Author: "Yoon K" / Topic: internal medicine - Searchworks@Jio Institute Digital Library Search Results

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129 results on '"Yoon K"'

1. Effect of SGLT2 Inhibitors on Stroke and Atrial Fibrillation in Diabetic Kidney Disease: Results From the CREDENCE Trial and Meta-Analysis

Author: Zhou Z., Jardine M. J., Li Q., Neuen B. L., Cannon C. P., De Zeeuw D., Edwards R., Levin A., Mahaffey K. W., Perkovic V., Neal B., Lindley R. I., Guerrero R. A. A., Aizenberg D., Albisu J. P., Alvarisqueta A., Bartolacci I., Berli M. A., Bordonava A., Calella P., Cantero M. C., Cartasegna L. R., Cercos E., Coloma G. C., Colombo H., Commendatore V., Cuadrado J., Cuneo C. A., Cusumano A. M., Douthat W. G., Dran R. D., Farias E., Fernandez M. F., Finkelstein H., Fragale G., Fretes J. O., Garcia N. H., Gastaldi A., Gelersztein E., Glenny J. A., Gonzalez J. P., Del Carmen Gonzalez Colaso P., Goycoa C., Greloni G. C., Guinsburg A., Hermida S., Juncos L. I., Klyver M. I., Kraft F., Krynski F., Lanchiotti P. V., De La Fuente R. A. L., Marchetta N., Mele P., Nicolai S., Novoa P. A., Orio S. I., Otreras F., Oviedo A., Raffaele P., Resk J. H., Rista L., Papini N. R., Sala J., Santos J. C., Schiavi L. B., Sessa H., Casabella T. S., Ulla M. R., Valdez M., Vallejos A., Villarino A., Visco V. E., Wassermann A., Zaidman C. J., Cheung N. W., Droste C., Fraser I., Johnson D., Mah P. M., Nicholls K., Packham D., Proietto J., Roberts A., Roger S., Tsang V., Raduan R. A., Da Costa F. A. A., Amodeo C., Turatti L. A. A., Bregman R., Sanches F. C. C., Canani L. H., Chacra A. R., Borges J. L. C., Vencio S. A. C., Da Silva Franco R. J., D'Avila D., De Souza Portes E., De Souza P., Deboni L. M., Filho F. F., Neto B. G., Gomes M., Kohara S. K., Keitel E., Saraiva J. F. K., Lisboa H. R. K., De Carvalho Contieri F. L., Milagres R., Junior R. M., De Brito C. M., Hissa M. N., Sabbag A. R. N., Noronha I., Panarotto D., Filho R. P., Pereira M. A., Saporito W., Scotton A. S., Schuch T., De Almeida R. S., Ramos C. S., Felicio J. S., Thome F., Hachmann J. C. T., Yamada S., Hayashida C. Y., Petry T. B. Z., Zanella M. T., Andreeva V., Angelova A., Dimitrov S., Genadieva V., Genova-Hristova G., Hristozov K., Kamenov Z., Koundurdjiev A., Lozanov L., Margaritov V., Nonchev B., Rangelov R., Shinkov A., Temelkova M., Velichkova E., Yakov A., Aggarwal N., Aronson R., Bajaj H., Cherney D., Chouinard G., Conway J., Cournoyer S., DaRoza G., De Serres S., Dube F., Goldenberg R., Gupta A., Gupta M., Henein S., Khandwala H., Leiter L., Madore F., Mc-Mahon A., Muirhead N., Pichette V., Rabasa-Lhoret R., Steele A., Tangri N., Torshizi A., Woo V., Zalunardo N., Montenegro M. A. F., Jorquera J. G. G., Farina M. M., Gajardo V. S., Vejar M., Chen N., Chen Q., Gan S., Kong Y., Li D., Li W., Li X., Lin H., Liu J., Lu W., Mao H., Ren Y., Song W., Sun J., Sun L., Tu P., Wang G., Yang J., Yin A., Yu X., Zhao M., Zheng H., Mendoza J. L. A., Arcos E., Avendano J., Ruiz J. E. A. D., Ortiz L. H. G., Gonzalez A., Triana E. H., Higuera J. D., Malaver N., De Salazar D. I. M., Rosero R., Lozano M. A. T., Cometa L. V., Valenzuela A., Alonso R. D. V., Villegas I., Yupanqui H., Bartaskova D., Barton P., Belobradkova J., Dohnalova L., Drasnar T., Ferkl R., Halciakova K., Klokocnikova V., Kovar R., Lastuvka J., Lukac M., Pesickova S., Peterka K., Pumprla J., Rychlik I., Saudek F., Tesar V., Valis M., Weiner P., Zemek S., Alamartine E., Borot S., Cariou B., Dussol B., Fauvel J. -P., Gourdy P., Klein A., Le Meur Y., Penfornis A., Roussel R., Saulnier P. -J., Thervet E., Zaoui P., Burst V., Faghih M., Faulmann G., Haller H., Jerwan-Keim R., Maxeiner S., Paschen B., Plassmann G., Rose L., Orellana R. A. G., Haase F. P., Diaz J. P. M., Roca L. A. R., Arenales J. A. S., Polo J. V. S., Juarez E. T., Csecsei G., Csiky B., Danos P., Deak L., Dudas M., Harcsa E., Keltai K., Keresztesi S., Kiss K., Konyves L., Major L., Mileder M., Molnar M., Mucsi J., Oroszlan T., Ory I., Paragh G., Peterfai E., Petro G., Revesz K., Takacs R., Vangel S., Vasas S., Zsom M., Oomman A., Raju S. B., Dewan D., Fernando M. E., Gopalakrishnan N., Gracious N., Alva H., Jain D., Keshavamurthy C. B., Khullar D., Sahay M., Peringat J., Prasad N., Rao K. S., Reddy S., Melemadathil S., Sudhakar B., Vyasam R. C., Bonadonna R., Castellino P., Ceriello A., Chiovato L., De Cosmo S., De Nicola L., Derosa G., Carlo A. D., Cianni G. D., Frasca G., Fuiano G., Gambaro G., Garibotto G., Giorda C., Malberti F., Mandreoli M., Mannucci E., Orsi E., Piatti P., Santoro D., Sasso F. C., Serviddio G., Stella A., Trevisan R., Veronelli A. M., Zanoli L., Akiyama H., Aoki H., Asano A., Iitsuka T., Kajiyama S., Kashine S., Kawada T., Kodera T., Kono H., Koyama K., Kumeda Y., Miyauchi S., Mizuyama K., Niiya T., Oishi H., Ota S., Sakakibara T., Takai M., Tomonaga O., Tsujimoto M., Wada T., Wakasugi M., Wakida Y., Watanabe T., Yamada M., Yanagida K., Yanase T., Yumita W., Gaupsiene E., Kozloviene D., Navickas A., Urbanaviciene E., Ghani R. A., Kadir K. A., Ali N., Yusof M. D. C., Gan C. L., Ismail M., Kong W. Y., Lam S. W., Lee L. Y., Lim S. K., Loh C. L., Manocha A. B., Ng K. S., Ahmad N. N. F. N., Ratnasingam V., Shudim S. S. B., Vengadasalam P., Munoz L. D. A., Salazar M. A., Cruz J. B., Soto M. B., Ramos J. C., Wong A. C., Rotter J. R. C., Escalante T. D., Sosa F. E. E., Lozano F. F., Cervera L. F. F., Baron P. F., Ballesteros C. G., Rangel J. D. G., Jimenez L. E. H., Santana S. S. I., Flores F. J., Molina H. L., Ceballos R. I. L., Del Campo Blanco B. M., Franco G. M., Loza O. T. M., Rocha C. M., Vera G. O., Castellanos R. O., Calcaneo J. P., Rosano M. A. R., Pattzi H. R., Guzman J. R., Joerg I. E. R., Sanchez S. B. S., Mijangos J. H. S., Sanson P. S., Tamayo Y Orozco J. A., Chavez E. T., Cepeda A. V., Carrillo L. V., Mesa J. V., Escobedo R. Z., Baker J., Noonan P., Scott R., Walker R., Watson E., Williams M., Young S., Abejuela Z., Agra J., Aquitania G., Caringal C., Comia R. S., Santos L. D., Gomez O., Jimeno C., Santos F., Tan G., Tolentino M., Yao C., Yap Y. E., Ygpuara M. D. L., Bijata-Bronisz R., Hotlos L., Januszewicz A., Kaczmarek B., Kaminska A., Lazuka L., Madej A., Mazur S., Mlodawska-Choluj D., Nowicki M., Orlowska-Kowalik G., Popenda G., Rewerska B., Sowinski D., Angelescu L. M., Anghel V., Avram R. -I., Busegeanu M. -M., Cif A., Cosma D., Crisan C., Demian L. D., Ferariu I. E., Halmagyi I., Hancu N., Munteanu M., Negru D., Onaca A. G., Petrica L., Popa A. R., Ranetti A. -E., Serafinceanu C., Toarba C., Agafyina A., Barbarash O., Barysheva O., Chizhov D., Dobronravov V., Dreval A., Glinkina I., Grineva E., Khirmanov V., Kolmakova E., Koroleva T., Kvitkova L., Marasaev V., Mkrtumyan A., Morugova T., Nagibovich G., Nagibovich O., Nedogoda S., Osipova I., Raskina T., Samoylova Y., Sazonova O., Shamkhalova M., Shutemova E., Shwartz Y., Uriasyev O., Vorobyev S., Zateyshchikova A., Zateyshshikov D., Zykova T., Antic S., Djordjevic M., Kendereski A., Lalic K., Lalic N., Popovic-Radinovic V., Babikova J., Benusova O., Buganova I., Culak J., Dzupina A., Dzuponova J., Fulop P., Ilavska A., Martinka E., Ochodnicka Z., Pella D., Smatanova I., Ahmed F., Badat A., Breedt J., Distiller L., Govender V., Govender R., Joshi M., Jurgens J., Latiff G., Lombard L., Mookadam M., Ngcakani N., Nortje H., Oosthuizen H., Pillay-Ramaya L., Prozesky H., Reddy J., Rheeder P., Seeber M., Chae D. -W., Cho Y. M., Jeong I. -K., Kim S. G., Kim Y. H., Kwon H. -S., Kwon M. J., Lee B. -W., Lee J., Lee M. -K., Nam M. -S., Oh K. -H., Park C. -Y., Park S. -H., Yoon K. H., Garcia P. A., Mercadal L. A., Barrios C., Castro F. C., Guldris S. C., Lopez M. D., De Los Rios J. E., Fresnedo G. F., Serrano A. G., Garcia I., Martinez F. J. G., Gimeno J. E. J., Mendoza M. L., Marin T. M., Portillo C. M., Vila M. A. M., Torres M. M., Iglesias J. N., Perez J. P., Vera M. P., Perez J. M. P., Simon M. A. Q., Canonge R. S., Gonzalez A. S., Riera M. T., Madueno F. J. T., Plaza M. V., Chang C. -T., Chuang L. -M., Hsia T. -L., Hsieh C. -H., Hwang S. -J., Lin C. -C., Lu Y. -C., Sheu W. H. -H., Barna O., Bilyk S. D., Botsyurko V., Dudar I., Fushtey I., Godlevska O., Golovchenko O., Gyrina O., Kazmirchuk A., Kolesnyk M., Komisarenko I., Korzh O., Kravchun N., Legun O., Mankovskyy B., Martynyuk L., Mostovoy Y., Pashkovska N., Pererva L., Pertseva T., Samoylov O., Smirnov I., Svyshchenko Y., Tomashkevych H., Topchii I., Tryshchuk N., Tseluyko V., Vizir V., Vlasenko M., Zlova T., Zub L., Abusnana S., Railey M., Abouglila K., Ainsworth P., Ali Z., Arutchelvam V., Barnard M., Bellary S., Davies E., Davies M., Davies S., Dawson A., Kossi M. E., English P., Fraser D., Gnudi L., Gunstone A., Hall T., Hanif W., Jackson A., Johnson A., Joseph F., Krishnan S., Kumwenda M., MacDougall I., Nixon P., O'Hare J., Philip S., Ramtoola S., Saxena M., Sennik D., Simon G., Singh B., Stephens J., Strzelecka A., Symonds R., Turner W., Wahba M., Wakeling J., Wheeler D., Winocour P., Abdallah J., Abdullah R., Abramowitz M., Acosta I., Aiello J., Akright L., Akyea-Djamson A., Alappan R., Alicic R., Al-Karadsheh A., Allison D. C., Arauz-Pacheco C., Arfeen S., Arif A., Arvind M., Atray N., Awad A., Bakris G., Barnhill P., Barranco E., Barrera C., Beacom M., Behara V., Belo D., Bentley-Lewis R., Berenguer R., Bermudez L., Bernardo M., Biscoveanu M., Bowman-Stroud C., Brandon D., Brusco O., Busch R., Canaan Y., Chilito A., Christensen T., Christiano C., Christofides E., Chuateco C., Cohen K., Cohen R., Cohen-Stein D., Cook C., Coyne D., Daboul N., Darwish R., Daswani A., Deck K., Desouza C., Dev D., Dhillon M., Dua S., Eder F., Elosegui A. M., El-Shahawy M., Ervin J., Esquenazi A., Evans J., Fishbane S., Frias J., Galindo-Ramos E., Galphin C., Ghazi A., Gonzalez E., Gorson D., Gowda A., Greco B., Grubb S., Gulati R., Hammoud J., Handelsman S., Hartman I., Hershon K., Hiser D., Hon G., Jacob R., Jaime M., Jamal A., Kaupke C., Keightley G., Kern E., Khanna R., Khitan Z., Kim S., Kopyt N., Kovesdy C., Krishna G., Kropp J., Kumar A., Kumar J., Kumar N., Kusnir J., Lane W., Lawrence M., Lehrner L., Lentz J., Levinson D., Lewis D., Liss K., Maddux A., Maheshwari H., Mandayam S., Marar I., Mehta B., Middleton J., Mordujovich J., Moreda R., Moustafa M., Trenche S. M., Narayanan M., Narvarte J., Nassar T., Newman G., Nichol B., Nicol P., Nisnisan J., Nossuli A. K., Obialo C., Olelewe S., Oliver M., O'Shaughnessy A., Padron J., Pankhaniya R., Parker R., Patel D., Patel G., Patel N., Pavon H., Perez A., Perez C., Perlman A., Pettis K., Pharr W., Phillips A., Purighalla R., Quesada-Suarez L., Ranjan R., Rastogi S., Rendell M., Rich L., Robinson M., Rodriguez H., Rosas S., Saba F., Sankaram R., Sarin R., Schreiman R., Scott D., Sekkarie M., Sensenbrenner J., Shakeel M., Shanik M., Shaw S., Smith S., Solomon R., Sprague A., Spry L., Suchinda P., Sultan S., Surampudi P., Sussman S., Tan A., Terrelonge A., Thompson M., Trespalacios F., Trippe B., Trueba P., Twahirwa M., Updegrove J., Van Buren P., Vannorsdall M., Varghese F., Velasquez-Mieyer P., Ventrapragada S., Vukotic G., Wadud K., Warren M., Watson H., Watts R., Weiner D., Welker J., Welsh J., Williams S., Zaniewski-Singh M., Zhou, Z., Jardine, M. J., Li, Q., Neuen, B. L., Cannon, C. P., De Zeeuw, D., Edwards, R., Levin, A., Mahaffey, K. W., Perkovic, V., Neal, B., Lindley, R. I., Guerrero, R. A. A., Aizenberg, D., Albisu, J. P., Alvarisqueta, A., Bartolacci, I., Berli, M. A., Bordonava, A., Calella, P., Cantero, M. C., Cartasegna, L. R., Cercos, E., Coloma, G. C., Colombo, H., Commendatore, V., Cuadrado, J., Cuneo, C. A., Cusumano, A. M., Douthat, W. G., Dran, R. D., Farias, E., Fernandez, M. F., Finkelstein, H., Fragale, G., Fretes, J. O., Garcia, N. H., Gastaldi, A., Gelersztein, E., Glenny, J. A., Gonzalez, J. P., Del Carmen Gonzalez Colaso, P., Goycoa, C., Greloni, G. C., Guinsburg, A., Hermida, S., Juncos, L. I., Klyver, M. I., Kraft, F., Krynski, F., Lanchiotti, P. V., De La Fuente, R. A. L., Marchetta, N., Mele, P., Nicolai, S., Novoa, P. A., Orio, S. I., Otreras, F., Oviedo, A., Raffaele, P., Resk, J. H., Rista, L., Papini, N. R., Sala, J., Santos, J. C., Schiavi, L. B., Sessa, H., Casabella, T. S., Ulla, M. R., Valdez, M., Vallejos, A., Villarino, A., Visco, V. E., Wassermann, A., Zaidman, C. J., Cheung, N. W., Droste, C., Fraser, I., Johnson, D., Mah, P. M., Nicholls, K., Packham, D., Proietto, J., Roberts, A., Roger, S., Tsang, V., Raduan, R. A., Da Costa, F. A. A., Amodeo, C., Turatti, L. A. A., Bregman, R., Sanches, F. C. C., Canani, L. H., Chacra, A. R., Borges, J. L. C., Vencio, S. A. C., Da Silva Franco, R. J., D'Avila, D., De Souza Portes, E., De Souza, P., Deboni, L. M., Filho, F. F., Neto, B. G., Gomes, M., Kohara, S. K., Keitel, E., Saraiva, J. F. K., Lisboa, H. R. K., De Carvalho Contieri, F. L., Milagres, R., Junior, R. M., De Brito, C. M., Hissa, M. N., Sabbag, A. R. N., Noronha, I., Panarotto, D., Filho, R. P., Pereira, M. A., Saporito, W., Scotton, A. S., Schuch, T., De Almeida, R. S., Ramos, C. S., Felicio, J. S., Thome, F., Hachmann, J. C. T., Yamada, S., Hayashida, C. Y., Petry, T. B. Z., Zanella, M. T., Andreeva, V., Angelova, A., Dimitrov, S., Genadieva, V., Genova-Hristova, G., Hristozov, K., Kamenov, Z., Koundurdjiev, A., Lozanov, L., Margaritov, V., Nonchev, B., Rangelov, R., Shinkov, A., Temelkova, M., Velichkova, E., Yakov, A., Aggarwal, N., Aronson, R., Bajaj, H., Cherney, D., Chouinard, G., Conway, J., Cournoyer, S., Daroza, G., De Serres, S., Dube, F., Goldenberg, R., Gupta, A., Gupta, M., Henein, S., Khandwala, H., Leiter, L., Madore, F., Mc-Mahon, A., Muirhead, N., Pichette, V., Rabasa-Lhoret, R., Steele, A., Tangri, N., Torshizi, A., Woo, V., Zalunardo, N., Montenegro, M. A. F., Jorquera, J. G. G., Farina, M. M., Gajardo, V. S., Vejar, M., Chen, N., Chen, Q., Gan, S., Kong, Y., Li, D., Li, W., Li, X., Lin, H., Liu, J., Lu, W., Mao, H., Ren, Y., Song, W., Sun, J., Sun, L., Tu, P., Wang, G., Yang, J., Yin, A., Yu, X., Zhao, M., Zheng, H., Mendoza, J. L. A., Arcos, E., Avendano, J., Ruiz, J. E. A. D., Ortiz, L. H. G., Gonzalez, A., Triana, E. H., Higuera, J. D., Malaver, N., De Salazar, D. I. M., Rosero, R., Lozano, M. A. T., Cometa, L. V., Valenzuela, A., Alonso, R. D. V., Villegas, I., Yupanqui, H., Bartaskova, D., Barton, P., Belobradkova, J., Dohnalova, L., Drasnar, T., Ferkl, R., Halciakova, K., Klokocnikova, V., Kovar, R., Lastuvka, J., Lukac, M., Pesickova, S., Peterka, K., Pumprla, J., Rychlik, I., Saudek, F., Tesar, V., Valis, M., Weiner, P., Zemek, S., Alamartine, E., Borot, S., Cariou, B., Dussol, B., Fauvel, J. -P., Gourdy, P., Klein, A., Le Meur, Y., Penfornis, A., Roussel, R., Saulnier, P. -J., Thervet, E., Zaoui, P., Burst, V., Faghih, M., Faulmann, G., Haller, H., Jerwan-Keim, R., Maxeiner, S., Paschen, B., Plassmann, G., Rose, L., Orellana, R. A. G., Haase, F. P., Diaz, J. P. M., Roca, L. A. R., Arenales, J. A. S., Polo, J. V. S., Juarez, E. T., Csecsei, G., Csiky, B., Danos, P., Deak, L., Dudas, M., Harcsa, E., Keltai, K., Keresztesi, S., Kiss, K., Konyves, L., Major, L., Mileder, M., Molnar, M., Mucsi, J., Oroszlan, T., Ory, I., Paragh, G., Peterfai, E., Petro, G., Revesz, K., Takacs, R., Vangel, S., Vasas, S., Zsom, M., Oomman, A., Raju, S. B., Dewan, D., Fernando, M. E., Gopalakrishnan, N., Gracious, N., Alva, H., Jain, D., Keshavamurthy, C. B., Khullar, D., Sahay, M., Peringat, J., Prasad, N., Rao, K. S., Reddy, S., Melemadathil, S., Sudhakar, B., Vyasam, R. C., Bonadonna, R., Castellino, P., Ceriello, A., Chiovato, L., De Cosmo, S., De Nicola, L., Derosa, G., Carlo, A. D., Cianni, G. D., Frasca, G., Fuiano, G., Gambaro, G., Garibotto, G., Giorda, C., Malberti, F., Mandreoli, M., Mannucci, E., Orsi, E., Piatti, P., Santoro, D., Sasso, F. C., Serviddio, G., Stella, A., Trevisan, R., Veronelli, A. M., Zanoli, L., Akiyama, H., Aoki, H., Asano, A., Iitsuka, T., Kajiyama, S., Kashine, S., Kawada, T., Kodera, T., Kono, H., Koyama, K., Kumeda, Y., Miyauchi, S., Mizuyama, K., Niiya, T., Oishi, H., Ota, S., Sakakibara, T., Takai, M., Tomonaga, O., Tsujimoto, M., Wada, T., Wakasugi, M., Wakida, Y., Watanabe, T., Yamada, M., Yanagida, K., Yanase, T., Yumita, W., Gaupsiene, E., Kozloviene, D., Navickas, A., Urbanaviciene, E., Ghani, R. A., Kadir, K. A., Ali, N., Yusof, M. D. C., Gan, C. L., Ismail, M., Kong, W. Y., Lam, S. W., Lee, L. Y., Lim, S. K., Loh, C. L., Manocha, A. B., Ng, K. S., Ahmad, N. N. F. N., Ratnasingam, V., Shudim, S. S. B., Vengadasalam, P., Munoz, L. D. A., Salazar, M. A., Cruz, J. B., Soto, M. B., Ramos, J. C., Wong, A. C., Rotter, J. R. C., Escalante, T. D., Sosa, F. E. E., Lozano, F. F., Cervera, L. F. F., Baron, P. F., Ballesteros, C. G., Rangel, J. D. G., Jimenez, L. E. H., Santana, S. S. I., Flores, F. J., Molina, H. L., Ceballos, R. I. L., Del Campo Blanco, B. M., Franco, G. M., Loza, O. T. M., Rocha, C. M., Vera, G. O., Castellanos, R. O., Calcaneo, J. P., Rosano, M. A. R., Pattzi, H. R., Guzman, J. R., Joerg, I. E. R., Sanchez, S. B. S., Mijangos, J. H. S., Sanson, P. S., Tamayo Y Orozco, J. A., Chavez, E. T., Cepeda, A. V., Carrillo, L. V., Mesa, J. V., Escobedo, R. Z., Baker, J., Noonan, P., Scott, R., Walker, R., Watson, E., Williams, M., Young, S., Abejuela, Z., Agra, J., Aquitania, G., Caringal, C., Comia, R. S., Santos, L. D., Gomez, O., Jimeno, C., Santos, F., Tan, G., Tolentino, M., Yao, C., Yap, Y. E., Ygpuara, M. D. L., Bijata-Bronisz, R., Hotlos, L., Januszewicz, A., Kaczmarek, B., Kaminska, A., Lazuka, L., Madej, A., Mazur, S., Mlodawska-Choluj, D., Nowicki, M., Orlowska-Kowalik, G., Popenda, G., Rewerska, B., Sowinski, D., Angelescu, L. M., Anghel, V., Avram, R. -I., Busegeanu, M. -M., Cif, A., Cosma, D., Crisan, C., Demian, L. D., Ferariu, I. E., Halmagyi, I., Hancu, N., Munteanu, M., Negru, D., Onaca, A. G., Petrica, L., Popa, A. R., Ranetti, A. -E., Serafinceanu, C., Toarba, C., Agafyina, A., Barbarash, O., Barysheva, O., Chizhov, D., Dobronravov, V., Dreval, A., Glinkina, I., Grineva, E., Khirmanov, V., Kolmakova, E., Koroleva, T., Kvitkova, L., Marasaev, V., Mkrtumyan, A., Morugova, T., Nagibovich, G., Nagibovich, O., Nedogoda, S., Osipova, I., Raskina, T., Samoylova, Y., Sazonova, O., Shamkhalova, M., Shutemova, E., Shwartz, Y., Uriasyev, O., Vorobyev, S., Zateyshchikova, A., Zateyshshikov, D., Zykova, T., Antic, S., Djordjevic, M., Kendereski, A., Lalic, K., Lalic, N., Popovic-Radinovic, V., Babikova, J., Benusova, O., Buganova, I., Culak, J., Dzupina, A., Dzuponova, J., Fulop, P., Ilavska, A., Martinka, E., Ochodnicka, Z., Pella, D., Smatanova, I., Ahmed, F., Badat, A., Breedt, J., Distiller, L., Govender, V., Govender, R., Joshi, M., Jurgens, J., Latiff, G., Lombard, L., Mookadam, M., Ngcakani, N., Nortje, H., Oosthuizen, H., Pillay-Ramaya, L., Prozesky, H., Reddy, J., Rheeder, P., Seeber, M., Chae, D. -W., Cho, Y. M., Jeong, I. -K., Kim, S. G., Kim, Y. H., Kwon, H. -S., Kwon, M. J., Lee, B. -W., Lee, J., Lee, M. -K., Nam, M. -S., Oh, K. -H., Park, C. -Y., Park, S. -H., Yoon, K. H., Garcia, P. A., Mercadal, L. A., Barrios, C., Castro, F. C., Guldris, S. C., Lopez, M. D., De Los Rios, J. E., Fresnedo, G. F., Serrano, A. G., Garcia, I., Martinez, F. J. G., Gimeno, J. E. J., Mendoza, M. L., Marin, T. M., Portillo, C. M., Vila, M. A. M., Torres, M. M., Iglesias, J. N., Perez, J. P., Vera, M. P., Perez, J. M. P., Simon, M. A. Q., Canonge, R. S., Gonzalez, A. S., Riera, M. T., Madueno, F. J. T., Plaza, M. V., Chang, C. -T., Chuang, L. -M., Hsia, T. -L., Hsieh, C. -H., Hwang, S. -J., Lin, C. -C., Lu, Y. -C., Sheu, W. H. -H., Barna, O., Bilyk, S. D., Botsyurko, V., Dudar, I., Fushtey, I., Godlevska, O., Golovchenko, O., Gyrina, O., Kazmirchuk, A., Kolesnyk, M., Komisarenko, I., Korzh, O., Kravchun, N., Legun, O., Mankovskyy, B., Martynyuk, L., Mostovoy, Y., Pashkovska, N., Pererva, L., Pertseva, T., Samoylov, O., Smirnov, I., Svyshchenko, Y., Tomashkevych, H., Topchii, I., Tryshchuk, N., Tseluyko, V., Vizir, V., Vlasenko, M., Zlova, T., Zub, L., Abusnana, S., Railey, M., Abouglila, K., Ainsworth, P., Ali, Z., Arutchelvam, V., Barnard, M., Bellary, S., Davies, E., Davies, M., Davies, S., Dawson, A., Kossi, M. 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C., Arauz-Pacheco, C., Arfeen, S., Arif, A., Arvind, M., Atray, N., Awad, A., Bakris, G., Barnhill, P., Barranco, E., Barrera, C., Beacom, M., Behara, V., Belo, D., Bentley-Lewis, R., Berenguer, R., Bermudez, L., Bernardo, M., Biscoveanu, M., Bowman-Stroud, C., Brandon, D., Brusco, O., Busch, R., Canaan, Y., Chilito, A., Christensen, T., Christiano, C., Christofides, E., Chuateco, C., Cohen, K., Cohen, R., Cohen-Stein, D., Cook, C., Coyne, D., Daboul, N., Darwish, R., Daswani, A., Deck, K., Desouza, C., Dev, D., Dhillon, M., Dua, S., Eder, F., Elosegui, A. M., El-Shahawy, M., Ervin, J., Esquenazi, A., Evans, J., Fishbane, S., Frias, J., Galindo-Ramos, E., Galphin, C., Ghazi, A., Gonzalez, E., Gorson, D., Gowda, A., Greco, B., Grubb, S., Gulati, R., Hammoud, J., Handelsman, S., Hartman, I., Hershon, K., Hiser, D., Hon, G., Jacob, R., Jaime, M., Jamal, A., Kaupke, C., Keightley, G., Kern, E., Khanna, R., Khitan, Z., Kim, S., Kopyt, N., Kovesdy, C., Krishna, G., Kropp, J., Kumar, A., Kumar, J., Kumar, N., Kusnir, J., Lane, W., Lawrence, M., Lehrner, L., Lentz, J., Levinson, D., Lewis, D., Liss, K., Maddux, A., Maheshwari, H., Mandayam, S., Marar, I., Mehta, B., Middleton, J., Mordujovich, J., Moreda, R., Moustafa, M., Trenche, S. M., Narayanan, M., Narvarte, J., Nassar, T., Newman, G., Nichol, B., Nicol, P., Nisnisan, J., Nossuli, A. 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Subjects: medicine.medical_specialty, Original Contributions, atrial fibrillation, canagliflozin, glomerular filtration rate, hemorrhagic stroke, ischemic stroke, Renal function, Disease, Brain Ischemia, Clinical and Population Sciences, Meta-Analysis as Topic, Internal medicine, CREDENCE Trial Investigators, Atrial Fibrillation, medicine, Diabetes Mellitus, Humans, Diabetic Nephropathies, Canagliflozin, Stroke, 1102 Cardiorespiratory Medicine and Haematology, Sodium-Glucose Transporter 2 Inhibitors, Advanced and Specialized Nursing, Neurology & Neurosurgery, business.industry, Atrial fibrillation, 1103 Clinical Sciences, medicine.disease, Diabetes Mellitus, Type 2, Meta-analysis, Cardiology, Albuminuria, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Neurology (clinical), medicine.symptom, Cardiology and Cardiovascular Medicine, business, 1109 Neurosciences, Kidney disease, medicine.drug
Abstract: Supplemental Digital Content is available in the text., Background and Purpose: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus. Methods: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-analysis. Results: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55–1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61–1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19–1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20–1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53–1.10]; n=115). The overall effects in the 4 CVOTs combined were: total stroke (HRpooled, 0.96 [95% CI, 0.82–1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89–1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30–0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49–1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71–0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (
Published: 2021

