keen, W, Westerhausen, D, Khurana, S, Agarwal, H, Birchem, J, Penny, W, Chang, M, Murphy, S, Schifferdecker, B, Gilbert, JM, Chalavarya, G, Eaton, C, Schmedtje, JF, Christenson, S, Denham, D, Macdonell, A, Gibson, P, Rahman, A, Al Joundi, T, Conrad, G, Kotha, P, Love, M, Giesler, G, Rubenstein, H, Akright, L, Krawczyk, J, Wells, T, Welker, J, Foster, R, Gilmore, R, Anderson, J, Jacoby, D, Gardner, G, Dandillaya, R, Vora, K, Kostis, J, Hunter, J, Laxson, D, Ball, E, Camp, A, Lopes, R, Egydio, F, Kawakami, A, Oliveira, J, Wozniak, J, Matthews, A, Ratky, C, Valiris, J, Berdan, L, Hepditch, A, Quintero, K, Rorick, T, Westbrook, M, Pascual, A, Rovito, C, Bezault, M, Drouet, E, Simon, T, Alsweiler, C, Luyten, A, Aylward, P, Butters, J, Griffith, L, Shaw, M, Hagstrom, E, Grunberg, L, Islam, S, Bregeault, MF, Bougon, N, Faustino, D, Fontecave, S, Murphy, J, Tamby, JF, Verrier, M, Agnetti, V, Andersen, D, Badreddine, E, Bekkouche, M, Bouancheau, C, Brigui, I, Brocklehurst, M, Cianciarulo, J, Devaul, D, Domokos, S, Gache, C, Gobillot, C, Guillou, S, Healy, J, Heath, M, Jaiwal, G, Javierre, C, Labeirie, J, Monier, M, Morales, U, Mrabti, A, Mthombeni, B, Okan, B, Smith, L, Sheller, J, Sopena, S, Pellan, V, Benbernou, F, Bengrait, N, Lamoureux, M, Kralova, K, Scemama, M, Bejuit, R, Coulange, A, Berthou, C, Repincay, J, Lorenzato, C, Etienne, A, Gouet, V, Loizeau, V, Normand, M, Ourliac, A, Rondel, C, Adamo, A, Beltran, P, Barraud, P, Dubois-Gache, H, Halle, B, Metwally, L, Mourgues, M, Sotty, M, Vincendet, M, Cotruta, R, Zhu, CY, Fournie-Lloret, D, Morrello, C, Perthuis, A, Picault, P, Zobouyan, I, ODYSSEY OUTCOMES Comm Inve, Ege Üniversitesi, Cardiology, and Internal Medicine
- Subjects
medicine.medical_specialty ,Acute coronary syndrome ,Time Factors ,acute coronary syndrome ,alirocumab ,global burden of disease ,hospitalization ,myocardial infarction ,PCSK9 ,030204 cardiovascular system & hematology ,Antibodies, Monoclonal, Humanized ,Placebo ,Patient Readmission ,Risk Assessment ,03 medical and health sciences ,Patient Admission ,0302 clinical medicine ,Risk Factors ,Internal medicine ,medicine ,Humans ,Angina, Unstable ,Hospital Mortality ,030212 general & internal medicine ,Myocardial infarction ,03.02. Klinikai orvostan ,Dyslipidemias ,Alirocumab ,Out of hospital ,business.industry ,Anticholesteremic Agents ,Cholesterol, HDL ,Cholesterol hdl ,Cholesterol, LDL ,medicine.disease ,Treatment Outcome ,Drug Therapy, Combination ,Human medicine ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Cardiology and Cardiovascular Medicine ,business ,Cardiovascular outcomes ,Biomarkers - Abstract
Sherwood, Matthew/0000-0002-4305-5883; Abbate, Antonio/0000-0002-1930-785X; Moris, Cesar/0000-0002-2871-190X; Ersanli, Murat/0000-0003-1847-3087; Taskinen, Marja-Riitta/0000-0002-6229-3588; bastos, jose/0000-0002-9526-3123; Reshetko, Olga/0000-0003-3107-7636; Nikolaev, Konstantin/0000-0003-4601-6203; Leonardi, Sergio/0000-0002-4800-6132; Raffel, Owen C/0000-0001-5470-7050; Racca, Vittorio/0000-0002-4465-3789; Podoleanu, Cristian/0000-0001-9987-2519; Gislason, Gunnar H/0000-0002-0548-402X; Muenzel, Thomas/0000-0001-5503-4150; Tse, Hung Fat/0000-0002-9578-7808; Chumakova, Galina A/0000-0002-2810-6531, WOS: 000502609000004, PubMed: 31707826, Background: in ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab), alirocumab was compared with placebo, added to high-intensity or maximum tolerated statin treatment after acute coronary syndrome in 18924 patients. Alirocumab reduced first occurrence of the primary composite end point-coronary heart disease death, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or hospitalization for unstable angina-as well as total nonfatal cardiovascular events and all-cause deaths. the present analysis determined whether alirocumab reduced total (first and subsequent) hospitalizations and death and increased days alive and out of hospital (DAOH) and percent DAOH in ODYSSEY OUTCOMES. Methods and Results: in prespecified analyses, hazard functions for total hospitalizations and death were jointly estimated by a semiparametric model, while in post hoc analyses, DAOH and percent DAOH were compared between treatment groups with Poisson regression and one-inflated beta regression, respectively. With 16629 total hospitalizations and 726 deaths, 331 fewer hospitalizations, and 58 fewer deaths were observed with alirocumab compared with placebo, translating to 15.6 total hospitalizations or deaths avoided with alirocumab per 1000 patient-years of assigned treatment. Alirocumab reduced total hospitalizations (hazard ratio, 0.96 [95% CI, 0.92-1.00]; P=0.04) and increased DAOH relative to placebo (rate ratio, 1.003 [95% CI, 1.000-1.007]; P=0.05), primarily through a reduction in days dead (rate ratio, 0.847 [95% CI, 0.728-0.986]; P=0.03). Patients randomized to alirocumab were also more likely to survive to the end of the study without hospitalization (odds ratio, 1.06 [95% CI, 1.00-1.13]; P=0.03). Conclusions: Alirocumab reduced total hospitalizations with corresponding small increases in DAOH and percent DAOH. These outcomes provide alternative patient-centered metrics to capture the totality of alirocumab clinical efficacy after acute coronary syndrome. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01663402., Fondation Assistance Publique-Hopitaux de Paris, Paris, France, We thank the patients, study coordinators, and investigators who participated in this trial. Sophie Rushton-Smith, PhD (MedLink Healthcare Communications, London) provided editorial assistance in the preparation of the article (limited to editing for style, referencing, and figure and table editing) and was funded by Fondation Assistance Publique-Hopitaux de Paris, Paris, France.
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- 2019
8. The genomic road to invasion – examining the similarities and differences in the genomes of associated oral pre-cancer and cancer samples
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Wood, HM, Daly, C, Chalkley, R, Senguven, B, Ross, L, Egan, P, Chengot, P, Graham, J, Sethi, N, Ong, TK, MacLennan, K, Rabbitts, P, and Conway, C
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Background: It is frequently assumed that pre-invasive lesions are simpler precursors of cancer, and will contain a limited subset of the genomic changes seen in their associated invasive disease. Driver mutations are thought to occur early, but it is not known how many of these are present in pre-invasive lesions. These assumptions need to be tested with the increasing focus on both personalised cancer treatments, and early detection methodologies. Methods: We examined genomic copy number changes in 256 pre-invasive and invasive samples from 69 oral cancer patients. Forty-eight samples from 16 patients were further examined using exome sequencing. Results: Evidence of a shared ancestor of both dysplasia and carcinoma was seen in all but one patient. One third of dysplasias showed independent copy number events. The remainder had a similar or simpler copy number pattern to the carcinoma. All dysplasias examined contained somatic mutations absent in the related carcinoma. Previously observed copy number changes and TP53 mutations were very frequently observed, and almost always shared between dysplasia and carcinoma. Other gene changes were more sporadic. Pathway analysis confirmed that each patient’s disease developed in a different way. Examining the numbers of shared mutations, and the rate of accumulation of mutations showed evidence that all samples contain a population of sub-clones, with little evidence of selective advantage of a subset of these. Conclusions: These findings suggest that most of the genomic changes driving oral cancer occur in the pre-cancerous state by way of gradual random accumulation rather than a dramatic single event.
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- 2017
9. Survival following surgery for oral cancer: A 30-year experience
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Ong, TK, Murphy, C, Smith, AB, Kanatas, AN, and Mitchell, DA
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Oral squamous cell carcinoma is the most common intraoral malignancy, for which we advocate radical primary resection with adjuvant treatment where indicated. The main aims of this paper are to identify the overall survival of a consecutive series of patients and to relate survival to clinical and pathological factors. Kaplan–Meier curves were produced for site, sex, TNM status, and use of postoperative radiotherapy. The data were analysed using IBM SPSS Statistics for Windows and probabilities of less than 0.05 were accepted as significant. A total of 921 patients were recorded in the database with a diagnosis of oral squamous cell carcinoma out of a total of 1958 with salivary gland conditions or other cancers of the head and neck (43.1%). The earliest date of diagnosis was 1973, and the data were censored at 31 March 2016. The database comprised 340 women (36.9%) and 581 men (63.1%). A total of 339 patients died (34.5%): 117 women (33.7%) and 222 men (65.5%). The mean (range) age at death was 73.4 (31.4–97.5) years for women and 68.7 (33.3–95.5) years for men (t (337) = 3.28, p = 0.001). Our overall survival was somewhat better than the 56% five-year survival reported for oral cancer in England in 2010, which may be a reflection of the treatment. This work supports the view that aggressive management may improve overall survival.
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- 2017
10. Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes
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Holman, Rr, Bethel, Ma, Mentz, Rj, Thompson, Vp, Lokhnygina, Y, Buse, Jb, Chan, Jc, Choi, J, Gustavson, Sm, Iqbal, N, Maggioni, Ap, Marso, Sp, Öhman, P, Pagidipati, Nj, Poulter, N, Ramachandran, A, Zinman, B, Hernandez, Af, EXSCEL Study Group, : Califf RM, Patel, R, George, J, Sourij, H, Wong, Yw, Hannan, K, Sellers, Ma, Gottlieb, P, Lavender, P, Leloudis, D, Meadows, Y, Larson, D, Anderson, H, Elkins, M, Stone, A, Tisch, A, Perkins, L, Sanders, K, Campbell, C, Kennedy, I, Heal, P, Masterson, M, Darbyshire, J, Mumtaz, L, Athwal, R, Ferch, A, Batra, P, Durborow, L, Vincent, J, Woodall, A, Flanagan, T, Katona, B, Reicher, B, Pozzi, E, Oulhaj, A, Coleman, R, Rouleau, Jl, Pocock, Sj, Gorelick, F, Mcmurray, J, Riddle, M, Gagel, R, Collier, T, Markovic, T, Kong, Aps, Hian, Sk, Scott, R, Panelo, A, Yoon, Kh, Sheu, W, Sritara, P, Linong, J, Pan, C, Yong, H, Schernthaner, G, Mathieu, C, Tankova, T, Widimsky, P, Hanefeld, M, Keltai, M, Wainstein, J, del Prato, S, Pirags, V, Jakuboniene, N, Kooy, A, Dziemidok, P, Veresiu, Ia, Dreval, Av, Murin, J, Torello, Al, Sattar, N, Parkhomenko, O, Omar, M, Diaz, R, Lopes, R, Lanas, F, Urina Triana, M, Leiva-Pons, Jl, Aguliera, D, Bergenstal, R, Goodman, S, Yale, Jf, Caterson, I, Weng, J, Hu, D, Junbo, G, Zannad, F, Anoop, M, Ambrish, M, Gallegos, Ja, Green, Jb, Akerblom, A, Alexander, K, Al-Khatib, S, Armaganijan, L, Barros, P, Batit, M, Bernacki, G, Bernandez, S, Bloomfield, G, Clausen, E, De Souza Brito, F, Devore, A, Dombrowski, K, Eapen, Z, Gellad, Z, George, D, Guimaraes, P, Halim, S, Harrison, R, Hawes, J, Hess, C, Hyland, K, Jackson, L, Jones, S, Jordan, D, Katz, M, Kong, D, Koshizaka, M, Lakey, W, Leblanc, T, Leonardi, S, Luo, N, Mahaffey, K, Mandawat, A, Mehta, R, Melloni, C, Morse, M, Pagidpati, N, Patel, C, Patel, K, Pokorney, S, Posvic, T, Rao, M, Roe, M, Shah, B, Tillmann, H, Truffa, A, Zazula, A, Zeitler, E, Sicer, M, Ulla, Mr, Maffei, L, Klyver, Mi, Calella, P, Alvarisqueta, A, De La Fuente RL, Aizenberg, D, Roque, F, Cruciani, A, Frechtel, G, Gelersztein, E, Villarino, A, Mallagray, M, Nardone, L, Zaidman, C, Novaretto, L, Bartolacci, I, de Salvo, M, Delcourt, C, Crimmins, D, Jackson, R, O’Neal, D, Colman, P, Jeffries, W, Mah, Pm, Wittert, G, Proietto, J, Amerena, J, Marks, S, Tan, R, Colquhoun, D, Pieber, T, Drexel, H, Prager, R, Schnack, C, Hoppichler, F, Fasching, P, Francesconi, C, Luger, A, Schoenherr, Hr, Ebenbichler, C, Paulweber, B, Shernthaner, G, Verhaegen, A, Vanuytsel, J, Thissen, Jp, e