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1. Effects of empagliflozin on progression of chronic kidney disease: a prespecified secondary analysis from the empa-kidney trial

Author: Staplin, N, Haynes, R, Judge, PK, Wanner, C, Green, JB, Emberson, J, Preiss, D, Mayne, KJ, Ng, SYA, Sammons, E, Zhu, D, Hill, M, Stevens, W, Wallendszus, K, Brenner, S, Cheung, AK, Liu, ZH, Li, J, Hooi, LS, Liu, WJ, Kadowaki, T, Nangaku, M, Levin, A, Cherney, D, Maggioni, AP, Pontremoli, R, Deo, R, Goto, S, Rossello, X, Tuttle, KR, Steubl, D, Petrini, M, Seidi, S, Landray, MJ, Baigent, C, Herrington, WG, Abat, S, Abd Rahman, R, Abdul Cader, R, Abdul Hafidz, MI, Abdul Wahab, MZ, Abdullah, NK, Abdul-Samad, T, Abe, M, Abraham, N, Acheampong, S, Achiri, P, Acosta, JA, Adeleke, A, Adell, V, Adewuyi-Dalton, R, Adnan, N, Africano, A, Agharazii, M, Aguilar, F, Aguilera, A, Ahmad, M, Ahmad, MK, Ahmad, NA, Ahmad, NH, Ahmad, NI, Ahmad Miswan, N, Ahmad Rosdi, H, Ahmed, I, Ahmed, S, Aiello, J, Aitken, A, AitSadi, R, Aker, S, Akimoto, S, Akinfolarin, A, Akram, S, Alberici, F, Albert, C, Aldrich, L, Alegata, M, Alexander, L, Alfaress, S, Alhadj Ali, M, Ali, A, Alicic, R, Aliu, A, Almaraz, R, Almasarwah, R, Almeida, J, Aloisi, A, Al-Rabadi, L, Alscher, D, Alvarez, P, Al-Zeer, B, Amat, M, Ambrose, C, Ammar, H, An, Y, Andriaccio, L, Ansu, K, Apostolidi, A, Arai, N, Araki, H, Araki, S, Arbi, A, Arechiga, O, Armstrong, S, Arnold, T, Aronoff, S, Arriaga, W, Arroyo, J, Arteaga, D, Asahara, S, Asai, A, Asai, N, Asano, S, Asawa, M, Asmee, MF, Aucella, F, Augustin, M, Avery, A, Awad, A, Awang, IY, Awazawa, M, Axler, A, Ayub, W, Azhari, Z, Baccaro, R, Badin, C, Bagwell, B, Bahlmann-Kroll, E, Bahtar, AZ, Bains, D, Bajaj, H, Baker, R, Baldini, E, Banas, B, Banerjee, D, Banno, S, Bansal, S, Barberi, S, Barnes, S, Barnini, C, Barot, C, Barrett, K, Barrios, R, Bartolomei Mecatti, B, Barton, I, Barton, J, Basily, W, Bavanandan, S, Baxter, A, Becker, L, Beddhu, S, Beige, J, Beigh, S, Bell, S, Benck, U, Beneat, A, Bennett, A, Bennett, D, Benyon, S, Berdeprado, J, Bergler, T, Bergner, A, Berry, M, Bevilacqua, M, Bhairoo, J, Bhandari, S, Bhandary, N, Bhatt, A, Bhattarai, M, Bhavsar, M, Bian, W, Bianchini, F, Bianco, S, Bilous, R, Bilton, J, Bilucaglia, D, Bird, C, Birudaraju, D, Biscoveanu, M, Blake, C, Bleakley, N, Bocchicchia, K, Bodine, S, Bodington, R, Boedecker, S, Bolduc, M, Bolton, S, Bond, C, Boreky, F, Boren, K, Bouchi, R, Bough, L, Bovan, D, Bowler, C, Bowman, L, Brar, N, Braun, C, Breach, A, Breitenfeldt, M, Brettschneider, B, Brewer, A, Brewer, G, Brindle, V, Brioni, E, Brown, C, Brown, H, Brown, L, Brown, R, Brown, S, Browne, D, Bruce, K, Brueckmann, M, Brunskill, N, Bryant, M, Brzoska, M, Bu, Y, Buckman, C, Budoff, M, Bullen, M, Burke, A, Burnette, S, Burston, C, Busch, M, Bushnell, J, Butler, S, Büttner, C, Byrne, C, Caamano, A, Cadorna, J, Cafiero, C, Cagle, M, Cai, J, Calabrese, K, Calvi, C, Camilleri, B, Camp, S, Campbell, D, Campbell, R, Cao, H, Capelli, I, Caple, M, Caplin, B, Cardone, A, Carle, J, Carnall, V, Caroppo, M, Carr, S, Carraro, G, Carson, M, Casares, P, Castillo, C, Castro, C, Caudill, B, Cejka, V, Ceseri, M, Cham, L, Chamberlain, A, Chambers, J, Chan, CBT, Chan, JYM, Chan, YC, Chang, E, Chant, T, Chavagnon, T, Chellamuthu, P, Chen, F, Chen, J, Chen, P, Chen, TM, Chen, Y, Cheng, C, Cheng, H, Cheng, MC, Ching, CH, Chitalia, N, Choksi, R, Chukwu, C, Chung, K, Cianciolo, G, Cipressa, L, Clark, S, Clarke, H, Clarke, R, Clarke, S, Cleveland, B, Cole, E, Coles, H, Condurache, L, Connor, A, Convery, K, Cooper, A, Cooper, N, Cooper, Z, Cooperman, L, Cosgrove, L, Coutts, P, Cowley, A, Craik, R, Cui, G, Cummins, T, Dahl, N, Dai, H, Dajani, L, D'Amelio, A, Damian, E, Damianik, K, Danel, L, Daniels, C, Daniels, T, Darbeau, S, Darius, H, Dasgupta, T, Davies, J, Davies, L, Davis, A, Davis, J, Davis, L, Dayanandan, R, Dayi, S, Dayrell, R, De Nicola, L, Debnath, S, Deeb, W, Degenhardt, S, DeGoursey, K, Delaney, M, DeRaad, R, Derebail, V, Dev, D, Devaux, M, Dhall, P, Dhillon, G, Dienes, J, Dobre, M, Doctolero, E, Dodds, V, Domingo, D, Donaldson, D, Donaldson, P, Donhauser, C, Donley, V, Dorestin, S, Dorey, S, Doulton, T, Draganova, D, Draxlbauer, K, Driver, F, Du, H, Dube, F, Duck, T, Dugal, T, Dugas, J, Dukka, H, Dumann, H, Durham, W, Dursch, M, Dykas, R, Easow, R, Eckrich, E, Eden, G, Edmerson, E, Edwards, H, Ee, LW, Eguchi, J, Ehrl, Y, Eichstadt, K, Eid, W, Eilerman, B, Ejima, Y, Eldon, H, Ellam, T, Elliott, L, Ellison, R, Epp, R, Er, A, Espino-Obrero, M, Estcourt, S, Estienne, L, Evans, G, Evans, J, Evans, S, Fabbri, G, Fajardo-Moser, M, Falcone, C, Fani, F, Faria-Shayler, P, Farnia, F, Farrugia, D, Fechter, M, Fellowes, D, Feng, F, Fernandez, J, Ferraro, P, Field, A, Fikry, S, Finch, J, Finn, H, Fioretto, P, Fish, R, Fleischer, A, Fleming-Brown, D, Fletcher, L, Flora, R, Foellinger, C, Foligno, N, Forest, S, Forghani, Z, Forsyth, K, Fottrell-Gould, D, Fox, P, Frankel, A, Fraser, D, Frazier, R, Frederick, K, Freking, N, French, H, Froment, A, Fuchs, B, Fuessl, L, Fujii, H, Fujimoto, A, Fujita, A, Fujita, K, Fujita, Y, Fukagawa, M, Fukao, Y, Fukasawa, A, Fuller, T, Funayama, T, Fung, E, Furukawa, M, Furukawa, Y, Furusho, M, Gabel, S, Gaidu, J, Gaiser, S, Gallo, K, Galloway, C, Gambaro, G, Gan, CC, Gangemi, C, Gao, M, Garcia, K, Garcia, M, Garofalo, C, Garrity, M, Garza, A, Gasko, S, Gavrila, M, Gebeyehu, B, Geddes, A, Gentile, G, George, A, George, J, Gesualdo, L, Ghalli, F, Ghanem, A, Ghate, T, Ghavampour, S, Ghazi, A, Gherman, A, Giebeln-Hudnell, U, Gill, B, Gillham, S, Girakossyan, I, Girndt, M, Giuffrida, A, Glenwright, M, Glider, T, Gloria, R, Glowski, D, Goh, BL, Goh, CB, Gohda, T, Goldenberg, R, Goldfaden, R, Goldsmith, C, Golson, B, Gonce, V, Gong, Q, Goodenough, B, Goodwin, N, Goonasekera, M, Gordon, A, Gordon, J, Gore, A, Goto, H, Gowen, D, Grace, A, Graham, J, Grandaliano, G, Gray, M, Greene, T, Greenwood, G, Grewal, B, Grifa, R, Griffin, D, Griffin, S, Grimmer, P, Grobovaite, E, Grotjahn, S, Guerini, A, Guest, C, Gunda, S, Guo, B, Guo, Q, Haack, S, Haase, M, Haaser, K, Habuki, K, Hadley, A, Hagan, S, Hagge, S, Haller, H, Ham, S, Hamal, S, Hamamoto, Y, Hamano, N, Hamm, M, Hanburry, A, Haneda, M, Hanf, C, Hanif, W, Hansen, J, Hanson, L, Hantel, S, Haraguchi, T, Harding, E, Harding, T, Hardy, C, Hartner, C, Harun, Z, Harvill, L, Hasan, A, Hase, H, Hasegawa, F, Hasegawa, T, Hashimoto, A, Hashimoto, C, Hashimoto, M, Hashimoto, S, Haskett, S, Hauske, SJ, Hawfield, A, Hayami, T, Hayashi, M, Hayashi, S, Hazara, A, Healy, C, Hecktman, J, Heine, G, Henderson, H, Henschel, R, Hepditch, A, Herfurth, K, Hernandez, G, Hernandez Pena, A, Hernandez-Cassis, C, Herzog, C, Hewins, S, Hewitt, D, Hichkad, L, Higashi, S, Higuchi, C, Hill, C, Hill, L, Himeno, T, Hing, A, Hirakawa, Y, Hirata, K, Hirota, Y, Hisatake, T, Hitchcock, S, Hodakowski, A, Hodge, W, Hogan, R, Hohenstatt, U, Hohenstein, B, Hooi, L, Hope, S, Hopley, M, Horikawa, S, Hosein, D, Hosooka, T, Hou, L, Hou, W, Howie, L, Howson, A, Hozak, M, Htet, Z, Hu, X, Hu, Y, Huang, J, Huda, N, Hudig, L, Hudson, A, Hugo, C, Hull, R, Hume, L, Hundei, W, Hunt, N, Hunter, A, Hurley, S, Hurst, A, Hutchinson, C, Hyo, T, Ibrahim, FH, Ibrahim, S, Ihana, N, Ikeda, T, Imai, A, Imamine, R, Inamori, A, Inazawa, H, Ingell, J, Inomata, K, Inukai, Y, Ioka, M, Irtiza-Ali, A, Isakova, T, Isari, W, Iselt, M, Ishiguro, A, Ishihara, K, Ishikawa, T, Ishimoto, T, Ishizuka, K, Ismail, R, Itano, S, Ito, H, Ito, K, Ito, M, Ito, Y, Iwagaitsu, S, Iwaita, Y, Iwakura, T, Iwamoto, M, Iwasa, M, Iwasaki, H, Iwasaki, S, Izumi, K, Izumi, T, Jaafar, SM, Jackson, C, Jackson, Y, Jafari, G, Jahangiriesmaili, M, Jain, N, Jansson, K, Jasim, H, Jeffers, L, Jenkins, A, Jesky, M, Jesus-Silva, J, Jeyarajah, D, Jiang, Y, Jiao, X, Jimenez, G, Jin, B, Jin, Q, Jochims, J, Johns, B, Johnson, C, Johnson, T, Jolly, S, Jones, L, Jones, S, Jones, T, Jones, V, Joseph, M, Joshi, S, Judge, P, Junejo, N, Junus, S, Kachele, M, Kadoya, H, Kaga, H, Kai, H, Kajio, H, Kaluza-Schilling, W, Kamaruzaman, L, Kamarzarian, A, Kamimura, Y, Kamiya, H, Kamundi, C, Kan, T, Kanaguchi, Y, Kanazawa, A, Kanda, E, Kanegae, S, Kaneko, K, Kang, HY, Kano, T, Karim, M, Karounos, D, Karsan, W, Kasagi, R, Kashihara, N, Katagiri, H, Katanosaka, A, Katayama, A, Katayama, M, Katiman, E, Kato, K, Kato, M, Kato, N, Kato, S, Kato, T, Kato, Y, Katsuda, Y, Katsuno, T, Kaufeld, J, Kavak, Y, Kawai, I, Kawai, M, Kawase, A, Kawashima, S, Kazory, A, Kearney, J, Keith, B, Kellett, J, Kelley, S, Kershaw, M, Ketteler, M, Khai, Q, Khairullah, Q, Khandwala, H, Khoo, KKL, Khwaja, A, Kidokoro, K, Kielstein, J, Kihara, M, Kimber, C, Kimura, S, Kinashi, H, Kingston, H, Kinomura, M, Kinsella-Perks, E, Kitagawa, M, Kitajima, M, Kitamura, S, Kiyosue, A, Kiyota, M, Klauser, F, Klausmann, G, Kmietschak, W, Knapp, K, Knight, C, Knoppe, A, Knott, C, Kobayashi, M, Kobayashi, R, Kobayashi, T, Koch, M, Kodama, S, Kodani, N, Kogure, E, Koizumi, M, Kojima, H, Kojo, T, Kolhe, N, Komaba, H, Komiya, T, Komori, H, Kon, SP, Kondo, M, Kong, W, Konishi, M, Kono, K, Koshino, M, Kosugi, T, Kothapalli, B, Kozlowski, T, Kraemer, B, Kraemer-Guth, A, Krappe, J, Kraus, D, Kriatselis, C, Krieger, C, Krish, P, Kruger, B, Ku Md Razi, KR, Kuan, Y, Kubota, S, Kuhn, S, Kumar, P, Kume, S, Kummer, I, Kumuji, R, Küpper, A, Kuramae, T, Kurian, L, Kuribayashi, C, Kurien, R, Kuroda, E, Kurose, T, Kutschat, A, Kuwabara, N, Kuwata, H, La Manna, G, Lacey, M, Lafferty, K, LaFleur, P, Lai, V, Laity, E, Lambert, A, Langlois, M, Latif, F, Latore, E, Laundy, E, Laurienti, D, Lawson, A, Lay, M, Leal, I, Lee, AK, Lee, J, Lee, KQ, Lee, R, Lee, SA, Lee, YY, Lee-Barkey, Y, Leonard, N, Leoncini, G, Leong, CM, Lerario, S, Leslie, A, Lewington, A, Li, N, Li, X, Li, Y, Liberti, L, Liberti, ME, Liew, A, Liew, YF, Lilavivat, U, Lim, SK, Lim, YS, Limon, E, Lin, H, Lioudaki, E, Liu, H, Liu, J, Liu, L, Liu, Q, Liu, X, Liu, Z, Loader, D, Lochhead, H, Loh, CL, Lorimer, A, Loudermilk, L, Loutan, J, Low, CK, Low, CL, Low, YM, Lozon, Z, Lu, Y, Lucci, D, Ludwig, U, Luker, N, Lund, D, Lustig, R, Lyle, S, Macdonald, C, MacDougall, I, Machicado, R, MacLean, D, Macleod, P, Madera, A, Madore, F, Maeda, K, Maegawa, H, Maeno, S, Mafham, M, Magee, J, Mah, DY, Mahabadi, V, Maiguma, M, Makita, Y, Makos, G, Manco, L, Mangiacapra, R, Manley, J, Mann, P, Mano, S, Marcotte, G, Maris, J, Mark, P, Markau, S, Markovic, M, Marshall, C, Martin, M, Martinez, C, Martinez, S, Martins, G, Maruyama, K, Maruyama, S, Marx, K, Maselli, A, Masengu, A, Maskill, A, Masumoto, S, Masutani, K, Matsumoto, M, Matsunaga, T, Matsuoka, N, Matsushita, M, Matthews, M, Matthias, S, Matvienko, E, Maurer, M, Maxwell, P, Mazlan, N, Mazlan, SA, Mbuyisa, A, McCafferty, K, McCarroll, F, McCarthy, T, McClary-Wright, C, McCray, K, McDermott, P, McDonald, C, McDougall, R, McHaffie, E, McIntosh, K, McKinley, T, McLaughlin, S, McLean, N, McNeil, L, Measor, A, Meek, J, Mehta, A, Mehta, R, Melandri, M, Mené, P, Meng, T, Menne, J, Merritt, K, Merscher, S, Meshykhi, C, Messa, P, Messinger, L, Miftari, N, Miller, R, Miller, Y, Miller-Hodges, E, Minatoguchi, M, Miners, M, Minutolo, R, Mita, T, Miura, Y, Miyaji, M, Miyamoto, S, Miyatsuka, T, Miyazaki, M, Miyazawa, I, Mizumachi, R, Mizuno, M, Moffat, S, Mohamad Nor, FS, Mohamad Zaini, SN, Mohamed Affandi, FA, Mohandas, C, Mohd, R, Mohd Fauzi, NA, Mohd Sharif, NH, Mohd