2. Efficacy and safety profile of statins in patients with cancer: a systematic review of randomised controlled trials

Author: Leo Alexandre, Yoon K. Loke, and John P. Thomas
Subjects: medicine.medical_specialty, Time Factors, Statin, medicine.drug_class, MEDLINE, Review, Drug Administration Schedule, 03 medical and health sciences, Clinical trials, 0302 clinical medicine, HMG-CoA, Neoplasms, Internal medicine, medicine, Humans, Pharmacology (medical), Adverse effect, Pravastatin, Randomized Controlled Trials as Topic, Cancer, 030304 developmental biology, Pharmacology, 0303 health sciences, Dose-Response Relationship, Drug, Adverse effects, business.industry, Hazard ratio, General Medicine, medicine.disease, Progression-Free Survival, Clinical trial, 030220 oncology & carcinogenesis, Observational study, Hydroxymethylglutaryl-CoA Reductase Inhibitors, business, medicine.drug
Abstract: Purpose A growing body of preclinical and observational research suggests that statins have potential as a therapeutic strategy in patients with cancer. This systematic review of randomised controlled trials (RCTs) in patients with solid tumours aimed to determine the efficacy of statin therapy on mortality outcomes, their safety profile and the risk of bias of included studies. Methods Full-text articles comparing statin therapy versus control in solid tumours and reporting mortality outcomes were identified from Medline and Embase from conception to February 2020. A systematic review with qualitative (primarily) and quantitative synthesis was conducted. This systematic review was prospectively registered (Prospero registration CRD42018116364). Results Eleven trials of 2165 patients were included. Primary tumour sites investigated included lung, colorectal, gastro-oesophageal, pancreatic and liver. Most trials recruited patients with advanced malignancy and used sub-maximal statin doses for relatively short durations. Aside from one trial which demonstrated benefit with allocation to pravastatin 40 mg in hepatocellular carcinoma, the remaining ten trials did not demonstrate efficacy with statins. The pooled hazard ratio for all-cause mortality with allocation to pravastatin in patients with hepatocellular carcinoma in two trials was 0.69 (95% confidence interval CI 0.30–1.61). Study estimates were imprecise. There were no clinically important differences in statin-related adverse events between groups. Overall, included trials were deemed low risk of bias. Conclusion The trial evidence is not sufficiently robust to confirm or refute the efficacy and safety of statins in patients with solid malignant tumours. Study and patient characteristics may explain this uncertainty. The potential role of high-dose statins in adjuvant settings deserves further research.
Published: 2020