Silva P, Barros, Gonzaga, C, Borges, J, Hissa, M, Rea, R, Rossi, P, Chacra, A, Eliaschewitz, F, Garbelini, B, Felicio, J, Rassi, N, Rossi, F, Nunes dos Santos, M, e Farias F, Bandeira, Lisboa, H, e Forti A, Costa, Saraiva, Jk, Kovacheva, S, Levterov, G, Sheinkova, G, Ilieva, E, Lyubenova, L, Damyanova, V, Gushterova, V, Mincheva, L, Illiev, D, Ivanov, V, Bobeva, R, Nikitov, Z, Shumkova, R, Lefterov, In, Zaharieva, S, Videva, V, Yakov, A, Cheung, S, Elliott, T, Mehta, P, Ross, S, Sigal, R, Woo, V, Jaffer, S, Kuritsky, R, Bell, A, Dumas, R, Gosselin, G, Robitaille, Y, Greenspoon, A, Lochnan, H, Tytus, R, Leiter, L, Pandey, A, Punthakee, Z, Dube, F, Sigalas, J, Pearce, M, Woodford, T, Paul, P, Bourgeois, R, Conway, R, Mazza, G, Hatheway, R, Misterski, J, Raffo, C, Olivares, C, Godoy, J, Potthoff, S, Santibañez, C, Larenas Yanez GJ, Gu, W, Shen, F, Ma, J, Guo, X, Li, Q, Du, Y, Hu, J, Ji, L, Li, Y, Deng, H, Feng, Y, Liu, L, Mu, Y, Ma, C, Qu, S, Wang, J, Wang, Y, Yuan, Z, Zhang, L, Zhou, S, Yang, T, Dong, Y, Liu, D, Coronel Arroyo, J, Perez Amador, G, Botero Lopes, R, Jaramilo, C, Orozco Linares, A, Cure Cure CA, Hernandez Triana, E, Molina de Salazar DI, Marin, Cr, Jaramilo Gomez CJ, Kellinerova, I, Adamkova, V, Krami, P, Brychta, T, Havelkova, J, Pantikova, K, Schoper, F, Pohl, W, Schumm-Draeger, Pm, Julius, U, Tschöpe, D, Hamann, A, Seissler, J, Schellong, S, Rose, L, Becker, B, Linn, T, Oerter, Em, Strotmann, Hj, Mölle, A, Pfutzner, A, Forst, T, Schäufele, T, Mugge, A, Lehrke, M, Meyer-Pannwitt, U, Mehling, H, Simon-Wagner, I, Schenkenberger, I, Busch, K, Hermes, S, Milek, K, Landers, B, Grueneberg, M, Braun, M, Nothroff, J, Kamke, W, Hergdt, G, Duengen, Hd, Kleinertz, K, Kuesters, D, Boenninghoff, Ah, Appel, Kf, Schaefer, A, Bieler, T, Ozaki, R, Luk, Aoy, Chu, Dw, Cheung-Wong, Mm, Siu, Dc, Yan, Bpy, Kung, K, Wong, Sys, Tsang, Cc, Yeung, Vt, Cheung, Bm, Tse, Hf, Hodi, G, Nagy, K, Lippai, J, Takacs, J, Fulop, T, Gaal, Z, Pauker, Z, Foldesi, I, Simon, J, Oroszan, T, Futo, L, Bezzegh, K, Nagy, A, Vandorfi, G, Kiss, J, Kesmarki, N, Kis, E, Papp, A, Kovacs, A, Szakal, I, Palinkas, A, Czegany, Z, Voros, P, Reiber, I, Kerenyi, Z, Dezso, E, Wittman, I, Penzes, J, Ples, Z, Taller, A, Farago, K, Kis, Jt, Zilahi, Z, Molnar, M, Barkai, L, Mileder, M, Szentpeteri, I, Peterfai, E, Lovasz, O, Mosenzon, O, Minuchin, O, Jaffe, A, Vishlitsky, V, Shimon, I, Bashkin, A, Stern, N, Elias, N, Bental, T, Butnaru, A, Lewis, B, Adawi, F, Nseir, W, Klainman, E, Herskovits, T, Cignarelli, M, Rotella, Cm, Ambrosio, G, Pozzilli, P, Genovese, S, Cavarape, A, Salvioni, A, Sokolova, J, Strautina, I, Teterovska, D, Stalte, V, Pastare, S, Leitane, I, Lagzdina, L, Andersone, I, Eglite, R, Stelmane, I, Levinger, A, Barsiene, L, Sulskiene, M, Varanauskiene, E, Danyte, E, Urbanaviciene, E, Urbanavicius, V, Zabuliene, L, Juskiene, R, Velaviciene, A, Kakariekiene, V, Augusteniene, A, Velickiene, D, Lasiene, J, Dauksiene, D, Caponis, J, Tan, At, Ramanathan, L, Hassan, Mra, Tan, F, Ong, Tk, Foo, Sh, Ghani, Ra, Cheah, Wk, Sanchez Mijangos JH, Cabrera Jardines, R, Barrientos Perez, M, Sauque Reyna, L, Alcocer Gamba MA, Villeda Espinosa, E, Tamez Perez HE, De La Garza Hernandez NE, Lopes, Sm, Ramirez Diaz SP, Reyes Sanchez, R, Márquez-Rodriguez, E, Köse, V, Voors-Pette, C, Oldenburg-Ligtenberg, Pc, van Kempen WW, Cox, K, Hoogendyk, J, Swinkels-Diepenmaat, L, Rojas-Lingan, G, Kentgens, S, Schipperen, S, de Valk HW, Swart, H, van Bemmel, B, Hoogslag, Pam, Diamant, M, Serné, Eh, Hamer, A, Wilson, S, Fisher, N, Dixon, P, Chaudhri, O, Crawford, V, Quinn, D, Nirmalaraj, K, Dunn, P, Gillies, J, Cutfield, R, Krebs, J, Helm, C, Kerr, J, Pryke, J, Ebo, G, Denopol, M, Ang, E, Uy, N, Jimeno, C, Mirasoi, R, Paz Pacheco, E, Custodio, M, Nicodemus, N Jr, Catindig, Ea, Magno, M, Tirador, L, Cylkowska, B, Stasinksa, T, Silwinska, T, Sroka, M, Piepiorka, M, Korzeniak, R, Mirecka, H, Zaluska, R, Pupek-Musialik, D, Homenda, W, Grabowska, A, Okopien, B, Niegowska, J, Pogorzelska, H, Mikolajczyk-Swatko, A, Sikorski, M, Sowinski, D, Tahk, Sj, Kim, Yn, Nam, Cw, Rim, Sj, Kim, Cj, Choi, Km, Lee, Ik, Kim, Ij, Namgung, J, Moon, Kw, Kim, Ks, Oh, Bh, Lee, Wy, Choi, Sh, Kim, Es, Moon, S, Mindrescu, Nm, Aron, G, Graur, M, Hancu, N, Mlitaru, C, Nafornita, V, Szilagyi, I, Popa, Ar, Angelescu, Lm, Negrisanu, Gd, Zaharie, Dg, Culman, Mi, Vacaru, G, Munteanu, M, Constantinescu, S, Tivadar, S, Dreval, A, Barbarash, O, Strongin, L, Dogadin, S, Suplotova, L, Izmozherova, N, Marasaev, V, Khokhlov, A, Repin, A, Turova, E, Bondar, I, Samoylova, Y, Sherenkov, A, Smolenskaya, O, Zrahevskiy, K, Koshelskaya, O, Obrezan, A, Dzupina, A, Stevlik, J, Buganova, I, Pella, D, Vinanska, D, Jascur, J, Micko, K, Sosovec, D, Philippiova, A, Olexa, P, Fedacko, J, Selecky, J, Nicolau, J, Mediavilla Garcia, J, Botella Serrano, M, Lecube, A, Arguelles, I, Sabán, J, Gómez Cerezo, F, Soto, A, Bellido, D, Sucunza Alfonso, N, Vendrell Ortega, J, Alvarez, L, Garcia Puig, J, Angustias Quesada, M, Contreras Gilbert, J, Almeida, Ca, Tinahones, Fj, Garcia Ortiz, L, Gómez Marcos MA, Aomar, I, Fernández Balsells, M, Distiller, L, Padayachee, T, Badat, A, Ebrahim, I, Naiker, P, Ranjith, N, Kelfkens, Y, Makan, H, Mogashoa, S, Fulat, M, Carim-Ganey, N, Coetzee, K, Govender, T, Nortje, H, Wilhase, A, Seedat, S, Gani, M, Ellis, G, Rheeder, P, Wing, J, Blignaut, S, Kaplan, H, Lottering, H, Pillai, P, Louw, C, Coetzer, T, Sheu, Whh, Chen, Jf, Yang, Cy, Tseng, St, Wang, Cy, Lai, Wt, Hung, Yj, Hsieh, Ic, Su, Sl, Pei, D, Benjasuratwong, Y, Purewal, T, Milward, A, Dimitropoulos, I, Kumar, S, Barber, T, Wiles, P, Dang, C, Adler, A, Philip, S, Bellary, S, Price, D, Oelbaum, R, Heller, S, Sathayapalan, T, Clark, J, Leese, G, Simpson, H, Kilvert, A, Dawson, A, Hall, T, Takhar, A, Bundy, C, Harvey, P, Maxwell, S, Asamoah-Owusu, Nj, Mcknight, J, Chatterjee, S, Calvert, J, Wright, A, Macrury, S, Macfarlane, D, Johnson, A, Litchfield, J, Field, B, Koval, O, Larin, O, Levchenko, O, Martynyuk, L, Maslyanko, V, Rudyk, I, Suprun, Y, Tseluyko, V, Botsyurko, V, Vatutin, M, Fushtey, I, Grishyna, O, Kuskalo, P, Panina, S, Pererva, L, Prysupa, L, Teliatnikova, Z, Sokolova, L, Vlasenko, M, Berenfus, V, Gyrina, O, Kopytsya, M, Vizir, V, Vayda, M, Shanik, M, Headapohl, D, Pahl, J, Aronoff, S, Bartkowiak, A Jr, Chang, A, Gaudiani, L, Kayne, D, Look, M, Patel, N, Moran, J, Stout, E, Tsao, J, Struble, R, Fishman, N, Rodbard, H, Lucas, K, Dugano-Daphnis, P, Merrick, B, Nadar, V, Severa, L, Sorli, C, Chang, M, Reed, J III, Grunberger, G, Bain, C, Bestermann, W Jr, Morawski, E, White, J, Azizad, M, Ukwade, P, Anekwe, A, Jimenez, A, Weiss, D, Green, S, Overcash, J, Eaton, C, Roseman, H, Soler, N, Mikell, F, Manos, P, Levinson, L, Claxton, E Jr, Weiss, R, Argoud, G, Bickel, L, Wilson, J, Short, B, Webster, B, Mcneill, R, Schnall, A, Force, R, Phillips, L, Bybee, K, Forker, A, Denham, D, Vonderhaar, T, Pullman, J, Kruger, D, Whitehouse, F, Wysham, C, Baron, M, Kravitz, A, Dushkin, H, Manning, Mb, Wine, A, Jaffrani, N, Chadha, C, Sperl-Hillen, J, Busch, R, Estevez, R, Robbins, D, Rassouli, N, Garvey, T, Oparil, S, Eckel, R, Mcdermott, M, Rasouli, N, Mcgill, J, Corder, C, Klonoff, D, Mills, R, Earl, J, Kessel, J, Cuddihy, R, Zimmerman, R, Dayamani, P, Oral, E, Zimering, M, Marks, J, Farnsworth, K, Sugimoto, D, Toth, P, Bhargava, A, Mcguire, D, Rohatgi, A, Davies, M, Peden, E, Wyne, K, Alfonso, L, Seyoum, B, Akpunonu, B, Feinglos, M, Reaven, P, Soule, J, Luttrell, L, Schactman, B, Canadas, R, Boggs, B, Abbott, L, Herring, C, Roberts, L, Hage-Korban, E, Schubart, U, Taylon, A, Tannenbaum, A, Kingsley, J, Lenhard, J, Biscoveanu, M, Cohen, J, Donovan, D, Laferrere, B, Thompson, N, Wade, T, Detweiler, R, Henson, B, White, A, Cavale, A, Ravi, C, Thomas, A, Goodman, H, Kalen, V, Fox, D, Dauber, I, Rizvi, S, Marcus, A, Mulford, M, Higgins, A, Chane, M, Bland, V, Osunkoya, A, Suresh, D, Khan, S, Anastasi, L, Bajaj, M, Eisen, H, Mudaliar, Sr, Powell, S, Carr, K, Tripathy, D, Azad, N, Wakefield, P, Acheatel, R, Bressler, P, Dean, J, El Shahawy, M, Gilbert, J, Haque, I, Humiston, D, Ison, R, Karounos, D, Lillestol, M, Ferrier, N, Labroo, A, Vo, A, D’Agostino, R, Dulin, M, Mcwilliams, A, Hargrove, J, Blumberg, E, Jackson, B, Staniloae, C, Salacata, A, Hidalgo, H Jr, Nicol, P, Digiovanna, M, Soufer, J, Mahabadi, V, Akinboboye, O, Arauz-Pacheco, C, Neutel, J, Dungan, K, Benson, M, Powell, T, Gandy, W, Rovner, S, Berk, M, Khan, A, Ledesma, G, Madu, I, Erickson, B, Radbill, M, Graves, M, Kaczmarek, G, Giep, S, Baldauf, C, Golden, G, Lesh, K, Davis, C, Godbole, N, Kirby, W, Razzaque, N, Bhatt, B, Wilson, M., Internal medicine, ACS - Diabetes & metabolism, and ACS - Microcirculation
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Male ,medicine.medical_specialty ,EXSCEL Study Group ,Injections, Subcutaneous ,030209 endocrinology & metabolism ,Type 2 diabetes ,Kaplan-Meier Estimate ,030204 cardiovascular system & hematology ,Placebo ,Article ,Drug Administration Schedule ,GLP1-agonists ,03 medical and health sciences ,0302 clinical medicine ,Double-Blind Method ,Interquartile range ,Internal medicine ,Diabetes mellitus ,General & Internal Medicine ,medicine ,Humans ,Hypoglycemic Agents ,Least-Squares Analysis ,Aged ,Glycated Hemoglobin ,business.industry ,Venoms ,Semaglutide ,Incidence ,Type 2 diabetes, GLP1-agonists, exenatide, cardiovascular effects ,General Medicine ,11 Medical And Health Sciences ,Middle Aged ,medicine.disease ,Surgery ,Albiglutide ,Editorial ,Diabetes Mellitus, Type 2 ,Cardiovascular Diseases ,Exenatide ,Dulaglutide ,Female ,business ,Peptides ,cardiovascular effects ,medicine.drug - Abstract
BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown. METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy. RESULTS: In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P
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- 2017
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11. A novel genomic signature reclassifies an oral cancer subtype
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Samman, M, Wood, HM, Conway, C, Stead, L, Daly, C, Chalkley, R, Berri, S, Senguven, B, Ross, L, Egan, P, Chengot, P, Ong, TK, Pentenero, M, Gandolfo, S, Cassenti, P, Al Ajlan, A, Samkari, A, Barrett, W, MacLennan, K, High, A, and Rabbitts, P
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stomatognathic diseases - Abstract
Verrucous carcinoma of the oral cavity (OVC) is considered a subtype of classical oral squamous cell carcinoma (OSCC). Diagnosis is problematic, and additional biomarkers are needed to better stratify patients. To investigate their molecular signature, we performed low coverage copy number sequencing on 57 OVC and exome and RNA sequencing on a subset of these and compared the data to the same OSCC parameters. Copy number results showed that OVC lacked any of the classical OSCC patterns such as gain of 3q and loss of 3p and demonstrated considerably fewer genomic rearrangements compared to the OSCC cohort. OVC and OSCC samples could be clearly differentiated. Exome sequencing showed that OVC samples lacked mutations in genes commonly associated with OSCC (TP53, NOTCH1, NOTCH2, CDKN2A and FAT1). RNA sequencing identified genes that were differentially expressed between the groups. In silico functional analysis showed that the mutated and differentially expressed genes in OVC samples were involved in cell adhesion and keratinocyte proliferation, while those in the OSCC cohort were enriched for cell death and apoptosis pathways. This is the largest and most detailed genomic and transcriptomic analysis yet performed on this tumour type, which, as an example of non-metastatic cancer, may shed light on the nature of metastases. These three independent investigations consistently show substantial differences between the cohorts. Taken together they lead to the conclusion that OVC is not a subtype of OSCC, but should be classified as a distinct entity.