Yusoff, Y, Moist, L, Moncada, A, Montasser, M, Moon, A, Moran, C, Morgan, N, Moriarty, J, Morig, G, Morinaga, H, Morino, K, Morisaki, T, Morishita, Y, Morlok, S, Morris, A, Morris, F, Mostafa, S, Mostefai, Y, Motegi, M, Motherwell, N, Motta, D, Mottl, A, Moys, R, Mozaffari, S, Muir, J, Mulhern, J, Mulligan, S, Munakata, Y, Murakami, C, Murakoshi, M, Murawska, A, Murphy, K, Murphy, L, Murray, S, Murtagh, H, Musa, MA, Mushahar, L, Mustafa, R, Mustafar, R, Muto, M, Nadar, E, Nagano, R, Nagasawa, T, Nagashima, E, Nagasu, H, Nagelberg, S, Nair, H, Nakagawa, Y, Nakahara, M, Nakamura, J, Nakamura, R, Nakamura, T, Nakaoka, M, Nakashima, E, Nakata, J, Nakata, M, Nakatani, S, Nakatsuka, A, Nakayama, Y, Nakhoul, G, Naverrete, G, Navivala, A, Nazeer, I, Negrea, L, Nethaji, C, Newman, E, Ng, TJ, Ngu, LLS, Nimbkar, T, Nishi, H, Nishi, M, Nishi, S, Nishida, Y, Nishiyama, A, Niu, J, Niu, P, Nobili, G, Nohara, N, Nojima, I, Nolan, J, Nosseir, H, Nozawa, M, Nunn, M, Nunokawa, S, Oda, M, Oe, M, Oe, Y, Ogane, K, Ogawa, W, Ogihara, T, Oguchi, G, Ohsugi, M, Oishi, K, Okada, Y, Okajyo, J, Okamoto, S, Okamura, K, Olufuwa, O, Oluyombo, R, Omata, A, Omori, Y, Ong, LM, Ong, YC, Onyema, J, Oomatia, A, Oommen, A, Oremus, R, Orimo, Y, Ortalda, V, Osaki, Y, Osawa, Y, Osmond Foster, J, O'Sullivan, A, Otani, T, Othman, N, Otomo, S, O'Toole, J, Owen, L, Ozawa, T, Padiyar, A, Page, N, Pajak, S, Paliege, A, Pandey, A, Pandey, R, Pariani, H, Park, J, Parrigon, M, Passauer, J, Patecki, M, Patel, M, Patel, R, Patel, T, Patel, Z, Paul, R, Paulsen, L, Pavone, L, Peixoto, A, Peji, J, Peng, BC, Peng, K, Pennino, L, Pereira, E, Perez, E, Pergola, P, Pesce, F, Pessolano, G, Petchey, W, Petr, EJ, Pfab, T, Phelan, P, Phillips, R, Phillips, T, Phipps, M, Piccinni, G, Pickett, T, Pickworth, S, Piemontese, M, Pinto, D, Piper, J, Plummer-Morgan, J, Poehler, D, Polese, L, Poma, V, Postal, A, Pötz, C, Power, A, Pradhan, N, Pradhan, R, Preiss, E, Preston, K, Prib, N, Price, L, Provenzano, C, Pugay, C, Pulido, R, Putz, F, Qiao, Y, Quartagno, R, Quashie-Akponeware, M, Rabara, R, Rabasa-Lhoret, R, Radhakrishnan, D, Radley, M, Raff, R, Raguwaran, S, Rahbari-Oskoui, F, Rahman, M, Rahmat, K, Ramadoss, S, Ramanaidu, S, Ramasamy, S, Ramli, R, Ramli, S, Ramsey, T, Rankin, A, Rashidi, A, Raymond, L, Razali, WAFA, Read, K, Reiner, H, Reisler, A, Reith, C, Renner, J, Rettenmaier, B, Richmond, L, Rijos, D, Rivera, R, Rivers, V, Robinson, H, Rocco, M, Rodriguez-Bachiller, I, Rodriquez, R, Roesch, C, Roesch, J, Rogers, J, Rohnstock, M, Rolfsmeier, S, Roman, M, Romo, A, Rosati, A, Rosenberg, S, Ross, T, Roura, M, Roussel, M, Rovner, S, Roy, S, Rucker, S, Rump, L, Ruocco, M, Ruse, S, Russo, F, Russo, M, Ryder, M, Sabarai, A, Saccà, C, Sachson, R, Sadler, E, Safiee, NS, Sahani, M, Saillant, A, Saini, J, Saito, C, Saito, S, Sakaguchi, K, Sakai, M, Salim, H, Salviani, C, Sampson, A, Samson, F, Sandercock, P, Sanguila, S, Santorelli, G, Santoro, D, Sarabu, N, Saram, T, Sardell, R, Sasajima, H, Sasaki, T, Satko, S, Sato, A, Sato, D, Sato, H, Sato, J, Sato, T, Sato, Y, Satoh, M, Sawada, K, Schanz, M, Scheidemantel, F, Schemmelmann, M, Schettler, E, Schettler, V, Schlieper, GR, Schmidt, C, Schmidt, G, Schmidt, U, Schmidt-Gurtler, H, Schmude, M, Schneider, A, Schneider, I, Schneider-Danwitz, C, Schomig, M, Schramm, T, Schreiber, A, Schricker, S, Schroppel, B, Schulte-Kemna, L, Schulz, E, Schumacher, B, Schuster, A, Schwab, A, Scolari, F, Scott, A, Seeger, W, Segal, M, Seifert, L, Seifert, M, Sekiya, M, Sellars, R, Seman, MR, Shah, S, Shainberg, L, Shanmuganathan, M, Shao, F, Sharma, K, Sharpe, C, Sheikh-Ali, M, Sheldon, J, Shenton, C, Shepherd, A, Shepperd, M, Sheridan, R, Sheriff, Z, Shibata, Y, Shigehara, T, Shikata, K, Shimamura, K, Shimano, H, Shimizu, Y, Shimoda, H, Shin, K, Shivashankar, G, Shojima, N, Silva, R, Sim, CSB, Simmons, K, Sinha, S, Sitter, T, Sivanandam, S, Skipper, M, Sloan, K, Sloan, L, Smith, R, Smyth, J, Sobande, T, Sobata, M, Somalanka, S, Song, X, Sonntag, F, Sood, B, Sor, SY, Soufer, J, Sparks, H, Spatoliatore, G, Spinola, T, Squyres, S, Srivastava, A, Stanfield, J, Staylor, K, Steele, A, Steen, O, Steffl, D, Stegbauer, J, Stellbrink, C, Stellbrink, E, Stevenson, A, Stewart-Ray, V, Stickley, J, Stoffler, D, Stratmann, B, Streitenberger, S, Strutz, F, Stubbs, J, Stumpf, J, Suazo, N, Suchinda, P, Suckling, R, Sudin, A, Sugamori, K, Sugawara, H, Sugawara, K, Sugimoto, D, Sugiyama, H, Sugiyama, T, Sullivan, M, Sumi, M, Suresh, N, Sutton, D, Suzuki, H, Suzuki, R, Suzuki, Y, Swanson, E, Swift, P, Syed, S, Szerlip, H, Taal, M, Taddeo, M, Tailor, C, Tajima, K, Takagi, M, Takahashi, K, Takahashi, M, Takahashi, T, Takahira, E, Takai, T, Takaoka, M, Takeoka, J, Takesada, A, Takezawa, M, Talbot, M, Taliercio, J, Talsania, T, Tamori, Y, Tamura, R, Tamura, Y, Tan, CHH, Tan, EZZ, Tanabe, A, Tanabe, K, Tanaka, A, Tanaka, N, Tang, S, Tang, Z, Tanigaki, K, Tarlac, M, Tatsuzawa, A, Tay, JF, Tay, LL, Taylor, J, Taylor, K, Te, A, Tenbusch, L, Teng, KS, Terakawa, A, Terry, J, Tham, ZD, Tholl, S, Thomas, G, Thong, KM, Tietjen, D, Timadjer, A, Tindall, H, Tipper, S, Tobin, K, Toda, N, Tokuyama, A, Tolibas, M, Tomita, A, Tomita, T, Tomlinson, J, Tonks, L, Topf, J, Topping, S, Torp, A, Torres, A, Totaro, F, Toth, P, Toyonaga, Y, Tripodi, F, Trivedi, K, Tropman, E, Tschope, D, Tse, J, Tsuji, K, Tsunekawa, S, Tsunoda, R, Tucky, B, Tufail, S, Tuffaha, A, Turan, E, Turner, H, Turner, J, Turner, M, Tye, YL, Tyler, A, Tyler, J, Uchi, H, Uchida, H, Uchida, T, Udagawa, T, Ueda, S, Ueda, Y, Ueki, K, Ugni, S, Ugwu, E, Umeno, R, Unekawa, C, Uozumi, K, Urquia, K, Valleteau, A, Valletta, C, van Erp, R, Vanhoy, C, Varad, V, Varma, R, Varughese, A, Vasquez, P, Vasseur, A, Veelken, R, Velagapudi, C, Verdel, K, Vettoretti, S, Vezzoli, G, Vielhauer, V, Viera, R, Vilar, E, Villaruel, S, Vinall, L, Vinathan, 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Published: 2024
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2. Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Author: Judge, PK, Staplin, N, Mayne, KJ, Wanner, C, Green, JB, Hauske, SJ, Emberson, JR, Preiss, D, Ng, SYA, Roddick, AJ, Sammons, E, Zhu, D, Hill, M, Stevens, W, Wallendszus, K, Brenner, S, Cheung, AK, Liu, ZH, Li, J, Hooi, LS, Liu, WJ, Kadowaki, T, Nangaku, M, Levin, A, Cherney, D, Maggioni, AP, Pontremoli, R, Deo, R, Goto, S, Rossello, X, Tuttle, KR, Steubl, D, Massey, D, Landray, MJ, Baigent, C, Haynes, R, Herrington, WG, Abat, S, Abd Rahman, R, Abdul Cader, R, Abdul Hafidz, MI, Abdul Wahab, MZ, Abdullah, NK, Abdul-Samad, T, Abe, M, Abraham, N, Acheampong, S, Achiri, P, Acosta, JA, Adeleke, A, Adell, V, Adewuyi-Dalton, R, Adnan, N, Africano, A, Agharazii, M, Aguilar, F, Aguilera, A, Ahmad, M, Ahmad, MK, Ahmad, NA, Ahmad, NH, Ahmad, NI, Ahmad Miswan, N, Ahmad Rosdi, H, Ahmed, I, Ahmed, S, Aiello, J, Aitken, A, AitSadi, R, Aker, S, Akimoto, S, Akinfolarin, A, Akram, S, Alberici, F, Albert, C, Aldrich, L, Alegata, M, Alexander, L, Alfaress, S, Alhadj Ali, M, Ali, A, Alicic, R, Aliu, 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Miyatsuka, T, Miyazaki, M, Miyazawa, I, Mizumachi, R, Mizuno, M, Moffat, S, Mohamad Nor, FS, Mohamad Zaini, SN, Mohamed Affandi, FA, Mohandas, C, Mohd, R, Mohd Fauzi, NA, Mohd Sharif, NH, Mohd Yusoff, Y, Moist, L, Moncada, A, Montasser, M, Moon, A, Moran, C, Morgan, N, Moriarty, J, Morig, G, Morinaga, H, Morino, K, Morisaki, T, Morishita, Y, Morlok, S, Morris, A, Morris, F, Mostafa, S, Mostefai, Y, Motegi, M, Motherwell, N, Motta, D, Mottl, A, Moys, R, Mozaffari, S, Muir, J, Mulhern, J, Mulligan, S, Munakata, Y, Murakami, C, Murakoshi, M, Murawska, A, Murphy, K, Murphy, L, Murray, S, Murtagh, H, Musa, MA, Mushahar, L, Mustafa, R, Mustafar, R, Muto, M, Nadar, E, Nagano, R, Nagasawa, T, Nagashima, E, Nagasu, H, Nagelberg, S, Nair, H, Nakagawa, Y, Nakahara, M, Nakamura, J, Nakamura, R, Nakamura, T, Nakaoka, M, Nakashima, E, Nakata, J, Nakata, M, Nakatani, S, Nakatsuka, A, Nakayama, Y, Nakhoul, G, Naverrete, G, Navivala, A, Nazeer, I, Negrea, L, Nethaji, C, Newman, E, Ng, TJ, Ngu, LLS, 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S, Sakaguchi, K, Sakai, M, Salim, H, Salviani, C, Sampson, A, Samson, F, Sandercock, P, Sanguila, S, Santorelli, G, Santoro, D, Sarabu, N, Saram, T, Sardell, R, Sasajima, H, Sasaki, T, Satko, S, Sato, A, Sato, D, Sato, H, Sato, J, Sato, T, Sato, Y, Satoh, M, Sawada, K, Schanz, M, Scheidemantel, F, Schemmelmann, M, Schettler, E, Schettler, V, Schlieper, GR, Schmidt, C, Schmidt, G, Schmidt, U, Schmidt-Gurtler, H, Schmude, M, Schneider, A, Schneider, I, Schneider-Danwitz, C, Schomig, M, Schramm, T, Schreiber, A, Schricker, S, Schroppel, B, Schulte-Kemna, L, Schulz, E, Schumacher, B, Schuster, A, Schwab, A, Scolari, F, Scott, A, Seeger, W, Segal, M, Seifert, L, Seifert, M, Sekiya, M, Sellars, R, Seman, MR, Shah, S, Shainberg, L, Shanmuganathan, M, Shao, F, Sharma, K, Sharpe, C, Sheikh-Ali, M, Sheldon, J, Shenton, C, Shepherd, A, Shepperd, M, Sheridan, R, Sheriff, Z, Shibata, Y, Shigehara, T, Shikata, K, Shimamura, K, Shimano, H, Shimizu, Y, Shimoda, H, Shin, K, Shivashankar, G, Shojima, N, Silva, R, Sim, CSB, Simmons, K, Sinha, S, Sitter, T, Sivanandam, S, Skipper, M, Sloan, K, Sloan, L, Smith, R, Smyth, J, Sobande, T, Sobata, M, Somalanka, S, Song, X, Sonntag, F, Sood, B, Sor, SY, Soufer, J, Sparks, H, Spatoliatore, G, Spinola, T, Squyres, S, Srivastava, A, Stanfield, J, Staylor, K, Steele, A, Steen, O, Steffl, D, Stegbauer, J, Stellbrink, C, Stellbrink, E, Stevenson, A, Stewart-Ray, V, Stickley, J, Stoffler, D, Stratmann, B, Streitenberger, S, Strutz, F, Stubbs, J, Stumpf, J, Suazo, N, Suchinda, P, Suckling, R, Sudin, A, Sugamori, K, Sugawara, H, Sugawara, K, Sugimoto, D, Sugiyama, H, Sugiyama, T, Sullivan, M, Sumi, M, Suresh, N, Sutton, D, Suzuki, H, Suzuki, R, Suzuki, Y, Swanson, E, Swift, P, Syed, S, Szerlip, H, Taal, M, Taddeo, M, Tailor, C, Tajima, K, Takagi, M, Takahashi, K, Takahashi, M, Takahashi, T, Takahira, E, Takai, T, Takaoka, M, Takeoka, J, Takesada, A, Takezawa, M, Talbot, M, Taliercio, J, Talsania, T, Tamori, Y, Tamura, R, Tamura, Y, Tan, CHH, Tan, EZZ, 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Vinall, L, Vinathan, J, Visnjic, M, Voigt, E, von-Eynatten, M, Vourvou, M, Wada, J, Wada, T, Wada, Y, Wakayama, K, Wakita, Y, Walters, T, Wan Mohamad, WH, Wang, L, Wang, W, Wang, X, Wang, Y, Wanninayake, S, Watada, H, Watanabe, K, Watanabe, M, Waterfall, H, Watkins, D, Watson, S, Weaving, L, Weber, B, Webley, Y, Webster, A, Webster, M, Weetman, M, Wei, W, Weihprecht, H, Weiland, L, Weinmann-Menke, J, Weinreich, T, Wendt, R, Weng, Y, Whalen, M, Whalley, G, Wheatley, R, Wheeler, A, Wheeler, J, Whelton, P, White, K, Whitmore, B, Whittaker, S, Wiebel, J, Wiley, J, Wilkinson, L, Willett, M, Williams, A, Williams, E, Williams, K, Williams, T, Wilson, A, Wilson, P, Wincott, L, Wines, E, Winkelmann, B, Winkler, M, Winter-Goodwin, B, Witczak, J, Wittes, J, Wittmann, M, Wolf, G, Wolf, L, Wolfling, R, Wong, C, Wong, E, Wong, HS, Wong, LW, Wong, YH, Wonnacott, A, Wood, A, Wood, L, Woodhouse, H, Wooding, N, Woodman, A, Wren, K, Wu, J, Wu, P, Xia, S, Xiao, H, Xiao, X, Xie, Y, Xu, C, Xu, Y, Xue, H, Yahaya, H, Yalamanchili, H, Yamada, A, Yamada, N, Yamagata, K, Yamaguchi, M, Yamaji, Y, Yamamoto, A, Yamamoto, S, Yamamoto, T, Yamanaka, A, Yamano, T, Yamanouchi, Y, Yamasaki, N, Yamasaki, Y, Yamashita, C, Yamauchi, T, Yan, Q, Yanagisawa, E, Yang, F, Yang, L, Yano, S, Yao, S, Yao, Y, Yarlagadda, S, Yasuda, Y, Yiu, V, Yokoyama, T, Yoshida, S, Yoshidome, E, Yoshikawa, H, Young, A, Young, T, Yousif, V, Yu, H, Yu, Y, Yuasa, K, Yusof, N, Zalunardo, N, Zander, B, Zani, R, Zappulo, F, Zayed, M, Zemann, B, Zettergren, P, Zhang, H, Zhang, L, Zhang, N, Zhang, X, Zhao, J, Zhao, L, Zhao, S, Zhao, Z, Zhong, H, Zhou, N, Zhou, S, Zhu, L, Zhu, S, Zietz, M, Zippo, M, Zirino, F, and Zulkipli, FH
Published: 2024
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3. Nephrology in Malaysia