3. Neuropathological Correlates of Cumulative Benzodiazepine and Anticholinergic Drug Use

Author: Chris Fox, Antony Arthur, Yoon K. Loke, George M. Savva, Nicholas Steel, Ian Maidment, Malaz Boustani, Noll L. Campbell, Stephen B. Wharton, Kathryn Richardson, Louise Robinson, Carlota M. Grossi, Carol Brayne, Phyo K. Myint, Fiona E. Matthews, Brayne, Carol [0000-0001-5307-663X], and Apollo - University of Cambridge Repository
Subjects: Male, 0301 basic medicine, Drug, Aging, medicine.medical_specialty, medicine.drug_class, media_common.quotation_subject, Population, Neuropathology, Cholinergic Antagonists, Benzodiazepines, 03 medical and health sciences, Cognition, 0302 clinical medicine, Cost of Illness, Alzheimer Disease, Internal medicine, Anticholinergic, medicine, Humans, Dementia, Cognitive decline, education, Aged, media_common, Aged, 80 and over, Cerebral Cortex, neuropathology, Benzodiazepine, education.field_of_study, basal nucleus of Meynert, business.industry, General Neuroscience, Neurofibrillary Tangles, General Medicine, Odds ratio, neuritic plaques, medicine.disease, Substantia Nigra, Psychiatry and Mental health, Clinical Psychology, 030104 developmental biology, Female, Atrophy, Geriatrics and Gerontology, business, Alzheimer’s disease, 030217 neurology & neurosurgery
Abstract: Background:\ud Benzodiazepines and anticholinergic drugs have been implicated in causing cognitive decline and potentially increasing dementia risk. However, evidence for an association with neuropathology is limited.\ud \ud Objective:\ud To estimate the correlation between neuropathology at death and prior use of benzodiazepines and anticholinergic drugs.\ud \ud Methods:\ud We categorized 298 brain donors from the population-based Medical Research Council Cognitive Function and Ageing Study, according to their history of benzodiazepine (including Z-drugs) or anticholinergic medication (drugs scoring 3 on the Anticholinergic Cognitive Burden scale) use. We used logistic regression to compare dichotomized neuropathological features for those with and without history of benzodiazepine and anticholinergic drug use before dementia, adjusted for confounders.\ud \ud Results:\ud Forty-nine (16%) and 51 (17%) participants reported benzodiazepine and anticholinergic drug use. Alzheimer’s disease neuropathologic change was similar whether or not exposed to either drug, for example 46% and 57% had intermediate/high levels among those with and without anticholinergic drug use. Although not significant after multiple testing adjustments, we estimated an odds ratio (OR) of 0.40 (95% confidence interval [95% CI] 0.18–0.87) for anticholinergic use and cortical atrophy. For benzodiazepine use, we estimated ORs of 4.63 (1.11–19.24) and 3.30 (1.02–10.68) for neuronal loss in the nucleus basalis and substantial nigra. There was evidence of neuronal loss in the nucleus basalis with anticholinergic drug use, but the association reduced when adjusted for confounders.\ud \ud Conclusions:\ud We found no evidence that benzodiazepine or anticholinergic drug use is associated with typical pathological features of Alzheimer’s disease; however, we cannot rule out effects owing to small numbers.
Published: 2020

4. The effect of statin therapy on disease-related outcomes in idiopathic pulmonary fibrosis: a systematic review and meta-analysis

Author: Yoon K. Loke, Andrew M. Wilson, J.W. Kim, and K. Barrett
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Statin, medicine.drug_class, business.industry, medicine.disease, Idiopathic Pulmonary Fibrosis, Pulmonary function testing, FEV1/FVC ratio, Idiopathic pulmonary fibrosis, Fibrosis, Meta-analysis, Internal medicine, medicine, Humans, Prospective Studies, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Adverse effect, Prospective cohort study, business
Abstract: Background Idiopathic pulmonary fibrosis is a progressive disease and antifibrotic therapies do not reverse existing fibrosis. There has been emerging evidence of potential role for statins in idiopathic pulmonary fibrosis. The aim of this review is to synthesise the evidence on the efficacy of statins in idiopathic pulmonary fibrosis, focusing on associations with all-cause mortality, disease-specific mortality and change in pulmonary function. Methods Medline and Embase were reviewed to identify relevant publications. Studies were selected if they examined disease-related outcomes including mortality, pulmonary function and adverse events in people with idiopathic pulmonary fibrosis receiving statin therapy. Results Five studies with a total of 3407 people with IPF were selected and analysed. The overall risk of bias of five included studies was moderate to serious. In the fixed effect meta-analysis, statin use was associated with a reduction in mortality (RR 0.8; 95% CI 0.72–0.99). However, in the random effects model, there was no longer any significant association between statin use and all-cause mortality (RR 0.87; 95% CI 0.68–1.12). There was no statistically significant association between statin use and decline in FVC % predicted. Conclusion There is currently insufficient evidence to conclude the effect of statin therapy on disease-related outcomes in idiopathic pulmonary fibrosis. Considering the limitations of available literature, we would recommend a prospective cohort study with capture of dosage and preparation of statin, statin adherence and use of concurrent antifibrotic treatment. PROSPERO registration number CRD42019122745.
Published: 2021

5. Smoking cessation after acute coronary syndrome: A systematic review and meta‐analysis

Author: Robert Butler, Ashish Patwala, Saul Lovatt, Yoon K. Loke, Chun Shing Kwok, Christian D Mallen, Chun Wai Wong, Eric W Holroyd, and Thanh Phan
Subjects: Acute coronary syndrome, medicine.medical_specialty, Rehabilitation, business.industry, medicine.medical_treatment, MEDLINE, General Medicine, RC666, medicine.disease, R1, Internal medicine, Diabetes mellitus, Meta-analysis, medicine, Smoking cessation, Myocardial infarction, business, RA, Depression (differential diagnoses)
Abstract: Background: Smoking cessation is an effective secondary prevention measure after acute coronary syndrome (ACS). We conducted a systematic review with the aim to better understand which patients have a greater propensity to quit smoking and the risk factors for continued smoking after ACS. Methods: We searched MEDLINE and EMBASE for studies that evaluated smoking cessation after ACS. The pooled rate of smoking cessation across included studies was performed. Random effects meta-analysis for different variables and their association with smoking cessation was conducted. Results: A total of 39 studies with 11 228 patients were included in this review. The pooled rate of smoking cessation following ACS across 38 studies was 45.0%. Factors associated with greater likelihood of smoking cessation were attendance at cardiac rehabilitation (OR 1.90 95% CI 1.44-2.51), married/not alone (OR 1.68 95% CI 1.32-2.13), intention/attempt to quit smoking (OR 1.27 95% CI 1.11-1.46), diabetes mellitus (OR 1.24 95% CI 1.03-1.51) and hospitalised duration (OR 1.09 95% CI 1.02-1.15). Variables associated with a lower likelihood of smoking cessation were depression (OR 0.57 95% CI 0.43-0.75), chronic obstructive pulmonary disease/lung disease (OR 0.73 95% CI 0.57-0.93), previous admission with acute myocardial infarction/cardiac admission (OR 0.61 95% CI 0.47-0.80), cerebrovascular disease/transient ischaemic attack (OR 0.42 95% CI 0.30-0.58) and unemployment (OR 0.37 95% CI 0.17-0.80). Conclusions: The majority of smokers with an ACS continue to smoke after admission. Patients attending cardiac rehabilitation show increased odds of quitting while people who are depressed and those with chronic lung disease were less likely to quit smoking and should be targeted for intensive smoking cessation interventions.
Published: 2021

6. miR-10a regulates cell death and inflammation in adipose tissue of male mice with diet-induced obesity

Author: Sumin Lee, Yoon Keun Cho, Heeseong Kim, Cheoljun Choi, Sangseob Kim, and Yun-Hee Lee
Subjects: Obesity, microRNA, Adipose tissue, Cell death, Inflammation, Internal medicine, RC31-1245
Abstract: Objective: Adipose tissue remodeling plays a critical role in obesity-induced metabolic dysfunction, but the underlying molecular mechanisms remain incompletely understood. This study investigates the role of miR-10a-5p in adipose tissue inflammation and metabolic dysfunction induced by a high-fat diet (HFD). Methods: Male miR-10a knockout (KO) mice were fed a HFD to induce obesity for up to 16 weeks. RNA sequencing (RNA-seq) analysis was performed to profile mRNA expression and assess the effects of miR-10a-5p KO in gonadal white adipose tissue (gWAT). Additional analyses included immunoblotting, qPCR, histological examination, and validation of the miR-10a-5p target sequence using a dual-luciferase reporter assay. Results: miR-10a-5p was highly expressed in gWAT but decreased after 8 weeks of HFD feeding. Over the 16-week HFD period, miR-10a KO mice exhibited greater weight gain and reduced energy expenditure compared to wild-type (WT) controls. gWAT of miR-10a KO mice on a HFD showed an increased population of proinflammatory macrophages, elevated inflammation, and increased cell death, characterized by upregulated apoptosis and necrosis markers. This was also associated with increased triglyceride accumulation in liver. Mechanistically, the proapoptotic gene Bcl2l11 was identified as a direct target of miR-10a-5p. Loss of miR-10a-5p led to BIM-mediated adipocyte death and inflammation, contributing to mitochondrial metabolic dysregulation, increased fibrosis marker expression, and the onset of inflammation in adipose tissue. Conclusions: This study demonstrates the significant role of miR-10a-5p and its downstream target BIM in regulating adipocyte death during diet-induced obesity. This signaling pathway presents a potential therapeutic target for modulating obesity-induced inflammation and cell death in adipose tissue.
Published: 2024
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7. Non-specific chest pain and subsequent serious cardiovascular readmissions

Author: Purvi Parwani, Yoon K. Loke, Glen P. Martin, Harriette G.C. Van Spall, Chun Shing Kwok, David L. Fischman, Evangelos Kontopantelis, Jessica Potts, Mamas A. Mamas, Mary Norine Walsh, David L. Brown, and Aditya Bharadwaj
Subjects: Male, Chest Pain, medicine.medical_specialty, Acute coronary syndrome, medicine.medical_treatment, Aortic dissection, 030204 cardiovascular system & hematology, Chest pain, Patient Readmission, Cohort Studies, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, 030212 general & internal medicine, Aged, Retrospective Studies, Aged, 80 and over, Vascular disease, business.industry, Pulmonary embolism, Percutaneous coronary intervention, Retrospective cohort study, Middle Aged, medicine.disease, Cardiovascular Diseases, Female, medicine.symptom, Cardiology and Cardiovascular Medicine, business
Abstract: BackgroundThe rates of readmission for serious cardiovascular events among patients admitted with a diagnosis of non-specific chest pain are unknown.MethodsA national retrospective cohort study in the United States was undertaken to evaluate the rates, trends and predictors of readmission for serious cardiovascular events (acute coronary syndrome (ACS), pulmonary embolism (PE) and aortic dissection (AD)) after an inpatient episode with a primary diagnosis of non-specific chest pain.ResultsAmong 1,172,430 patients with an index diagnosis of non-specific chest pain between 2010 and 2014, 2.4% were readmitted with an ACS, 0.4% with a PE and 0.06% with an AD within 6 months of discharge. Predictors of ACS readmissions were diabetes (OR 1.49 95% CI 1.17–1.32), coronary artery disease (OR 2.29 95% CI 2.15–2.44), previous percutaneous coronary intervention (OR 1.65 95% CI 1.56–1.75), previous CABG (OR 1.52 95% CI 1.43–1.61) and discharge against medical advice (OR 1.94 95% CI 1.78–2.12). Female patients (OR 0.82 95% CI 0.78–0.86) and patients in whom a coronary angiogram was undertaken (OR 0.48 95% CI 0.45–0.52) were less likely to be readmitted for ACS. For PE, predictors of readmission were pulmonary circulatory disorder (OR 2.20 95% CI 1.09–4.43), anemia (OR 1.62 95% CI 1.40–1.86) and cancer (OR 4.15 95% CI 3.43–5.02). Peripheral vascular disease (OR 8.63 95% CI 5.47–13.60), renal failure (OR 2.08 95% CI 1.34–3.24) were predictors of AD.ConclusionsNon-specific chest pain may not be a benign condition as readmissions for serious cardiovascular events occur in 3% of patients within 180 days. Research is needed to define measures that may mitigate readmissions among these patients.
Published: 2019

8. Meta-analysis: Association between hypoglycemia and serious adverse events in older patients treated with glucose-lowering agents

Author: Yoon K. Loke and Katharina Mattishent
Subjects: medicine.medical_specialty, Aging, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, Hypoglycemia, lcsh:Diseases of the endocrine glands. Clinical endocrinology, older people, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Internal medicine, Diabetes mellitus, medicine, Dementia, Humans, Hypoglycemic Agents, Adverse effect, Aged, Aged, 80 and over, lcsh:RC648-665, diabetes, business.industry, Confounding, Age Factors, Patient Acuity, medicine.disease, Confidence interval, meta-analysis, Systematic review, hypoglycemia, Diabetes Mellitus, Type 2, Meta-analysis, adverse effects, Systematic Review, business
Abstract: AimsWe conducted a meta-analysis of serious adverse events (dementia, macro- and micro-vascular events, falls and fractures, and death) associated with hypoglycemia in older patients treated with glucose lowering drugs.Materials and MethodsMeta-analysis of studies reporting on hypoglycemia and adverse events. The search included studies from two previously published systematic reviews, and an updated search of MEDLINE and EMBASE from April 2014 to November 2019. We assessed study validity based on ascertainment of hypoglycemia, adverse events and adjustment for confounders, and conducted a random effects meta-analyses, assessing heterogeneity using the I2 statistic.ResultsWe included 44 studies involving 2,507,434 participants. Most of the studies used adjusted analysis for confounders and hypoglycaemic events were typically identified based on healthcare databases (severe events). Hypoglycemia was associated with increased likelihood of death in a meta-analysis of eighteen studies, pooled OR 2.02 (95% Confidence Interval 1.75–2.32). Studies assessing mortality signal a time-response relationship with a higher risk of adverse events occurring within the first 90 days after hypoglycemia. Our meta-analysis of nine studies demonstrated that hypoglycaemic episodes were associated with dementia – pooled OR 1.50 (95% CI 1.29–1.74). Our meta-analysis of nineteen studies demonstrated associations between hypoglycaemia and macrovascular complications, pooled OR 1.81 (95% CI 1.70–1.94), and microvascular complications (two studies) pooled OR 1.77 (95% CI 1.49–2.10). There is also an association between hypoglycemia and cardiovascular death (six studies) – pooled OR 2.11 (95% CI 1.55 to 2.87). Similarly, our meta-analysis of six studies demonstrated an association between hypoglycemia and falls and fractures, pooled OR 1.78 (95% CI 1.44–2.21) and 1.68 (95% CI 1.37–2.07) respectively.ConclusionThis meta-analysis confirms previously reported concerns of serious harm following hypoglycemia, especially in the immediate time period after a hypoglycaemic event. Avoidance of hypoglycaemic episodes should be a priority in this vulnerable population.
Published: 2021

9. Calcium intake, calcium supplementation and cardiovascular disease and mortality in the British population: EPIC-norfolk prospective cohort study and meta-analysis

Author: Samuel R. Neal, Phyo K. Myint, Mamas A. Mamas, Yoon K. Loke, Robert Luben, Hamid Reza Baradaran, Tiberiu A Pana, Chun Shing Kwok, Kay-Tee Khaw, Adrian D. Wood, Mohsen Dehghani, Pana, Tiberiu A [0000-0002-1423-8111], and Apollo - University of Cambridge Repository
Subjects: Adult, Male, medicine.medical_specialty, Epidemiology, Population, chemistry.chemical_element, Calcium, Diet Surveys, Internal medicine, Cause of Death, medicine, Humans, Myocardial infarction, Prospective Studies, Mortality, Prospective cohort study, education, Stroke, Aged, Proportional Hazards Models, Aged, 80 and over, education.field_of_study, business.industry, Vascular disease, R735, Calcium supplements, Middle Aged, Protective Factors, medicine.disease, Cardiovascular disease, RC666, United Kingdom, Calcium, Dietary, Meta-analysis, chemistry, Cardiovascular Diseases, Heart failure, Dietary Supplements, Systematic review, Female, business, Dietary calcium, Follow-Up Studies
Abstract: The role of dietary calcium in cardiovascular disease prevention is unclear. We aimed to determine the association between calcium intake and incident cardiovascular disease and mortality. Data were extracted from the European Prospective Investigation of Cancer, Norfolk (EPIC-Norfolk). Multivariable Cox regressions analysed associations between calcium intake (dietary and supplemental) and cardiovascular disease (myocardial infarction, stroke, heart failure, aortic stenosis, peripheral vascular disease) and mortality (cardiovascular and all-cause). The results of this study were pooled with those from published prospective cohort studies in a meta-analsyis, stratifying by average calcium intake using a 700 mg/day threshold. A total of 17,968 participants aged 40–79 years were followed up for a median of 20.36 years (20.32–20.38). Compared to the first quintile of calcium intake (
Published: 2020