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- 2015
12. The clonal relationships between pre-cancer and cancer revealed by ultra-deep sequencing
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Wood, HM, Conway, C, Daly, C, Chalkley, R, Berri, S, Senguven, B, Stead, L, Ross, L, Egan, P, Chengot, P, Graham, J, Sethi, N, Ong, TK, High, A, MacLennan, K, and Rabbitts, P
- Abstract
The study of the relationships between pre-cancer and cancer and identification of early driver mutations is becoming increasingly important as the value of molecular markers of early disease and personalised drug targets is recognized, especially now the extent of clonal heterogeneity in fully invasive disease is being realized. It has been assumed that pre-cancerous lesions exhibit a fairly passive progression to invasive disease; the degree to which they, too, are heterogeneous is unknown. We performed ultra-deep sequencing of thousands of selected mutations, together with copy number analysis, from multiple, matched pre-invasive lesions, primary tumours and metastases from five patients with oral cancer, some with multiple primary tumours presenting either synchronously or metachronously, totalling 75 samples. This allowed the clonal relationships between the samples to be observed for each patient. We expose for the first time the unexpected variety and complexity of the relationships between this group of oral dysplasias and their associated carcinomas and, ultimately, the diversity of processes by which tumours are initiated, spread and metastasize. Instead of a series of genomic precursors of their adjacent invasive disease, we have shown dysplasia to be a distinct dynamic entity, refuting the belief that pre-cancer and invasive tumours with a close spatial relationship always have linearly related genomes. We show that oral pre-cancer exhibits considerable subclonal heterogeneity in its own right, that mutational changes in pre-cancer do not predict the onset of invasion, and that the genomic pathway to invasion is neither unified nor predictable. Sequence data from this study have been deposited in the European Nucleotide Archive, Accession No. PRJEB6588. Copyright (c) 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
- Published
- 2015
13. First report of the global SYMPLICITY registry on the effect of renal artery denervation in patients with uncontrolled hypertension
- Author
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Böhm, M, Mahfoud, F, Ukena, C, Hoppe, U, Narkiewicz, K, Negoita, M, Ruilope, L, Schlaich, M, Schmieder, R, Whitbourn, R, Williams, B, Zeymer, U, Zirlik, A, Mancia, G, Aguirre, L, Ahn, T, Al Habib, K, Al Jarallah, M, Alimbaev, S, Ammerer, M, Andersson, B, Andersson, J, Andresen, D, Anné, W, Baumgartner, I, Bergmann, M, Berland, J, Bilger, J, Blumenstein, M, Brachmann, J, Branny, M, Brussee, H, Clifford, P, Cornelis, K, Cunnington, M, Cyrne de Carvalho, H, Dandona, S, Danilov, N, Dasgupta, I, Dong Ju, C, Dorsch, M, Drieghe, B, Ebrahim, I, Echeverri, D, Eckert, S, Fajadet, J, Fichtlscherer, S, Fleck, E, Frey, N, Gahnim, D, Galyavich, A, Giannattasio, C, Göing, O, Gomes, M, Goncalves, P, Grossman, E, Grund, M, Gutierrez, E, Gwon, H, Hausberg, M, Hoffmann, E, Ibrahim, R, Jardine, A, Jung, W, Jung, J, Katritsis, D, Kerschbaum, J, Kim, C, Kim, H, Konradi, A, Krasowski, W, Kuznetsov, V, Kwok, O, Kwon, H, Leong, G, Lotan, C, Lurz, P, Luscher, T, Mackinnon, M, Malik, F, Mangos, G, Martinez, C, Mccann, A, Misonis, N, Mölmann, H, Mordovin, V, Mortensen, K, Mueller, O, Muller, O, Münzel, T, Ntsekhe, M, Oliveira, E, Ong, T, Ong, P, Ormiston, J, Oswald, H, Park, S, Park, C, Plehn, A, Pressley, L, Reith, S, Reuter, H, Rosenschein, U, Rottbauer, W, Rump, L, Scheinert, D, Schillinger, S, M, Schultheiss, H, Sechtem, U, Seung, K, Sharif, F, Sharpe, A, Shetty, S, Sievert, H, Soo, J, Teik, L, Stefanadis, C, Stellbrink, C, Sticherling, C, Stoel, M, Strasser, R, Thambar, S, Tonino, P, Udayachalerm, W, Unterseeh, T, Vaclavik, J, von Scheidt, W, Voskuil, M, Wan Ahmad, W, Weber, T, Wedekind, H, Weil, J, Werner, N, Winkens, M, Winter, K, Witkowski, A, Wyffels, E, Yip, T, Zambahari, R, Zeller, T, Zürn, C, MANCIA, GIUSEPPE, Ahn, TH, Ebrahim, IO, GIANNATTASIO, CRISTINA, Gwon, HC, Kim, CJ, Kim, HS, Kwok, OH, Kwon, HM, MacKinnon, M, Malik, FT, McCann, A, Ong, TK, Park, SJ, Park, CG, Rump, LC, Schillinger, Schlaich, Schultheiss, HP, Seung, KB, Soo, JY, Teik, LS, Wan Ahmad, WA, Winter, KD, Zürn, C., Böhm, M, Mahfoud, F, Ukena, C, Hoppe, U, Narkiewicz, K, Negoita, M, Ruilope, L, Schlaich, M, Schmieder, R, Whitbourn, R, Williams, B, Zeymer, U, Zirlik, A, Mancia, G, Aguirre, L, Ahn, T, Al Habib, K, Al Jarallah, M, Alimbaev, S, Ammerer, M, Andersson, B, Andersson, J, Andresen, D, Anné, W, Baumgartner, I, Bergmann, M, Berland, J, Bilger, J, Blumenstein, M, Brachmann, J, Branny, M, Brussee, H, Clifford, P, Cornelis, K, Cunnington, M, Cyrne de Carvalho, H, Dandona, S, Danilov, N, Dasgupta, I, Dong Ju, C, Dorsch, M, Drieghe, B, Ebrahim, I, Echeverri, D, Eckert, S, Fajadet, J, Fichtlscherer, S, Fleck, E, Frey, N, Gahnim, D, Galyavich, A, Giannattasio, C, Göing, O, Gomes, M, Goncalves, P, Grossman, E, Grund, M, Gutierrez, E, Gwon, H, Hausberg, M, Hoffmann, E, Ibrahim, R, Jardine, A, Jung, W, Jung, J, Katritsis, D, Kerschbaum, J, Kim, C, Kim, H, Konradi, A, Krasowski, W, Kuznetsov, V, Kwok, O, Kwon, H, Leong, G, Lotan, C, Lurz, P, Luscher, T, Mackinnon, M, Malik, F, Mangos, G, Martinez, C, Mccann, A, Misonis, N, Mölmann, H, Mordovin, V, Mortensen, K, Mueller, O, Muller, O, Münzel, T, Ntsekhe, M, Oliveira, E, Ong, T, Ong, P, Ormiston, J, Oswald, H, Park, S, Park, C, Plehn, A, Pressley, L, Reith, S, Reuter, H, Rosenschein, U, Rottbauer, W, Rump, L, Scheinert, D, Schillinger, S, M, Schultheiss, H, Sechtem, U, Seung, K, Sharif, F, Sharpe, A, Shetty, S, Sievert, H, Soo, J, Teik, L, Stefanadis, C, Stellbrink, C, Sticherling, C, Stoel, M, Strasser, R, Thambar, S, Tonino, P, Udayachalerm, W, Unterseeh, T, Vaclavik, J, von Scheidt, W, Voskuil, M, Wan Ahmad, W, Weber, T, Wedekind, H, Weil, J, Werner, N, Winkens, M, Winter, K, Witkowski, A, Wyffels, E, Yip, T, Zambahari, R, Zeller, T, Zürn, C, MANCIA, GIUSEPPE, Ahn, TH, Ebrahim, IO, GIANNATTASIO, CRISTINA, Gwon, HC, Kim, CJ, Kim, HS, Kwok, OH, Kwon, HM, MacKinnon, M, Malik, FT, McCann, A, Ong, TK, Park, SJ, Park, CG, Rump, LC, Schillinger, Schlaich, Schultheiss, HP, Seung, KB, Soo, JY, Teik, LS, Wan Ahmad, WA, Winter, KD, and Zürn, C.
- Abstract
This study aimed to assess the safety and effectiveness of renal denervation using the Symplicity system in real-world patients with uncontrolled hypertension (NCT01534299). The Global SYMPLICITY Registry is a prospective, open-label, multicenter registry. Office and 24-hour ambulatory blood pressures (BPs) were measured. Change from baseline to 6 months was analyzed for all patients and for subgroups based on baseline office systolic BP, diabetic status, and renal function; a cohort with severe hypertension (office systolic pressure, ≥160 mm Hg; 24-hour systolic pressure, ≥135 mm Hg; and ≥3 antihypertensive medication classes) was also included. The analysis included protocol-defined safety events. Six-month outcomes for 998 patients, including 323 in the severe hypertension cohort, are reported. Mean baseline office systolic BP was 163.5±24.0 mm Hg for all patients and 179.3±16.5 mm Hg for the severe cohort; the corresponding baseline 24-hour mean systolic BPs were 151.5±17.0 and 159.0±15.6 mm Hg. At 6 months, the changes in office and 24-hour systolic BPs were -11.6±25.3 and -6.6±18.0 mm Hg for all patients (P<0.001 for both) and -20.3±22.8 and -8.9±16.9 mm Hg for those with severe hypertension (P<0.001 for both). Renal denervation was associated with low rates of adverse events. After the procedure through 6 months, there was 1 new renal artery stenosis >70% and 5 cases of hospitalization for a hypertensive emergency. In clinical practice, renal denervation resulted in significant reductions in office and 24-hour BPs with a favorable safety profile. Greater BP-lowering effects occurred in patients with higher baseline pressures. Clinical Trial Registration - URL: www.clinicaltrials.gov. Unique identifier: NCT01534299.
- Published
- 2015
14. Thrombin-receptor antagonist vorapaxar in acute coronary syndromes
- Author
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Tricoci, P, Huang, Z, Held, C, Moliterno, Dj, Armstrong, Pw, Van de Werf, F, White, Hd, Aylward, Pe, Wallentin, L, Chen, E, Lokhnygina, Y, Pei, J, Leonardi, S, Rorick, Tl, Kilian, Am, Jennings, Lh, Ambrosio, G, Bode, C, Cequier, A, Cornel, Jh, Diaz, R, Erkan, A, Huber, K, Hudson, Mp, Jiang, L, Jukema, Jw, Lewis, Bs, Lincoff, Am, Montalescot, G, Nicolau, Jc, Ogawa, H, Pfisterer, M, Prieto, Jc, Ruzyllo, W, Sinnaeve, Pr, Storey, Rf, Valgimigli, M, Whellan, Dj, Widimsky, P, Strony, J, Harrington, Ra, Mahaffey, Kw, Huo, Y, Lixin, J, Isaza, D, Grande, P, Laine, M, Wong, L, Ofner, P, Yamaguchi, T, Park, Sj, Nordrehaug, Je, Providencia, L, Cheem, Th, Dalby, A, Betriu, A, Chen, Mf, Verheugt, F, Frye, Rl, Hochman, J, Steg, Pg, Bailey, Kr, Easton, Jd, Lincoff, A, Underwood, Fd, Wrestler, J, Larson, D, Vandyne, B, Kilian, A, Harmelin-Kadouri, R, Layton, L, Lipka, L, Petrauskas, S, Qidwai, M, Sorochuck, C, Temple, T, Mason, D, Sydlowski, D, Gallagher, B, Villasin, A, Beernaert, A, Douglas, S, Garrett, J, Wiering, J, Adriaenssens, T, Ganame, J, Hulselmans, M, Katz, Jn, Kayaert, P, La Gerche, A, Onsea, K, Zalewski, J, Johnson, A, O'Briant, J, Smith, M, Akerblom, A, Armaganijan, L, Bertolami, A, Brennan, M, da Ponte Nacif SA, de Campos Gonzaga, C, Dequadros, A, Déry, Jp, Dev, S, Ducrocq, G, Eapen, Zp, Echenique, L, Eggers, K, Garcia, H, Guimaraes, Hp, Hagstrom, E, Hanet, C, James, S, Jonelid, B, Kolls, Bj, Leiria, T, Leite, R, Lombardi, C, Lopes, Rd, Malagutti, P, Mathews, R, Mehta, Rh, Melloni, C, Piccini, Jp, Rodriques Soares, P, Roe, Mt, Shah, Br, Stashenko, G, Szczech, La, Truffa, A, Varenhorst, C, Vranckx, P, Williams, J, Kilaru, R, White, Ja, Binkowitz, B, He, W, Ramos, Ms, Hasbani, E, Farras, Ha, Luz del Valle, L, Zapata, G, Centeno, Ep, Hominal, M, Beloscar, J, Panno, M, Berli, M, Carlevaro, O, Wasserman, T, Lembo, L, Diez, F, Bettinotti, M, Allall, O, Macin, S, Hii, C, Bett, N, Aroney, C, Roberts-Thomson, P, Arstall, M, Horowitz, J, Prasan, A, Farshid, A, Rankin, J, Duffy, S, Sinhal, A, Hendricks, R, Waites, J, Hill, A, French, J, Adams, M, Soward, A, Dick, R, Jepson, N, Nelson, G, Thompson, P, Neunteufl, T, Pachinger, O, Leisch, F, Siostrzonek, P, Roithinger, F, Pieske, B, Weber, H, Eber, B, Zenker, G, Sinnaeve, P, Roosen, J, Vervoort, G, Coussement, P, Striekwold, H, Boland, J, Van Dorpe, A, Dujardin, K, Mertens, D, Vanneste, L, Celen, H, Lesseliers, H, Vrolix, M, Leone, A, De Maeseneire, S, Hellemans, S, Silva, Fa, Franken, M, Moraes JB Jr, Mora, R, Michalaros, Y, Perin, M, Guimaraes, Ae, da Silva DG, Mattos, Ma, Alves AR Jr, Hernandes, Me, Golin, V, da Silva SA, Ardito, W, Dery, Jp, Mukherjee, A, Tanguay, Jf, Kornder, J, Lutchmedial, S, Degrace, M, Klinke, P, Constance, C, Nogareda, G, Wong, G, Macdonald, P, Senaratne, M, Rupka, D, Halperin, F, Ramanathan, K, Natarajan, M, Lai, C, Brossoit, R, Tymchak, W, Rose, B, Dupuis, R, Mansour, S, Bata, I, Zadra, R, Turek, M, Madan, M, Le May, M, Leon, L, Perez, L, Yovaniniz, P, Pedemonte, O, Campos, P, Pincetti, C, Sepulveda, P, Li, W, Zhao, R, Li, Z, Yang, Y, Chen, J, Li, H, Jiang, Y, Li, D, Qu, P, Sun, Y, Zheng, Y, Zhou, C, Zhang, F, Wei, M, Wang, D, Lemus, J, Fernandez, Rl, Jaramillo, C, Ochoa, J, Velez, S, Cano, N, Lutz, J, Botero, R, Jaramillo, M, Saaib, J, Sanchez, G, Hernandez, H, Mendoza, F, Rizcala, A, Urina, M, Polasek, R, Motovska, Z, Zemanek, D, Ostransky, J, Kettner, J, Spinar, J, Groch, L, Ramik, C, Stumar, J, Linhart, A, Pleva, L, Niedobova, E, Macha, J, Vojacek, J, Stipal, R, Galatius, S, Eggert, S, Mickley, H, Egstrup, K, Pedersen, O, Hvilsted, L, Sykulski, R, Skagen, K, Dodt, K, Klarlund, K, Husted, S, Jensen, G, Melchior, T, Sjoel, A, Steffensen, Fh, Airaksinen, Ke, Laukkanen, Ja, Syvanne, Ms, Kotila, Mj, Mikael, K, Naveri, Hk, Hekkala, Am, Mustonen, Jn, Halkosaari, M, Ohlmann, P, Khalife, K, Dibon, O, Hirsch, Jl, Furber, A, Nguyen-Khac, Jo, Delarche, N, Probst, V, Lim, P, Bayet, G, Dauphin, R, Levai, L, Galinier, M, Belhassane, A, Wiedemann, Jy, Fouche, R, Coisne, D, Henry, P, Schiele, F, Boueri, Z, Vaquette, B, Davy, Jm, Cottin, Y, D'Houdain, F, Danchin, N, Cassat, C, Messner, P, Elbaz, M, Coste, P, Zemour, G, Maupas, E, Feldman, L, Soto, Fx, Ferrari, E, Haltern, G, Heuer, H, Genth-Zotz, S, Loges, C, Stellbrink, C, Terres, W, Ferrar, M, Zeymer, U, Brachmann, J, Mudra, H, Vohringer, Hf, vom Dah, J, Kreuzer, J, Hill, S, Kleinertz, K, Kadel, C, Appel, Kf, Nienabe, C, Behrens, S, Frantz, S, Mehrhof, F, Krings, P, Hengstenberg, C, Lueders, S, Hanefel, C, Krulls-Munch, J, Dorse, T, Leschke, M, Nogai, K, Butter, C, Darius, H, Fichtlscherer, Hp, Schmitt, C, Kasisk, Hp, Dorr, M, Fran, N, Jereczek, M, Wiemer, M, Nickenig, G, Boudriot, E, Werner, G, Altila, T, Strasser, R, Baldus, S, Desaga, M, Buerke, M, Land, S, Schunkert, H, Schulze, Ho, Holmer, S, Sohn, Hy, Burkhardt, W, Lauer, B, Schwimmbeck, P, Schoeller, R, Lapp, H, Gross, M, Kindermann, I, Schuster, P, Yu, Cm, Lee, S, Merkely, B, Apro, D, Lupkovics, G, Edes, I, Ungi, I, Piroth, Z, Csapo, K, Dezsi, Ca, Herczeg, B, Sereg, M, Butnaru, A, Lewis, B, Rosenschein, U, Mosseri, M, Turgeman, Y, Pollak, A, Shotan, A, Hammerman, H, Rozenman, Y, Gottlieb, S, Atar, S, Weiss, A, Marmor, A, Iakobishvili, Z, Mascia, F, De Cesare, N, Piovaccari, G, Ceravolo, R, Fiscella, A, Salvioni, A, Silvestri, O, Moretti, L, Severi, S, Carmina, Mg, De Caterina, R, Fattore, L, Terrosu, P, Trimarco, B, Ardissino, D, Uguccioni, L, Auguadro, C, Gregorio, G, De Ferrari, G, Testa, R, Evola, R, De Servi, S, Sganzerla, P, Vassanelli, C, Brunelli, C, Scherillo, M, Tamburino, C, Limido, A, Luzza, F, Percoco, Gf, Sinagra, G, Volpe, M, Crea, F, Fedele, F, Rasetti, G, Cinelli, F, Merlini, P, Sisto, F, Biancoli, S, Fresco, C, Corrada, E, Casolo, G, Santini, M, D'Alessandro, B, Antoniucci, D, Tuccillo, B, Assennato, P, Puccioni, E, Pasquetto, G, Perna, Gp, Morgagni, G, Takizawa, K, Kato, K, Oshima, S, Yagi, M, Asai, T, Kamiya, H, Hirokami, M, Sakota, S, Sueyoshi, A, Shimomura, H, Hashimoto, T, Miyahara, M, Matsumura, T, Nakao, K, Kakuta, T, Nakamura, S, Nishi, Y, Kawajiri, K, Nagai, Y, Takahashi, A, Ikari, Y, Hara, K, Koga, T, Fujii, K, Tobaru, T, Tsunoda, R, Uchiyama, T, Hirayama, H, Fujimoto, K, Sakurai, S, Tanigawa, T, Ohno, M, Yamamoto, E, Ikuta, S, Kato, A, Kikuta, K, Takami, A, Chong, Wp, Ong, Tk, Yusof, A, Maskon, O, Kahar, A, Breedveld, Rw, Bendermacher, Pe, Hamer, Bj, Oude Ophuis AJ, Nierop, Pr, Westendorp, Ic, Beijerbacht, Hp, Herrman, Jp, van 't Hof AW, Troquay, Rp, van der Meer, P, Peters, Rh, van Rossum, P, Liem, A, Pieterse, Mg, van Eck JW, van der