Author: Hooi, L. S., Bavanandan, S., Ahmad, G., Lim, Y. N., Bee, B. C., Morad, Z., Moura-Neto, José A., editor, Divino-Filho, José Carolino, editor, and Ronco, Claudio, editor
Published: 2021
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4. Comparing survival in patients with chronic kidney disease across three countries - Results from the study of heart and renal protection-extended review.

Author: Talbot, B, Cass, A, Walker, R, Hooi, L, Jardine, M, Jun, M, Rogers, K, Sukkar, L, Smyth, B, Gallagher, M, Talbot, B, Cass, A, Walker, R, Hooi, L, Jardine, M, Jun, M, Rogers, K, Sukkar, L, Smyth, B, and Gallagher, M
Abstract: AIM: This study examined whether survival and causes of death differed between participants enrolled from Australia (AUS), Malaysia (MYL), and New Zealand (NZ) in extended follow-up of the Study of Heart and Renal Protection (SHARP), a randomized controlled trial (RCT) of participants with moderate to severe chronic kidney disease comparing placebo to combination therapy with Simvastatin and Ezetimibe. METHODS: All participants alive at final SHARP study visit in participating centres were eligible for inclusion. Consenting participants were re-enrolled following final SHARP Study visit and followed for 5 years. Data collection included: significant medical events, hospital admissions and requirement for kidney replacement therapy. Data linkage was performed to national kidney and mortality registries. The primary outcome was all-cause mortality compared across the three countries. RESULTS: The SHARP trial randomized 2029 participants from AUS (1043/2029, 51%), MYL (701/2029, 35%), and NZ (285/2029, 14%), with 1136 participants alive and eligible for extended follow-up at the end of SHARP. In multivariable analysis, risk of death was increased for participants in MYL (HR 1.37, 95% CI 1.17-1.61, p < .001) and NZ (HR 1.28, 95% CI 1.04-1.57, p = .02) when compared to AUS participants. Adjustment for kidney transplantation as a competing risk did not explain the variation seen between countries. CONCLUSION: This study allows a better understanding of the differences in long-term mortality risk across participants from AUS, MYL, and NZ in extended follow-up of the SHARP study and demonstrates the feasibility and value of extended follow-up of participants enrolled in RCTs.
Published: 2022

5. Genetic evaluation of a complete diallel cross involving three populations of freshwater prawn (Macrobrachium rosenbergii) from different geographical regions of India

Author: Pillai, Bindu R., Mahapatra, Kanta Das, Ponzoni, Raul W., Sahoo, Lopamudra, Lalrinsanga, P.L., Nguyen, Nguyen H., Mohanty, Swagathika, Sahu, Swagathika, Vijaykumar, Sahu, Sovan, Khaw, Hooi L., Patra, Gunamaya, Patnaik, Sivani, and Rath, Suresh C.
Published: 2011
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6. Dietary habits in australian, new zealand and malaysian patients with end stage kidney disease; a pre-specified analysis of the favoured trial participants.