10. Adverse effects of Z-drugs for sleep disturbance in people living with dementia: a population-based cohort study

Author: Chris Fox, George M. Savva, Robert Howard, Nicholas Steel, Clive Ballard, Ian Maidment, Yoon K. Loke, Kathryn Richardson, Penelope J Boyd, Antony Arthur, and Clare F Aldus
Subjects: Male, Sleep Wake Disorders, medicine.medical_specialty, Piperazines, Cohort Studies, Benzodiazepines, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Acetamides, medicine, Humans, Dementia, Sleep initiation and maintenance disorders, 030212 general & internal medicine, Adverse effect, Stroke, Accidental falls, Aged, 80 and over, Zopiclone, Sleep disorder, Hip fracture, business.industry, Hazard ratio, General Medicine, medicine.disease, Confidence interval, Zolpidem, Pyrimidines, Hip fractures, Female, Alzheimer disease, business, Azabicyclo Compounds, 030217 neurology & neurosurgery, Research Article, medicine.drug
Abstract: BackgroundSleep disturbance is common in dementia and often treated with Z-drugs (zopiclone, zaleplon, and zolpidem). While some observational studies suggest that Z-drugs are associated with adverse events such as falls and fracture risks in older people, this has not been studied in dementia.MethodsWe used data from 27,090 patients diagnosed with dementia between January 2000 and March 2016 from the Clinical Practice Research Datalink linked to Hospital Episodes Statistics data in England. We compared adverse events for 3532 patients newly prescribed Z-drugs by time-varying dosage to (1) 1833 non-sedative-users with sleep disturbance; (2) 10,214 non-sedative-users with proximal GP consultation matched on age, sex, and antipsychotic use; and (3) 5172 patients newly prescribed benzodiazepines. We defined higher dose Z-drugs and benzodiazepines as prescriptions equivalent to ≥ 7.5 mg zopiclone or > 5 mg diazepam daily. Cox regression was used to estimate hazard ratios (HRs) for incident fracture, hip fracture, fall, mortality, acute bacterial infection, ischaemic stroke/transient ischaemic attack, and venous thromboembolism over a 2-year follow-up, adjusted for demographic- and health-related covariates.ResultsThe mean (SD) age of patients was 83 (7.7) years, and 16,802 (62%) were women. Of 3532 patients prescribed Z-drugs, 584 (17%) were initiated at higher doses. For patients prescribed higher dose Z-drugs relative to non-users with sleep disturbance, the HRs (95% confidence interval) for fractures, hip fractures, falls, and ischaemic stroke were 1.67 (1.13–2.46), 1.96 (1.16–3.31), 1.33 (1.06–1.66), and 1.88 (1.14–3.10), respectively. We observed similar associations when compared to non-sedative-users with proximal GP consultation. Minimal or inconsistent excess risks were observed at ≤ 3.75 mg zopiclone or equivalent daily, and for mortality, infection, and venous thromboembolism. We observed no differences in adverse events for Z-drugs compared to benzodiazepines, except lower mortality rates with Z-drugs (HR [95% confidence interval] of 0.73 [0.64–0.83]).ConclusionsHigher dose Z-drug use in dementia is associated with increased fracture and stroke risks, similar or greater to that for higher dose benzodiazepines. Higher dose Z-drugs should be avoided, if possible, in people living with dementia, and non-pharmacological alternatives preferentially considered. Prescriptions for higher dose Z-drugs in dementia should be regularly reviewed.Trial registrationENCePP e-register of studies,EUPAS18006
Published: 2020

11. Anticholinergic drugs and incident dementia, mild cognitive impairment and cognitive decline:a meta-analysis

Author: Louise Robinson, Toby O. Smith, Carol Brayne, Wei-Yee Chan, Kathryn Richardson, Antony Arthur, Carlota M. Grossi, Fiona E. Matthews, Chris Fox, Nina T Pieper, Ian Maidment, Clara Haroulis, Yoon K. Loke, George M. Savva, Nicholas Steel, and Phyo K. Myint
Subjects: cognition, Aging, medicine.medical_specialty, medicine.drug_class, Anticholinergic agents, Cholinergic Antagonists, older people, AcademicSubjects/MED00280, Internal medicine, medicine, Anticholinergic, Humans, Dementia, Cognitive Dysfunction, anticholinergics, Cognitive decline, business.industry, General Medicine, Odds ratio, medicine.disease, Confidence interval, Cognitive test, meta-analysis, Pharmaceutical Preparations, Meta-analysis, Systematic Review, Geriatrics and Gerontology, business
Abstract: Background the long-term effect of the use of drugs with anticholinergic activity on cognitive function remains unclear. Methods we conducted a systematic review and meta-analysis of the relationship between anticholinergic drugs and risk of dementia, mild cognitive impairment (MCI) and cognitive decline in the older population. We identified studies published between January 2002 and April 2018 with ≥12 weeks follow-up between strongly anticholinergic drug exposure and the study outcome measurement. We pooled adjusted odds ratios (OR) for studies reporting any, and at least short-term (90+ days) or long-term (365+ days) anticholinergic use for dementia and MCI outcomes, and standardised mean differences (SMD) in global cognition test scores for cognitive decline outcomes. Statistical heterogeneity was measured using the I2 statistic and risk of bias using ROBINS-I. Results twenty-six studies (including 621,548 participants) met our inclusion criteria. ‘Any’ anticholinergic use was associated with incident dementia (OR 1.20, 95% confidence interval [CI] 1.09–1.32, I2 = 86%). Short-term and long-term use were also associated with incident dementia (OR 1.23, 95% CI 1.17–1.29, I2 = 2%; and OR 1.50, 95% CI 1.22–1.85, I2 = 90%). ‘Any’ anticholinergic use was associated with cognitive decline (SMD 0.15; 95% CI 0.09–0.21, I2 = 3%) but showed no statistically significant difference for MCI (OR 1.24, 95% CI 0.97–1.59, I2 = 0%). Conclusions anticholinergic drug use is associated with increased dementia incidence and cognitive decline in observational studies. However, a causal link cannot yet be inferred, as studies were observational with considerable risk of bias. Stronger evidence from high-quality studies is needed to guide the management of long-term use.
Published: 2020

12. Increasing prevalence of anticholinergic medication use in older people in England over 20 years: cognitive function and ageing study I and II

Author: Kathryn Richardson, Carol Brayne, Louise Robinson, George M. Savva, Nicholas Steel, Phyo K. Myint, Ian Maidment, Chris Fox, Carlota M. Grossi, Antony Arthur, Fiona E. Matthews, Yoon K. Loke, Maidment, Ian D. [0000-0003-4152-9704], and Apollo - University of Cambridge Repository
Subjects: Aging, medicine.medical_specialty, Activities of daily living, medicine.drug_class, Population, Anticholinergic burden, lcsh:Geriatrics, Cholinergic Antagonists, 03 medical and health sciences, Cognition, 0302 clinical medicine, Internal medicine, Activities of Daily Living, Prevalence, medicine, Anticholinergic, Health services research, Humans, Dementia, 030212 general & internal medicine, Cognitive decline, education, Aged, Aged, 80 and over, education.field_of_study, Mini–Mental State Examination, medicine.diagnostic_test, business.industry, Odds ratio, medicine.disease, Confidence interval, lcsh:RC952-954.6, Cognitive impairment, England, Geriatrics and Gerontology, business, 030217 neurology & neurosurgery, Research Article
Abstract: Background Anticholinergic medication use is linked with increased cognitive decline, dementia, falls and mortality, and their use should be limited in older people. Here we estimate the prevalence of anticholinergic use in England’s older population in 1991 and 2011, and describe changes in use by participant’s age, sex, cognition and disability. Methods We compared data from participants aged 65+ years from the Cognitive Function and Ageing Studies (CFAS I and II), collected during 1990–1993 (N = 7635) and 2008–2011 (N = 7762). We estimated the prevalence of potent anticholinergic use (Anticholinergic Cognitive Burden [ACB] score = 3) and average anticholinergic burden (sum of ACB scores), using inverse probability weights standardised to the 2011 UK population. These were stratified by age, sex, Mini-Mental State Examination score, and activities of daily living (ADL) or instrumental ADL (IADL) disability. Results Prevalence of potent anticholinergic use increased from 5.7% (95% Confidence Interval [CI] 5.2–6.3%) of the older population in 1990–93 to 9.9% (9.3–10.7%) in 2008–11, adjusted odds ratio of 1.90 (95% CI 1.67–2.16). People with clinically significant cognitive impairment (MMSE [Mini Mental State Examination] 21 or less) were the heaviest users of potent anticholinergics in CFAS II (16.5% [95% CI 12.0–22.3%]). Large increases in the prevalence of the use medication with ‘any’ anticholinergic activity were seen in older people with clinically significant cognitive impairment (53.3% in CFAS I to 71.5% in CFAS II). Conclusions Use of potent anticholinergic medications nearly doubled in England’s older population over 20 years with some of the greatest increases amongst those particularly vulnerable to anticholinergic side-effects.
Published: 2020

13. Adjuvant statin therapy for oesophageal adenocarcinoma: the STAT‐ROC feasibility study

Author: S. M. Dresner, Simon L. Parsons, H. Warren, Yoon K. Loke, Edward Cheong, Matthew Hammond, Megan Jones, Ann Marie Swart, Erika J. Sims, Leo Alexandre, S. S. Kadirkamanathan, Michael P. Lewis, Andrew Hart, S. Walton, Allan Clark, Bhaskar Kumar, and Marcus Flather
Subjects: Male, 0301 basic medicine, Simvastatin, medicine.medical_specialty, Esophageal Neoplasms, lcsh:Surgery, Adenocarcinoma, Placebo, Medication Adherence, law.invention, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, Quality of life, Randomized controlled trial, law, Internal medicine, Diabetes mellitus, medicine, Upper GI, Humans, Adverse effect, Aged, Aspirin, business.industry, Cholesterol, LDL, General Medicine, lcsh:RD1-811, Middle Aged, medicine.disease, Combined Modality Therapy, United Kingdom, Esophagectomy, Randomized Clinical Trials, Treatment Outcome, 030104 developmental biology, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Randomized Clinical Trial, Quality of Life, Feasibility Studies, Female, Observational study, Hydroxymethylglutaryl-CoA Reductase Inhibitors, business, medicine.drug
Abstract: Background Statins inhibit proliferative signalling in oesophageal adenocarcinoma (OAC) and their use is associated with better survival in observational studies. The present study was undertaken to examine the feasibility of assessing adjuvant statin therapy in patients with operable OAC in a phase III RCT. Methods For this multicentre, double‐blind, parallel‐group, randomized, placebo‐controlled feasibility trial, adults with OAC (including Siewert I–II lesions) who had undergone oesophagectomy were centrally allocated (1 : 1) to simvastatin 40 mg or matching placebo by block randomization, stratified by centre. Participants, clinicians and investigators were blinded to treatment allocation. Patients received treatment for up to 1 year. Feasibility outcomes were recruitment, retention, drug absorption, adherence, safety, quality of life, generalizability and survival. Results A total of 120 patients were assessed for eligibility at four centres, of whom 32 (26·7 per cent) were randomized, 16 in each group. Seven patients withdrew. Participants allocated to simvastatin had lower low‐density lipoprotein cholesterol levels by 3 months (adjusted mean difference −0·83 (95 per cent c.i. −1·4 to −0·22) mmol/l; P = 0·009). Median adherence to medication was greater than 90 per cent between 3 and 12 months' follow‐up. Adverse events were similar between the groups. Quality‐of‐life data were complete for 98·3 per cent of questionnaire items. Cardiovascular disease, diabetes and aspirin use were more prevalent in the non‐randomized group, whereas tumour site, stage and grade were similar between groups. Survival estimates were imprecise. Conclusion This RCT supports the conduct and informs the design considerations for a future phase III trial of adjuvant statin therapy in patients with OAC. Registration number: ISRCTN98060456 (http://www.isrctn/com)., After oesophagectomy for oesophageal adenocarcinoma (OAC), the 5‐year survival rate is currently only 30 per cent. There is strong observational evidence that statin use is associated with reduced all‐cause and cancer‐specific mortality in patients with OAC. This multicentre, double‐blind, parallel‐group, randomized, placebo‐controlled trial has established the feasibility of a future phase III trial of adjuvant statin therapy in patients treated with curative intent for invasive OAC. Justification for a full trial
Published: 2020

14. Effect of Antiplatelet Therapy (Aspirin + Dipyridamole Versus Clopidogrel) on Mortality Outcome in Ischemic Stroke

Author: Allan Clark, Isobel Ford, John F. Potter, Phyo K. Myint, Raphae S. Barlas, Mamas A. Mamas, Yoon K. Loke, Anthony K. Metcalf, Joao H. Bettencourt-Silva, and Kristian M. Bowles
Subjects: Male, medicine.medical_specialty, Kaplan-Meier Estimate, Lower risk, Brain Ischemia, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Secondary Prevention, Humans, Medicine, Registries, cardiovascular diseases, 030212 general & internal medicine, Myocardial infarction, Stroke, Aged, Retrospective Studies, Aged, 80 and over, Aspirin, business.industry, Hazard ratio, Dipyridamole, Middle Aged, medicine.disease, Clopidogrel, Regimen, Treatment Outcome, Cardiology, Drug Therapy, Combination, Female, Cardiology and Cardiovascular Medicine, business, Platelet Aggregation Inhibitors, 030217 neurology & neurosurgery, medicine.drug
Abstract: The optimal regimen of antiplatelet therapy for secondary prevention in noncardioembolic ischemic stroke remains controversial. We aimed to determine which regimen was associated with the greatest reduction in adverse outcomes. We analysed prospectively collected data from the Norfolk and Norwich University Hospital Stroke Register. The sample population consisted of 3,572 participants (mean age 74.96 ± 12.67) with ischemic stroke, who were consecutively admitted between 2003 and 2015. Patients were placed on one of three antiplatelet regimens at hospital discharge; aspirin monotherapy, aspirin plus dipyridamole and clopidogrel. Clopidogrel and aspirin plus dipyridamole were compared to aspirin. A direct comparison between clopidogrel and aspirin plus dipyridamole was also performed. Outcomes included all-cause mortality and a combined end point of all-cause mortality and incidence of major adverse cardiac events (stroke or myocardial infarction). Cox-regression models adjusted for potential confounders at the following time periods after discharge; 0 to 90 days, 91 to 365 days, and 1 to 3 years. Aspirin plus dipyridamole was associated with a lower risk of mortality at 0 to 90 days; hazard ratio (HR) 0.62 (0.43 to 0.91). Clopidogrel was associated with a lower risk of mortality at 1 to 3 years; HR of 0.39 (0.26 to 0.60). Similar HRs were observed for the corresponding time points in the composite outcome. In conclusion, patients with noncardioembolic stroke may gain maximum benefits from aspirin plus dipyridamole initially (≤1 year) with a subsequent switch to clopidogrel, with regard to mortality and major adverse cardiac eventsoutcomes.
Published: 2018

15. The effect of co-trimoxazole on serum potassium concentration: safety evaluation of a randomized controlled trial

Author: Allan Clark, Andrew M. Wilson, Yoon K. Loke, and Wei Yee Chan
Subjects: medicine.medical_specialty, Hyperkalemia, Urinary system, Potassium, chemistry.chemical_element, 030204 cardiovascular system & hematology, Placebo, Gastroenterology, law.invention, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, medicine, Pharmacology (medical), 030212 general & internal medicine, Adverse effect, Pharmacology, Creatinine, business.industry, Surgery, chemistry, Concomitant, medicine.symptom, business
Abstract: AIMS: Co-trimoxazole maintains a well-established role in the treatment of Pneumocystis jirovecii and Toxoplasma gondii, as well as urinary tract infections. Observational studies report hyperkalemia associated with co-trimoxazole which may stem from an amiloride-like potassium sparing effect. Our study reports on changes in serum potassium on patients without acute infections, and the influence of concomitant anti-kaliuretic drugs on this effect. METHODS: Post-hoc analysis of a randomised controlled trial in patients with interstitial lung disease who were assigned to placebo or 960 mg twice daily co-trimoxazole. Serum potassium and creatinine were measured at baseline, six weeks, 6, 9 and 12 months. Primary outcome was difference in mean serum potassium concentrations between co-trimoxazole and placebo at six weeks. RESULTS: Mean serum potassiums were similar at baseline, 4.24 (±0.44) mmol/L in the 87 co-trimoxazole group participants and 4.25 (±0.39) mmol/L in the 83 control participants. Co-trimoxazole significantly increased mean serum potassium at 6 weeks, difference between means compared to placebo of 0.21 mmol/L (95% Confidence Intervals [CI] 0.09-0.34; p = 0.001). This significant increase in serum potassium was detectable even after exclusion of patients on anti-kaliuretic drugs, difference between means for co-trimoxazole compared to placebo 0.23 mmol/L (95% CI 0.09-0.38, p = 0.002). There were 5/87 (5.7%) patients on co-trimoxazole whose serum potassium reached concentrations ≥5.5 mmol/L during the study period. CONCLUSIONS: Co-trimoxazole significantly increases serum potassium concentration, even in participants not using anti-kaliuretic drugs. Whilst the magnitude of increase is often minor, a small proportion in our outpatient cohort developed hyperkalaemia of clinical importance.
Published: 2017