Zwaan, C, Pasupati, S, Elliott, J, Tisch, J, Hart, H, Luke, R, Scott, D, Ternouth, I, White, H, Hamer, A, Harding, S, Wilkins, G, O'Meeghan, T, Harrison, N, Nilsen, D, Thalamus, J, Aaberge, L, Brunvand, H, Lutterbey, G, Omland, Tm, Eritsland, J, Wiseth, R, Aase, O, Campos, C, Horna, M, Toce, L, Salazar, M, Przewlocki, T, Ponikowski, P, Kasprzak, J, Kopaczewski, J, Musial, W, Mazurek, W, Kawecka-Jaszcz, K, Pluta, W, Dobrzycki, S, Loboz-Grudzien, K, Lewczuk, J, Karwowski, D, Grajek, S, Dudek, D, Trusz-Gluza, M, Kornacewicz-Jach, Z, Gil, R, Ferreira, J, Gavina, C, Ferreira, R, Martins, D, Garcia-Rinaldi, R, Ufret, R, Vazquez-Tanus, J, Banchs, H, Wong, A, Tan, Hc, Guerra, M, Ebrahim, I, Roux, J, Blomerus, P, Saaiman, A, Corbett, C, Pillay, T, Freeman, V, Horak, A, Zambakides, C, Burgess, L, Yoon, Jh, Ahn, Th, Gwon, Hc, Seong, Iw, Kim, Hs, Jeong, Mh, Kim, Yd, Chae, Sc, Hernandez, Jm, Pique, M, Fernandez Portales, J, Paz, Ma, Lopez Palop, R, Iniguez, A, Diaz Fernandez, J, Alvarez, P, Sanz, E, Heras, M, Sala, J, Goicolea, J, Cruz Fernandez, J, Serra, A, Fernandez Ortiz, A, Calle, G, Barriales, V, Albarran, A, Curos, A, Molano Casimiro FJ, Suarez, Ma, Franco, Sn, Bayon, J, Suarez, J, Belchi, J, Moreu, J, San Martin, M, Melgares Moreno, R, Aguirre Salcedo, J, Gonzalez Juanatey JR, Martinez Romero, P, Galache Osuna JG, Albertsson, P, Diderholm, E, Lycksell, M, Rasmanis, G, Swahn, E, Cherfan, P, Christensen, K, Lundman, P, Larson, Le, Vasko, P, Pripp, Cm, Johansson, A, Moccetti, T, Corti, R, Pieper, M, Mach, F, Eberli, F, Jeger, R, Rickli, H, Vogt, P, Windecker, S, Wu, Cj, Kao, Hl, Charng, Mj, Chang, Kc, Chen, Zc, Tsa, Cd, Shyu, Kg, Lai, Wt, Hsieh, Ic, Hou, Jy, Yeh, Hi, Ueng, Kc, Yin, Wh, Timurkaynak, T, Yigit, Z, Yilmaz, M, Boyaci, A, Sahin, M, Goktekin, O, Bozkurt, E, Ercan, E, Yildirir, A, Muthusamy, R, Keeling, P, Levy, T, Zaman, A, Cohen, A, Gorog, D, Baumbach, A, Oldroyd, K, Kadr, H, Tait, G, Bellenger, N, Davis, G, Shakespeare, C, Senior, R, Bruce, D, Uren, N, Trouton, T, Ahsan, A, Hamed, A, Malik, I, Sarma, J, Millar-Craig, M, Robson, H, Kennon, S, Sprigings, D, Brodie, B, Kang, Gs, Thomas, G, Cheng, Sc, Espinoza, A, Kassas, S, Jafar, Z, Kumar, P, Izzo, M, Wiseman, A, Chandna, H, Felten, W, D'Urso, M, Gudipati, Cr, Coram, R, Gill, S, Bengtson, J, Chang, M, Raisinghani, A, Blankenship, J, Harbor, Wf, Kraft, P, Ashraf, R, Chambers, J, Albirini, A, Malik, A, Ziada, K, Slepian, M, Taussig, A, Vernon, H, Jetty, P, Islam, Ma, Canaday, D, Martin, T, Burchenal, Jj, Gencheff, N, Nygaard, T, Panchal, V, Merritt, R, Abrahams, L, Lambert, C, Reyes, P, Leimbach, W, Chhabra, A, Caputo, R, Imburgia, M, Erickson, B, Kleiman, N, Hunter, J, Dehning, M, Graham, B, Strain, J, White, Jk, Mcgarvey, J Jr, Henderson, D, Treasure, C 2nd, Mirro, M, Pancholy, S, Helmy, T, Westerhausen, D, Dib, N, Penny, W, Kim, H, Degregorio, M, Jay, D, Kmonicek, J, Berlowitz, M, Starling, M, Langevin, E, Nelson, R, Singer, A, Siachos, A, Gibson, G, Parrott, C, Held, J, Puleo, P, Wolford, T, Omar, B, Brilakis, E, Lewis, S, Heller, L, Brener, S, Addo, T, Lieberman, S, Eisenberg, D, Feldman, R, Waksman, R, Waltman, J, Schulman, S, Bounds, C, Voyce, S, Batchelor, W, Dobies, D, Pasnoori, V, Chandrashekhar, Y, Vetrovec, G, Azrin, M, Spriggs, D, Hirsch, C, Smucker, M, Chetcuti, S, Stella, R, Levite, H, Shoukfeh, M, Vidovich, M, Saucedo, J, Fintel, D, Low, R, Gellman, J, Ahsan, C, Unks, Dm, Tolleson, T, Ceccoli, H, Aggarwal, K, Bhaktaram, V, Olson, C, Decaro, M, Kaluski, E, Mehta, V, Puma, J, Singh, V, Fulmer, J, Lewis, D, Khadra, S, Staniloae, C, East, M, Sundram, Ps, Anderson, J, Wasserman, H, Guy, D, Brill, D, Kruse, K, Ebrahimi, R, Nguyen, T, Keating, F, Srivastava, R, Wassmer, P, Todd, J 3rd, Stein, M, Hamzeh, I, Laxson, D, Hodson, R, Puri, S, Vijayaraghavan, K, Gazmuri, R, Chu, A, Vijay, N, Rabinowitz, A, Block, T, Agarwal, H, Martin, J, Zetterlund, P, Fortuin, D, Macdonell, A 3rd, Zouzoulas, S, Chepuri, V, Schmalfuss, C, Karve, M, Aviles, R, Lieberman, E, Amlani, M, Murphy, S, Shapiro, T, Herzog, E, Ariani, K, Bhagwat, R, Hockstad, E, Kai, W, Saririan, M, Roth, R, Weiland, F, Atassi, K, Harjai, K, Muhlestein, J, Marsh, R, Shokooh, S, Nahhas, A, Labroo, A, Mayor, M, Koshy, S, Tariq, M, Rayos, G, Jones, S, Klugherz, B, Dewey, R, Rashid, Hu, Wohns, D, Feiring, A, Bowles, M, Rohrbeck, S, Monroe, Vs, De Gottlieb, A, Gumm, D, Brown, C 3rd, Chang, D, Kalaria, V, Minisi, A, Joumaa, M, Josephson, R, Kleczka, J, Silver, K, Coleman, P, Brachfeld, C, Saltiel, F, Reiner, J, Carell, E, Hanovich, G, Rosenberg, M, Das, G, Blick, D, and Universitat de Barcelona
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Male ,Pyridines ,medicine.medical_treatment ,Kaplan-Meier Estimate ,law.invention ,Lactones ,Randomized controlled trial ,law ,Thrombin receptor antagonist ,clopidogrel ,placebo ,thienopyridine derivative ,vorapaxar ,antithrombocytic agent ,lactone ,proteinase activated receptor 1 ,pyridine derivative ,Coronary Artery Bypass ,Vorapaxar ,Cardiovascular diseases [NCEBP 14] ,Drugs ,General Medicine ,Middle Aged ,Combined Modality Therapy ,Cardiovascular diseases ,Cardiovascular Diseases ,Cardiology ,Platelet aggregation inhibitor ,Drug Therapy, Combination ,Female ,Plaquetes sanguínies ,Intracranial Hemorrhages ,Major bleeding ,Medicaments ,medicine.drug ,medicine.medical_specialty ,Acute coronary syndrome ,Bypass cardiopulmonary ,Hemorrhage ,Pharmacotherapy ,Blood platelets ,Double-Blind Method ,Angioplasty ,Internal medicine ,medicine ,Humans ,Receptor, PAR-1 ,Acute Coronary Syndrome ,Aged ,business.industry ,Malalties cardiovasculars ,medicine.disease ,Surgery ,Bypass cardiopulmonar ,business ,Platelet Aggregation Inhibitors ,Follow-Up Studies - Abstract
Item does not contain fulltext BACKGROUND: Vorapaxar is a new oral protease-activated-receptor 1 (PAR-1) antagonist that inhibits thrombin-induced platelet activation. METHODS: In this multinational, double-blind, randomized trial, we compared vorapaxar with placebo in 12,944 patients who had acute coronary syndromes without ST-segment elevation. The primary end point was a composite of death from cardiovascular causes, myocardial infarction, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization. RESULTS: Follow-up in the trial was terminated early after a safety review. After a median follow-up of 502 days (interquartile range, 349 to 667), the primary end point occurred in 1031 of 6473 patients receiving vorapaxar versus 1102 of 6471 patients receiving placebo (Kaplan-Meier 2-year rate, 18.5% vs. 19.9%; hazard ratio, 0.92; 95% confidence interval [CI], 0.85 to 1.01; P=0.07). A composite of death from cardiovascular causes, myocardial infarction, or stroke occurred in 822 patients in the vorapaxar group versus 910 in the placebo group (14.7% and 16.4%, respectively; hazard ratio, 0.89; 95% CI, 0.81 to 0.98; P=0.02). Rates of moderate and severe bleeding were 7.2% in the vorapaxar group and 5.2% in the placebo group (hazard ratio, 1.35; 95% CI, 1.16 to 1.58; P
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- 2012
15. cost-analysis-on-ticagrelor-utilisation-in-the-treatment-of-patients-with-acute-coronary-syndrome-a-preliminary-study
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Fong, >AYY, primary, Anchah, >L, additional, and Ong, >TK, additional
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- 2015
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16. Using next-generation sequencing for high resolution multiplex analysis of copy number variation from nanogram quantities of DNA from formalin-fixed paraffin-embedded specimens.
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Wood, HM, Belvedere, O, Conway, C, Daly, C, Chalkley, R, Bickerdike, M, McKinley, C, Egan, P, Ross, L, Hayward, B, Morgan, J, Davidson, L, MacLennan, K, Ong, TK, Papagiannopoulos, K, Cook, I, Adams, DJ, Taylor, GR, Rabbitts, P, Wood, HM, Belvedere, O, Conway, C, Daly, C, Chalkley, R, Bickerdike, M, McKinley, C, Egan, P, Ross, L, Hayward, B, Morgan, J, Davidson, L, MacLennan, K, Ong, TK, Papagiannopoulos, K, Cook, I, Adams, DJ, Taylor, GR, and Rabbitts, P
- Abstract
The use of next-generation sequencing technologies to produce genomic copy number data has recently been described. Most approaches, however, reply on optimal starting DNA, and are therefore unsuitable for the analysis of formalin-fixed paraffin-embedded (FFPE) samples, which largely precludes the analysis of many tumour series. We have sought to challenge the limits of this technique with regards to quality and quantity of starting material and the depth of sequencing required. We confirm that the technique can be used to interrogate DNA from cell lines, fresh frozen material and FFPE samples to assess copy number variation. We show that as little as 5 ng of DNA is needed to generate a copy number karyogram, and follow this up with data from a series of FFPE biopsies and surgical samples. We have used various levels of sample multiplexing to demonstrate the adjustable resolution of the methodology, depending on the number of samples and available resources. We also demonstrate reproducibility by use of replicate samples and comparison with microarray-based comparative genomic hybridization (aCGH) and digital PCR. This technique can be valuable in both the analysis of routine diagnostic samples and in examining large repositories of fixed archival material.
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- 2010
17. Internal Fixation of Unstable Pelvic Ring Injuries via the Modified Stoppa Approach
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Ong, TK, primary, Khoo, EH, additional, and Osman, Z, additional
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- 2011
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18. Fixation of Comminuted Patellar Fracture with Combined Cerclage and Tension Band Wiring Technique
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Ong, TK, primary, Chee, EK, additional, Wong, CL, additional, and Thevarajan, K, additional
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- 2008
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19. Acquired factor VIII deficiency presenting as a floor of the mouth swelling.
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Al-Hilou, Ahmed, Reid, Johnny, Kelly, Richard, and Ong, TK
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- 2011
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20. Solvent abuse. An anaesthetic management problem
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Ong, TK, Rustage, KJ, Harrison, KM, and Brook, IM
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- 1988
21. Unique characteristics of Asians with hypertension: what is known and what can be done?
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Loo G, Puar T, Foo R, Ong TK, Wang TD, Nguyen QN, Chin CT, and Chin CWL
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- Humans, Prevalence, Blood Pressure, Risk Factors, Asia epidemiology, Obesity complications, Obesity epidemiology, Hyperaldosteronism complications, Hyperaldosteronism ethnology, Hyperaldosteronism epidemiology, Hypertension epidemiology, Hypertension physiopathology, Hypertension ethnology, Asian People
- Abstract
Hypertension remains the leading modifiable risk factor for cardiovascular disease worldwide. Over the past 30 years, the prevalence of hypertension has been increasing in East and Southeast Asia to a greater extent as compared with other Western countries. Asians with hypertension have unique characteristics. This can be attributed to increased impact of obesity on Asians with hypertension, excessive salt intake and increased salt sensitivity, loss of diurnal rhythm in blood pressure and primary aldosteronism. The impact of hypertension on cardiovascular (particularly strokes) and chronic kidney disease is greater in Asians. These unique characteristics underpinned by the diverse socioeconomic backgrounds pose its own challenges in the diagnosis and management of hypertension in Asia., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)
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- 2024
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22. A clinical audit on the diagnosis and management of infective endocarditis in a tertiary heart centre in Malaysia.
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Ho YH, Lim CT, Chua CZF, Chua HH, and Ong TK
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- Humans, Malaysia, Male, Female, Middle Aged, Retrospective Studies, Adult, Anti-Bacterial Agents therapeutic use, Echocardiography, Aged, Tertiary Care Centers, Clinical Audit, Endocarditis diagnosis, Endocarditis therapy
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Introduction: Infective endocarditis (IE) has a high mortality rate in developing countries including Malaysia. This clinical audit aims to identify the shortcomings in the diagnosis and management of IE patients in a local tertiary centre to implement changes for improvement., Materials and Methods: This retrospective audit had two cycles - the first includes all IE patients in Sarawak Heart Centre, Malaysia from January 2020 to December 2022 with different parameters (blood culture, echocardiogram, the appropriateness of antibiotics and surgery) assessed against Malaysian Clinical Practice Guideline (CPG); and reaudit from July 2023 to December 2023. Interventions before re-audit include presentation at different hospital levels and continuing medical education., Results: Fifty patients were recruited (37 in the first cycle, 13 in the second cycle). The median age was 48.5 years with male predominance. Valve prosthesis (12.0%) and rheumatic heart disease (10.0%) were the commonest predisposing factors. Native mitral (44.0%) and aortic valves (28.0%) were most commonly involved. Twenty-eight (56.0%) patients were culture-positive. In the first cycle, most parameters (culture technique 0.0%, vegetation measured 54.1%, empirical 5.4%, culture-guided 29.7% antibiotics therapy, indicated surgery 0.0%) did not achieve the expected standard except timeliness of echocardiograms and blood culture incubation period. After initial interventions, all parameters showed statistically significant improvement (culture technique p<0.001, echocardiography p<0.001, empirical p<0.001, culture-guided p=0.021, surgery p<0.001) during the re-audit., Conclusion: Compliance with clinical practice guidelines (CPG) on IE management was suboptimal during the first audit but improved after interventions. Hence, regular continuing medical education (CME) is essential, and a written hospital protocol may be useful. Regular audits alongside multidisciplinary teamwork are crucial efforts.
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- 2024
23. The clinical and geographical characteristics, health-seeking behaviours of ST-segment elevation myocardial infarction patients with their total ischaemic time and short-term cardiac mortality outcomes: a local geographical perspective from a developing country.