Author: Conley M., Kerr P.G., Polkinghorne K.R., Hooi L., Pascoe E.M., Paul-Brent P., Cass A., Voss D., Ong L., Viecelli A.K., Mori T.A., Lenhoff K., Hawley C.M., Irish A.B., Barden A., Conley M., Kerr P.G., Polkinghorne K.R., Hooi L., Pascoe E.M., Paul-Brent P., Cass A., Voss D., Ong L., Viecelli A.K., Mori T.A., Lenhoff K., Hawley C.M., Irish A.B., and Barden A.
Abstract: Aim: We report the dietary habits of people with advanced CKD and their adherence to country specific Dietary Guidelines. Background(s): Dietary management plays an important role in patients with kidney failure. Current dietary habits of Australians and New Zealanders (ANZ) and Malaysians with advanced chronic kidney disease (CKD stage 4-5) is not well described. Method(s): Participants with CKD 4-5, receiving or planning dialysis commencement within 12-months, enrolled in the FAVOURED trial completed a lifestyle questionnaire at baseline on their dietary habits of key food groups including fruit, vegetables, chicken, meat, fish, and alcohol consumption. Result(s): Of 567 participants (mean age 54.8 +/- 14.3 years, 63% male), 538 (ANZ n = 386, Malaysian n = 152) completed the dietary and lifestyle questionnaire. Dietary fruit and vegetable intakes were higher in ANZ participants; 49% consumed >=2 serves/day of fruit and 61% ate >=2 serves/day of vegetables compared to 24% and 34% of Malaysians respectively (P < 0.0001). Only 4% of ANZ participants met Australian Dietary recommendations of 2 fruit and 5 vegetable serves/day. Fish consumption was higher in Malaysians with 83% consuming >=2 serves/week compared to 21% of ANZ participants (P < 0.0001). Red meat intake was significantly higher in ANZ participants however chicken consumption was similar; 48% consumed >2 chicken serves/week and 65% ate >2 serves/week of red meat compared to 43% and 15% of Malaysians, respectively. Nearly two thirds (62%) of participants in Malaysia and ANZ did not use added salt. Alcohol was consumed by 5% of Malaysians compared with 41% of ANZ participants. Conclusion(s): Significant regional variation in dietary intake for fruit, vegetables and animal protein are described which likely reflect cultural and economic differences. Barriers to meeting recommended dietary intakes requires further study.
Published: 2021

7. Selective breeding of giant freshwater prawn ( Macrobrachium rosenbergii ) in India: Response to selection for harvest body weight and on‐farm performance evaluation

Author: Pillai, Bindu R., primary, Lalrinsanga, Pa L., additional, Ponzoni, Raul W., additional, Khaw, Hooi L., additional, Mahapatra, Kanta D., additional, Sahu, Sovan, additional, Mohanty, Swagathika, additional, Patra, Gunamaya, additional, Naik, Namita, additional, and Pradhan, Harmohan, additional
Published: 2020
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8. A randomized trial on the effect of phosphate reduction on vascular end points in CKD (improve-CKD).

Author: McMahon L.P., Vilayur E., Cooper B., Wong M.G., Tan K.-S., van Eps C., Cho Y., Barbara J., Paizis K., Nelson C., Gafor A.H.A., Meng O.L., Mushahar L., Maher E., Toussaint N.D., Pedagogos E., Lioufas N.M., Elder G.J., Pascoe E.M., Badve S.V., Valks A., Block G.A., Boudville N., Cameron J.D., Campbell K.L., Chen S.S.M., Faull R.J., Holt S.G., Jackson D., Jardine M.J., Johnson D.W., Kerr P.G., Lau K.K., Hooi L.-S., Narayan O., Perkovic V., Polkinghorne K.R., Pollock C.A., Reidlinger D., Robison L., Smith E.R., Walker R.J., Wang A.Y.M., Hawley C.M., Wyndham R., McMahon L.P., Vilayur E., Cooper B., Wong M.G., Tan K.-S., van Eps C., Cho Y., Barbara J., Paizis K., Nelson C., Gafor A.H.A., Meng O.L., Mushahar L., Maher E., Toussaint N.D., Pedagogos E., Lioufas N.M., Elder G.J., Pascoe E.M., Badve S.V., Valks A., Block G.A., Boudville N., Cameron J.D., Campbell K.L., Chen S.S.M., Faull R.J., Holt S.G., Jackson D., Jardine M.J., Johnson D.W., Kerr P.G., Lau K.K., Hooi L.-S., Narayan O., Perkovic V., Polkinghorne K.R., Pollock C.A., Reidlinger D., Robison L., Smith E.R., Walker R.J., Wang A.Y.M., Hawley C.M., and Wyndham R.
Abstract: Background Hyperphosphatemia is associated with increased fibroblast growth factor 23 (FGF23), arterial calcification, and cardiovascular mortality. Effects of phosphate-lowering medication on vascular calcification and arterial stiffness in CKD remain uncertain. Methods To assess the effects of non-calcium-based phosphate binders on intermediate cardiovascular markers, we conducted a multicenter, double-blind trial, randomizing 278 participants with stage 3b or 4 CKD and serum phosphate.1.00 mmol/L (3.10 mg/dl) to 500 mg lanthanum carbonate or matched placebo thrice daily for 96 weeks. We analyzed the primary outcome, carotid-femoral pulse wave velocity, using a linear mixed effects model for repeated measures. Secondary outcomes included abdominal aortic calcification and serum and urine markers of mineral metabolism. Results A total of 138 participants received lanthanum and 140 received placebo (mean age 63.1 years; 69% male, 64% White). Mean eGFR was 26.6 ml/min per 1.73 m2; 45% of participants had diabetes and 32% had cardiovascular disease. Mean serum phosphate was 1.25 mmol/L (3.87 mg/dl), mean pulse wave velocity was 10.8 m/s, and 81.3% had abdominal aortic calcification at baseline. At 96 weeks, pulse wave velocity did not differ significantly between groups, nor did abdominal aortic calcification, serum phosphate, parathyroid hormone, FGF23, and 24-hour urinary phosphate. Serious adverse events occurred in 63 (46%) participants prescribed lanthanum and 66 (47%) prescribed placebo. Although recruitment to target was not achieved, additional analysis suggested this was unlikely to have significantly affected the principle findings. Conclusions In patients with stage 3b/4 CKD, treatment with lanthanum over 96 weeks did not affect arterial stiffness or aortic calcification compared with placebo. These findings do not support the role of intestinal phosphate binders to reduce cardiovascular risk in patients with CKD who have normophosphatemia. Clinical Trial r
Published: 2020

9. Identifying critically important vascular access outcomes for trials in haemodialysis: An international survey with patients, caregivers and health professionals.

Author: Irish A.B., Mori T.A., Polkinghorne K.R., Hawley C.M., Viecelli A.K., Howell M., Tong A., Teixeira-Pinto A., O'Lone E., Ju A., Craig J.C., Hooi L.-S., Lee T., Lok C.E., Quinn R.R., Vachharajani T.J., Vanholder R., Zuo L., Tordoir J., Pecoits-Filho R., Yuo T., Kopperschmidt P., Johnson D.W., Pascoe E.M., Smith R., Irish A.B., Mori T.A., Polkinghorne K.R., Hawley C.M., Viecelli A.K., Howell M., Tong A., Teixeira-Pinto A., O'Lone E., Ju A., Craig J.C., Hooi L.-S., Lee T., Lok C.E., Quinn R.R., Vachharajani T.J., Vanholder R., Zuo L., Tordoir J., Pecoits-Filho R., Yuo T., Kopperschmidt P., Johnson D.W., Pascoe E.M., and Smith R.
Abstract: Background: Vascular access outcomes reported across haemodialysis (HD) trials are numerous, heterogeneous and not always relevant to patients and clinicians. This study aimed to identify critically important vascular access outcomes. Method(s): Outcomes derived from a systematic review, multi-disciplinary expert panel and patient input were included in a multilanguage online survey. Participants rated the absolute importance of outcomes using a 9-point Likert scale (7-9 being critically important). The relative importance was determined by a best-worst scale using multinomial logistic regression. Open text responses were analysed thematically. Result(s): The survey was completed by 873 participants [224 (26%) patients/caregivers and 649 (74%) health professionals] from 58 countries. Vascular access function was considered the most important outcome (mean score 7.8 for patients and caregivers/8.5 for health professionals, with 85%/95% rating it critically important, and top ranked on best-worst scale), followed by infection (mean 7.4/8.2, 79%/92% rating it critically important, second rank on best-worst scale). Health professionals rated all outcomes of equal or higher importance than patients/caregivers, except for aneurysms. We identified six themes: necessity for HD, applicability across vascular access types, frequency and severity of debilitation, minimizing the risk of hospitalization and death, optimizing technical competence and adherence to best practice and direct impact on appearance and lifestyle. Conclusion(s): Vascular access function was the most critically important outcome among patients/caregivers and health professionals. Consistent reporting of this outcome across trials in HD will strengthen their value in supporting vascular access practice and shared decision making in patients requiring HD.Copyright © 2019 The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
Published: 2020

10. SUN-119 COMPARING SURVIVAL IN PATIENTS WITH CHRONIC KIDNEY DISEASE ACROSS THREE COUNTRIES - RESULTS FROM THE STUDY OF HEART AND RENAL PROTECTION-EXTENDED REVIEW (SHARP-ER)

Author: TALBOT, B., primary, Sukkar, L., additional, Smyth, B., additional, Jun, M., additional, Jardine, M., additional, Cass, A., additional, Walker, R., additional, Reith, C., additional, Hooi, L., additional, and Gallagher, M., additional
Published: 2020
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11. Cause of death varies across Australia, New Zealand and Malaysia in those on renal replacement therapy - Results from the Study of Heart And Renal Protection-Extended Review (SHARP-ER)

Author: Talbot, B, Sukkar, L, Smyth, B, Jun, M, Jardine, M, Cass, A, Walker, R, Reith, C, Hooi, L, and Gallagher, M
Abstract: The mortality rate among dialysis patients is high with regional variability. The Study of Heart and Renal Protection-Extended Review (SHARP-ER) comprised extended 5-year follow up of eligible participants in Australia, New Zealand and Malaysia alive at the end of SHARP (a randomised double-blind trial of simvastatin and ezetimibe vs. placebo in chronic kidney disease). We compared survival and cause of death between countries in dialysis patients in the SHARP-ER cohort.
Published: 2018

12. Dual αVβ6/αVβ1 Inhibitor PLN-74809 Reduces Fibrogenesis in Ex Vivo and In Vivo Models of IPF

Author: Decaris, M., primary, Schaub, J., additional, Chen, C., additional, Cha, J., additional, Lee, G., additional, Rexhepaj, M., additional, Rao, V., additional, Kotak, P., additional, Hooi, L., additional, Wu, J., additional, Martin, S., additional, Chen, T., additional, Munoz, M., additional, Hom, T., additional, Leftheris, K., additional, Morgans, D., additional, Turner, S., additional, and Andre, P., additional
Published: 2019
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13. Protocol for the Study of Heart and Renal Protection-Extended Review: Additional 5-Year Follow-up of the Australian, New Zealand, and Malaysian SHARP Cohort

Author: Sukkar, L, Talbot, B, Jun, M, Dempsey, E, Walker, R, Hooi, L, Cass, A, Jardine, M, Gallagher, M, Sukkar, L, Talbot, B, Jun, M, Dempsey, E, Walker, R, Hooi, L, Cass, A, Jardine, M, and Gallagher, M
Abstract: Background: There are limited studies on the effects of statins on outcomes in the moderate chronic kidney disease (CKD) population and their trajectory to end-stage kidney disease. Objective: To examine the long-term effects of lipid-lowering therapy on all-cause mortality, cardiovascular morbidity, CKD progression, and socioeconomic well-being in Australian, New Zealand, and Malaysian SHARP (Study of Heart and Renal Protection) trial participants—a randomized controlled trial of a combination of simvastatin and ezetimibe, compared with placebo, for the reduction of cardiovascular events in moderate to severe CKD. Design: Protocol for an extended prospective observational follow-up. Setting: Australian, New Zealand, and Malaysian participating centers in patients with advanced CKD. Patients: All SHARP trial participants alive at the final study visit. Measurements: Primary outcomes were measured by participant self-report and verified by hospital administrative data. In addition, secondary outcomes were measured using a validated study questionnaire of health-related quality of life, a 56-item economic survey. Methods: Participants were followed up with alternating face-to-face visits and telephone calls on a 6-monthly basis until 5 years following their final SHARP Study visit. In addition, there were 6-monthly follow-up telephone calls in between these visits. Data linkage to health registries in Australia, New Zealand, and Malaysia was also performed. Results: The SHARP-Extended Review (SHARP-ER) cohort comprised 1136 SHARP participants with a median of 4.6 years of follow-up. Compared with all SHARP participants who originally participated in the Australian, New Zealand, and Malaysian regions, the SHARP-ER participants were younger (57.2 [48.3-66.4] vs 60.5 [50.3-70.7] years) with a lower proportion of men (61.5% vs 62.8%). There were a lower proportion of participants with hypertension (83.7% vs 85.0%) and diabetes (20.0% vs 23.5%). Limitations: As a long-term
Published: 2019

14. Fish oil and aspirin effects on arteriovenous fistula function: Secondary outcomes of the randomised omega-3 fatty acids (Fish oils) and Aspirin in Vascular access OUtcomes in REnal Disease (FAVOURED) trial.