16. Change in loneliness after intervention with cochlear implants or hearing aids

Author: Kevin J. Contrera, Frank R. Lin, Joshua Betz, Yoon K. Sung, and Lingsheng Li
Subjects: Hearing aid, medicine.medical_specialty, Hearing loss, business.industry, medicine.medical_treatment, Loneliness, Audiology, medicine.disease, Confidence interval, 03 medical and health sciences, 0302 clinical medicine, Otorhinolaryngology, Acquired immunodeficiency syndrome (AIDS), Cochlear implant, Internal medicine, Diabetes mellitus, medicine, 030212 general & internal medicine, medicine.symptom, 030223 otorhinolaryngology, business, Cohort study
Abstract: Objective To investigate the impact of hearing aid (HA) and cochlear implant (CI) use on loneliness in adults. Study Design Prospective observational cohort study. Methods One hundred and thirteen adults, aged ≥ 50 years, with postlingual hearing loss and receiving routine clinical care at a tertiary academic medical center, were evaluated with the University of California at Los Angeles Loneliness Scale before and 6 and 12 months after intervention with HAs or CIs. Change in score was assessed using linear mixed effect models adjusted for age; gender; education; and history of hypertension, diabetes, and smoking. Results Significant improvements in loneliness scores were observed in CI users from baseline to 6 months (−3.79 [95% confidence interval): −5.73, −1.85], P
Published: 2017

17. P12 Asthma breathomics – a systematic review of exhaled volatile organic compounds associated with diagnosis and disease characteristics

Author: Adam Peel, Andrew M. Wilson, Yoon K. Loke, Maxim Wilkinson, Ashnish Sinha, and SJ Fowler
Subjects: medicine.medical_specialty, business.industry, Concordance, Asthma phenotypes, Disease, medicine.disease, Checklist, Critical appraisal, Internal medicine, medicine, Disease characteristics, Sampling (medicine), business, Asthma
Abstract: Introduction Breathomics is the study of the metabolome – those metabolites associated with a biological system – via the sampling of exhaled breath. As a potential non-invasive indicator of disease processes, breathomics has been applied to a wide range of diseases including asthma. We aimed to assess the evidence for the use of breathomics in the identification of disease and disease characteristics in adults with asthma. Design A systematic review and qualitative analysis of the published literature on exhaled volatile organic compounds in adult asthma. Methods We conducted online databases searches - including PubMed, Embase and OVID medline - in November 2018. We included studies of adult asthma (physician diagnosed or diagnosed according to recognised guidelines), collecting exhaled breath volatiles by any method and presenting primary data. Results Twenty studies were identified; methodologically heterogenous they exhibited a variable risk of bias. Meta-analysis was deemed inappropriate and a qualitative, narrative analysis presented. Assessment using the CASP diagnostic checklist (Critical Appraisal Skills Programme, 2017) revealed studies to be of largely good quality, however, scores were reduced due to the hypothesis-generating stage of the research; none were studies of diagnostic test accuracy. Those studies comparing healthy controls and participants with asthma reported moderate or greater accuracy in the discrimination of samples, or significant differences in compound levels. Asthma phenotypes were differentiated with similarly high levels of accuracy in all but one study. Nine studies named those compounds which they had identified as significant; seventy six compounds were reported in total, of which nine were reported in two papers, and two (acetone and isoprene) featured in three. Conclusion Results are encouraging but there was little concordance between studies in respect of the compounds upon which discriminatory models were based, and models based on such large data-sets are at risk of over-fitting. Validation using independent prospective cohorts and larger participant numbers is required; success would constitute an important step towards non-invasive disease monitoring and the development of personalised medicine in asthma.
Published: 2019

18. Propensity score methods in real-world epidemiology: A practical guide for first-time users

Author: Yoon K. Loke and Katharina Mattishent
Subjects: education.field_of_study, Actuarial science, Models, Statistical, business.industry, Endocrinology, Diabetes and Metabolism, Population, Confounding, Psychological intervention, Outcome (probability), Causality, Endocrinology, Bias, Causal inference, Covariate, Propensity score matching, Internal Medicine, Medicine, Humans, business, education, Baseline (configuration management), Propensity Score, Algorithms
Abstract: Real-world epidemiology gives us the unique opportunity to observe large numbers of people, and the actions and events that characterize their encounters with healthcare providers. However, the heterogeneity and sheer diversity of the population and healthcare systems makes it impossible for researchers to compare "like with like" when attempting to draw causal inferences about interventions and outcomes. The critical issue in epidemiological datasets relates to high risk of bias due to confounders that stem from baseline differences between groups. Propensity score (PS) techniques are statistical approaches that have been used to tackle potential imbalance in the comparison groups. The PS is the estimated probability (based on measured baseline covariates) that the patient receives a particular intervention. Patients that share similar PS will most likely have the same distributions of underlying covariates included in the PS. Implementation of PS methods may achieve better balance of covariates, but there is no consensus on the best way of capturing all relevant confounders for incorporation into the PS model. Should covariates be selected by clinical or epidemiological experts, or would data-driven algorithms (machine learning) offer more efficient and reliable methods of estimating PS and controlling for confounding? The PS can be incorporated into the analysis in different ways, each with its own strengths and limitations, and researchers must choose the best fit for their study objectives. PS methods are particularly advantageous in situations where there are large numbers of measured covariates but relatively few outcome events captured in healthcare administrative databases.
Published: 2019

19. The effects of hypoglycemia and dementia on cardiovascular events, falls and fractures and all-cause mortality in older people:a retrospective cohort study

Author: George M. Savva, Chris Fox, Ketan Dhatariya, Kathryn Richardson, Yoon K. Loke, and Katharina Mattishent
Subjects: Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Type 2 diabetes, 030204 cardiovascular system & hematology, Hypoglycemia, Diabetes Complications, 03 medical and health sciences, Fractures, Bone, 0302 clinical medicine, Endocrinology, Internal medicine, Cause of Death, Internal Medicine, medicine, Diabetes Mellitus, Dementia, Humans, Adverse effect, Aged, Retrospective Studies, Aged, 80 and over, Type 1 diabetes, business.industry, Hazard ratio, Retrospective cohort study, medicine.disease, England, Accidental Falls, Female, business, Cohort study
Abstract: Older individuals with diabetes are susceptible to harm as the result of hypoglycaemia; however, the consequences of hypoglycaemia in older individuals with dementia are not known. We aimed to test the association between hypoglycaemia and serious adverse events in older patients with diabetes and dementia, and whether the consequences of hypoglycaemia were affected by the presence of dementia.This was a cohort study using the Clinical Practice Research Datalink in England (1997-2016). We selected participants, intervention (exposure) and follow-up to mirror two hypothetical target randomized controlled trials. The exposure of target trial 1 was hypoglycaemia in patients with dementia. Target trial 2 examined adverse effects of hypoglycaemia according to dementia status. We used Cox proportional hazard regression to estimate adjusted hazard ratios (aHR) for falls, fractures, cardiovascular events and mortality.In target trial 1, hypoglycaemia was associated with increased risk during a 12-month follow-up period for falls and fractures (aHR, 1.94 [95% CI, 1.67-2.24]), for cardiovascular events (aHR, 2.00 [95% CI, 1.61-2.48]) and for mortality (aHR, 2.36 [95% CI, 2.09-2.67]). In target trial 2, the presence of dementia was associated with increased risk of adverse events, following hypoglycaemia, during a 12-month follow-up period for falls and factures (aHR, 1.72 [95% CI, 1.51-1.96]) and for mortality (aHR, 1.27 [95% CI, 1.15-1.41]), but dementia had no effect on cardiovascular events (aHR, 1.14 [95% CI, 0.95 to 1.36]).Hypoglycaemia is associated with early increased risk of serious adverse events in older individuals with diabetes and dementia.
Published: 2019

20. Effectiveness of 80% vs 30–35% fraction of inspired oxygen in patients undergoing surgery: an updated systematic review and meta-analysis

Author: Matthias Egger, Joseph S. Solomkin, Asad Latif, Sean M. Berenholtz, Yoon K. Loke, Marja A. Boermeester, Stijn W. de Jonge, Benedetta Allegranzi, Surgery, AGEM - Digestive immunity, ACS - Heart failure & arrhythmias, Graduate School, and APH - Methodology
Subjects: medicine.medical_specialty, business.industry, Incidence (epidemiology), Perioperative, Guideline, Confidence interval, Anesthesiology and Pain Medicine, Relative risk, Internal medicine, Fraction of inspired oxygen, Meta-analysis, Medicine, General anaesthesia, business, 610 Medicine & health, 360 Social problems & social services
Abstract: Background In 2016, the World Health Organization (WHO) strongly recommended the use of a high fraction of inspired oxygen (FiO2) in adult patients undergoing general anaesthesia to reduce the risk of surgical site infection (SSI). Since then, further trials have been published, trials included previously have come under scrutiny, and one article was retracted. We updated the systematic review on which the recommendation was based. Methods We performed a systematic literature search from January 1990 to April 2018 for RCTs comparing the effect of high (80%) vs standard (30–35%) FiO2 on the incidence of SSI. Studies retracted or under investigation were excluded. A random effects model was used for meta-analyses; the sources of heterogeneity were explored using meta-regression. Results Of 21 RCTs included, six were newly identified since the publication of the WHO guideline review; 17 could be included in the final analyses. Overall, no evidence for a reduction of SSI after the use of high FiO2 was found [relative risk (RR): 0.89; 95% confidence interval (CI): 0.73–1.07]. There was evidence that high FiO2 was beneficial in intubated patients [RR: 0.80 (95% CI: 0.64–0.99)], but not in non-intubated patients [RR: 1.20 (95% CI: 0.91–1.58); test of interaction; P=0.048]. Conclusions The WHO updated analyses did not show definite beneficial effect of the use of high perioperative FiO2, overall, but there was evidence of effect of reducing the SSI risk in surgical patients under general anaesthesia with tracheal intubation. However, the evidence for this beneficial effect has become weaker and the strength of the recommendation needs to be reconsidered.
Published: 2019

21. Incidentally Raised Cardiac Troponin I Has a Worse Prognosis in Older Patients Compared to Those with Normal Cardiac Troponin I and Patients with Acute Coronary Syndrome: A Cohort Study

Author: M Justin Zaman, Robert Spooner, Allan Clark, K Honney, Joao H. Bettencourt-Silva, Yoon K. Loke, Phyo K. Myint, and Gurdeep S. Mannu
Subjects: Male, Aging, medicine.medical_specialty, Acute coronary syndrome, Renal function, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Troponin I, medicine, Humans, Prospective Studies, 030212 general & internal medicine, Acute Coronary Syndrome, Hospitals, Teaching, Prospective cohort study, Aged, Aged, 80 and over, Incidental Findings, biology, business.industry, C-reactive protein, Age Factors, Odds ratio, Length of Stay, Prognosis, medicine.disease, Confidence interval, Surgery, C-Reactive Protein, biology.protein, Female, Geriatrics and Gerontology, business, Biomarkers, Cohort study
Abstract: Background: Incidentally elevated cardiac troponin I (cTnI) levels are common in acutely unwell older patients. However, little is known about how this impacts on the prognosis of these patients. Objective: We aimed to investigate whether incidentally elevated cTnI levels (group 1) are associated with poorer outcome when compared to age- and sex-matched patients without an elevated cTnI level (group 2), and to patients diagnosed with acute coronary syndrome (group 3). Patients and Methods: This prospective, matched cohort study placed patients ≥75 years old who were admitted to a University teaching hospital into groups 1-3, based on the cTnI levels and underlying diagnosis. Outcomes were compared between the groups using mixed-effects regression models and adjusted for renal function and C-reactive protein. All-cause mortality at discharge, at 1 month and 3 months, alongside the length of hospital stay (LOS), were recorded. Results: In total, 315 patients were included, with 105 patients in each of the 3 groups. The mean age was 84.8 ± 5.5 years, with 41.9% males. All patients were followed up for 3 months. The percent all-cause mortality at discharge and the LOS for groups 1, 2 and 3 were 12.4, 3.8 and 8.6% and 11.2, 8.5 and 7.7 days, respectively. Group 1 had significantly increased mortality at 3 months [odds ratio (OR) 2.80, 95% confidence interval (CI) 1.12-6.96; p = 0.040] and LOS (OR 1.39, 95% CI 1.08-1.79; p = 0.008) compared to group 2 and did not differ significantly when compared to 3-month mortality (OR 2.39, 95% CI 0.91-6.29; p = 0.079) or LOS (OR 1.26, 95% CI 0.96-1.66; p = 0.097) in group 3. Conclusion: There is a significant association between an incidental rise in cTnI level with mortality and LOS in older patients. Further research is required to evaluate whether a more systematic management of these patients would improve the prognosis.
Published: 2016

22. Safety of 80% vs 30-35% fraction of inspired oxygen in patients undergoing surgery: a systematic review and meta-analysis

Author: Ashnish Sinha, Stijn W. de Jonge, Matthias Egger, Katharina Mattishent, Sean M. Berenholtz, Menaka Thavarajah, Joseph S. Solomkin, Yoon K. Loke, Adam Peel, Asad Latif, and Benedetta Allegranzi
Subjects: Adult, medicine.medical_specialty, Population, Atelectasis, Internal medicine, Fraction of inspired oxygen, medicine, Intubation, Intratracheal, Humans, Surgical Wound Infection, General anaesthesia, 610 Medicine & health, education, Adverse effect, education.field_of_study, business.industry, Length of Stay, medicine.disease, Confidence interval, Oxygen, Anesthesiology and Pain Medicine, Treatment Outcome, Relative risk, Meta-analysis, business, 360 Social problems & social services
Abstract: Background Evidence-based guidelines from the World Health Organization (WHO) have recommended a high (80%) fraction of inspired oxygen (FiO2) to reduce surgical site infection in adult surgical patients undergoing general anaesthesia with tracheal intubation. However, there is ongoing debate over the safety of high FiO2. We performed a systematic review to define the relative risk of clinically relevant adverse events (AE) associated with high FiO2. Methods We reviewed potentially relevant articles from the WHO review supporting the recommendation, including an updated (July 2018) search of EMBASE and PubMed for randomised and non-randomised controlled studies reporting AE in surgical patients receiving 80% FiO2 compared with 30–35% FiO2. We assessed study quality and performed meta-analyses of risk ratios (RR) comparing 80% FiO2 against 30–35% for major complications, mortality, and intensive care admission. Results We included 17 moderate–good quality trials and two non-randomised studies with serious-critical risk of bias. No evidence of harm with high FiO2 was found for major AE in the meta-analysis of randomised trials: atelectasis RR 0.91 [95% confidence interval (CI) 0.59–1.42); cardiovascular events RR 0.90 (95% CI 0.32–2.54); intensive care admission RR 0.93 (95% CI 0.7–1.12); and death during the trial RR 0.49 (95% CI 0.17–1.37). One non-randomised study reported that high FiO2 was associated with major respiratory AE [RR 1.99 (95% CI 1.72–2.31)]. Conclusions No definite signal of harm with 80% FiO2 in adult surgical patients undergoing general anaesthesia was demonstrated and there is little evidence on safety-related issues to discourage its use in this population.
Published: 2018

23. Detection of asymptomatic drug-induced hypoglycemia using continuous glucose monitoring in older people – Systematic review

Author: Yoon K. Loke and Katharina Mattishent
Subjects: Blood Glucose, Pediatrics, medicine.medical_specialty, endocrine system diseases, Endocrinology, Diabetes and Metabolism, MEDLINE, Blood sugar, 030209 endocrinology & metabolism, Hypoglycemia, Asymptomatic, law.invention, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Randomized controlled trial, law, Diabetes mellitus, Diabetes Mellitus, Internal Medicine, Humans, Hypoglycemic Agents, Medicine, 030212 general & internal medicine, Adverse effect, Aged, Randomized Controlled Trials as Topic, Aged, 80 and over, business.industry, Blood Glucose Self-Monitoring, Age Factors, nutritional and metabolic diseases, medicine.disease, Observational Studies as Topic, Asymptomatic Diseases, Observational study, medicine.symptom, business
Abstract: Aim We conducted a systematic review of the use of continuous glucose monitoring (CGM) in older patients, in order to consolidate the growing evidence base in this area. Methods Our protocol was registered on PROSPERO (CRD42017068523). We searched SCI Web of Science, Ovid SP MEDLINE and EMBASE from January 2010 to June 2017 for observational studies and randomized controlled trial of CGM in older patients (mean age 65 or older) with diabetes. We excluded studies that involved only hospitalized patients. Two reviewers independently extracted data blood sugar values (in particular, hypoglycemic episodes) captured with the use of CGM. We also assessed adverse events and acceptability of CGM. Results After screening 901 abstracts, we included nine studies with a total of 989 older patients with diabetes. The CGM studies reveal that hypoglycemic episodes were occurring in a sizeable proportion (28–65%) of participants. Most (80–100%) of these episodes were asymptomatic, with some patients spending nearly 2 h per day in the hypoglycemic range. Older people with diabetes found CGM acceptable and experienced improved health-related well-being. Conclusion CGM frequently picks up asymptomatic hypoglycemic episodes in older patients with diabetes. Users of CGM report improved well-being, and reduction of diabetes-related stress.
Published: 2018