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Lim CT, Ho YH, Fong AYY, and Ong TK
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- Humans, Middle Aged, Female, Male, Malaysia, Aged, Time-to-Treatment, Adult, Developing Countries, Patient Acceptance of Health Care statistics & numerical data, Time Factors, ST Elevation Myocardial Infarction mortality, ST Elevation Myocardial Infarction therapy, Percutaneous Coronary Intervention mortality
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Introduction: Ischaemic heart disease including ST-segment elevation myocardial infarction (STEMI) is the leading cause of death among Malaysians. Total ischaemic time (TIT) which consists of patient delay and systemic delay is a strong predictor of cardiovascular outcome in STEMI. Primary percutaneous coronary intervention (PPCI) is superior to medical thrombolysis in improving STEMI patients' survival outcomes. Our study aims to provide an insight into the clinical and geographical characteristics of STEMI patients, their health-seeking behaviour, TIT, interventions received and short-term cardiac mortality outcomes in the effort to improve the existing coronary care service., Materials and Methods: This is a descriptive study looking into patients who were diagnosed with STEMI and presented to or were referred to Sarawak Heart Centre between 1st July 2022 and 31st December 2022., Results: A total of 183 patients were recruited and 33.3% were <50 years old. The majority were in a different division during symptom onset from where the local PPCI centre is located and some underwent one or two transits before arrival at the revascularisation centre. More presented outof- hour and they were more likely to present within the PPCI window. The median TIT for the study population was 3.3 hours. The short-term cardiac mortalities were 9.3% and only the Killip class was found to have a significant association. In this study, TIT was not significantly associated with short-term mortalities but those who died had a longer median TIT., Conclusion: A local STEMI network should be set up using the 'Hub-and-Spoke' model in a staged-wise approach to reduce TIT given that PPCI is now the gold standard of treatment alongside continuous effort in patient education.
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- 2024
24. Characteristics of patients admitted with heart failure: Insights from the first Malaysian Heart Failure Registry.
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Wan Ahmad WA, Abdul Ghapar AK, Zainal Abidin HA, Karthikesan D, Ross NT, S K Abdul Kader MA, Loch A, Mahendran K, Ramli AW, Ong TK, Mohd Amin NH, Lee CY, Che Hassan HH, Zainal Abidin SK, Liew HB, Ho WS, and Mohd Ghazi A
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- Humans, Male, Middle Aged, Aged, Female, Prospective Studies, Length of Stay, Registries, Hospitalization, Heart Failure therapy
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Aims: Heart failure (HF) is a growing health problem, yet there are limited data on patients with HF in Malaysia. The Malaysian Heart Failure (MY-HF) Registry aims to gain insights into the epidemiology, aetiology, management, and outcome of Malaysian patients with HF and identify areas for improvement within the national HF services., Methods and Results: The MY-HF Registry is a 3-year prospective, observational study comprising 2717 Malaysian patients admitted for acute HF. We report the description of baseline data at admission and outcomes of index hospitalization of these patients. The mean age was 60.2 ± 13.6 years, 66.8% were male, and 34.3% had de novo HF. Collectively, 55.7% of patients presented with New York Heart Association (NYHA) Class III or IV; ischaemic heart disease was the most frequent aetiology (63.2%). Most admissions (87.3%) occurred via the emergency department, with 13.7% of patients requiring intensive care, and of these, 21.8% needed intubation. The proportion of patients receiving guideline-directed medical therapy increased at discharge (84.2% vs. 93.6%). The median length of stay (LOS) was 5 days, and in-hospital mortality was 2.9%. Predictors of LOS and/or in-hospital mortality were age, NYHA class, estimated glomerular filtration rate, and comorbid anaemia. LOS and in-hospital mortality were similar regardless of ejection fraction., Conclusions: The MY-HF Registry showed that the HF population in Malaysia is younger, predominantly male, and ischaemic-driven and has good prospects with hospitalization for optimization of treatment. These findings suggest a need to reassess current clinical practice and guide resource allocation to improve patient outcomes., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)
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- 2024
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25. A Comparison of 2 Paclitaxel-Coated Balloon Systems in Treatment of De Novo Coronary Artery Lesions.
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Fong AYY, Said A, Oon YY, Koh KT, Ho KH, Shu FEP, Tan CT, Bhavnani CD, Lee SWH, Liu KT, Cham YL, and Ong TK
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Background: In percutaneous coronary intervention (PCI) of de novo lesions, drug-coated balloons (DCB) have been shown to be a promising strategy to improve clinical outcomes of patients with small vessel disease. Evidence of this strategy in PCI of de novo coronary lesions in a real-world setting is limited. The objective of this study was to compare the 12-month outcomes of 2 paclitaxel-coated balloon systems for the treatment of all de novo coronary artery lesions., Methods: All patients who were treated for de novo coronary artery stenosis with either SeQuent Please or In.Pact Falcon DCB at a single center from January 2014 to December 2018 were included. The primary end point was the composite of cardiac death, nonfatal myocardial infarction, and target vessel revascularization (3-point major adverse cardiovascular events) at 12 months., Results: A total of 496 patients with 623 lesions, of which 144 were treated with SeQuent Please and 352 were treated with In.Pact Falcon were included in the study. Baseline patient, lesion and procedural characteristics at baseline were similar between groups. At 12-month follow-up, 3-point major adverse cardiovascular event outcomes were similar (4.2% vs 2.3% respectively; P = .272). Deaths due to cardiovascular events were few and similar between groups (2.7% vs 1.1% respectively; P = .20)., Conclusions: Both paclitaxel DCB systems have similar efficacy and safety outcomes, suggesting that both may be an appropriate treatment choice for patients with de novo lesions. However, a larger randomized controlled study is needed to confirm these findings., (© 2024 The Author(s).)
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- 2024
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26. Everolimus-Eluting Stents or Bypass Surgery for Multivessel Disease in Diabetics: The BEST Extended Follow-Up Study.
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Kim H, Kang DY, Ahn JM, Lee J, Choi Y, Hur SH, Park HJ, Tresukosol D, Kang WC, Kwon HM, Rha SW, Lim DS, Jeong MH, Lee BK, Huang H, Lim YH, Bae JH, Kim BO, Ong TK, Ahn SG, Chung CH, Park DW, and Park SJ
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- Humans, Follow-Up Studies, Everolimus adverse effects, Treatment Outcome, Stents, Coronary Artery Disease diagnostic imaging, Coronary Artery Disease surgery, Drug-Eluting Stents adverse effects, Percutaneous Coronary Intervention adverse effects, Myocardial Infarction etiology, Diabetes Mellitus diagnosis
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Background: Diabetes mellitus is associated with more complex coronary artery diseases. Coronary artery bypass grafting (CABG) is a preferred revascularization strategy over percutaneous coronary intervention (PCI) in diabetics with multivessel coronary artery disease (MVD)., Objectives: This study sought to examine the different prognostic effects of revascularization strategies according to the diabetes status from the randomized BEST (Randomized Comparison of Coronary Artery Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients With Multivessel Coronary Artery Disease) trial., Methods: Patients (n = 880) with MVD were randomly assigned to undergo PCI with an everolimus-eluting stent vs CABG stratified by diabetics (n = 363) and nondiabetics (n = 517). The primary endpoint was the composite of death, myocardial infarction, or target vessel revascularization during a median follow-up of 11.8 years (IQR: 10.6-12.5 years)., Results: In diabetics, the primary endpoint rate was significantly higher in the PCI group than in the CABG group (43% and 32%; HR: 1.53; 95% CI: 1.12-2.08; P = 0.008). However, in nondiabetics, no significant difference was found between the groups (PCI group, 29%; CABG group, 29%; HR: 0.97; 95% CI: 0.67-1.39; P = 0.86; P
interaction = 0.009). Irrespective of the presence of diabetes, no significant between-group differences were found in the rate of a safety composite of death, myocardial infarction, or stroke and mortality rate. However, the rate of any repeat revascularization was significantly higher in the PCI group than in the CABG group., Conclusions: In diabetics with MVD, CABG was associated with better clinical outcomes than PCI. However, the mortality rate was similar between PCI and CABG irrespective of diabetes status during an extended follow-up. (Ten-Year Outcomes of Randomized Comparison of Coronary Artery Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients With Multivessel Coronary Artery Disease [BEST Extended], NCT05125367; Randomized Comparison of Coronary Artery Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients With Multivessel Coronary Artery Disease [BEST], NCT00997828)., Competing Interests: Funding Support and Author Disclosures This research was supported by a grant from the Korea Health Technology R and D Project through the Korea Health Industry Development Institute funded by the Ministry of Health and Welfare, Republic of Korea (grant number HC19C0022). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)- Published
- 2023
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27. Pseudo-infarction electrocardiographic changes in delayed onset hypoparathyroidism: A case report.
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Chow HB, Lim CT, Ho YH, Cham YL, Fong AYY, Said A, and Ong TK
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Key Clinical Message: The high-risk "Shark Fin" electrocardiogram (ECG) pattern has been associated with transmural ischemia but can also result from electrolyte anomalies. Therefore, the decision for invasive coronary catheterization requires a detailed history and dedicated biochemical tests., Abstract: Pseudo-infarction ECG pattern resembling "Shark Fin" was demonstrated in a 76-year-old lady with a previous total thyroidectomy who presented with unspecific symptoms. An incidental finding of hypokalemia and hypocalcemia was thought to be related to delayed onset hypoparathyroidism. Potential etiologies like coronary vasospasm and catecholamine-associated myocardial injury were suggested., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2023 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)
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- 2023
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28. Are Two- and Three-Dimensional Computed Tomographic Scan Measurements of Tibial Tubercle-Trochlear Groove Distance Equivalent? A Comparative Study.
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Teo SH, Ong TK, Merican AM, Hashim MS, Ng WM, Al-Fayyadh MZM, and Ali MRM
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Background: Accurate planning for patellar instability correction is important in obtaining good post-operative outcome. The main challenge in the current two-dimensional (2-D) computed tomographic (CT) scans method is the difficulty in choosing reliable bony landmarks. This study aimed to compare the reliabilities between the 2-D and three-dimensional (3-D) methods of measuring tibial tubercle-trochlear groove (TT-TG) distance. We hypothesize that the proposed 3-D method will result in measurements with narrower error margin, providing higher reliability and accuracy., Materials and Methods: We traced CT scans of 106 knees with no patellofemoral pathology from 59 subjects from the database system and converted all 2-D images into 3-D models to determine the values for each parameter. We compared the intra- and interobserver reliability of each method using intraclass correlation (ICC) and Bland-Altman method., Results: The values of TT-TG measured by 2-D and 3-D methods were 16.1 ± 4.6 mm and 16.2 ± 4.2 mm, respectively. The ICC values of both methods were comparable (95% limits of agreement between the same observer: - 3.3 to 3.8 mm versus - 2.4 to 2.7 mm and different observers: - 4.3 to 4.9 mm versus - 3.9 to 2.7 mm), with 3-D method results in narrower limits of agreement., Conclusion: TT-TG measurement is reliable using the 2-D method without using advanced radiographic software. The 3-D method of measuring TT-TG provides measurement with narrower variation when compared with the 2-D method. However, both TT-TG distances' measurement methods in the current study were comparable as the variations are not significant., Competing Interests: Conflict of InterestAll authors declare that there are no conflicting interests., (© Indian Orthopaedics Association 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)
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- 2023
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29. FACTORS INFLUENCING THE TREATMENT OUTCOME OF INTENTIONAL REPLANTATION ON TEETH WITH PERIAPICAL PERIODONTITIS: A SYSTEMATIC REVIEW AND META-ANALYSIS.
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Ong TK, Lim D, Singh M, and Fial AV
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- Humans, Prospective Studies, Retrospective Studies, Treatment Outcome, Periapical Periodontitis surgery
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Objectives: The purpose of this review was to appraise the quality of evidence of the existing publications on IR, and to perform a meta-analysis on the treatment outcomes of IR., Methods: The specific PIO questions were as follows: Population: Patients with periapical periodontitis either before or after non-surgical endodontic therapy., Intervention: IR performed with retrograde preparation and retrograde filling., Outcomes: the healing, treatment complications, and the factors influencing these outcomes after IR. Electronic and hand searches were performed in the Web of Science, PubMed, CINAHL, and Cochrane Library databases. Two authors independently screened the titles and abstracts for eligibility. The risk of bias was performed using the NIH Quality Assessment Tool, and each study was rated as "Good", "Fair" or "Poor". The analyses were performed on the treatment outcome (healing and complications), and the factors influencing the outcome of the procedure., Results: Fourteen articles were included in the qualitative and quantitative syntheses. One was a prospective cohort study, and the other 13 were retrospective cohort studies. Overall, the evidence of this review was of poor-to-fair quality. The pooled healing rate was 80.2%, and there was a 21.7% of complication rate. Longer follow-up period, the presence of perio-endo disease, the use of non-bioceramic material as retrograde filling, longer extraoral time, and maxillary molar were found to be associated with lower healing rates. However, the differences between the subgroups were not statistically significant., Conclusions: The present review showed IR yielded a good overall healing rate with a low complication rate. Taking the quality of evidence into account, more high-quality studies are required to evaluate the validity of the factors that may influence the treatment outcome of IR., (Copyright © 2022 Elsevier Inc. All rights reserved.)
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- 2022
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30. Cardiovascular Risk Reduction After Renal Denervation According to Time in Therapeutic Systolic Blood Pressure Range.
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Mahfoud F, Mancia G, Schmieder RE, Ruilope L, Narkiewicz K, Schlaich M, Williams B, Ribichini F, Weil J, Kao HL, Rodriguez-Leor O, Noory E, Ong TK, Unterseeh T, de Araújo Gonçalves P, Zirlik A, Almerri K, Sharif F, Lauder L, Wanten M, Fahy M, and Böhm M
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- Humans, Female, Middle Aged, Aged, Male, Blood Pressure physiology, Treatment Outcome, Prospective Studies, Risk Factors, Kidney surgery, Blood Pressure Monitoring, Ambulatory, Antihypertensive Agents therapeutic use, Heart Disease Risk Factors, Denervation, Sympathectomy methods, Cardiovascular Diseases epidemiology, Cardiovascular Diseases drug therapy, Hypertension epidemiology, Hypertension surgery, Hypertension drug therapy
- Abstract
Background: Renal denervation (RDN) has been shown to lower blood pressure (BP), but its effects on cardiovascular events have only been preliminarily evaluated. Time in therapeutic range (TTR) of BP is associated with cardiovascular events., Objectives: This study sought to assess the impact of catheter-based RDN on TTR and its association with cardiovascular outcomes in the GSR (Global SYMPLICITY Registry)., Methods: Patients with uncontrolled hypertension were enrolled and treated with radiofrequency RDN. Office and ambulatory systolic blood pressure (OSBP and ASBP) were measured at 3, 6, 12, 24, and 36 months postprocedure and used to derive TTR. TTR through 6 months was assessed as a predictor of cardiovascular events from 6 to 36 months using a Cox proportional hazard regression model., Results: As of March 1, 2022, 3,077 patients were enrolled: 42.2% were female; mean age was 60.5 ± 12.2 years; baseline OSBP was 165.6 ± 24.8 mm Hg; and baseline ASBP was 154.3 ± 18.7 mm Hg. Patients were prescribed 4.9 ± 1.7 antihypertensive medications at baseline and 4.8 ± 1.9 at 36 months. At 36 months, mean changes were -16.7 ± 28.4 and -9.0 ± 20.2 mm Hg for OSBP and ASBP, respectively. TTR through 6 months was 30.6%. A 10% increase in TTR after RDN through 6 months was associated with significant risk reductions from 6 to 36 months of 15% for major adverse cardiovascular events (P < 0.001), 11% cardiovascular death (P = 0.010), 15% myocardial infarction (P = 0.023), and 23% stroke (P < 0.001)., Conclusions: There were sustained BP reductions and higher TTR through 36 months after RDN. A 10% increase in TTR through 6 months was associated with significant risk reductions in major cardiovascular events from 6 to 36 months. (Global SYMPLICITY Registry [GSR] DEFINE; NCT01534299)., Competing Interests: Funding Support and Author Disclosures This study was funded by Medtronic. Prof Mahfoud has received support from the Deutsche Gesellschaft für Kardiologie, Deutsche Forschungsgemeinschaft (SFB TRR219), and Deutsche Herzstiftung; and has received scientific support and/or speaker honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Medtronic and ReCor Medical. Prof Mancia has received speaker fees from Servier, Sanofi, Medtronic, Menarini, Merck, and Recordati. Prof Schmieder has received speaker and consulting honoraria from Medtronic, ReCor Medical , and Ablative Solutions; and has received research grants given to his institution from Medtronic, ReCor Medical, and Ablative Solutions. Prof Narkiewicz has received speaker and consulting honoraria from Berlin-Chemie/Menarini, Egis, Idorsia, Gedeon Richter, Krka, Medtronic, Novo Nordisk, Polpharma, Recordati, Sandoz, and Servier. Prof Schlaich has received support from a National Health and Medical Research Council Senior Research Fellowship; and has received consulting fees and/or travel and research support from Medtronic, Abbott, Novartis, Servier, Pfizer, and Boehringer Ingelheim. Dr Ribichini has received consulting fees and research support from Abbott Vascular, Boston Scientific, Edwards Lifesciences, Medtronic, and Volcano-Philips. Dr Weil has received support from Medtronic, ReCor Medical, Novartis, and AstraZeneca. Dr Kao has received honoraria from Asahi INTECC, Terumo, MicroPort, and Abbott; has received research grants from Medtronic, Elixir, and Abiomed; and is a member of Medtronic International Advisory Board. Dr Rodriguez-Leor has received speaker fees from Medtronic. Dr Noory has received speaker fees from Medtronic. Dr Ong has received speaker and consultant fees from Medtronic; and his institution received educational grants from Medtronic. Dr Zirlik has received consulting fees and/or research support from Medtronic, Abbott, Edwards, Abiomed, Cardiac Dimensions, Novartis, AstraZeneca, Astellas, Sanofi, Boehringer Ingelheim, Pfizer, Janssen Cilag, Novo Nordisk, Amgen, Bristol Myers Squibb, and Daichi-Sankyo. Dr Almerri is a member of the Advisory Committee in the Gulf Cooperation Council; and has received speaker and proctor honoraria from Medtronic. Dr Sharif has received speaker and consulting fees and research support from Medtronic. Dr Lauder has received speaker honoraria from Medtronic and ReCor Medical. Ms Wanten is an employee of Medtronic. Mr Fahy is an employee of Medtronic. Prof Böhm has received support from the Deutsche Forschungsgemeinschaft (German Research Foundation; TTR 219, project number 322900939); and has received personal fees from Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Medtronic, Novartis, ReCor Medical, Servier, and Vifor during the conduct of the study. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2022
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31. Improve the Prevention of Sudden Cardiac Arrest in Patients With Post-Acute Myocardial Infarction.