Author: Paul-Brent P.-A., Irish A.B., Cass A., Hooi L.-S., Badve S.V., Hawley C.M., Viecelli A.K., Polkinghorne K.R., Pascoe E.M., Kerr P.G., Mori T.A., Ong L.-M., Voss D., Johnson D.W., Paul-Brent P.-A., Irish A.B., Cass A., Hooi L.-S., Badve S.V., Hawley C.M., Viecelli A.K., Polkinghorne K.R., Pascoe E.M., Kerr P.G., Mori T.A., Ong L.-M., Voss D., and Johnson D.W.
Abstract: Background Arteriovenous fistulas (AVF) for haemodialysis often experience early thrombosis and maturation failure requiring intervention and/or central venous catheter (CVC) placement. This secondary and exploratory analysis of the FAVOURED study determined whether omega-3 fatty acids (fish oils) or aspirin affected AVF usability, intervention rates and CVC requirements. Methods In 567 adult participants planned for AVF creation, all were randomised to fish oil (4g/d) or placebo, and 406 to aspirin (100mg/d) or placebo, starting one day pre-surgery and continued for three months. Outcomes evaluated within 12 months included AVF intervention rates, CVC exposure, late dialysis suitability failure, and times to primary patency loss, abandonment and successful cannulation. Results Final analyses included 536 participants randomised to fish oil or placebo (mean age 55 years, 64% male, 45% diabetic) and 388 randomised to aspirin or placebo. Compared with placebo, fish oil reduced intervention rates (0.82 vs 1.14/1000 patient-days, incidence rate ratio [IRR] 0.72, 95% confidence interval [CI] 0.54-0.97), particularly interventions for acute thrombosis (0.09 vs 0.17/1000 patient-days, IRR 0.53, 95% CI 0.34-0.84). Aspirin significantly reduced rescue intervention rates (IRR 0.45, 95% CI 0.27-0.78). Neither agent significantly affected CVC exposure, late dialysis suitability failure or time to primary patency loss, AVF abandonment or successful cannulation. Conclusion Although fish oil and low-dose aspirin given for 3 months reduced intervention rates in newly created AVF, they had no significant effects on CVC exposure, AVF usability and time to primary patency loss or access abandonment. Reduction in access interventions benefits patients, reduces costs and warrants further study.Copyright © 2019 Viecelli et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduct
Published: 2019

15. Fish oil and aspirin effects on arteriovenous fistula function: Secondary outcomes of the randomised omega-3 fatty acids (Fish oils) and Aspirin in Vascular access OUtcomes in REnal Disease (FAVOURED) trial

Author: Puebla, I, Viecelli, AK, Polkinghorne, KR, Pascoe, EM, Paul-Brent, P-A, Hawley, CM, Badve, SV, Cass, A, Hooi, L-S, Kerr, PG, Mori, TA, Ong, L-M, Voss, D, Johnson, DW, Irish, AB, Peh, CA, Beller, E, Dogra, S, Gracey, D, Haluszkiewicz, E, Hawley, C, Hutchison, C, Irish, A, Kerr, P, Mather, A, McDonald, S, McIntyre, C, Mori, T, Pascoe, E, Polkinghorne, K, Robertson, A, Rosman, J, Forbes, A, Levin, A, Wheeler, DC, Puebla, I, Viecelli, AK, Polkinghorne, KR, Pascoe, EM, Paul-Brent, P-A, Hawley, CM, Badve, SV, Cass, A, Hooi, L-S, Kerr, PG, Mori, TA, Ong, L-M, Voss, D, Johnson, DW, Irish, AB, Peh, CA, Beller, E, Dogra, S, Gracey, D, Haluszkiewicz, E, Hawley, C, Hutchison, C, Irish, A, Kerr, P, Mather, A, McDonald, S, McIntyre, C, Mori, T, Pascoe, E, Polkinghorne, K, Robertson, A, Rosman, J, Forbes, A, Levin, A, and Wheeler, DC
Abstract: BACKGROUND: Arteriovenous fistulas (AVF) for haemodialysis often experience early thrombosis and maturation failure requiring intervention and/or central venous catheter (CVC) placement. This secondary and exploratory analysis of the FAVOURED study determined whether omega-3 fatty acids (fish oils) or aspirin affected AVF usability, intervention rates and CVC requirements. METHODS: In 567 adult participants planned for AVF creation, all were randomised to fish oil (4g/d) or placebo, and 406 to aspirin (100mg/d) or placebo, starting one day pre-surgery and continued for three months. Outcomes evaluated within 12 months included AVF intervention rates, CVC exposure, late dialysis suitability failure, and times to primary patency loss, abandonment and successful cannulation. RESULTS: Final analyses included 536 participants randomised to fish oil or placebo (mean age 55 years, 64% male, 45% diabetic) and 388 randomised to aspirin or placebo. Compared with placebo, fish oil reduced intervention rates (0.82 vs 1.14/1000 patient-days, incidence rate ratio [IRR] 0.72, 95% confidence interval [CI] 0.54-0.97), particularly interventions for acute thrombosis (0.09 vs 0.17/1000 patient-days, IRR 0.53, 95% CI 0.34-0.84). Aspirin significantly reduced rescue intervention rates (IRR 0.45, 95% CI 0.27-0.78). Neither agent significantly affected CVC exposure, late dialysis suitability failure or time to primary patency loss, AVF abandonment or successful cannulation. CONCLUSION: Although fish oil and low-dose aspirin given for 3 months reduced intervention rates in newly created AVF, they had no significant effects on CVC exposure, AVF usability and time to primary patency loss or access abandonment. Reduction in access interventions benefits patients, reduces costs and warrants further study.
Published: 2019

16. Purification and characterisation of epithiospecifier protein from Brassica napus: enzymic intramolecular sulphur addition within alkenyl thiohydroximates derived from alkenyl glucosinolate hydrolysis

Author: Foo, Hooi L., Grønning, Line M., Goodenough, Lucy, Bones, Atle M., Danielsen, Brit-Eli, Whiting, Don A., and Rossiter, John T.
Published: 2000
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17. Vascular Access Outcomes Reported in Maintenance Hemodialysis Trials: A Systematic Review.

Author: Irish A.B., Zuo L., Mori T.A., Hawley C.M., Viecelli A.K., O'Lone E., Sautenet B., Craig J.C., Tong A., Chemla E., Hooi L.-S., Lee T., Lok C., Polkinghorne K.R., Quinn R.R., Vachharajani T., Vanholder R., Johnson D.W., Pascoe E.M., Irish A.B., Zuo L., Mori T.A., Hawley C.M., Viecelli A.K., O'Lone E., Sautenet B., Craig J.C., Tong A., Chemla E., Hooi L.-S., Lee T., Lok C., Polkinghorne K.R., Quinn R.R., Vachharajani T., Vanholder R., Johnson D.W., and Pascoe E.M.
Abstract: Background: Many randomized controlled trials have been performed with the goal of improving outcomes related to hemodialysis vascular access. If the reported outcomes are relevant and measured consistently to allow comparison of interventions across trials, such trials can inform decision making. This study aimed to assess the scope and consistency of vascular access outcomes reported in contemporary hemodialysis trials. Study Design: Systematic review. Setting & Population: Adults requiring maintenance hemodialysis. Selection Criteria: All randomized controlled trials and trial protocols reporting vascular access outcomes identified from ClinicalTrials.gov, Embase, MEDLINE, and the Cochrane Kidney and Transplant Specialized Register from January 2011 to June 2016. Intervention(s): Any hemodialysis-related intervention. Outcome(s): The frequency and characteristics of vascular access outcome measures were analyzed and classified. Result(s): From 168 relevant trials, 1,426 access-related outcome measures were extracted and classified into 23 different outcomes. The 3 most common outcomes were function (136 [81%] trials), infection (63 [38%]), and maturation (31 [18%]). Function was measured in 489 different ways, but most frequently reported as "mean access blood flow (mL/min)" (37 [27%] trials) and "number of thromboses" (30 [22%]). Infection was assessed in 136 different ways, with "number of access-related infections" being the most common measure. Maturation was assessed in 44 different ways at 15 different time points and most commonly characterized by vein diameter and blood flow. Patient-reported outcomes, including pain (19 [11%]) and quality of life (5 [3%]), were reported infrequently. Only a minority of trials used previously standardized outcome definitions. Limitation(s): Restricted sampling frame for feasibility and focus on contemporary trials. Conclusion(s): The reporting of access outcomes in hemodialysis trials is very heterogeneous, with limited p
Published: 2018

18. Report of the Standardized Outcomes in Nephrology-Hemodialysis (SONG-HD) Consensus Workshop on Establishing a Core Outcome Measure for Hemodialysis Vascular Access.

Author: Caskey F., Hawley C.M., Levin A., Wang A., Porter A., Sautenent B., Reddy B., Hemmelgarn B., Schiller B., Wheeler D., Harris D., Schatell D., Lacson E., Bavlovlenkov E., Strippoli G., Feldman H., Apata I., Tordoir J., Flythe J., Gill J., Kusek J., Abbott K., Dember L., Cervantes L., Moist L., Poole L., Tonelli M., Gallieni M., Elliot M., Klusmeyer M., Josephson M., Robbin M., Riella M., Evangelidis N., Tugwell P., Ravani P., Roy-Chaudhury P., Mehrotra R., Pecoits-Filho R., Crowe S., Evered S., Segerer S., Fadem S., McDonald S., Sprague S., Palmer S., Poma T., Sikirica V., Jha V., van Biesen W., Winkelmayer W., Mayers A., Bell B., Carter J., Hardy K., Ennis M., Johnson M., Rouse N., Wright S., Harris T., Muhammad U., McNorton V., Mayers D., Ennis D., Kerr P., Polkinghorne K.R., Viecelli A.K., Tong A., O'Lone E., Ju A., Hanson C.S., Sautenet B., Craig J.C., Manns B., Howell M., Chemla E., Hooi L.-S., Johnson D.W., Lee T., Lok C.E., Quinn R.R., Vachharajani T., Vanholder R., Zuo L., Caskey F., Hawley C.M., Levin A., Wang A., Porter A., Sautenent B., Reddy B., Hemmelgarn B., Schiller B., Wheeler D., Harris D., Schatell D., Lacson E., Bavlovlenkov E., Strippoli G., Feldman H., Apata I., Tordoir J., Flythe J., Gill J., Kusek J., Abbott K., Dember L., Cervantes L., Moist L., Poole L., Tonelli M., Gallieni M., Elliot M., Klusmeyer M., Josephson M., Robbin M., Riella M., Evangelidis N., Tugwell P., Ravani P., Roy-Chaudhury P., Mehrotra R., Pecoits-Filho R., Crowe S., Evered S., Segerer S., Fadem S., McDonald S., Sprague S., Palmer S., Poma T., Sikirica V., Jha V., van Biesen W., Winkelmayer W., Mayers A., Bell B., Carter J., Hardy K., Ennis M., Johnson M., Rouse N., Wright S., Harris T., Muhammad U., McNorton V., Mayers D., Ennis D., Kerr P., Polkinghorne K.R., Viecelli A.K., Tong A., O'Lone E., Ju A., Hanson C.S., Sautenet B., Craig J.C., Manns B., Howell M., Chemla E., Hooi L.-S., Johnson D.W., Lee T., Lok C.E., Quinn R.R., Vachharajani T., Vanholder R., and Zuo L.
Abstract: Vascular access outcomes in hemodialysis are critically important for patients and clinicians, but frequently are neither patient relevant nor measured consistently in randomized trials. A Standardized Outcomes in Nephrology-Hemodialysis (SONG-HD) consensus workshop was convened to discuss the development of a core outcome measure for vascular access. 13 patients/caregivers and 46 professionals (clinicians, policy makers, industry representatives, and researchers) attended. Participants advocated for vascular access function to be a core outcome based on the broad applicability of function regardless of access type, involvement of a multidisciplinary team in achieving a functioning access, and the impact of access function on quality of life, survival, and other access-related outcomes. A core outcome measure for vascular access required demonstrable feasibility for implementation across different clinical and trial settings. Participants advocated for a practical and flexible outcome measure with a simple actionable definition. Integrating patients' values and preferences was warranted to enhance the relevance of the measure. Proposed outcome measures for function included "uninterrupted use of the access without the need for interventions" and "ability to receive prescribed dialysis," but not "access blood flow," which was deemed too expensive and unreliable. These recommendations will inform the definition and implementation of a core outcome measure for vascular access function in hemodialysis trials.Copyright © 2018 National Kidney Foundation, Inc.
Published: 2018

19. Updates on baseline characteristics of the omega-3 fatty acids (Fish oils) and Aspirin in Vascular access OUtcomes in REnal Disease (FAVOURED) study.

Author: Irish A.B., Kerr P.G., Mori T.A., Scaria A., Hooi L.-S., Ong L.-M., Viecelli A.K., Pascoe E.M., Polkinghorne K.R., Hawley C.M., Paul-Brent P.-A., Badve S.V., Cass A., Johnson D.W., Irish A.B., Kerr P.G., Mori T.A., Scaria A., Hooi L.-S., Ong L.-M., Viecelli A.K., Pascoe E.M., Polkinghorne K.R., Hawley C.M., Paul-Brent P.-A., Badve S.V., Cass A., and Johnson D.W.
Published: 2017

20. Effect of fish oil supplementation and aspirin use on arteriovenous fistula failure in patients requiring hemodialysis a randomized clinical trial.