24. Oral direct-acting antivirals and the incidence or recurrence of hepatocellular carcinoma: a systematic review and meta-analysis

Author: Sonal Singh, Yoon K. Loke, and Amit Nautiyal
Subjects: medicine.medical_specialty, Hepatology, business.industry, Incidence (epidemiology), Gastroenterology, Controlled studies, medicine.disease, DIRECT ACTING ANTIVIRALS, digestive system diseases, 03 medical and health sciences, 0302 clinical medicine, Primary outcome, Liver, 030220 oncology & carcinogenesis, Internal medicine, Meta-analysis, Hepatocellular carcinoma, medicine, 030211 gastroenterology & hepatology, Observational study, business, After treatment
Abstract: BackgroundThe influence of direct-acting antiviral (DAA) therapy for chronic hepatitis C virus on the risk of hepatocellular carcinoma (HCC) is conflicting.MethodsWe conducted a systematic review and meta-analysis to determine the incidence or recurrence of HCC associated with oral DAA therapy. We searched PubMed, Scopus, Embase from inception to August 2017 to identify observational studies reporting on HCC among patients treated with DAAs. Two independent reviewers extracted data and assessed the risk of bias. Data were pooled by random-effects model. The primary outcome was the proportion of participants with incidence or recurrence of HCC (PROSPERO number CRD42017057040).ResultsAfter reviewing 2080 citations, we included 8 controlled studies and 36 uncontrolled studies. The pooled proportion for incident HCC was 1.5 % (95% CI 1.0% to 2.1%; I2=90.1%; n= 542/39 145) from 18 uncontrolled studies and 3.3% (95% CI 1.2% to 9%; I2 =96%; n=109/6909) from 5 controlled studies, respectively. The pooled proportion for recurrent HCC was 16.7% (95% CI 10.2% to 26%; I2=84.8%; n=136/867) from 12 uncontrolled studies and 20.1% (95% CI 5.5% to 52.1%; I2=87.5%; n=36/225) from 3 controlled studies, respectively. There was no statistically significant effect on the risk of recurrent HCC (OR 0.50, 95%CI 0.16 to 1.59; I2 =73.4%) in a meta-analysis of three studies.ConclusionsOur findings show low proportion of incident HCC, but high proportion of recurrent HCC on treatment with DAAs. Continued active surveillance for HCC after treatment with DAAs remains prudent.
Published: 2018

25. Anticholinergic drugs and risk of dementia: case-control study

Author: Louise Robinson, Antony Arthur, Noll L. Campbell, Ian Maidment, Kathryn Richardson, George M. Savva, Katharina Mattishent, Malaz Boustani, Phyo K. Myint, Nicholas Steel, Fiona E. Matthews, Chris Fox, Kathleen Bennett, Carlota M. Grossi, Carol Brayne, and Yoon K. Loke
Subjects: Male, medicine.medical_specialty, medicine.drug_class, Antidepressive Agents, Tricyclic, Corrections, Risk Assessment, Cholinergic Antagonists, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, mental disorders, Odds Ratio, medicine, Anticholinergic, Humans, media_common.cataloged_instance, Dementia, 030212 general & internal medicine, European union, Aged, media_common, Aged, 80 and over, business.industry, Research, Case-control study, General Medicine, Odds ratio, medicine.disease, United Kingdom, Confidence interval, Antiparkinson drug, Drug class, Case-Control Studies, Female, Health Services Research, business, 030217 neurology & neurosurgery
Abstract: Objectives To estimate the association between the duration and level of exposure to different classes of anticholinergic drugs and subsequent incident dementia. Design Case-control study. Setting General practices in the UK contributing to the Clinical Practice Research Datalink. Participants 40 770 patients aged 65-99 with a diagnosis of dementia between April 2006 and July 2015, and 283 933 controls without dementia. Interventions Daily defined doses of anticholinergic drugs coded using the Anticholinergic Cognitive Burden (ACB) scale, in total and grouped by subclass, prescribed 4-20 years before a diagnosis of dementia. Main outcome measures Odds ratios for incident dementia, adjusted for a range of demographic and health related covariates. Results 14 453 (35%) cases and 86 403 (30%) controls were prescribed at least one anticholinergic drug with an ACB score of 3 (definite anticholinergic activity) during the exposure period. The adjusted odds ratio for any anticholinergic drug with an ACB score of 3 was 1.11 (95% confidence interval 1.08 to 1.14). Dementia was associated with an increasing average ACB score. When considered by drug class, gastrointestinal drugs with an ACB score of 3 were not distinctively linked to dementia. The risk of dementia increased with greater exposure for antidepressant, urological, and antiparkinson drugs with an ACB score of 3. This result was also observed for exposure 15-20 years before a diagnosis. Conclusions A robust association between some classes of anticholinergic drugs and future dementia incidence was observed. This could be caused by a class specific effect, or by drugs being used for very early symptoms of dementia. Future research should examine anticholinergic drug classes as opposed to anticholinergic effects intrinsically or summing scales for anticholinergic exposure. Trial registration Registered to the European Union electronic Register of Post-Authorisation Studies EUPAS8705.
Published: 2018

26. Influenza, influenza-like symptoms and their association with cardiovascular risks: a systematic review and meta-analysis of observational studies

Author: S Aslam, Chun Shing Kwok, Mahvash Zaman, Yoon K. Loke, Mamas A. Mamas, Phyo K. Myint, Evangelos Kontopantelis, and Iain Buchan
Subjects: medicine.medical_specialty, Pathology, Myocardial Infarction, Cardiovascular, Risk Factors, Internal medicine, Influenza, Human, Odds Ratio, medicine, Humans, Myocardial infarction, Stroke, Heart Failure, business.industry, Confounding, General Medicine, Odds ratio, medicine.disease, Confidence interval, Observational Studies as Topic, Study heterogeneity, Meta-analysis, Observational study, Systematic Review, business
Abstract: Summary Aims To synthesise the evidence relating influenza and influenza‐like symptoms to the risks of myocardial infarction (MI), heart failure (HF) and stroke. Methods We conducted a systematic review and meta‐analysis of the evidence relating influenza and influenza‐like symptoms to the risks of MI, HF and stroke. We systematically searched all MEDLINE and EMBASE entries up to August 2014 for studies of influenza vs. the cardiovascular outcomes above. We conducted random effects meta‐analysis using inverse variance method for pooled odds ratios (OR) and evaluated statistical heterogeneity using the I 2 statistic. Results We identified 12 studies with a total of 84,003 participants. The pooled OR for risk of MI vs. influenza (serologically confirmed) was 1.27 (95% CI, confidence interval 0.54–2.95), I 2 = 47%, which was significant for the only study that adjusted for confounders (OR 5.50, 95% CI 1.31–23.13). The pooled OR for risk of MI vs. influenza‐like symptoms was 2.17 (95% CI 1.68–2.80), I 2 = 0%, which was significant for both unadjusted (OR 2.23, 95% CI 1.65–3.01, five studies) and adjusted studies (OR 2.01, 95% CI 1.24–3.27, two studies). We found one study that evaluated stroke risk, one study in patients with HF, and one that evaluated mortality from MI – all of these studies suggested increased risks of events with influenza‐like symptoms. Conclusions There is an association between influenza‐like illness and cardiovascular events, but the relationship is less clear with serologically diagnosed influenza. We recommend renewed efforts to apply current clinical guidelines and maximise the uptake of annual influenza immunisation among patients with cardiovascular diseases, to decrease their risks of MI and stroke.
Published: 2015

27. PWE-109 A feasibility study of adjuvant statin therapy in the prevention of post-operative recurrence of oesophageal adenocarcinoma (the stat-roc feasibility study)

Author: S. Walton, Ann Marie Swart, Allan Clark, Bhaskar Kumar, Simon L. Parsons, S. S. Kadirkamanathan, Leo Alexandre, Yoon K. Loke, Andrew Hart, Michael P. Lewis, Edward Cheong, S. M. Dresner, and H. Warren
Subjects: Oncology, medicine.medical_specialty, Aspirin, business.industry, 030503 health policy & services, medicine.disease, Placebo, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Quality of life, law, Simvastatin, Internal medicine, Diabetes mellitus, medicine, Observational study, 030212 general & internal medicine, 0305 other medical science, Adverse effect, business, medicine.drug
Abstract: Introduction Preclinical studies have demonstrated statins inhibit proliferation, promote apoptosis and limit invasiveness of oesophageal adenocarcinoma (OAC) cell lines. Observational research has demonstrated significant improvements in mortality associated with statin use after diagnosis of OAC. We aimed to determine the feasibility of assessing adjuvant statin therapy in patients with operable OAC in a phase III randomised controlled trial. Method For this multi-centre, double-blind, parallel group, randomised, placebo-controlled trial, eligible patients were adults with OAC or Siewert type I/II adenocarcinoma due surgery. Participants were recruited from four UK centres and randomly assigned (1:1) to simvastatin 40 mg or matching placebo by block randomisation, stratified by centre. Participants, clinicians and investigators were blinded to treatment allocation. Treatment started from the date of discharge following surgery and continued for up to one year. Feasibility assessments of recruitment, retention, drug absorption, adherence, safety, quality of life, generalisability, all-cause and disease-free survival were made. Trial registration: ISRCTN98060456. Results Between 23rd November 2014 and 22nd July 2016, 120 patients were assessed for eligibility, of which 32 (26.7%) were randomised. Of patients meeting eligibility criteria, 59.3% (32/54) were randomised. Patients allocated to simvastatin had significantly lower LDL cholesterol levels by three months (adjusted mean difference, −0.83 mmol/L, 95% CI −1.4 to −0.22, p=0.009). Median medication adherence for the preceding three months of follow-up at 3, 6, 9 and 12 months, respectively, was 83%, 94%, 99%, and 94%, with no significant differences in adherence between treatment groups. In total, 87.5% in the simvastatin group and 92.9% in the placebo group (p=0.626) experienced at least one adverse event. Completion of quality of life data was high (98.3% of questionnaire items) with no clinically significant differences observed between treatment groups. Cardiovascular disease (p=0.003), diabetes (p=0.003) and aspirin use (p=0.01) were more prevalent in the non-randomised group compared with the randomised group. There were no significant differences between groups for overall (p=0.716) or disease-free survival (p=0.807). Conclusion This RCT supports the feasibility of assessing adjuvant statin therapy in a future phase III trial in patients with operable OAC. Disclosure of Interest None Declared
Published: 2017

28. OC-042 The impact of statins on the incidence of oesophageal carcinoma, particularly oesophageal adenocarcinoma: an updated meta-analysis

Author: Ilp Beales, Yoon K. Loke, and Tom Thomas
Subjects: Oncology, medicine.medical_specialty, education.field_of_study, Statin, medicine.drug_class, business.industry, Incidence (epidemiology), Hazard ratio, Population, Odds ratio, Internal medicine, Relative risk, Meta-analysis, Cohort, medicine, education, business
Abstract: Introduction Oesophageal carcinoma (OC) is the sixth leading cause of cancer-related mortality in the world. Experimental 1 and clinical 2 evidence have shown that statins could potentially play a role in reducing OC incidence. This effect has been studied in new observational data.This is a meta-analysis examining available evidence to assess the impact of statin use on the incidence of OC. Method A systematic literature search of Medline, Embase was used to identify studies that were pertinent to the research objective. Included studies were assigned into one of three subgroup analyses examining incidence of: adenocarcinoma (OAC) in Barrett’s oesophagus (BO) cohort, OAC in population cohorts and all types of OC in population cohorts. Forty-seven studies were identified through the literature search. Review Manager (Revman) version 5.3 was used to calculate the pooled risk ratio, compiling odds ratios (OR) or hazard ratios (HR) from individual studies using the inverse variance method, random effects model. Due to the relative rarity of outcomes, OR were considered as approximations of HR and relative risk (RR). Results Eighteen studies qualified for inclusion in statistical analysis. Adjusted data showed that statin use exhibited a protective effect on the incidence of OAC in the BO cohort (OR 0.59; 95% CI 0.50 to 0.68) – 41% decrease. This effect was apparent even in unadjusted data which showed OR 0.54; 95% CI (0.46 to 0.63). No significant heterogeneity was observed. Statins were also shown to have a protective effect on the incidence of OAC in the population cohort (OR 0.57; 95% CI 0.43 to 0.76) – 43% decrease and incidence of all types of OC in the population cohort (OR 0.82; 95% CI 0.76 to 0.88) – 18% decrease. No significant heterogeneity was observed in the adjusted datasets. Due to the heterogeneity in data reporting, statistical analysis was deemed unreliable for examining any relationship between statin characteristics and OC incidence. Conclusion Statin use could potentially be protective against oesophageal carcinoma, particularly against OAC in a risk-stratified BO cohort. This meta-analysis is an update on the literature aiming to clarify the potential clinical impact of statin use through analysis of approximately 3 73 263 cases of OC and 6,104,647 cases of BO and other non-cancer patients. Further research is merited to examine its potential role in chemopreventative strategies. References . Ogunwubi OO. Beales IL. “Statins inhibit proliferation and induce apoptosis in Barrett’s esophageal adenocarcinoma cells”American Journal of Gastroenterology (2008);103:825–837 . Beales IL, et al. “Reduced esophageal cancer incidence in statin users, particularly with cyclo-oxygenase inhibition” World Journal of Gastrointestinal Pharmacology and Therapeutics (2013);4(3):69–79 Disclosure of Interest None Declared
Published: 2017

29. Comparative coronary risks of apixaban, rivaroxaban and dabigatran: a meta-analysis and adjusted indirect comparison

Author: Chun Shing Kwok, Jessica Ka Yan Yeong, Shiva Pradhan, and Yoon K. Loke
Subjects: Pharmacology, medicine.medical_specialty, Acute coronary syndrome, Rivaroxaban, business.industry, medicine.drug_class, Odds ratio, Vitamin K antagonist, medicine.disease, Dabigatran, law.invention, Randomized controlled trial, law, Anesthesia, Internal medicine, medicine, Pharmacology (medical), Apixaban, Myocardial infarction, business, medicine.drug
Abstract: AIMS: There are concerns regarding increased risk of acute coronary syndrome with dabigatran. We aimed to assess whether alternative treatment options such as rivaroxaban or apixaban carry a similar risk as compared with dabigatran. METHODS: We searched MEDLINE and EMBASE for randomized controlled trials of apixaban, dabigatran or rivaroxaban against control (placebo, heparin or vitamin K antagonist). We pooled odds ratios (OR) for adverse coronary events (acute coronary syndrome or myocardial infarction) using fixed effect meta-analysis and assessed heterogeneity with I(2) . We conducted adjusted indirect comparisons to compare risk of adverse coronary events with apixaban or rivaroxaban vs. dabigatran. RESULTS: Twenty-seven randomized controlled trials met the inclusion criteria. Dabigatran was associated with a significantly increased risk of adverse coronary events in pooled analysis of nine trials (OR 1.45, 95% CI 1.14, 1.86). There was no signal for coronary risk with apixaban from nine trials (pooled OR 0.89, 95% CI 0.78, 1.03) or rivaroxaban from nine trials (pooled OR 0.81, 95% CI 0.72, 0.93). Overall, adjusted indirect comparison suggested that both apixaban (OR 0.61, 95% CI 0.44, 0.85) and rivaroxaban (OR 0.54; 95% CI 0.39, 0.76) were associated with lower coronary risk than dabigatran. Restricting the indirect comparison to a vitamin K antagonist as a common control, yielded similar findings, OR 0.57 (95% CI 0.39, 0.85) for apixaban vs. dabigatran and 0.53 (95% CI 0.37, 0.77) for rivaroxaban vs. dabigatran. CONCLUSIONS: There are significant differences in the comparative safety of apixaban, rivaroxaban and dabigatran with regards to acute coronary adverse events.
Published: 2014

30. Thiazolidinediones and associated risk of bladder cancer: a systematic review and meta-analysis

Author: Chun Shing Kwok, Chen Chen-Turner, Yoon K. Loke, Sonal Singh, Chinedu A. Maduakor, and Richard M. Turner
Subjects: Pharmacology, Oncology, medicine.medical_specialty, Bladder cancer, medicine.drug_class, business.industry, urologic and male genital diseases, medicine.disease, female genital diseases and pregnancy complications, Meta-analysis, Diabetes mellitus, Internal medicine, medicine, Pharmacology (medical), Thiazolidinedione, business, Rosiglitazone, Pioglitazone, medicine.drug
Abstract: Aims To determine whether thiazolidinedione use is associated with a risk of bladder cancer.
Published: 2014