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Zhang S, Chen WJ, Sankardas MA, Ahmed WH, Liew HB, Gwon HC, Nesa Malik FT, Tang B, Haggui A, Oh IY, Ong TK, Cheng CI, Liu X, Seth A, Choi YJ, Qamar N, Rungpradubvong V, Wang CC, Jeon J, Wong G, Lemme F, Van Dorn B, Lexcen D, and Huang D
- Abstract
Background: Implantable cardioverter-defibrillator (ICD) implantation to prevent sudden cardiac death (SCD) in post-myocardial infarction (MI) patients varies by geography but remains low in many regions despite guideline recommendations., Objectives: This study aimed to characterize the care pathway of post-MI patients and understand barriers to referral for further SCD risk stratification and management in patients meeting referral criteria., Methods: This prospective, nonrandomized, multi-nation study included patients ≥18 years of age, with an acute MI ≤30 days and left ventricular ejection fraction <50% ≤14 days post-MI. The primary endpoint was defined as the physician's decision to refer a patient for SCD stratification and management., Results: In total, 1,491 post-MI patients were enrolled (60.2 ± 12.0 years of age, 82.4% male). During the study, 26.7% (n = 398) of patients met criteria for further SCD risk stratification; however, only 59.3% of those meeting criteria (n = 236; 95% CI: 54.4%-64.0%) were referred for a visit. Of patients referred for SCD risk stratification and management, 94.9% (n = 224) attended the visit of which 56.7% (n =127; 95% CI: 50.1%-63.0%) met ICD indication criteria. Of patients who met ICD indication criteria, 14.2% (n = 18) were implanted., Conclusions: We found that ∼40% of patients meeting criteria were not referred for further SCD risk stratification and management and ∼85% of patients who met ICD indications did not receive a guideline-directed ICD. Physician and patient reasons for refusing referral to SCD risk stratification and management or ICD implant varied by geography suggesting that improvement will require both physician- and patient-focused approaches. (Improve Sudden Cardiac Arrest [SCA] Bridge Study; NCT03715790)., Competing Interests: This study was funded by Medtronic Inc. Dr Zhang has received speaker fees/consulting fees from Boston Scientific, Medtronic, Abbott, and Biotronik; and has received steering committee fees from Medtronic. Dr Chen has received honorariums from Medtronic, Biotronik, Abbott, and Boston Scientific. Dr Liew has received speaker fees and honorarium from Medtronic and Boston Scientific. Dr Haggui has received honorariums from Medtronic, Abbott, and Boston Scientific. Dr Ong has received speaker/consultant fees from Boston Scientific, Medtronic, Abbott Vascular, Biotronic, OrbusNeich, Alvimedica, B Braun, Novartis, AstraZeneca, Bayer, and Boehringer Ingelheim. Dr Rungpradubvong has received honoraria from Medtronic, Abbott, Boston Scientific, Biotronik, Johnson & Johnson, Pfizer, Daiichi Sankyo, Boehringer Ingelheim, and Bayer. Dr Wang has received honorariums from Medtronic, Abbott, and Biotronik. JinKyung Jeon, Grace Wong, Dr Lemme, Brian Van Dorn, and Dr Lexcen are employees of Medtronic Inc. Dr Huang has received speaker fees/consulting fees from Boston Scientific, Bayer, Boehringer-Ingelheim, and Abbott. All other authors have reported that there are no relationships relevant to the contents of this paper to disclose., (© 2022 The Authors.)
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- 2022
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32. Combined Analysis of Two Parallel Randomized Trials of Sirolimus-Coated and Paclitaxel-Coated Balloons in Coronary In-Stent Restenosis Lesions.
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Scheller B, Mangner N, Abdul Kader MASK, Wan Ahmad WA, Jeger R, Wöhrle J, Ong TK, Liew HB, Gori T, Mahfoud F, Nuruddin AA, Woitek F, Abidin IZ, Schwenke C, Schnorr B, and Mohd Ali R
- Subjects
- Constriction, Pathologic chemically induced, Humans, Paclitaxel adverse effects, Randomized Controlled Trials as Topic, Sirolimus adverse effects, Stents, Treatment Outcome, Angioplasty, Balloon, Coronary adverse effects, Coronary Restenosis diagnostic imaging, Coronary Restenosis etiology, Coronary Restenosis therapy, Drug-Eluting Stents, Polychlorinated Biphenyls
- Abstract
Background: Paclitaxel-coated balloons (PCBs) are a preferred treatment option for coronary in-stent restenosis. To date, data from randomized trials of alternative drug coatings are lacking. The aim of the randomized Malaysian and German-Swiss randomized trials was to investigate a novel sirolimus-coated balloon (SCB) compared with a PCB in in-stent restenosis., Methods: One hundred one patients with drug-eluting stent in-stent restenosis were enrolled in 2 identical randomized trials comparing the novel SCB (SeQuent SCB, 4 μg/mm²) with the clinically proven PCB (SeQuent Please, 3 μg/mm²). Primary end point was angiographic late lumen loss at 6 months. Secondary end points included procedural success, major adverse cardiac events, and individual clinical end points such as stent thrombosis, cardiac death, target lesion myocardial infarction, clinically driven target lesion revascularization, and binary restenosis., Results: Quantitative coronary angiography revealed no differences in baseline parameters. After 6 months, in-segment late lumen loss was 0.25±0.57 mm in the PCB group versus 0.26±0.60 mm in the SCB group. Mean difference between SCB and PCB was 0.01 (95% CI, -0.23 to 0.24). Noninferiority at a predefined margin of 0.35 was shown. Clinical events up to 12 months did not differ between the groups., Conclusions: This first-in man comparison of a novel SCB with a crystalline coating showed similar angiographic and clinical outcomes in the treatment of coronary drug-eluting stent in-stent restenosis compared with PCB., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT02996318, NCT03242096.
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- 2022
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33. 2022 Malaysian Working Group Consensus Statement on Renal Denervation for management of arterial hypertension.
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Chia YC, Wan Ahmad WA, Fong AYY, Rosman A, Abdul Rahman AR, Choo GH, Lim SK, Abu Bakar MZ, and Ong TK
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- Blood Pressure, Denervation methods, Humans, Kidney, Sympathectomy methods, Treatment Outcome, Antihypertensive Agents pharmacology, Antihypertensive Agents therapeutic use, Hypertension drug therapy, Hypertension surgery
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Hypertension is highly prevalent and a major contributor to cardiovascular mortality and morbidity. In spite of the availability of efficacious, safe and affordable anti-hypertensive drugs, hypertension remains poorly controlled in the majority of hypertensive patients. Various reasons including non-adherence to the anti-hypertensive drugs, account for the poor control. Resistant hypertension is also one of the reasons for poor control of blood pressure (BP). The sympathetic nervous system (SNS) has long been recognized as one of the determinants in the pathophysiology of a raised BP. Overactivity of the SNS is a contributor to sustained arterial hypertension. Renal denervation (RDN) is increasingly recognized as a safe and effective adjunctive therapy to control BP with or without pharmacotherapy. Hence for patients who remain uncontrolled despite all efforts, renal denervation (RDN) is a novel treatment that can potentially improve BP control, hence reducing the major adverse cardiovascular events (MACE). More recent randomized, sham control trials of RDN have shown that RDN produces a sustained lowering of BP. To date, this lowering of BP through RDN is maintained for at least 3 years. Furthermore, this procedure has been found to be safe. Hence this consensus summarises the science behind RDN and the available clinical data to support the use of this therapy. It is hoped that this consensus will offer guidance on the importance of identifying patients who will benefit most from this therapy. A multidisciplinary team approach in the management of the patient undergoing RDN is recommended., (© 2022. The Author(s).)
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- 2022
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34. Treatment of Coronary De Novo Lesions by a Sirolimus- or Paclitaxel-Coated Balloon.
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Ahmad WAW, Nuruddin AA, Abdul Kader MASK, Ong TK, Liew HB, Ali RM, Mahmood Zuhdi AS, Ismail MD, Yusof AKM, Schwenke C, Kutschera M, and Scheller B
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- Coronary Angiography, Humans, Paclitaxel adverse effects, Prospective Studies, Sirolimus adverse effects, Treatment Outcome, Angioplasty, Balloon, Coronary adverse effects, Cardiovascular Agents adverse effects, Coronary Artery Disease diagnostic imaging, Coronary Artery Disease therapy, Coronary Restenosis diagnostic imaging, Coronary Restenosis etiology
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Objectives: The aim of this randomized controlled trial was to investigate a novel sirolimus-coated balloon (SCB) compared with the best investigated paclitaxel-coated balloon (PCB)., Background: There is increasing clinical evidence for the treatment of coronary de novo disease using drug-coated balloons. However, it is unclear whether paclitaxel remains the drug of choice or if sirolimus is an alternative, in analogy to drug-eluting stents., Methods: Seventy patients with coronary de novo lesions were enrolled in a randomized, multicenter trial to compare a novel SCB (SeQuent SCB, B. Braun Melsungen; 4 μg/mm
2 ) with a PCB (SeQuent Please, B. Braun Melsungen; 3 μg/mm2 ). The primary endpoint was angiographic late lumen loss (LLL) at 6 months. Secondary endpoints included major adverse cardiovascular events and individual clinical endpoints such as cardiac death, target lesion myocardial infarction, clinically driven target lesion revascularization, and binary restenosis., Results: Quantitative coronary angiography revealed no differences in baseline parameters. After 6 months, in-segment LLL was 0.01 ± 0.33 mm in the PCB group versus 0.10 ± 0.32 mm in the SCB group. The mean difference between SCB and PCB was 0.08 (95% CI: -0.07 to 0.24). Noninferiority at a predefined margin of 0.35 was shown. However, negative LLL was more frequent in the PCB group (60% of lesions vs 32% in the SCB group; P = 0.019). Major adverse cardiovascular events up to 12 months also did not differ between the groups., Conclusions: This first-in-human comparison of a novel SCB with a crystalline coating showed similar angiographic outcomes in the treatment of coronary de novo disease compared with a clinically proven PCB. However, late luminal enlargement was more frequently observed after PCB treatment. (Treatment of Coronary De-Novo Stenosis by a Sirolimus Coated Balloon or a Paclitaxel Coated Balloon Catheter Malaysia [SCBDNMAL]; NCT04017364)., Competing Interests: Funding Support and Author Disclosures Dr Scheller is a shareholder in InnoRa. Dr Schwenke is consultant to InnoRa on a honorary basis. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)- Published
- 2022
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35. Evaluation of β-blocker Dose Optimisation Among Patients Attending Heart Failure Clinic at Sarawak Heart Centre, Malaysia.
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Wong YC, Ong TK, and Cham YL
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- 2021
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36. Improving quality of life through the routine use of the patient concerns inventory for head and neck cancer patients: main results of a cluster preference randomised controlled trial.
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Rogers SN, Allmark C, Bekiroglu F, Edwards RT, Fabbroni G, Flavel R, Highet V, Ho MWS, Humphris GM, Jones TM, Khattak O, Lancaster J, Loh C, Lowe D, Lowies C, Macareavy D, Moor J, Ong TK, Prasai A, Roland N, Semple C, Spencer LH, Tandon S, Thomas SJ, Schache A, Shaw RJ, and Kanatas A
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- Emotions, Humans, Referral and Consultation, Surveys and Questionnaires, Head and Neck Neoplasms therapy, Quality of Life
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Purpose: The patient concerns inventory (PCI) is a prompt list allowing head and neck cancer (HNC) patients to discuss issues that otherwise might be overlooked. This trial evaluated the effectiveness of using the PCI at routine outpatient clinics for one year after treatment on health-related QOL (HRQOL)., Methods: A pragmatic cluster preference randomised control trial with 15 consultants, 8 'using' and 7 'not using' the PCI intervention. Patients treated with curative intent (all sites, disease stages, treatments) were eligible., Results: Consultants saw a median (inter-quartile range) 16 (13-26) patients, with 140 PCI and 148 control patients. Of the pre-specified outcomes, the 12-month results for the mean University of Washington Quality of Life (UW-QOLv4) social-emotional subscale score suggested a small clinical effect of intervention of 4.6 units (95% CI 0.2, 9.0), p = 0.04 after full adjustment for pre-stated case-mix. Results for UW-QOLv4 overall quality of life being less than good at 12 months (primary outcome) also favoured the PCI with a risk ratio of 0.83 (95% CI 0.66, 1.06) and absolute risk 4.8% (- 2.9%, 12.9%) but without achieving statistical significance. Other non-a-priori analyses, including all 12 UWQOL domains and at consultant level also suggested better HRQOL with PCI. Consultation times were unaffected and the number of items selected decreased over time., Conclusion: This novel trial supports the integration of the PCI approach into routine consultations as a simple low-cost means of benefiting HNC patients. It adds to a growing body of evidence supporting the use of patient prompt lists more generally., (© 2020. The Author(s).)
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- 2021
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37. Economic Burden of Heart Failure in Asian Countries with Different Healthcare Systems.
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Yingchoncharoen T, Wu TC, Choi DJ, Ong TK, Liew HB, and Cho MC
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Background and Objectives: Heart failure (HF) poses substantial economic burden, primarily driven by high hospitalization and mortality rates. This study aimed to understand the economic burden of HF in 4 Asian countries under varying healthcare systems., Methods: This was a non-interventional, retrospective study conducted in South Korea, Taiwan, Thailand and Malaysia through medical chart review. Eligible patients included those who had either ≥1 hospitalization or ≥2 outpatient visits from January 1st to December 31st, 2014, and at least one year of follow-up. Resource use and direct healthcare costs (adjusted to 2015 USD) of HF were assessed. HF costs for subgroups stratified by age and sex were assessed., Results: A total of 568 patients were recruited from South Korea (n=200), Taiwan (n=200), Thailand (n=100) and Malaysia (n=68). The proportion of patients hospitalized ranged from 20.0% to 93.5% (South Korea 20.0%, Thailand 49.0%, Malaysia 70.6%, and Taiwan 93.5%). The overall annual HF cost per patient was $2,357, $4,513, $3,513 and $1,443 in South Korea, Taiwan, Thailand, and Malaysia, respectively; hospitalized HF care costs were $10,714, $4,790, $7,181 and $1,776, respectively. The length of stay was more than 12.2 days except in Malaysia. No specific trend was observed in subgroup analysis., Conclusions: In Asia, HF poses significant economic burden and hospitalization has emerged as the major cost driver among healthcare costs. A streamlined treatment strategy reducing hospitalization rate can minimize the economic burden., Competing Interests: T.Y., T.C.W., D.J.C., O.T.K., H.B.L., and M.C.C report grants from Novartis. Any financial or other conflicts that could impact study conclusion does not exist., (Copyright © 2021. The Korean Society of Cardiology.)
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- 2021
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38. Smartphone electrocardiogram for detecting atrial fibrillation after a cerebral ischaemic event: a multicentre randomized controlled trial.