Author: Cass A., Paul-Brent P.-A., Badve S.V., Mori T.A., Kerr P.G., Polkinghorne K.R., Ong L.-M., Voss D., Irish A.B., Viecelli A.K., Hawley C.M., Hooi L.-S., Pascoe E.M., Cass A., Paul-Brent P.-A., Badve S.V., Mori T.A., Kerr P.G., Polkinghorne K.R., Ong L.-M., Voss D., Irish A.B., Viecelli A.K., Hawley C.M., Hooi L.-S., and Pascoe E.M.
Abstract: IMPORTANCE Vascular access dysfunction is a leading cause of morbidity and mortality in patients requiring hemodialysis. Arteriovenous fistulae are preferred over synthetic grafts and central venous catheters due to superior long-term outcomes and lower health care costs, but increasing their use is limited by early thrombosis and maturation failure. ?-3 Polyunsaturated fatty acids (fish oils) have pleiotropic effects on vascular biology and inflammation and aspirin impairs platelet aggregation, which may reduce access failure. OBJECTIVE To determine whether fish oil supplementation (primary objective) or aspirin use (secondary objective) is effective in reducing arteriovenous fistula failure. DESIGN, SETTING, AND PARTICIPANTS The Omega-3 Fatty Acids (Fish Oils) and Aspirin in Vascular Access Outcomes in Renal Disease (FAVOURED) study was a randomized, double-blind, controlled clinical trial that recruited participants with stage 4 or 5 chronic kidney disease from 2008 to 2014 at 35 dialysis centers in Australia, Malaysia, New Zealand, and the United Kingdom. Participants were observed for 12 months after arteriovenous fistula creation. INTERVENTIONS Participants were randomly allocated to receive fish oil (4 g/d) or matching placebo. A subset (n = 406) was also randomized to receive aspirin (100mg/d) or matching placebo. Treatment started 1 day prior to surgery and continued for 12 weeks. MAIN OUTCOMES AND MEASURES The primary outcomewas fistula failure, a composite of fistula thrombosis and/or abandonment and/or cannulation failure, at 12 months. Secondary outcomes included the individual components of the primary outcome. RESULTS Of 1415 eligible participants, 567 were randomized (359 [63%] male, 298 [53%] white, 264 [47%] with diabetes; mean [SD] age, 54.8 [14.3] y). The same proportion of fistula failures occurred in the fish oil and placebo arms (128 of 270 [47%] vs 125 of 266 [47%]; relative risk [RR] adjusted for aspirin use, 1.03; 95%CI, 0.86-1.23; P = .78)
Published: 2017

21. A comparison of arteriovenous fistula failure between malaysian and australian and new zealand participants enrolled in the favoured trial.

Author: Voss D., Irish A., Kerr P., Hawley C., Johnson D., Viecelli A., Pascoe E., Polkinghorne K., Paul-Brent P., Darssan D., Hooi L., Ong L., Mori T., Badve S., Cass A., Voss D., Irish A., Kerr P., Hawley C., Johnson D., Viecelli A., Pascoe E., Polkinghorne K., Paul-Brent P., Darssan D., Hooi L., Ong L., Mori T., Badve S., and Cass A.
Abstract: Aim: To describe and compare arteriovenous fistula failure between Australia and New Zealand (ANZ) and Malaysia. Background(s): Arteriovenous fistulae (AVF) are the preferred haemodialysis access but limited by early failure in 20-50%. Failure rates in ANZ and Malaysia are unknown. Method(s): We assessed 353 participants from ANZ and Malaysia included in the omega-3 fatty acids (Fish oils) and Aspirin in Vascular access OUtcomes in REnal Disease (FAVOURED) randomized-controlled trial. AVF failure was defined as a composite of AVF thrombosis and/or abandonment and/or cannulation failure. The composite and each component were compared between participants from ANZ (n = 209) and Malaysia (n= 144) using log binomial regression with adjustment for predictors of AVF failure. Result(s): The mean age was 55 years, 64%weremale and 52% diabetic. At twelvemonths after AVF creation, 47%ofAVF had failed. AVF failure was significantly lower in participants in Malaysia compared to participants in ANZ (54/144 [38%] versus 113/209 [54%], p<0.01). This remained significant after adjustment (risk ratio [RR] 0.71, 95% confidence interval [CI] 0.53-0.96, p = 0.02). This difference in AVF failure was driven by a lower risk of cannulation failure (42/144 [29%] versus 98/209 [47%], adjusted RR 0.63, 95% CI 0.44-0.91, p<0.01), while the proportions of AVF thrombosis (25/144 [17%] versus 42/209 [20%], p = 0.91) and abandonment (36/144 [25%] versus 49/209 [23%], p = 0.91) were not different. Conclusion(s): This analysis confirms the high proportion of AVF failure. However, the risk of AVF failure was significantly lower in Malaysia compared to ANZ and was driven by a lower risk of cannulation failure. Differences in practice patterns, including patient selection, surgical and/or cannulation techniques, likely contributed to the observed differences in outcomes and warrant further investigation.
Published: 2016

22. Effect of fish oil and aspirin on arteriovenous fistula failure in haemodialysis-a randomized controlled trial.

Author: Hooi L., Cass A., Kerr P., Voss D., Ong L., Polkinghorne K., Mori T., Irish A., Viecelli A., Hawley C., Pascoe E., Badve S., Paul-Brent P., Hooi L., Cass A., Kerr P., Voss D., Ong L., Polkinghorne K., Mori T., Irish A., Viecelli A., Hawley C., Pascoe E., Badve S., and Paul-Brent P.
Abstract: Aim: To determine whether fish oil or aspirin is effective in reducing arteriovenous fistula (AVF) failure. Background(s): Increasing the use of AVF to improve haemodialysis access outcomes is limited by early thrombosis and maturation failure. Omega-3 polyunsaturated fatty acids (fish oils) have pleiotropic effects upon vascular biology and inflammation, and aspirin impairs platelet aggregation, which may reduce access failure. Method(s): In this double-blind, placebo-controlled trial, 567 participants from Australia, Malaysia, New Zealand and the United Kingdom planning to undergo AVF surgery were randomized to fish oil (4 g/day) or placebo for 12weeks. Of these, 406 participants were also randomized to aspirin (100mg/day) or placebo for 12weeks. The primary outcome was AVF failure at 12months, a composite of AVF thrombosis and/or abandonment and/or cannulation failure. Result(s): The proportion of AVF failure in the fish oil and placebo arms was similar (47% versus 47%, relative risk [RR] adjusted for aspirin use 1.03, 95% confidence interval [CI] 0.86-1.23, p = 0.78). Fish oil did not reduce the risk of AVF thrombosis (22% versus 23%, RR 0.98, 95% CI 0.72-1.34, p = 0.90), abandonment (19% versus 22%, RR 0.87, 95% CI 0.62-1.22, p = 0.43) or cannulation failure (40% versus 39%, RR 1.03, 95% CI 0.83-1.26, p = 0.81). There were no significant differences in adverse drug events (9% versus 13%, p = 0.15) including bleeding complications (6% versus 4%, p = 0.26) between the fish oil and placebo arms. The risk of AVF failure did not differ between the aspirin and placebo arms (45% versus 43%, RR 1.05, 95% CI 0.84-1.31, p = 0.68), and adverse events including bleeding were comparable between participants assigned to aspirin or placebo. Conclusion(s): Neither fish oil nor aspirin was effective in preventing AVF failure.
Published: 2016

23. Genetic parameters for uniformity of harvest weight and body size traits in the GIFT strain of Nile tilapia

Author: Marjanovic, Jovana, Mulder, H.A., Khaw, Hooi L., Bijma, Piter, Marjanovic, Jovana, Mulder, H.A., Khaw, Hooi L., and Bijma, Piter
Abstract: Background: Animal breeding programs have been very successful in improving the mean levels of traits through selection. However, in recent decades, reducing the variability of trait levels between individuals has become a highly desirable objective. Reaching this objective through genetic selection requires that there is genetic variation in the variability of trait levels, a phenomenon known as genetic heterogeneity of environmental (residual) variance. The aim of our study was to investigate the potential for genetic improvement of uniformity of harvest weight and body size traits (length, depth, and width) in the genetically improved farmed tilapia (GIFT) strain. In order to quantify the genetic variation in uniformity of traits and estimate the genetic correlations between level and variance of the traits, double hierarchical generalized linear models were applied to individual trait values. Results: Our results showed substantial genetic variation in uniformity of all analyzed traits, with genetic coefficients of variation for residual variance ranging from 39 to 58 %. Genetic correlation between trait level and variance was strongly positive for harvest weight (0.60 ± 0.09), moderate and positive for body depth (0.37 ± 0.13), but not significantly different from 0 for body length and width. Conclusions: Our results on the genetic variation in uniformity of harvest weight and body size traits show good prospects for the genetic improvement of uniformity in the GIFT strain. A high and positive genetic correlation was estimated between level and variance of harvest weight, which suggests that selection for heavier fish will also result in more variation in harvest weight. Simultaneous improvement of harvest weight and its uniformity will thus require index selection.
Published: 2016

24. Genetic parameters for uniformity of harvest weight and body size traits in the GIFT strain of Nile tilapia

Author: Marjanovic, Jovana, primary, Mulder, Han A., additional, Khaw, Hooi L., additional, and Bijma, Piter, additional
Published: 2016
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25. 1228 CHARACTERIZATION OF NOVEL, HIGHLY POTENT NS5A INHIBITORS WITH QD DOSING POTENTIAL AND ROBUST ACTIVITY IN AN HCV CHIMERIC ANIMAL MODEL

Author: Nicholas, J.B., primary, Buckman, B.O., additional, Serebryany, V., additional, Schaefer, C.J., additional, Kossen, K., additional, Ruhrmund, D., additional, Hooi, L., additional, Aleskovski, N., additional, Arfsten, A., additional, Lim, S.R., additional, Pan, L., additional, Huang, L., additional, Rajagopalan, R., additional, Misialek, S., additional, and Seiwert, S., additional
Published: 2011
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26. 1196 NOVEL, POTENT, PAN-GENOTYPIC HCV NS3/4A PROTEASE INHIBITORS WITH A HIGH BARRIER TO RESISTANCE

Author: Buckman, B.O., primary, Kossen, K., additional, Nicholas, J.B., additional, Serebryany, V., additional, Ruhrmund, D., additional, Rajagopalan, R., additional, Misialek, S., additional, Hooi, L., additional, Aleskovski, N., additional, Pan, L., additional, Huang, L., additional, Schaefer, C.J., additional, Rajyaguru, S., additional, Le Pogam, S., additional, Nájera, I., additional, Klumpp, K., additional, and Seiwert, S., additional
Published: 2011
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27. Feeding of different levels of metabolite combinations produced by Lactobacillus plantarum on growth performance, fecal microflora, volatile fatty acids and villi height in broilers

Author: LOH, Teck C., primary, THANH, Nguyen T., additional, FOO, Hooi L., additional, HAIR‐BEJO, Mohd, additional, and AZHAR, Bin K., additional
Published: 2010
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28. Crystal structure of HCV NS5b 1b with (1,1-dioxo-2H-[1,2,4]benzothiadiazin-3-yl) azolo[1,5-a]pyrimidine derivative

Author: Wang, G., primary, Lei, H., additional, Wang, X., additional, Das, D., additional, Mackinnon, C., additional, Montalbetti, C.A.G., additional, Mears, R., additional, Gai, X., additional, Bailey, S., additional, Ruhrmund, D., additional, Hooi, L., additional, Misialek, S., additional, Rajagopalan, R., additional, Cheng, R.K.Y., additional, Barker, J.L., additional, Felicetti, B., additional, Stoycheva, A., additional, Buckman, B., additional, Kossen, K., additional, and Seiwert, S, additional
Published: 2009
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29. 936 COMBINATION OF THE NS3/4A PROTEASE INHIBITOR ITMN-191 WITH THE ALLOSTERIC NS5B POLYMERASE INHIBITOR ITMN-8020 ENHANCES REPLICON CLEARANCE AND REDUCES THE EMERGENCE OF DRUG RESISTANT VARIANTS

Author: Tan, H., primary, Wang, G., additional, Moy, C., additional, Kossen, K., additional, Rajagopalan, R., additional, Misialek, S., additional, Ruhrmund, D., additional, Hooi, L., additional, Snarskaya, N., additional, Stoycheva, A., additional, Buckman, B., additional, Seiwert, S., additional, and Beigelman, L., additional
Published: 2009
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30. 938 DISCOVERY OF POTENT, BIOAVAILABLE HCV NS3/4A INHIBITORS THAT DISPLAY UNIMPAIRED ACTIVITY AGAINST AN NS3 SEQUENCE VARIANT ASSOCIATED WITH RESISTANCE TO LINEAR TETRAPEPTIDES AND MACROCYCLIC INHIBITORS

Author: Buckman, B., primary, Kossen, K., additional, Ruhrmund, D., additional, Rajagopalan, R., additional, Stevens, S., additional, Hooi, L., additional, Snarskaya, L., additional, Wang, T., additional, Hong, J., additional, Lim, S., additional, Pan, L., additional, Huang, L., additional, Stoycheva, N., additional, Beigelman, L., additional, and Seiwert, S., additional
Published: 2009
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31. The Omega-3 fatty acids (Fish Oils) and Aspirin in Vascular access OUtcomes in REnal Disease (FAVOURED) study: the updated final trial protocol and rationale of post-initiation trial modifications.