31. Bone Mineral Density and Incidence of Stroke

Author: Kay-Tee Khaw, Nicholas J. Wareham, Robert Luben, Chun Shing Kwok, Phyo K. Myint, Jessica Ka Yan Yeong, Yoon K. Loke, and Allan Clark
Subjects: Adult, Male, Risk, medicine.medical_specialty, Bone density, Population, Osteoporosis, Cohort Studies, Sex Factors, Bone Density, Internal medicine, medicine, Humans, education, Stroke, Aged, Proportional Hazards Models, Ultrasonography, Aged, 80 and over, Advanced and Specialized Nursing, education.field_of_study, business.industry, Incidence, Smoking, Hazard ratio, Age Factors, Middle Aged, medicine.disease, United Kingdom, Confidence interval, Europe, Observational Studies as Topic, Meta-analysis, Multivariate Analysis, Cohort, Physical therapy, Regression Analysis, Female, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, Follow-Up Studies
Abstract: Background and Purpose— The prospective link between osteoporosis and future risk of stroke requires evidence from large-scale population-based long-term studies. Methods— Calcaneum broadband ultrasound attenuation was measured in the Norfolk cohort of the European Prospective Investigation into Cancer-Norfolk between 1997 and 2000. Incident strokes were ascertained by hospital record linkage and death certificates in March 2009 and December 2011, respectively. A search of MEDLINE and EMBASE was performed to evaluate the relationship between bone mineral density and incident stroke. After data extraction of relevant studies, pooled risk of stroke was estimated using meta-analysis. Results— In 14 290 participants (mean follow-up of 9.3 years; total person-years 132 574), there were 599 incident strokes. Participants in the lowest 10% of the calcaneum broadband ultrasound attenuation distribution had an increased stroke risk (hazard ratio 1.41; 95% confidence intervals, 1.02–1.94) compared with those in the top 30% of the distribution after adjustments. A decrease of ~1 standard deviation in broadband ultrasound attenuation (20 db/MHz) was associated with a 17% increase in relative risk of stroke (95% confidence intervals, 5%–30%). Meta-analysis of 4 studies (25 760 participants, 1237 cases of stroke) found that for every decrease in 1 standard deviation in bone mineral density, there was an increased risk of incident stroke among women (pooled relative risk 1.22; 95% confidence intervals, 1.09–1.37; I 2 =0%, 3 studies) but not in men (pooled relative risk 1.05; 95% confidence intervals, 0.94–1.17; I 2 =0%, 2 studies). Conclusions— Bone mineral density predicts total stroke risk. The evidence is stronger in women with regard to the continuous relationship.
Published: 2014

32. Prognosis of multi-lobar pneumonia in community-acquired pneumonia: A systematic review and meta-analysis

Author: Yoon K. Loke, James Peter Curtain, Kelum Nadeesha Pelpola, Phyo K. Myint, and Gurdeep S. Mannu
Subjects: Mechanical ventilation, medicine.medical_specialty, business.industry, medicine.medical_treatment, Pneumonia, Prognosis, Random effects model, medicine.disease, Severity of Illness Index, Community-Acquired Infections, Study heterogeneity, Community-acquired pneumonia, Meta-analysis, Internal medicine, Lobar pneumonia, Odds Ratio, Internal Medicine, medicine, Humans, Risk factor, Intensive care medicine, business
Abstract: Background Pneumonia is the leading cause of infection related mortality. Multilobar pneumonia (MLP) may have poorer outcomes and is a constituent of some prognostic indices. Our aim was to systematically-review and meta-analyse the impact of multi-lobar involvement in pneumonia. Methods We searched PubMed in June 2012 for studies reporting on the association between MLP and clinical outcomes. Potentially relevant studies were cross checked by two independent reviewers before final inclusion. Odds-ratios (OR) for the association between MLP and mortality, unfavourable outcomes, and poor treatment response were pooled using random effects meta-analysis. Results Twenty-two studies were included in this report. There were a total of 11,456 pneumonia patients including 2897 (25.3%) patients with MLP. As there was substantial clinical and statistical heterogeneity in the overall dataset, we limited the main meta-analysis to patients with community-acquired pneumonia (CAP). This showed that MLP was associated with increased mortality, OR 2.57 (95% CI: 1.83–3.61), with no statistical heterogeneity (I2 = 0%). Evidence from other settings suggests that MLP may also be associated with higher likelihood of other poor outcomes such as worsening clinical/radiological status, delayed resolution, and need for mechanical ventilation. Conclusion MLP appears to be an independent risk factor for mortality in CAP. It may be possible to improve commonly used prognostic indices in CAP by addition of MLP as a criterion.
Published: 2013

33. Prednisolone combined with adjunctive immunosuppression is not superior to prednisolone alone in terms of efficacy and safety in giant cell arteritis: meta-analysis

Author: Max Yates, Alex J. MacGregor, Richard A. Watts, and Yoon K. Loke
Subjects: Male, Vasculitis, medicine.medical_specialty, Prednisolone, Giant Cell Arteritis, Anti-Inflammatory Agents, Antibodies, Monoclonal, Humanized, Rheumatology, Recurrence, Internal medicine, medicine, Humans, Randomized Controlled Trials as Topic, Immunosuppression Therapy, business.industry, Remission Induction, Adalimumab, Antibodies, Monoclonal, Hydroxychloroquine, General Medicine, medicine.disease, Infliximab, Surgery, Clinical trial, Regimen, Giant cell arteritis, Methotrexate, Treatment Outcome, Meta-analysis, Relative risk, Female, business, Dapsone, Immunosuppressive Agents, medicine.drug
Abstract: To conduct a meta-analysis of published data of the effectiveness of drug treatment in giant cell arteritis (GCA) to provide evidence to support the optimal use of glucocorticoids (GCs) and adjunct therapy. MEDLINE, CENTRAL and EMBASE searches were used to identify randomised control trials on the treatment of GCA. Studies included were trials in which: (1) the participants were classified as having GCA by the 1990 ACR criteria or biopsy proven disease; (2) parallel-group randomised control of at least 16 weeks duration had been conducted with at least 20 participants; (3) the design included either alternative adjunct immunosuppressant regimens, alternative GCs dosing or routes of administration; and (4) outcome data was included on either relapse rates or rates of infection. One thousand eight hundred thirty-six articles were retrieved, of which only 37 met the primary inclusion criteria. Sixteen of these studies reported some information about the GCs or adjuvant regimen used. Only ten studies were of sufficient quality to be included in the meta-analysis. Together these comprised 638 participants of which 72 % were female. Three studies compared various GCs regimens, with two comparing IV GCs, the latter showing a marginal benefit with respect to relapse (risk ratio (RR) = 0.78, 95 % CI = 0.54 to 1.12) but a greater risk of infection (RR = 1.58, 95 % CI = 0.90 to 2.78). Another three used methotrexate as an adjunctive agent and showed marginal benefit with respect to relapse (RR = 0.85, 95 % CI = 0.66 to 1.11). The remaining four trials compared prednisolone to dapsone, infliximab, adalimumab and hydroxychloroquine, respectively. There are various clinical trials of varying quality. The results from this meta-analysis show that the use of adjunct agents is not associated with improved outcome.
Published: 2013

34. No consistent evidence of differential cardiovascular risk amongst proton-pump inhibitors when used with clopidogrel: Meta-analysis

Author: Chun Shing Kwok, Yoon K. Loke, Vinodh Jeevanantham, and Buddhadeb Dawn
Subjects: medicine.medical_specialty, Ticlopidine, medicine.drug_class, Lansoprazole, Proton-pump inhibitor, law.invention, Esomeprazole, Randomized controlled trial, Risk Factors, law, Internal medicine, Humans, Medicine, Drug Interactions, Registries, Omeprazole, Randomized Controlled Trials as Topic, Clinical Trials as Topic, business.industry, Proton Pump Inhibitors, Odds ratio, Clopidogrel, Observational Studies as Topic, Cardiovascular Diseases, Anesthesia, Meta-analysis, Drug Therapy, Combination, Cardiology and Cardiovascular Medicine, business, Platelet Aggregation Inhibitors, medicine.drug
Abstract: Background Data from pharmacokinetic and pharmacodynamic studies indicate that the adverse clopidogrel – proton pump inhibitor (PPI) interaction may vary between PPIs, with pantoprazole considered relatively less problematic. We aimed to evaluate systematically whether individual PPIs differ in their risk for cardiovascular events when concomitantly administered with clopidogrel. Methods We searched MEDLINE, EMBASE and Cochrane Trials Register up to December 2011 for randomized and non-randomized studies that reported adverse cardiovascular events with exposure to specific PPIs in patients receiving clopidogrel. We performed random effects meta-analysis, and assessed heterogeneity using the I 2 statistic. Results A total of 23 studies with 222,311 participants were included. Meta-analysis of major adverse cardiovascular events was mostly limited by moderate-substantial heterogeneity. Pooled estimates of cardiovascular risk were significantly elevated for individual PPIs such as omeprazole, esomeprazole, lansoprazole, and pantoprazole when used with clopidogrel. However, meta-analysis of adverse cardiovascular risk in seven observational studies reporting on PPI therapy alone (without concomitant clopidogrel) also found an elevated odds ratio of 1.28 (95% CI 1.14–1.44) compared with no clopidogrel/no PPI exposure. Meta-analysis of two randomized controlled trials did not show significant adverse cardiovascular effect from omeprazole or esomeprazole. Conclusions The absence of consistent evidence on differential cardiovascular risk amongst PPIs (particularly regarding safety of pantoprazole) is in direct opposition to the platelet function and pharmacokinetic data. Our findings of increased cardiovascular risk with PPIs in the absence of clopidogrel suggest that confounding and bias are strong possibilities. The clinical validity or relevance of the hypothesized PPI-clopidogrel interaction remains questionable.
Published: 2013

35. Impact of Hemoglobin Levels and Anemia on Mortality in Acute Stroke: Analysis of UK Regional Registry Data, Systematic Review, and Meta‐Analysis

Author: Stephen J. McCall, Raphae S. Barlas, Kristian M. Bowles, Yoon K. Loke, Mamas A. Mamas, K Honney, Allan Clark, John F. Potter, Anthony K. Metcalf, Joao H. Bettencourt-Silva, and Phyo K. Myint
Subjects: Male, medicine.medical_specialty, Epidemiology, Anemia, Population, 030204 cardiovascular system & hematology, Odds, Hemoglobins, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Humans, Registries, Intensive care medicine, education, Stroke, Original Research, Intracranial Hemorrhage, Ischemic Stroke, education.field_of_study, business.industry, Confounding, Odds ratio, hemoglobin, medicine.disease, R1, mortality, United Kingdom, Meta-analysis, Acute Disease, Cohort, Cerebrovascular Disease/Stroke, Female, prognosis, Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery
Abstract: Background The impact of hemoglobin levels and anemia on stroke mortality remains controversial. We aimed to systematically assess this association and quantify the evidence. Methods and Results We analyzed data from a cohort of 8013 stroke patients (mean± SD , 77.81±11.83 years) consecutively admitted over 11 years (January 2003 to May 2015) using a UK Regional Stroke Register. The impact of hemoglobin levels and anemia on mortality was assessed by sex‐specific values at different time points (7 and 14 days; 1, 3, and 6 months; 1 year) using multiple regression models controlling for confounders. Anemia was present in 24.5% of the cohort on admission and was associated with increased odds of mortality at most of the time points examined up to 1 year following stroke. The association was less consistent for men with hemorrhagic stroke. Elevated hemoglobin was also associated with increased mortality, mainly within the first month. We then conducted a systematic review using the Embase and Medline databases. Twenty studies met the inclusion criteria. When combined with the cohort from the current study, the pooled population had 29 943 patients with stroke. The evidence base was quantified in a meta‐analysis. Anemia on admission was found to be associated with an increased risk of mortality in both ischemic stroke (8 studies; odds ratio 1.97 [95% CI 1.57–2.47]) and hemorrhagic stroke (4 studies; odds ratio 1.46 [95% CI 1.23–1.74]). Conclusions Strong evidence suggests that patients with anemia have increased mortality with stroke. Targeted interventions in this patient population may improve outcomes and require further evaluation.
Published: 2016

36. Meta-analysis of the prognostic impact of anemia in patients undergoing percutaneous coronary intervention

Author: Phyo K. Myint, Olivier F. Bertrand, James Nolan, Nick Curzen, Yoon K. Loke, Chun Shing Kwok, Mamas A. Mamas, Philip Urban, Ashish Pradhan, Andreas Y. Andreou, Denise Tiong, and Azfar Zaman
Subjects: medicine.medical_specialty, Anemia, medicine.medical_treatment, Myocardial Infarction, Coronary Artery Disease, 030204 cardiovascular system & hematology, Hematocrit, Postoperative Hemorrhage, 03 medical and health sciences, Hemoglobins, 0302 clinical medicine, Percutaneous Coronary Intervention, Postoperative Complications, Risk Factors, Internal medicine, medicine, Risk of mortality, Odds Ratio, Prevalence, Humans, 030212 general & internal medicine, Mortality, medicine.diagnostic_test, business.industry, Percutaneous coronary intervention, Odds ratio, medicine.disease, Prognosis, R1, Relative risk, Conventional PCI, Cardiology, Cardiology and Cardiovascular Medicine, business, Mace
Abstract: Anemia is common in patients undergoing percutaneous coronary intervention (PCI), and current guidelines fail to offer recommendations for its management. This review aims to examine the relation between baseline anemia and mortality, major adverse cardiovascular events (MACE), and major bleeding in patients undergoing PCI. We searched MEDLINE and EMBASE for studies that evaluated mortality and adverse outcomes in anemic and nonanemic patients who underwent PCI. Data were collected on study design, participant characteristics, definition of anemia, follow-up, and adverse outcomes. Random effects meta-analysis of risk ratios was performed using inverse variance method. A total of 44 studies were included in the review with 230,795 participants. The prevalence of baseline anemia was 26,514 of 170,914 (16%). There was an elevated risk of mortality and MACE with anemia compared with no anemia-pooled risk ratio (RR) 2.39 (2.02 to 2.83), p
Published: 2016

37. Meta-analysis: Association between hypoglycaemia and serious adverse events in older patients

Author: Yoon K. Loke and Katharina Mattishent
Subjects: Pediatrics, medicine.medical_specialty, Aging, Endocrinology, Diabetes and Metabolism, Frail Elderly, 030209 endocrinology & metabolism, Comorbidity, Hypoglycemia, 03 medical and health sciences, Fractures, Bone, 0302 clinical medicine, Endocrinology, Internal Medicine, medicine, Humans, 030212 general & internal medicine, Vascular Diseases, Mortality, Adverse effect, Aged, Aged, 80 and over, Evidence-Based Medicine, business.industry, Confounding, nutritional and metabolic diseases, Odds ratio, medicine.disease, Confidence interval, Surgery, Observational Studies as Topic, Meta-analysis, Observational study, Accidental Falls, business, Diabetic Angiopathies
Abstract: Aims We aimed to conduct a meta-analysis of serious adverse events (macro- and microvascular events, falls and fractures, death) associated with hypoglycaemia in older patients. Methods We searched MEDLINE and EMBASE spanning a ten-year period up to March 2015 (with automated PubMed updates to October 2015). We selected observational studies reporting on hypoglycaemia and associated serious adverse events, and conducted a meta-analysis. We assessed study validity based on ascertainment of hypoglycaemia, adverse events and adjustment for confounders. Results We included 17 studies involving 1.86 million participants. Meta-analysis of eight studies demonstrated that hypoglycemic episodes were associated with macrovascular complications, odds ratio (OR) 1.83 (95% confidence interval [CI] 1.64, 2.05), and microvascular complications in two studies OR 1.77 (95% CI 1.49, 2.10). Meta-analysis of four studies demonstrated an association between hypoglycaemia and falls or fractures, OR 1.89 (95% CI 1.54, 2.32) and 1.92 (95% CI 1.56, 2.38) respectively. Hypoglycaemia was associated with increased likelihood of death in a meta-analysis of eight studies, OR 2.04 (95% Confidence Interval 1.68, 2.47). Conclusion Our meta-analysis raises major concerns about a range of serious adverse events associated with hypoglycaemia. Clinicians should prioritize individualized therapy and closer monitoring strategies to avoid hypoglycaemia in susceptible older patients.
Published: 2016