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Koh KT, Law WC, Zaw WM, Foo DHP, Tan CT, Steven A, Samuel D, Fam TL, Chai CH, Wong ZS, Xaviar S, Bhavnani CD, Tan JSH, Oon YY, Said A, Fong AYY, and Ong TK
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- Electrocardiography, Electrocardiography, Ambulatory, Humans, Middle Aged, Smartphone, Atrial Fibrillation diagnosis, Brain Ischemia diagnosis, Ischemic Attack, Transient diagnosis, Stroke diagnosis
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Aims: Atrial fibrillation (AF) is a preventable cause of ischaemic stroke but it is often undiagnosed and undertreated. The utility of smartphone electrocardiogram (ECG) for the detection of AF after ischaemic stroke is unknown. The aim of this study is to determine the diagnostic yield of 30-day smartphone ECG recording compared with 24-h Holter monitoring for detecting AF ≥30 s., Methods and Results: In this multicentre, open-label study, we randomly assigned 203 participants to undergo one additional 24-h Holter monitoring (control group, n = 98) vs. 30-day smartphone ECG monitoring (intervention group, n = 105) using KardiaMobile (AliveCor®, Mountain View, CA, USA). Major inclusion criteria included age ≥55 years old, without known AF, and ischaemic stroke or transient ischaemic attack (TIA) within the preceding 12 months. Baseline characteristics were similar between the two groups. The index event was ischaemic stroke in 88.5% in the intervention group and 88.8% in the control group (P = 0.852). AF lasting ≥30 s was detected in 10 of 105 patients in the intervention group and 2 of 98 patients in the control group (9.5% vs. 2.0%; absolute difference 7.5%; P = 0.024). The number needed to screen to detect one AF was 13. After the 30-day smartphone monitoring, there was a significantly higher proportion of patients on oral anticoagulation therapy at 3 months compared with baseline in the intervention group (9.5% vs. 0%, P = 0.002)., Conclusions: Among patients ≥55 years of age with a recent cryptogenic stroke or TIA, 30-day smartphone ECG recording significantly improved the detection of AF when compared with the standard repeat 24-h Holter monitoring., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)
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- 2021
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39. One-Year COMBO Stent Outcomes in Acute Coronary Syndrome: from the COMBO Collaboration.
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Chandrasekhar J, de Winter VC, Kalkman DN, Sartori S, Chandiramani R, Aquino MB, de Wilde P, Zeebregts D, Woudstra P, Beijk MA, Hájek P, Atzev B, Hudec M, Ong TK, Mates M, Borisov B, Warda HM, den Heijer P, Wojcik J, Iniguez A, Coufal Z, Lee M, Tijssen JG, Koch KT, Baber U, Dangas GD, Colombo A, de Winter RJ, and Mehran R
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- Acute Coronary Syndrome classification, Acute Coronary Syndrome complications, Acute Coronary Syndrome mortality, Angina, Unstable complications, Coronary Thrombosis epidemiology, Drug-Eluting Stents adverse effects, Humans, Myocardial Infarction classification, Myocardial Infarction complications, Prosthesis Design, Risk Factors, Sirolimus administration & dosage, Time Factors, Acute Coronary Syndrome surgery, Drug-Eluting Stents statistics & numerical data, Endothelial Progenitor Cells metabolism, Percutaneous Coronary Intervention methods
- Abstract
Purpose: The COMBO biodegradable polymer sirolimus-eluting stent includes endothelial progenitor cell capture (EPC) technology for rapid endothelialization, which may offer advantage in acute coronary syndromes (ACS). We sought to analyze the performance of the COMBO stent by ACS status and ACS subtype., Methods: The COMBO collaboration (n = 3614) is a patient-level pooled dataset from the MASCOT and REMEDEE registries. We evaluated outcomes by ACS status, and ACS subtype in patients with ST segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) versus unstable angina (UA). The primary endpoint was 1-year target lesion failure (TLF), composite of cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularization. Secondary outcomes included stent thrombosis (ST)., Results: We compared 1965 (54%) ACS and 1649 (46.0%) non-ACS patients. ACS presentations included 40% (n = 789) STEMI, 31% (n = 600) NSTEMI, and 29% (n = 576) UA patients. Risk of 1-year TLF was greater in ACS patients (4.5% vs. 3.3%, HR 1.51 95% CI 1.01-2.25, p = 0.045) without significant differences in definite/probable ST (1.1% vs 0.5%, HR 2.40, 95% CI 0.91-6.31, p = 0.08). One-year TLF was similar in STEMI, NSTEMI, and UA (4.8% vs 4.8% vs. 3.7%, p = 0.60), but definite/probable ST was higher in STEMI patients (1.9% vs 0.5% vs 0.7%, p = 0.03). Adjusted outcomes were not different in MI versus UA patients., Conclusions: Despite the novel EPC capture technology, COMBO stent PCI was associated with somewhat greater risk of 1-year TLF in ACS than in non-ACS patients, without significant differences in stent thrombosis. No differences were observed in 1-year TLF among ACS subtypes.
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- 2021
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40. Sex differences in 1-year clinical outcomes after percutaneous coronary intervention with COMBO stents: From the COMBO collaboration.
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Chandrasekhar J, Kerkmeijer LS, Kalkman DN, Sartori S, Aquino MB, Woudstra P, Beijk MA, Tijssen JG, Koch KT, Hájek P, Atzev B, Hudec M, Ong TK, Mates M, Borisov B, Warda HM, den Heijer P, Wojcik J, Iñiguez A, Coufal Z, Khashaba A, Munawar M, Gerber RT, Yan BP, Lee M, Baber U, Dangas GD, Colombo A, de Winter RJ, and Mehran R
- Subjects
- Female, Humans, Male, Prosthesis Design, Risk Factors, Sex Characteristics, Stents, Time Factors, Treatment Outcome, Coronary Artery Disease diagnostic imaging, Coronary Artery Disease surgery, Drug-Eluting Stents, Percutaneous Coronary Intervention adverse effects
- Abstract
Background: The COMBO drug eluting stent is a novel device with luminal endothelial progenitor cell capture technology for rapid homogeneous endothelialization., Methods and Results: We examined for sex differences in 1-year outcomes after COMBO stenting from the COMBO collaboration, a pooled patient-level dataset from the MASCOT and REMEDEE multicenter registries. The primary endpoint was 1-year target lesion failure (TLF), composite of cardiac death, target vessel-myocardial infarction (TV-MI), or clinically driven target lesion revascularization (CD-TLR). Secondary outcomes included stent thrombosis (ST). Adjusted outcomes were assessed using Cox regression methods. The study included 861 (23.8%) women and 2,753 (76.2%) men. Women were older with higher prevalence of several comorbidities including diabetes mellitus. Risk of 1-year TLF was similar in both sexes (3.8% vs. 3.9%, HR 0.92, 95% CI 0.59-1.42, p = .70), without sex differences in the incidence of cardiac death (1.6% vs. 1.5%, p = .78), TV-MI (1.5% vs. 1.1%, p = .32), or CD-TLR (2.0% vs. 2.2%, p = .67). Definite or probable ST occurred in 0.4% women and 1.0% men (HR 0.26, 95% CI 0.06-1.11, p = .069)., Conclusions: Despite greater clinical risks at baseline, women treated with COMBO stents had similarly low 1-year TLF and other ischemic outcomes compared to men., (© 2020 Wiley Periodicals, Inc.)
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- 2021
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41. Quantitative Assessment of Root Development after Regenerative Endodontic Therapy: A Systematic Review and Meta-Analysis.
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Ong TK, Lim GS, Singh M, and Fial AV
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- Dentition, Permanent, Humans, Prospective Studies, Retrospective Studies, Root Canal Therapy, Dental Pulp Necrosis therapy, Regenerative Endodontics
- Abstract
Introduction: The purposes of this review were to appraise the level of evidence of the existing regenerative endodontic therapy (RET) publications, perform a meta-analysis on the survival and healing rates of necrotic immature permanent teeth treated with RET, and run a meta-analysis on the quantitative assessment of the root development of those teeth., Methods: Electronic searches were performed in Web of Science, PubMed, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and Cochrane Library databases. Two authors independently screened the titles and abstracts for eligibility. The analyses were performed on the clinical outcomes (ie, survival, healing, and root development) of the procedure., Results: Eleven articles were included in the qualitative and quantitative syntheses. Three studies were randomized controlled trials, 6 were prospective cohort studies, and 2 were retrospective cohort studies. The pooled survival and healing rates were 97.3% and 93.0%, respectively. The pooled rates of root lengthening, root thickening, and apical closure were 77.3%, 90.6%, and 79.1%, respectively. However, if 20% radiographic changes were used as a cutoff point, there were only 16.1% root lengthening and 39.8% root thickening., Conclusions: Within the limitations of the present study, it can be concluded that RET yielded high survival and healing rates with a good root development rate. However, clinical meaningful root development after RET was unpredictable., (Copyright © 2020 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)
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- 2020
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42. Improving quality of life through the routine use of the patient concerns inventory for head and neck cancer patients: baseline results in a cluster preference randomised controlled trial.
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Rogers SN, Allmark C, Bekiroglu F, Edwards RT, Fabbroni G, Flavel R, Highet V, Ho MWS, Humphris GM, Jones TM, Khattak O, Lancaster J, Loh C, Lowe D, Lowies C, Macareavy D, Moor J, Ong TK, Prasai A, Roland N, Semple C, Spencer LH, Tandon S, Thomas SJ, Schache A, Shaw RJ, and Kanatas A
- Subjects
- Humans, Neoplasm Staging, Referral and Consultation, Surveys and Questionnaires, Head and Neck Neoplasms therapy, Quality of Life
- Abstract
Purpose: The main aim of this paper is to present baseline demographic and clinical characteristics and HRQOL in the two groups of the Patient Concerns Inventory (PCI) trial. The baseline PCI data will also be described., Methods: This is a pragmatic cluster preference randomised control trial with 15 consultant clusters from two sites either 'using' (n = 8) or 'not using' (n = 7) the PCI at a clinic for all of their trial patients. The PCI is a 56-item prompt list that helps patients raise concerns that otherwise might be missed. Eligibility was head and neck cancer patients treated with curative intent (all sites, stage of disease, treatments)., Results: From 511 patients first identified as eligible when screening for the multi-disciplinary tumour board meetings, 288 attended a first routine outpatient baseline study clinic after completion of their treatment, median (IQR) of 103 (71-162) days. At baseline, the two trial groups were similar in demographic and clinical characteristics as well as in HRQOL measures apart from differences in tumour location, tumour staging and mode of treatment. These exceptions were cluster (consultant) related to Maxillofacial and ENT consultants seeing different types of cases. Consultation times were similar, with PCI group times taking about 1 min longer on average (95% CL for the difference between means was from - 0.7 to + 2.2 min)., Conclusion: Using the PCI in routine post-treatment head and neck cancer clinics do not elongate consultations. Recruitment has finished but 12-month follow-up is still ongoing.
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- 2020
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43. 1-Year Outcomes with COMBO Stents in Small-Vessel Coronary Disease: Subgroup Analysis From the COMBO Collaboration.
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Chandrasekhar J, Zeebregts D, Kalkman DN, Sartori S, Roumeliotis A, Aquino MB, de Wilde P, de Winter VC, Baber U, Woudstra P, Beijk MA, Hájek P, Atzev B, Hudec M, Ong TK, Mates M, Borisov B, Warda HM, den Heijer P, Wojcik J, Iniguez A, Lee M, Tijssen JG, Koch KT, Dangas GD, Colombo A, Mehran R, and de Winter RJ
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- Female, Humans, Prosthesis Design, Risk Factors, Treatment Outcome, Coronary Artery Disease, Percutaneous Coronary Intervention, Stents
- Abstract
Background: Small vessel diameter is associated with higher risk of target lesion revascularization (TLR) after percutaneous coronary intervention (PCI). The COMBO sirolimus-eluting biodegradable-polymer stent has a proprietary anti-CD34 antibody layer to enhance homogeneous endothelialization, which may be advantageous in treating small vessels., Objective: We examined for differences in 1-year clinical outcomes after PCI by maximum implanted stent diameter from the COMBO collaboration., Methods: The COMBO collaboration (n = 3614) is a patient-level pooled dataset of patients undergoing PCI with COMBO stents in the MASCOT and REMEDEE multicenter registries. Stent diameter was available in 3590 (99.3%) patients. We compared patients receiving COMBO stents <3 mm versus ≥3 mm. The primary endpoint was 1-year target lesion failure (TLF), composite of cardiac death, target vessel-myocardial infarction (TV-MI) or clinically driven TLR. Secondary outcomes included stent thrombosis (ST). Adjusted outcomes were assessed using Cox regression methods., Results: The study included 792 (22%) patients with small stents <3 mm and 2798 (78%) patients with large stents ≥3 mm. Small stent patients included more women with lower body mass index and higher prevalence of diabetes but similar prevalence of acute coronary syndrome. Risk of 1-year TLF was similar in small and large stent groups (4.4% vs. 3.8%, HR 1.12, 95% CI 0.74-1.72, p = 0.58). There were no differences in the rates of cardiac death (1.7% vs. 1.5%, p = 0.74), TV-MI (1.4% vs. 1.2%, p = 0.58) or TLR (2.7% vs. 2.1%, p = 0.31). Definite or probable ST occurred in 1.3% of the small stent and 0.7% of the large stent PCI patients, p = 0.14, HR 2.13, 95% CI 0.93-5.00, p = 0.07., Conclusions: One-year ischemic outcomes after COMBO PCI were similar irrespective of stent diameter in this all-comers international cohort., (Copyright © 2020 Elsevier Inc. All rights reserved.)
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- 2020
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44. Two-year outcomes post-discharge in Asian patients with acute coronary syndrome: Findings from the EPICOR Asia study.
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Huo Y, Lee SW, Sawhney JPS, Kim HS, Krittayaphong R, Pocock SJ, Nhan VT, Alonso-Garcia Á, Chin CT, Jiang J, Jan S, Vega AM, Hayashi N, and Ong TK
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- Aftercare, Asia epidemiology, Female, Fibrinolytic Agents therapeutic use, Humans, Male, Middle Aged, Patient Discharge, Prospective Studies, Risk Factors, Treatment Outcome, Acute Coronary Syndrome diagnosis, Acute Coronary Syndrome epidemiology, Acute Coronary Syndrome therapy
- Abstract
Aims: Approximately half of cases of cardiovascular disease (CVD) worldwide occur in Asia, with acute coronary syndrome (ACS) a leading cause of mortality. Long-term ACS-related outcomes data in Asia are limited. This analysis examined 2-year ACS-related outcomes in patients enrolled in the EPICOR Asia study, and the association between patient characteristics and management on outcomes., Methods: EPICOR Asia is a multinational, prospective, primary data collection study of real-world management of Asian patients with ACS. Overall, 12,922 eligible adults (hospitalized for ACS within 48 h of symptom onset and who survived to discharge) were enrolled from 219 centers in eight Asian countries. Patients were followed up post-discharge for 2 years and clinical outcomes recorded., Results: Patients were of mean age 60 years and 76% were male. Diagnoses were STEMI (51.2%), NSTEMI (19.9%), and UA (28.9%). During follow-up, 5.2% of patients died; NSTEMI patients had the highest risk profile. Mortality rate (adjusted HR [95% CI]) was similar in NSTEMI (0.97 [0.81-1.17]) and lower in UA (0.52 [0.33-0.82]) vs STEMI. Similar trends (adjusted) were seen for the composite endpoint of death, myocardial infarction, or ischemic stroke, and bleeding rates did not differ significantly. For all three diagnoses, patients who were medically managed had a markedly elevated risk of both death and the composite endpoint., Conclusions: During 2-year follow-up, adjusted risks of mortality, the composite endpoint, and bleeding rates were similar in NSTEMI and STEMI patients. Outcomes risk was better for invasive management. Long-term management strategies in Asia need to be optimized., Competing Interests: Declaration of Competing Interest Yong Huo, Stephen W-L Lee, Jitendra PS Sawhney, Hyo-Soo Kim, Ángeles Alonso-Garcia, Jie Jiang, and Stephen Jan have nothing to disclose. Rungroj Krittayaphong has been a consultant or advisory board member for AstraZeneca and Boehringer Ingelheim. Stuart J Pocock receives research funds from AstraZeneca. Vo T Nhan has received research grants from AstraZeneca, Servier, Sanofi, and Boston Scientific, and has been a consultant or advisory board member for AstraZeneca, Pfizer, Sanofi, Boehringer Ingelheim, Servier, MSD, Abbott, Bayer, Novartis, Merck Serono, Biosensor, Biotronic, Boston Scientific, Terumo, and Medtronic. Chee Tang Chin has received research support from Eli Lilly and honoraria from Medtronic, and has been a consultant or advisory board member for AstraZeneca. Ana M Vega was a former employee of AstraZeneca and Nobuya Hayashi is a current employee of AstraZeneca. Tiong Kiam Ong has acted as a consultant or advisory board member for Sanofi-Aventis, Abbott Vascular, Boston Scientific, Boehringer Ingelheim, Novartis, and AstraZeneca., (Copyright © 2020. Published by Elsevier B.V.)