Author: Viecelli, Andrea K., Pascoe, Elaine, Polkinghorne, Kevan R., Hawley, Carmel, Paul-Brent, Peta-Anne, Badve, Sunil V., Cass, Alan, Heritier, Stephane, Kerr, Peter G., Mori, Trevor A., Robertson, Amanda, Seong, Hooi L., and Irish, Ashley B.
Subjects: ARTERIAL catheterization, FISH oils, ASPIRIN, KIDNEY diseases, HEMODIALYSIS, CHRONIC kidney failure, POPULATION aging
Abstract: Background: The FAVOURED study is an international multicentre, double-blind, placebo-controlled trial which commenced recruitment in 2008 and examines whether omega-3 polyunsaturated fatty acids (omega-3 PUFAs) either alone or in combination with aspirin will effectively reduce primary access failure of de novo arteriovenous fistulae (AVF) in patients with stage 4 and 5 chronic kidney disease. Publication of new evidence derived from additional studies of clopidogrel and a high screen failure rate due to prevalent aspirin usage prompted an updated trial design. Methods/design: The original trial protocol published in 2009 has undergone two major amendments, which were implemented in 2011. Firstly, the primary outcome 'early thrombosis' at 3 months following AVF creation was broadened to a more clinically relevant outcome of 'AVF access failure'; a composite of thrombosis, AVF abandonment and cannulation failure at 12 months. Secondly, participants unable to cease using aspirin were allowed to be enrolled and randomised to omega-3 PUFAs or placebo. The revised primary aim of the FAVOURED study is to test the hypothesis that omega-3 PUFAs will reduce rates of AVF access failure within 12 months following AVF surgery. The secondary aims are to examine the effect of omega-3 PUFAs and aspirin on the individual components of the primary end-point, to examine the safety of study interventions and assess central venous catheter requirement as a result of access failure. Discussion: This multicentre international clinical trial was amended to address the clinically relevant question of whether the usability of de novo AVF at 12 months can be improved by the early use of omega-3 PUFAs and to a lesser extent aspirin. This study protocol amendment was made in response to a large trial demonstrating that clopidogrel is effective in safely preventing primary AVF thrombosis, but ineffective at increasing functional patency. Secondly, including patients taking aspirin will enrol a more representative cohort of haemodialysis patients, who are significantly older with a higher prevalence of cardiovascular disease and diabetes which may increase event rates and the power of the study [ABSTRACT FROM AUTHOR]
Published: 2015
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32. Chemical imaging of microvias in flip chip pin grid array packages using time-of-flight secondary ion mass spectroscopy.

Author: Khong, Yoon L. and Lee, Hooi L.
Published: 2000
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33. Chemical imaging of microvias in flip chip pin grid array packages using time-of-flight secondary ion mass spectroscopy

Author: Khong, Yoon L., primary and Lee, Hooi L., additional
Published: 2000
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34. Outcome assessment of the Ministry of Health Malaysia dialysis programme

Author: Lim, T. O., Lim, Y. N., Hin-Seng Wong, Ahmad, G., Singam, T. S., Morad, Z., Suleiman, A. B., Rozina, G., Ong, L. M., Hooi, L. S., Shaariah, W., Tan, C. C., and Loo, C. S.

35. VASCULAR ACCESS OUTCOMES REPORTED IN RANDOMISED TRIALS CONDUCTED IN PATIENTS REQUIRING HAEMODIALYSIS: A SYSTEMATIC REVIEW

Author: Viecelli, A. K., O Lone, E., Sautenet, B., Jonathan Craig, Tong, A., Chemla, E., Hooi, L. S., Lee, T., Lok, C., Polkinghorne, K. R., Quinn, R. R., Vachharajani, T., Vanholder, R., Zuo, L., Irish, A. B., Mori, T. A., Pascoe, E. M., Johnson, D. W., and Hawley, C. M.

36. REPORT OF THE STANDARDISED OUTCOMES IN NEPHROLOGY-HAEMODIALYSIS (SONG-HD) CONSENSUS WORKSHOP ON ESTABLISHING A CORE OUTCOME MEASURE FOR VASCULAR ACCESS IN HAEMODIALYSIS

Author: Viecelli, A. K., Tong, A., O Lone, E., Ju, A., Hanson, C., Sautenet, B., Craig, J. C., Manns, B., Howell, M., Chemla, E., Hooi, L. S., Johnson, D. W., Lee, T., Lok, C., Polkinghorne, K. R., Quinn, R. R., Tushar Vachharajani, Vanholder, R., Zuo, L., and Hawley, C. M.

37. Acceptance level of push technology-based online shopping widget among malaysians: Application of technology acceptance theory

Author: Hooi, L. Y., Mohd Azam Osman, Idrus, R., and Shiang-Yen, T.

38. A randomized, multicenter, open-label trial to establish therapeutic equivalence between the carex and ultra disconnect systems in patients on continuous ambulatory peritoneal dialysis

Author: Ong, L. -M, Lim, T. -O, Hooi, L. -S, Morad, Z., Tan, P. -C, Hin-Seng Wong, Lim, Y. -N, Ghazalli, R., Tan, C. -C, Shaariah, W., and Liew, B. -S

39. Effect of fish oil supplementation and aspirin use on arteriovenous fistula failure in patients requiring hemodialysis: A randomized clinical trial,Das Problem des Shunt-versagens: Hilfe durch Fischöl-Supplementation und Aspirin?

Author: Irish, A. B., Viecelli, A. K., Hawley, C. M., Hooi, L. S., Pascoe, E. M., Paul-Brent, P. A., Sunil Badve, Mori, T. A., Cass, A., Kerr, P. G., Voss, D., Ong, L. M., and Polkinghorne, K. R.

40. TRADITIONAL SPORTS-BASED LEARNING: INNOVATIVE LEARNING METHOD TO IMPROVE FUNDAMENTAL MOVEMENT SKILLS AND LEARNING MOTIVATION

Author: Festiawan, R., Hooi, L. B., Nor, M. A. M., Ngadiman, N., Widiawati, P., Erick Burhaein, and Phytanza, D. T. P.

41. Flash optimization of drug combinations for Acinetobacter baumannii with IDentif.AI-AMR.

Author: You K, Binte Mohamed Yazid N, Chong LM, Hooi L, Wang P, Zhuang I, Chua S, Lim E, Kok AZX, Marimuthu K, Vasoo S, Ng OT, Chan CEZ, Chow EK, and Ho D
Abstract: Antimicrobial resistance (AMR) is an emerging threat to global public health. Specifically, Acinetobacter baumannii (A. baumannii), one of the main pathogens driving the rise of nosocomial infections, is a Gram-negative bacillus that displays intrinsic resistance mechanisms and can also develop resistance by acquiring AMR genes from other bacteria. More importantly, it is resistant to nearly 90% of standard of care (SOC) antimicrobial treatments, resulting in unsatisfactory clinical outcomes and a high infection-associated mortality rate of over 30%. Currently, there is a growing challenge to sustainably develop novel antimicrobials in this ever-expanding arms race against AMR. Therefore, a sustainable workflow that properly manages healthcare resources to ultra-rapidly design optimal drug combinations for effective treatment is needed. In this study, the IDentif.AI-AMR platform was harnessed to pinpoint effective regimens against four A. baumannii clinical isolates from a pool of nine US FDA-approved drugs. Notably, IDentif.AI-pinpointed ampicillin-sulbactam/cefiderocol and cefiderocol/polymyxin B/rifampicin combinations were able to achieve 93.89 ± 5.95% and 92.23 ± 11.89% inhibition against the bacteria, respectively, and they may diversify the reservoir of treatment options for the indication. In addition, polymyxin B in combination with rifampicin exhibited broadly applicable efficacy and strong synergy across all tested clinical isolates, representing a potential treatment strategy for A. baumannii. IDentif.AI-pinpointed combinations may potentially serve as alternative treatment strategies for A. baumannii., Competing Interests: Competing interests: D.H. is one of the inventors of previously filed pending patents on artificial intelligence-based therapy development. E.K.-H.C. and D.H. are co-founders and shareholders of KYAN Therapeutics, which is commercializing intellectual property pertaining to AI-based personalized medicine. The findings from this study are being made available for public benefit, and no intellectual property rights arising from the work reported here are being pursued. The remaining authors declare no conflicts of interest., (© 2025. The Author(s).)
Published: 2025
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42. Audit on data accuracy of the Malaysian Dialysis and Transplant Registry (MDTR).

Author: Thong KM, Jalalonmuhali M, Choo CL, Yee SY, Yahya R, Jeremiah PN, Bavanandan S, and Hooi LS
Subjects: Humans, Renal Dialysis adverse effects, Data Accuracy, Registries, Kidney Failure, Chronic surgery, Diabetes Mellitus
Abstract: Diabetes mellitus is the main aetiology of end stage kidney disease (ESKD) in Malaysia. However, there may be concerns of over-reporting of diabetes mellitus as the cause of ESKD in the Malaysian Dialysis and Transplant Registry (MDTR). The objective of this audit is to assess the accuracy of data collected in the MDTR. There were 151 centres/source data providers (SDP) with a total of 1977 patients included in this audit. The audit showed that 80.2% of doctors' records matched the MDTR data. The results were comparable with published validation studies in other countries.
Published: 2024

43. A functional personalised oncology approach against metastatic colorectal cancer in matched patient derived organoids.

Author: Thng DKH, Hooi L, Siew BE, Lee KY, Tan IJ, Lieske B, Lin NS, Kow AWC, Wang S, Rashid MBMA, Ang C, Koh JJM, Toh TB, Tan KK, and Chow EK
Abstract: Globally, colorectal cancer (CRC) is the third most frequently occurring cancer. Progression on to an advanced metastatic malignancy (metCRC) is often indicative of poor prognosis, as the 5-year survival rates of patients decline rapidly. Despite the availability of many systemic therapies for the management of metCRC, the long-term efficacies of these regimens are often hindered by the emergence of treatment resistance due to intratumoral and intertumoral heterogeneity. Furthermore, not all systemic therapies have associated biomarkers that can accurately predict patient responses. Hence, a functional personalised oncology (FPO) approach can enable the identification of patient-specific combinatorial vulnerabilities and synergistic combinations as effective treatment strategies. To this end, we established a panel of CRC patient-derived organoids (PDOs) as clinically relevant biological systems, of which three pairs of matched metCRC PDOs were derived from the primary sites (ptCRC) and metastatic lesions (mCRC). Histological and genomic characterisation of these PDOs demonstrated the preservation of histopathological and genetic features found in the parental tumours. Subsequent application of the phenotypic-analytical drug combination interrogation platform, Quadratic Phenotypic Optimisation Platform, in these pairs of PDOs identified patient-specific drug sensitivity profiles to epigenetic-based combination therapies. Most notably, matched PDOs from one patient exhibited differential sensitivity patterns to the rationally designed drug combinations despite being genetically similar. These findings collectively highlight the limitations of current genomic-driven precision medicine in guiding treatment strategies for metCRC patients. Instead, it suggests that epigenomic profiling and application of FPO could complement the identification of novel combinatorial vulnerabilities to target synchronous ptCRC and mCRC., (© 2024. The Author(s).)
Published: 2024
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44. Red Blood Cell-Derived Extracellular Vesicles Display Endogenous Antiviral Effects and Enhance the Efficacy of Antiviral Oligonucleotide Therapy.

Author: Jayasinghe MK, Gao C, Yap G, Yeo BZJ, Vu LT, Tay DJW, Loh WX, Aw ZQ, Chen H, Phung DC, Hoang DV, Prajogo RC, Hooi L, Lim FQ, Pirisinu M, Mok CK, Lim KW, Tang SJ, Tan KS, Chow EK, Chen L, Phan AT, Chu JJH, and Le MT
Subjects: Humans, Antiviral Agents pharmacology, Oligonucleotides, Pandemics, SARS-CoV-2, Erythrocytes, COVID-19, Extracellular Vesicles
Abstract: The COVID-19 pandemic has resulted in a large number of fatalities and, at present, lacks a readily available curative treatment for patients. Here, we demonstrate that unmodified red blood cell-derived extracellular vesicles (RBCEVs) can inhibit SARS-CoV-2 infection in a phosphatidylserine (PS) dependent manner. Using T cell immunoglobulin mucin domain-1 (TIM-1) as an example, we demonstrate that PS receptors on cells can significantly increase the adsorption and infection of authentic and pseudotyped SARS-CoV-2 viruses. RBCEVs competitively inhibit this interaction and block TIM-1-mediated viral entry into cells. We further extend the therapeutic efficacy of this antiviral treatment by loading antisense oligonucleotides (ASOs) designed to target conserved regions of key SARS-CoV-2 genes into RBCEVs. We establish that ASO-loaded RBCEVs are efficiently taken up by cells in vitro and in vivo to suppress SARS-CoV-2 replication. Our findings indicate that this RBCEV-based SARS-CoV-2 therapeutic displays promise as a potential treatment capable of inhibiting SARS-CoV-2 entry and replication.
Published: 2023
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45. Histone-lysine N-methyltransferase EHMT2 (G9a) inhibition mitigates tumorigenicity in Myc-driven liver cancer.

Author: Thng DKH, Hooi L, Toh CCM, Lim JJ, Rajagopalan D, Syariff IQC, Tan ZM, Rashid MBMA, Zhou L, Kow AWC, Bonney GK, Goh BKP, Kam JH, Jha S, Dan YY, Chow PKH, Toh TB, and Chow EK
Subjects: Humans, Epigenesis, Genetic, Histocompatibility Antigens genetics, Histocompatibility Antigens metabolism, Histocompatibility Antigens therapeutic use, Histone-Lysine N-Methyltransferase genetics, Histone-Lysine N-Methyltransferase metabolism, Methylation, Carcinoma, Hepatocellular drug therapy, Carcinoma, Hepatocellular genetics, Carcinoma, Hepatocellular pathology, Liver Neoplasms drug therapy, Liver Neoplasms genetics, Liver Neoplasms pathology
Abstract: Hepatocellular carcinoma (HCC) is the third deadliest and sixth most common cancer in the world. Histone-lysine N-methyltransferase EHMT2 (also known as G9a) is a histone methyltransferase frequently overexpressed in many cancer types, including HCC. We showed that Myc-driven liver tumours have a unique H3K9 methylation pattern with corresponding G9a overexpression. This phenomenon of increased G9a was further observed in our c-Myc-positive HCC patient-derived xenografts. More importantly, we showed that HCC patients with higher c-Myc and G9a expression levels portend a poorer survival with lower median survival months. We demonstrated that c-Myc interacts with G9a in HCC and cooperates to regulate c-Myc-dependent gene repression. In addition, G9a stabilises c-Myc to promote cancer development, contributing to the growth and invasive capacity in HCC. Furthermore, combination therapy between G9a and synthetic-lethal target of c-Myc, CDK9, demonstrates strong efficacy in patient-derived avatars of Myc-driven HCC. Our work suggests that targeting G9a could prove to be a potential therapeutic avenue for Myc-driven liver cancer. This will increase our understanding of the underlying epigenetic mechanisms of aggressive tumour initiation and lead to improved therapeutic and diagnostic options for Myc-driven hepatic tumours., (© 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)
Published: 2023
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46. A prospective study of incidence and outcome of acute kidney injury among hospitalised patients in Malaysia (My-AKI).

Author: Goh CY, Visvanathan R, Leong CT, Hooi LS, Ch'ng CC, Yee SY, Abd Manaf KA, Mushahar L, Goh KW, Liew YF, Manocha AB, and Ong LM
Subjects: Adult, Female, Humans, Male, Middle Aged, Incidence, Kidney, Malaysia epidemiology, Prospective Studies, Retrospective Studies, Risk Factors, Aged, Acute Kidney Injury epidemiology, Acute Kidney Injury etiology, Acute Kidney Injury therapy
Abstract: Introduction: The incidence of acute kidney injury (AKI) among hospitalised patients has not been well studied in Malaysia., Materials and Methods: We conducted a prospective, multicentre study in seven hospitals in West Malaysia. All the adults admitted in March 2017 fulfilling Kidney Disease Improving Global Outcomes (KDIGO) criteria for AKI were included., Results: Of the 34,204 patients screened, 2,457 developed AKI (7.18%), 13.1% of which occurred in intensive care unit (ICU). There were 60.2% males with a mean age of 57.8 (±17.5) years. The most common comorbidities were hypertension (55.0%), diabetes (46.6%), ischaemic heart disease (15.1%) and chronic kidney disease (12.0%). The commonest causes of AKI were sepsis (41.7%), pre-renal (24.2%) and cardiorenal syndrome (10.8%). Nephrotoxin exposure was reported in 31%. At diagnosis, the proportion of AKI stages 1, 2 and 3 were 79.1%, 9.7%, 11.2%, respectively. Referral to nephrologists was reported in 16.5%. Dialysis was required in 176 (7.2%) patients and 55.6% were performed in the ICU. Acidosis (46.2%), uraemia (31.6%) and electrolyte disturbance (11.1%) were the commonest indications. Continuous renal replacement therapy (CRRT) was required in 14%. The average length of hospital stay was 9.5 days. In-hospital mortality was 16.4%. Among survivors, full and partial renal recovery was seen in 74.7% and 16.4% respectively while 8.9% failed to recover. After a mean follow-up of 13.7 months, 593 (30.2%) of survivors died and 38 (1.9%) initiated chronic dialysis. Mortality was highest among those with malignancies (Hazard Ratio, HR 2.14), chronic liver disease (HR 2.13), neurological disease (HR 1.56) and cardiovascular disease (HR 1.17)., Conclusion: AKI is common in hospitalised patients and is with associated high mortality during and after hospitalisation.
Published: 2023

47. Comparing survival in patients with chronic kidney disease across three countries - Results from the study of heart and renal protection-extended review.

Author: Talbot B, Cass A, Walker R, Hooi L, Jardine M, Jun M, Rogers K, Sukkar L, Smyth B, and Gallagher M
Subjects: Humans, Ezetimibe therapeutic use, Simvastatin therapeutic use, Kidney, Renal Insufficiency, Chronic therapy, Renal Insufficiency, Chronic drug therapy, Kidney Transplantation adverse effects
Abstract: Aim: This study examined whether survival and causes of death differed between participants enrolled from Australia (AUS), Malaysia (MYL), and New Zealand (NZ) in extended follow-up of the Study of Heart and Renal Protection (SHARP), a randomized controlled trial (RCT) of participants with moderate to severe chronic kidney disease comparing placebo to combination therapy with Simvastatin and Ezetimibe., Methods: All participants alive at final SHARP study visit in participating centres were eligible for inclusion. Consenting participants were re-enrolled following final SHARP Study visit and followed for 5 years. Data collection included: significant medical events, hospital admissions and requirement for kidney replacement therapy. Data linkage was performed to national kidney and mortality registries. The primary outcome was all-cause mortality compared across the three countries., Results: The SHARP trial randomized 2029 participants from AUS (1043/2029, 51%), MYL (701/2029, 35%), and NZ (285/2029, 14%), with 1136 participants alive and eligible for extended follow-up at the end of SHARP. In multivariable analysis, risk of death was increased for participants in MYL (HR 1.37, 95% CI 1.17-1.61, p < .001) and NZ (HR 1.28, 95% CI 1.04-1.57, p = .02) when compared to AUS participants. Adjustment for kidney transplantation as a competing risk did not explain the variation seen between countries., Conclusion: This study allows a better understanding of the differences in long-term mortality risk across participants from AUS, MYL, and NZ in extended follow-up of the SHARP study and demonstrates the feasibility and value of extended follow-up of participants enrolled in RCTs., (© 2022 The Authors. Nephrology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Nephrology.)
Published: 2023
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48. IDentif.AI-Omicron: Harnessing an AI-Derived and Disease-Agnostic Platform to Pinpoint Combinatorial Therapies for Clinically Actionable Anti-SARS-CoV-2 Intervention.

Author: Blasiak A, Truong ATL, Wang P, Hooi L, Chye H, Tan SB, You K, Remus A, Allen DM, Chai LYA, Chan CEZ, Lye DCB, Tan GG, Seah SGK, Chow EK, and Ho D
Subjects: Amides, Artificial Intelligence, Auranofin, Guanosine Monophosphate analogs & derivatives, Humans, Phosphoramides, Pyrazines, SARS-CoV-2, COVID-19 Drug Treatment
Abstract: Nanomedicine-based and unmodified drug interventions to address COVID-19 have evolved over the course of the pandemic as more information is gleaned and virus variants continue to emerge. For example, some early therapies (e.g., antibodies) have experienced markedly decreased efficacy. Due to a growing concern of future drug resistant variants, current drug development strategies are seeking to find effective drug combinations. In this study, we used IDentif.AI, an artificial intelligence-derived platform, to investigate the drug-drug and drug-dose interaction space of six promising experimental or currently deployed therapies at various concentrations: EIDD-1931, YH-53, nirmatrelvir, AT-511, favipiravir, and auranofin. The drugs were tested in vitro against a live B.1.1.529 (Omicron) virus first in monotherapy and then in 50 strategic combinations designed to interrogate the interaction space of 729 possible combinations. Key findings and interactions were then further explored and validated in an additional experimental round using an expanded concentration range. Overall, we found that few of the tested drugs showed moderate efficacy as monotherapies in the actionable concentration range, but combinatorial drug testing revealed significant dose-dependent drug-drug interactions, specifically between EIDD-1931 and YH-53, as well as nirmatrelvir and YH-53. Checkerboard validation analysis confirmed these synergistic interactions and also identified an interaction between EIDD-1931 and favipiravir in an expanded range. Based on the platform nature of IDentif.AI, these findings may support further explorations of the dose-dependent drug interactions between different drug classes in further pre-clinical and clinical trials as possible combinatorial therapies consisting of unmodified and nanomedicine-enabled drugs, to combat current and future COVID-19 strains and other emerging pathogens.
Published: 2022
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49. Addressing antimicrobial resistance with the IDentif.AI platform: Rapidly optimizing clinically actionable combination therapy regimens against nontuberculous mycobacteria.

Author: Mukherjee D, Wang P, Hooi L, Sandhu V, You K, Blasiak A, Chow EK, Ho D, and Ee PLR
Subjects: Humans, Amikacin pharmacology, Amikacin therapeutic use, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Microbial Sensitivity Tests, Levofloxacin pharmacology, Meropenem pharmacology, Drug Resistance, Bacterial, Rifabutin pharmacology, Artificial Intelligence, Nontuberculous Mycobacteria, Mycobacterium abscessus
Abstract: Background: Current standard of care (SOC) regimens against nontuberculous mycobacteria (NTM) usually result in unsatisfactory therapeutic responses, primarily due to multi-drug resistance and antibiotic susceptibility-guided therapies. In the midst of rising incidences in NTM infections, strategies to develop NTM-specific treatments have been explored and validated. Methods: To provide an alternative approach to address NTM-specific treatment, IDentif.AI was harnessed to rapidly optimize and design effective combination therapy regimens against Mycobacterium abscessus ( M. abscessus ), the highly resistant and rapid growth species of NTM. IDentif.AI interrogated the drug interaction space from a pool of 6 antibiotics, and pinpointed multiple clinically actionable drug combinations. IDentif.AI-pinpointed actionable combinations were experimentally validated and their interactions were assessed using Bliss independence model and diagonal measurement of n-way drug interactions. Results: Notably, IDentfi.AI-designed 3- and 4-drug combinations demonstrated greater %Inhibition efficacy than the SOC regimens. The platform also pinpointed two unique drug interactions (Levofloxacin (LVX)/Rifabutin (RFB) and LVX/Meropenem (MEM)) that may serve as the backbone of potential 3- and 4-drug combinations like LVX/MEM/RFB, which exhibited 58.33±4.99 %Inhibition efficacy against M. abscessus . Further analysis of LVX/RFB via Bliss independence model pointed to dose-dependent synergistic interactions in clinically actionable concentrations. Conclusions: IDentif.AI-designed combinations may provide alternative regimen options to current SOC combinations that are often administered with Amikacin, which has been known to induce ototoxicity in patients. Furthermore, IDentif.AI pinpointed 2-drug interactions may also serve as the backbone for the development of other effective 3- and 4-drug combination therapies. The findings in this study suggest that this platform may contribute to NTM-specific drug development., Competing Interests: Competing Interests: A.B., E.K.-H.C., and D.H. are co-inventors of previously filed pending patents on artificial intelligence-based therapy development. E.K.-H.C. and D.H. are co-founders and shareholders of KYAN Therapeutics, which is commercializing intellectual property pertaining to AI-based personalized medicine., (© The author(s).)
Published: 2022
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50. Splice-switch oligonucleotide-based combinatorial platform prioritizes synthetic lethal targets CHK1 and BRD4 against MYC-driven hepatocellular carcinoma.

Author: Thng DKH, Toh TB, Pigini P, Hooi L, Dan YY, Chow PK, Bonney GK, Rashid MBMA, Guccione E, Wee DKB, and Chow EK
Abstract: Deregulation of MYC is among the most frequent oncogenic drivers in hepatocellular carcinoma (HCC). Unfortunately, the clinical success of MYC-targeted therapies is limited. Synthetic lethality offers an alternative therapeutic strategy by leveraging on vulnerabilities in tumors with MYC deregulation. While several synthetic lethal targets of MYC have been identified in HCC, the need to prioritize targets with the greatest therapeutic potential has been unmet. Here, we demonstrate that by pairing splice-switch oligonucleotide (SSO) technologies with our phenotypic-analytical hybrid multidrug interrogation platform, quadratic phenotypic optimization platform (QPOP), we can disrupt the functional expression of these targets in specific combinatorial tests to rapidly determine target-target interactions and rank synthetic lethality targets. Our SSO-QPOP analyses revealed that simultaneous attenuation of CHK1 and BRD4 function is an effective combination specific in MYC-deregulated HCC, successfully suppressing HCC progression in vitro. Pharmacological inhibitors of CHK1 and BRD4 further demonstrated its translational value by exhibiting synergistic interactions in patient-derived xenograft organoid models of HCC harboring high levels of MYC deregulation. Collectively, our work demonstrates the capacity of SSO-QPOP as a target prioritization tool in the drug development pipeline, as well as the therapeutic potential of CHK1 and BRD4 in MYC-driven HCC., Competing Interests: Edward Kai‐Hua Chow is a shareholder in KYAN Therapeutics., (© 2022 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.)
Published: 2022
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