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- 2020
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45. Long-term antithrombotic management patterns in Asian patients with acute coronary syndrome: 2-year observations from the EPICOR Asia study.
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Zheng B, Huo Y, Lee SW, Sawhney JPS, Kim HS, Krittayaphong R, Pocock SJ, Nhan VT, Alonso Garcia A, Chin CT, Jiang J, Jan S, Vega AM, Hayashi N, and Ong TK
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- Acute Coronary Syndrome diagnosis, Acute Coronary Syndrome ethnology, Aged, Anticoagulants adverse effects, Asia, Asian People, Drug Administration Schedule, Drug Utilization trends, Dual Anti-Platelet Therapy, Female, Fibrinolytic Agents adverse effects, Healthcare Disparities trends, Humans, Male, Middle Aged, Platelet Aggregation Inhibitors adverse effects, Prospective Studies, Risk Assessment, Risk Factors, Thrombosis diagnosis, Thrombosis ethnology, Time Factors, Treatment Outcome, Acute Coronary Syndrome therapy, Anticoagulants administration & dosage, Fibrinolytic Agents administration & dosage, Myocardial Revascularization adverse effects, Platelet Aggregation Inhibitors administration & dosage, Practice Patterns, Physicians' trends, Thrombosis prevention & control
- Abstract
Background: Despite guideline recommendations, dual antiplatelet therapy (DAPT) is frequently used for longer than 1 year after an acute coronary syndrome (ACS) event. In Asia, information on antithrombotic management patterns (AMPs), including DAPT post discharge, is sparse. This analysis evaluated real-world AMPs up to 2 years post discharge for ACS., Hypothesis: There is wide variability in AMP use for ACS management in Asia., Methods: EPICOR Asia (NCT01361386) is a prospective observational study of patients discharged after hospitalization for an ACS in eight countries/regions in Asia, followed up for 2 years. Here, we describe AMPs used and present an exploratory analysis of characteristics and outcomes in patients who received DAPT for ≤12 months post discharge compared with >12 months., Results: Data were available for 12 922 patients; of 11 639 patients discharged on DAPT, 2364 (20.3%) received DAPT for ≤12 months and 9275 (79.7%) for >12 months, with approximately 60% still on DAPT at 2 years. Patients who received DAPT for >12 months were more likely to be younger, obese, lower Killip class, resident in India (vs China), and to have received invasive reperfusion. Clinical event rates during year 2 of follow-up were lower in patients with DAPT >12 vs ≤12 months, but no causal association can be implied in this non-randomized study., Conclusions: Most ACS patients remained on DAPT up to 1 year, in accordance with current guidelines, and over half remained on DAPT at 2 years post discharge. Patients not on DAPT at 12 months are a higher risk group requiring careful monitoring., (© 2020 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)
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- 2020
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46. Comparison of One-Year Outcomes in Patients >75 Versus ≤75 Years With Coronary Artery Disease Treated With COMBO Stents (From The MASCOT Registry).
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Chandrasekhar J, Sartori S, Aquino MB, Baber U, Hájek P, Atzev B, Hudec M, Ong TK, Mates M, Borisov B, Warda HM, den Heijer P, Wojcik J, Iniguez A, Coufal Z, Khashaba A, Schee A, Munawar M, Gerber RT, Yan BP, Tejedor P, Kala P, Liew HB, Lee M, Kalkman DN, Dangas GD, de Winter RJ, Colombo A, and Mehran R
- Subjects
- Aged, Aged, 80 and over, Coronary Angiography, Coronary Artery Disease diagnosis, Female, Global Health, Humans, Incidence, Male, Middle Aged, Prospective Studies, Prosthesis Design, Treatment Outcome, Absorbable Implants, Coronary Artery Disease surgery, Drug-Eluting Stents, Percutaneous Coronary Intervention methods, Polymers, Postoperative Complications epidemiology, Registries
- Abstract
Older patients who undergo coronary interventions are at greater risk of ischemic events and less likely to tolerate prolonged dual antiplatelet therapy (DAPT) due to bleeding risk. The COMBO biodegradable polymer sirolimus-eluting stent promotes rapid endothelialization through endothelial progenitor cell capture technology which may be advantageous in elderly patients. We compared 1-year clinical outcomes and DAPT cessation events in patients >75 versus ≤75 years from the MASCOT registry. MASCOT was a prospective, multicenter cohort study of all-comers undergoing attempted COMBO stenting. The primary endpoint was 1-year target lesion failure (TLF), composite of cardiac death, myocardial infarction (MI) not clearly attributed to a nontarget vessel or clinically driven target lesion revascularization. Bleeding was adjudicated using the Bleeding Academic Research Consortium criteria. Adjusted outcomes were analyzed using Cox regression methods. The study included 18% (n = 479) patients >75 years and 72% (n = 2,135) patients ≤75 years. One-year TLF occurred in 4.6% patients >75 years versus 3.1% patients ≤75years of age, p = 0.10; adj hazard ratio 1.36, 95% confidence intervals 0.77 to 2.38, p = 0.29. There were no significant differences in cardiac death (1.7% vs 1.3%, p = 0.55), MI (2.1% vs 1.2%, p = 0.14), target lesion revascularization (1.7% vs 1.4%, p = 0.60) and definite stent thrombosis (0.8% vs 0.4%, p = 0.19). Major Bleeding Academic Research Consortium 3,5 bleeding (3.1% vs 1.5%, p = 0.01) and DAPT cessation rates (32.4% vs 23.0%, p <0.001) were significantly higher in elderly patients. In conclusion, elderly patients >75 years treated with COMBO stents had similar TLF but significantly greater incidence of bleeding than younger patients and DAPT cessation in one-third of patients over 1 year., (Copyright © 2020. Published by Elsevier Inc.)
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- 2020
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47. Antithrombotic management and long-term outcomes following percutaneous coronary intervention for acute coronary syndrome in Asia.
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Zhang S, Wang W, Sawhney JPS, Krittayaphong R, Kim HS, Nhan VT, Lee SW, Ong TK, Chin CT, Pocock SJ, Huo Y, Qian J, and Ge J
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- Aftercare, Asia epidemiology, Asia, Eastern, Fibrinolytic Agents therapeutic use, Humans, India, Patient Discharge, Prospective Studies, Registries, Treatment Outcome, Acute Coronary Syndrome diagnosis, Acute Coronary Syndrome drug therapy, Acute Coronary Syndrome surgery, Percutaneous Coronary Intervention
- Abstract
Background: Cardiovascular diseases account for approximately half of all deaths in Asia. The present analysis aimed to evaluate characteristics, antithrombotic management patterns (AMPs), and outcomes in patients with acute coronary syndrome (ACS) who underwent in-hospital percutaneous coronary intervention (PCI) and survived to hospital discharge, using data from the EPICOR Asia registry (NCT01361386)., Methods: Two-year post-discharge follow-up data were analyzed from 8757 ACS PCI patients from EPICOR Asia (218 centers, eight countries). Major adverse cardiovascular events (MACE; death, non-fatal myocardial infarction [MI], non-fatal ischemic stroke), PCI characteristics, and AMPs were recorded. For MACE, time - to - event was analyzed using Cox regression., Results: Primary PCI was performed in 62.0% of ST-segment elevation MI (STEMI), 38.7% of non-STEMI (NSTEMI), and 24.2% of unstable angina (UA) patients. At 12 months, 88.1% of patients were on dual antiplatelet therapy (DAPT), with no differences by index event. Most (61.5%) still received DAPT at 2 years. Two-year incidences of mortality, composite MACE, and bleeding were 3.6%, 6.2%, and 6.6%, respectively. Risk of death and MACE was increased with STEMI and NSTEMI vs. UA. Patients from East Asia showed lower mortality and more bleeding vs. Southeast Asia/India., Conclusions: Many patients in EPICOR Asia underwent PCI and received DAPT up to 2 years post-discharge. These real-world findings improve our understanding of AMP impact on outcomes in Asian patients with ACS undergoing PCI., Competing Interests: Declaration of competing interest S.Z., W.W., J.P.S.S., H.S.K., S.W.L.L., Y.H., J.Q., and J.G. declare no conflict of interest. R.K. reports having been a consultant or advisory board member for AstraZeneca and Boehringer Ingelheim (both modest). V.T.N. reports research grants from AstraZeneca, Servier, Sanofi, and Boston Scientific, and has been a consultant or advisory board member for AstraZeneca, Pfizer, Sanofi, Boehringer Ingelheim, Servier, MSD, Abbott, Bayer, Novartis, Merck Serono, Biosensor, Biotronic, Boston Scientific, Terumo, and Medtronic (all modest). T.K.O. reports having acted as a consultant or advisory board member for Sanofi-Aventis, Abbott Vascular, Boston Scientific, Boehringer Ingelheim, Novartis, and AstraZeneca (all modest). C.T.C. reports research support from Eli Lilly, honoraria from Medtronic, and has been a consultant or advisory board member for AstraZeneca (all modest). S.J.P. reports receiving research funds from AstraZeneca (modest)., (Copyright © 2020. Published by Elsevier B.V.)
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- 2020
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48. 1-year results after PCI with the COMBO stent in all-comers in Asia versus Europe: Geographical insights from the COMBO collaboration.
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Chandrasekhar J, Kalkman DN, Aquino MB, Sartori S, Hájek P, Atzev B, Hudec M, Ong TK, Mates M, Borisov B, Warda HM, den Heijer P, Wojcik J, Iñiguez A, Coufal Z, Khashaba A, Schee A, Munawar M, Gerber RT, Yan BP, Tejedor P, Kala P, Liew HB, Lee M, Baber U, Vogel B, Dangas GD, Colombo A, de Winter RJ, and Mehran R
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- Asia epidemiology, Europe epidemiology, Female, Geography, Humans, Prosthesis Design, Risk Factors, Stents, Time Factors, Treatment Outcome, Coronary Artery Disease surgery, Drug-Eluting Stents, Percutaneous Coronary Intervention adverse effects
- Abstract
Background: The COMBO drug-eluting stent combines sirolimus-elution from a biodegradable polymer with an anti-CD34+ antibody coating for early endothelialization., Objective: We investigated for geographical differences in outcomes after percutaneous coronary intervention (PCI) with the COMBO stent among Asians and Europeans., Methods: The COMBO Collaboration is a pooled patient-level analysis of the MASCOT and REMEDEE registries of all-comers undergoing attempted COMBO stent PCI. The primary outcome was 1-year target lesion failure (TLF), composite of cardiac death, target vessel myocardial infarction (TV-MI) and target lesion revascularization (TLR)., Results: This study included 604 Asians (17.9%) and 2775 Europeans (82.1%). Asians were younger and included fewer females, with a higher prevalence of diabetes mellitus but lower prevalence of other comorbidities than Europeans. Asians had a higher prevalence of ACC/AHA C type lesions and received longer stent lengths. More Asians than Europeans were discharged on clopidogrel (86.5% vs 62.8%) rather than potent P2Y
12 inhibitors. One-year TLF occurred in 4.0% Asians and 4.1% of Europeans, p = 0.93. The incidence of cardiac death was higher in Asians (2.8% vs. 1.3%, p = 0.007) with similar rates of TV-MI (1.5% vs. 1.2%, p = 0.54) and definite stent thrombosis (0.3% vs. 0.5%, p = 0.84) and lower incidence of TLR than Europeans (1.0% vs. 2.5%, p = 0.025). After adjustment, differences for cardiac death and TLR were no longer significant., Conclusions: In the COMBO collaboration, although 1-year TLF was similar regardless of geography, Asians experienced higher rates of cardiac death and lower TLR than Europeans, while incidence of TV-MI and ST was similar in both regions. Adjusted differences did not reach statistical significance. CLINICALTRIAL., Gov Identifier-Numbers: NCT01874002 (REMEDEE Registry), NCT02183454 (MASCOT registry)., Competing Interests: Declaration of competing interest Dr. Mehran has received institutional research grant support from Eli Lilly/Daiichi-Sankyo Inc., AstraZeneca, The Medicines Company, Bristol-Myers Squibb, OrbusNeich, Beth Israel Deaconess, and Bayer; has served as a consultant for Boston Scientific, Cardiovascular Systems Inc., Medscape, and Shanghai BraccoSine Pharmaceutical; has received institutional advisory board funding from Bristol-Myers Squibb; has received institutional funding from Claret Medical; owns equity in Claret Medical and Elixir Medical; has served on the executive committee for Janssen Pharmaceuticals and Osprey Medical; has served on the data safety monitoring board for Watermark Research Partners; and has a spouse who has served as a consultant for Abiomed and the Medicines Company. Dr. Kala has served as a consultant for Boston Scientific; has received research support from AstraZeneca, Novartis, Zoll; has served on advisory board for Astra Zeneca, Bayer, Medtronic and Boston Scientific. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2020 Elsevier B.V. All rights reserved.)- Published
- 2020
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49. Renal Denervation in Asia: Consensus Statement of the Asia Renal Denervation Consortium.
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Kario K, Kim BK, Aoki J, Wong AY, Lee YH, Wongpraparut N, Nguyen QN, Ahmad WAW, Lim ST, Ong TK, and Wang TD
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- Blood Pressure physiology, Consensus, Humans, Hypertension physiopathology, Kidney physiopathology, Treatment Outcome, Denervation methods, Hypertension surgery, Kidney innervation
- Abstract
The Asia Renal Denervation Consortium consensus conference of Asian physicians actively performing renal denervation (RDN) was recently convened to share up-to-date information and regional perspectives, with the goal of consensus on RDN in Asia. First- and second-generation trials of RDN have demonstrated the efficacy and safety of this treatment modality for lowering blood pressure in patients with resistant hypertension. Considering the ethnic differences of the hypertension profile and demographics of cardiovascular disease demonstrated in the SYMPLICITY HTN (Renal Denervation in Patients With Uncontrolled Hypertension)-Japan study and Global SYMPLICITY registry data from Korea and Taiwan, RDN might be an effective hypertension management strategy in Asia. Patient preference for device-based therapy should be considered as part of a shared patient-physician decision process. A practical population for RDN treatment could consist of Asian patients with uncontrolled essential hypertension, including resistant hypertension. Opportunities to refine the procedure, expand the therapy to other sympathetically mediated diseases, and explore the specific effects on nocturnal and morning hypertension offer a promising future for RDN. Based on available evidence, RDN should not be considered a therapy of last resort but as an initial therapy option that may be applied alone or as a complementary therapy to antihypertensive medication.
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- 2020
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50. Effect of Dabigatran on Clotting Time in the Clotpro Ecarin Clotting Assay: A Prospective, Single-Arm, Open-Label Study.
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Fong AYY, Tiong LL, Tan SSN, Geruka D, Apil GG, Choo CW, and Ong TK
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- Aged, Antithrombins blood, Antithrombins pharmacology, Atrial Fibrillation blood, Blood Coagulation Tests, Dabigatran blood, Dabigatran pharmacology, Female, Humans, Male, Middle Aged, Preliminary Data, Prospective Studies, Antithrombins therapeutic use, Atrial Fibrillation drug therapy, Blood Coagulation drug effects, Dabigatran therapeutic use
- Abstract
Routine coagulation tests do not enable rapid, accurate determination of direct oral anticoagulant (DOAC) therapy. The ecarin clotting assay (ECA), performed on the ClotPro viscoelastic testing device, may enable sensitive and specific detection of dabigatran. We assessed the association between trough plasma dabigatran concentration and clotting time (CT) in the ClotPro ECA, in patients with non-valvular atrial fibrillation (NVAF). Each patient provided a single venous blood sample, ∼1 hour before dabigatran dosing. The study included 118 patients, of whom 64 were receiving dabigatran 110 mg twice daily and 54 were receiving 150 mg twice daily. ECA CT was moderately correlated with trough plasma dabigatran concentration ( r = 0.80, p < 0.001). Slight trends toward increased plasma dabigatran concentration and prolonged ECA CT were apparent with 150 mg versus the 110 mg dose (differences not statistically significant). Individuals with creatinine clearance below 50 mL/minute had significantly higher plasma dabigatran concentrations and significantly prolonged ECA CT versus those with creatinine clearance ≥50 mL/minute. In conclusion, this preliminary study has demonstrated that CT in the ClotPro ECA reflects the plasma concentration of dabigatran in patients with NVAF. The ECA could potentially be used to assess the impact of dabigatran on a patient's coagulation status.
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- 2020
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