38. Reduced risk of Barrett’s esophagus in statin users: case–control study and meta-analysis

Author: Leanne Dearman, Yoon K. Loke, Ian L P Beales, and Inna Vardi
Subjects: Male, medicine.medical_specialty, Time Factors, Physiology, Population, Gastroenterology, Risk Assessment, 03 medical and health sciences, Barrett Esophagus, 0302 clinical medicine, Risk Factors, Internal medicine, Gastroscopy, medicine, Odds Ratio, Humans, Esophagus, Risk factor, education, Aged, Aged, 80 and over, education.field_of_study, Chi-Square Distribution, Aspirin, business.industry, Incidence (epidemiology), Incidence, Anti-Inflammatory Agents, Non-Steroidal, Case-control study, Odds ratio, Esophageal cancer, Middle Aged, Protective Factors, medicine.disease, digestive system diseases, medicine.anatomical_structure, Logistic Models, England, 030220 oncology & carcinogenesis, Barrett's esophagus, Case-Control Studies, 030211 gastroenterology & hepatology, Hydroxymethylglutaryl-CoA Reductase Inhibitors, business
Abstract: Background: Use of statins has been associated with a reduced incidence of esophageal adenocarcinoma in population-based studies. However there are few studies examining statin use and the development of Barrett’s esophagus. Aim: The purpose of this study was to examine the association between statin use and the presence of Barrett’s esophagus in patients having their first gastroscopy. Methods: We have performed a case–control study comparing statin use between patients with, and without, an incident diagnosis of non-dysplastic Barrett’s esophagus. Male Barrett’s cases (134) were compared to 268 male age-matched controls in each of two control groups (erosive gastro-esophageal reflux and dyspepsia without significant upper gastrointestinal disease). Risk factor and drug exposure were established using standardised interviews. Logistic regression was used to compare statin exposure and correct for confounding factors. We performed a meta-analysis pooling our results with three other case–control studies. Results: Regular statin use was associated with a significantly lower incidence of Barrett’s esophagus compared to the combined control groups [adjusted OR 0.62 (95 % confidence intervals 0.37–0.93)]. This effect was more marked in combined statin plus aspirin users [adjusted OR 0.43 (95 % CI 0.21–0.89)]. The inverse association between statin or statin plus aspirin use and risk of Barrett’s was significantly greater with longer duration of use. Meta-analysis of pooled data (1098 Barrett’s, 2085 controls) showed that statin use was significantly associated with a reduced risk of Barrett’s esophagus [pooled adjusted OR 0.63 (95 % CI 0.51–0.77)]. Conclusions: Statin use is associated with a reduced incidence of a new diagnosis of Barrett’s esophagus.
Published: 2016

39. Risk of Clostridium difficile Infection With Acid Suppressing Drugs and Antibiotics: Meta-Analysis

Author: Sonal Singh, Chun Shing Kwok, Chukwudubem Ifeanyichukwu Anibueze, Aaron Kobina Arthur, Yoon K. Loke, and Rodrigo Cavallazzi
Subjects: medicine.medical_specialty, Hepatology, Clostridioides difficile, business.industry, Incidence, Gastroenterology, Proton Pump Inhibitors, Subgroup analysis, Odds ratio, Pharmacology, Confidence interval, Anti-Bacterial Agents, Study heterogeneity, Histamine H2 Antagonists, Recurrence, Risk Factors, Internal medicine, Concomitant, Meta-analysis, Cohort, Humans, Medicine, business, Risk assessment, Enterocolitis, Pseudomembranous
Abstract: OBJECTIVES: Several studies have raised concern regarding the possible association between proton-pump inhibitors (PPIs) and Clostridium difficile infection (CDI). We aimed to perform a systematic review of incident and recurrent CDI in PPI users, and to evaluate the relative impact of concurrent antibiotic use, or switching acid suppression to histamine-2-receptor antagonists (H2RAs). METHODS: We searched MEDLINE and EMBASE from inception to December 2011 for controlled observational studies that reported on the risk of CDI with and without PPI use. We performed random effects meta-analysis and assessed statistical heterogeneity using the I(2) statistic. RESULTS: We included 42 observational studies (30 case-control, 12 cohort) totalling 313,000 participants overall. Pooled analysis of 39 studies showed a statistically significant association between PPI use and risk of developing CDI, odds ratio (OR) 1.74 (95% confidence interval (CI) 1.47-2.85, P
Published: 2012

40. Functional polymorphisms of folate metabolism and response to chemotherapy for colorectal cancer, a systematic review and meta-analysis

Author: Victoria Matthews, Chun Shing Kwok, Barbara A. Jennings, Pawel Wawruch, Gavin Willis, and Yoon K. Loke
Subjects: Oncology, medicine.medical_specialty, Low protein, Genotype, Colorectal cancer, Biology, Bioinformatics, Deoxycytidine, Folic Acid, Polymorphism (computer science), Internal medicine, Databases, Genetic, Genetics, medicine, Humans, General Pharmacology, Toxicology and Pharmaceutics, Adverse effect, Molecular Biology, Capecitabine, Genetic Association Studies, Methylenetetrahydrofolate Reductase (NADPH2), Genetics (clinical), Genetic Variation, Thymidylate Synthase, medicine.disease, Gene Expression Regulation, Neoplastic, Tetrahydrofolate Dehydrogenase, Relative risk, Methylenetetrahydrofolate reductase, Meta-analysis, biology.protein, Molecular Medicine, Fluorouracil, Colorectal Neoplasms
Abstract: OBJECTIVES: Many primary studies have considered the association of polymorphisms of folate metabolism and response to 5-fluorouracil (5-FU) and capecitabine in patients with colorectal cancer. The conclusions from these studies have been conflicting and few have considered large cohorts of patients. Therefore, we have completed a systematic review and meta-analyses to summarize some of the findings to date. We conducted searches for any studies that had addressed the prognostic value of genotype analysis of thymidylate synthetase (TYMS), Methylenetetrahydrofolate reductase (MTHFR) and dihydrofolate reductase (DHFR). METHODS: We collected data on the study designs, and completed meta-analyses to pool congruent data about treatment effect. A narrative summary is presented for 39 studies that describe three TYMS genotypes and two MTHFR genotypes associated with response to 5-FU-based chemotherapy. RESULTS: Data were synthesized from up to 2402 patients for the most commonly studied markers TYMS 5' UTR repeat polymorphism (rs45445694) and MTHFR 677 C>T (rs1801133). We found that the TYMS genotype associated with the lowest protein expression (2R/2R) was significantly associated with improved clinical benefit; the pooled risk ratio was relative risk=1.36 [1.11, 1.65]; P=0.003. Moreover, the same trend was observed for adverse effects; the pooled risk ratio was 2.04 [1.42, 2.95]; P=0.0001. CONCLUSION: There is a small but statistically significant association between treatment effect (both intended effects and adverse events) and a TYMS genotype associated with low protein expression; however, the effect size is small and therefore indicates limited clinical utility.
Published: 2012

41. Effects of Proton Pump Inhibitors on Platelet Function in Patients Receiving Clopidogrel

Author: Chun Shing Kwok and Yoon K. Loke
Subjects: Blood Platelets, medicine.medical_specialty, Ticlopidine, Platelet Aggregation, medicine.drug_class, Proton-pump inhibitor, Pharmacology, Toxicology, Esomeprazole, Internal medicine, medicine, Humans, Drug Interactions, Pharmacology (medical), cardiovascular diseases, Omeprazole, Randomized Controlled Trials as Topic, Pantoprazole, business.industry, Clinical study design, Proton Pump Inhibitors, Clopidogrel, Platelet aggregation inhibitor, business, Platelet Aggregation Inhibitors, medicine.drug
Abstract: Background: There is considerable debate regarding the negative impact of concomitant proton pump inhibitor (PPI) therapy on the antiplatelet efficacy of clopidogrel. Aim: The aim of this study was to perform a systematic review of studies that have evaluated the platelet function of patients receiving clopidogrel alone compared with those receiving both clopidogrel and PPIs. Methods: We searched MEDLINE, EMBASE and the Cochrane Controlled Trials Register in February 2011 for randomized and non-randomized studies that reported platelet function results in patients taking clopidogrel, with or without PPIs. Results: Our review included 19 studies (13 trials and 6 observational studies) involving 4693 patients. There was considerable heterogeneity in the study designs, patient characteristics, laboratory tests of platelet function, and drug exposure (dose and duration of PPI and clopidogrel). There was some evidence against omeprazole, with five of nine studies demonstrating a significant interaction with clopidogrel. The available platelet function data on esomeprazole (six studies) or pantoprazole (six studies) did not demonstrate a significant interaction. Of the six studies that statistically analysed platelet function data with omeprazole compared with pantoprazole, three showed a significantly greater interaction between omeprazole and clopidogrel, whereas three studies with limited sample sizes were unable to find a significant difference in the effects of omeprazole and pantoprazole. Conclusion: Platelet function studies do not demonstrate a clear or consistent interaction between clopidogrel and PPIs. These studies are difficult to interpret given the lack of information on drug exposure (dose and duration), variation in laboratory methodology and lack of genetic information. Consequently, platelet function data are of uncertain clinical relevance in determining the risk of an adverse cardiovascular interaction between PPIs and clopidogrel. Clinicians should continue to clinically assess the gastrointestinal risk of the patients and make their prescribing decision for PPIs based on any anticipated benefits in reducing risk of peptic ulcers and gastrointestinal haemorrhage.
Published: 2012

42. Strengths and limitations of healthcare databases in the evaluation of hypoglycaemia

Author: Katharina Mattishent and Yoon K. Loke
Subjects: Gerontology, Pediatrics, medicine.medical_specialty, endocrine system diseases, business.industry, Endocrinology, Diabetes and Metabolism, Ethnic group, nutritional and metabolic diseases, 030209 endocrinology & metabolism, National health service, Large sample, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Social deprivation, Administrative database, 030225 pediatrics, Health care, Internal Medicine, Medicine, business, hormones, hormone substitutes, and hormone antagonists
Abstract: In this issue of DOM, Zaccardi et al. present an analysis of hypoglycaemia-related hospitalizations in the Hospital Episodes Statistics (HES) administrative database of the English National Health Service. [1] Notable strengths of the work include a large sample size involving more than 100 000 cases of hypoglycaemia, and nationwide capture spanning a duration of ten years. Key conclusions include the possibility of a U-shaped relationship between risk of hypoglycaemia and age, as well as possible associations between social deprivation and ethnicity with greater risk of hypoglycaemia.
Published: 2017

43. Meta-analysis: risk of esophageal adenocarcinoma with medications which relax the lower esophageal sphincter

Author: Leo Alexandre, Yoon K. Loke, Ian L P Beales, and T Broughton
Subjects: medicine.medical_specialty, Esophageal Neoplasm, business.industry, Gastroenterology, General Medicine, Anticholinergic agents, Odds ratio, medicine.disease, Gastric Cardia Adenocarcinoma, Obstructive lung disease, Confidence interval, Internal medicine, Anesthesia, Meta-analysis, Medicine, Adenocarcinoma, business
Abstract: Reasons for the rising annual incidence of esophageal adenocarcinoma (EAC) remain uncertain. Previous studies have given conflicting results, but some have suggested that drugs which relax the lower esophageal sphincter (LES) may increase the risk of EAC. This study is to determine systematically the risk of EAC associated with individual medications which relax the LES and compare risks with esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA). Relevant published studies were identified by systematic searching PubMed for case-control studies reporting on risk of EAC, ESCC or GCA with use of medications known to reduce LES pressure. Pooled odds ratios (ORs) were calculated for each malignancy. Data were analyzed from four case-control studies involving 9,412 participants. EAC was significantly associated with theophylline use (OR 1.55, 95% confidence interval [CI] 1.05-2.28; P= 0.03, I(2) = 0%) and anticholinergic medications (OR 1.66, 95% CI 1.13-2.44; P= 0.01, I(2) = 84%). This effect was not observed in cases of ESCC or GCA. Other drug groups including calcium channel modulators and nitrates did not increase the risk of EAC. An inverse relationship was observed between ESCC and nitrates and between GCA and benzodiazepines. The lack of increased EAC risk with many commonly used medications is reassuring. However, a significant correlation was found between EAC and the use of anticholinergics and theophyllines. This may reflect common causality between obstructive lung disease and EAC, and further studies to explore these relationships are warranted.
Published: 2011

44. Risk of serious adverse cardiovascular events associated with varenicline: a systematic review and meta-analysis

Author: Sonal Singh, Yoon K. Loke, Curt D. Furberg, and John G. Spangler
Subjects: medicine.medical_specialty, business.industry, medicine.medical_treatment, General Medicine, Publication bias, Sudden death, law.invention, chemistry.chemical_compound, Systematic review, Randomized controlled trial, chemistry, law, Internal medicine, Meta-analysis, Anesthesia, medicine, Smoking cessation, business, Adverse effect, Varenicline
Abstract: Background: There have been postmarketing reports of adverse cardiovascular events associated with the use of varenicline, a widely used smoking cessation drug. We conducted a systematic review and meta-analysis of randomized controlled trials to ascertain the serious adverse cardiovascular effects of varenicline compared with placebo among tobacco users. Methods: We searched MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews, websites of regulatory authorities and registries of clinical trials, with no date or language restrictions, through September 2010 (updated March 2011) for published and unpublished studies. We selected double-blind randomized controlled trials of at least one week’s duration involving smokers or people who used smokeless tobacco that reported on cardiovascular events (ischemia, arrhythmia, congestive heart failure, sudden death or cardiovascular-related death) as serious adverse events asociated with the use of varenicline. Results: We analyzed data from 14 double-blind randomized controlled trials involving 8216 participants. The trials ranged in duration from 7 to 52 weeks. Varenicline was associated with a significantly increased risk of serious adverse cardiovascular events compared with placebo (1.06% [52/4908] in varenicline group v. 0.82% [27/3308] in placebo group; Peto odds ratio [OR] 1.72, 95% confidence interval [CI] 1.09–2.71; I 2 = 0%). The results of various sensitivity analyses were consistent with those of the main analysis, and a funnel plot showed no publication bias. There were too few deaths to allow meaningful comparisons of mortality. Interpretation: Our meta-analysis raises safety concerns about the potential for an increased risk of serious adverse cardiovascular events associated with the use of varenicline among tobacco users.
Published: 2011

45. Risk of fractures with inhaled corticosteroids in COPD: systematic review and meta-analysis of randomised controlled trials and observational studies

Author: Yoon K. Loke, Sonal Singh, and Rodrigo Cavallazzi
Subjects: Male, Pulmonary and Respiratory Medicine, Budesonide, medicine.medical_specialty, MEDLINE, Inhaled corticosteroids, Risk Assessment, Fractures, Bone, Pulmonary Disease, Chronic Obstructive, Internal medicine, Administration, Inhalation, Humans, Medicine, Glucocorticoids, Aged, Randomized Controlled Trials as Topic, Fluticasone, COPD, Dose-Response Relationship, Drug, Inhalation, business.industry, Middle Aged, medicine.disease, Androstadienes, Meta-analysis, Physical therapy, Female, Observational study, business, medicine.drug
Abstract: Background The effect of inhaled corticosteroids (ICS) on fracture risk in patients with chronic obstructive pulmonary disease (COPD) remains uncertain. The aim of this study was to evaluate the association between ICS and fractures in COPD. Methods MEDLINE, EMBASE, regulatory documents and company registries were searched up to August 2010. Randomised controlled trials (RCTs) of budesonide or fluticasone versus control treatment for COPD (≥24 weeks duration) and controlled observational studies reporting on fracture risk with ICS exposure vs no exposure in COPD were included. Peto OR meta-analysis was used for fracture risk from RCTs while ORs from observational studies were pooled using the fixed effect inverse variance method. Dose–response analysis was conducted using variance-weighted least squares regression in the observational studies. Heterogeneity was assessed using the I 2 statistic. Results Sixteen RCTs (14 fluticasone, 2 budesonide) with 17 513 participants, and seven observational studies (n=69 000 participants) were included in the meta-analysis. ICSs were associated with a significantly increased risk of fractures (Peto OR 1.27; 95% CI 1.01 to 1.58; p=0.04; I 2 =0%) in the RCTs. In the observational studies, ICS exposure was associated with a significantly increased risk of fractures (OR 1.21; 95% CI 1.12 to 1.32; p 2 =37%), with each 500 μg increase in beclomethasone dose equivalents associated with a 9% increased risk of fractures, OR 1.09 (95% CI 1.06 to 1.12; p Conclusion Among patients with COPD, long-term exposure to fluticasone and budesonide is consistently associated with a modest but statistically significant increased likelihood of fractures.
Published: 2011

46. Atrial fibrillation and incidence of dementia: A systematic review and meta-analysis

Author: Rachel Hale, Chun Shing Kwok, Yoon K. Loke, John F. Potter, and Phyo K. Myint
Subjects: medicine.medical_specialty, education.field_of_study, Databases, Factual, business.industry, Incidence, Incidence (epidemiology), Population, Odds ratio, medicine.disease, Confidence interval, Surgery, Meta-analysis, Internal medicine, Atrial Fibrillation, Odds Ratio, Humans, Medicine, Dementia, Neurology (clinical), business, education, Prospective cohort study, Stroke
Abstract: Background: Previous systematic reviews that examined whether atrial fibrillation (AF) is associated with dementia have relied on different study designs (including retrospective ones) and did not evaluate risk using meta-analysis. Methods: We searched Medline, Embase, and PsychINFO in September 2010 for published prospective studies reporting on the association between baseline AF and incident dementia. Pooled odds ratios for AF and dementia were calculated using the random effects model, with heterogeneity assessed using I 2 . Results: We identified 15 relevant studies covering 46,637 participants, mean age 71.7 years. One study that reported no significant difference in Mini-Mental State Examination scores between patients with or without AF could not be pooled. Meta-analysis of the remaining 14 studies showed that AF was associated with a significant increase in dementia overall (odds ratio [OR] 2.0, 95% confidence interval [CI] 1.4 to 2.7, p I 2 = 75%). When stratified by participants, the association was significant (with little heterogeneity) in studies focusing solely on patients with stroke (7 studies, OR 2.4, 95% CI 1.7 to 3.5, p I 2 = 10%), and of borderline significance (with substantial heterogeneity) for studies in broader populations (7 studies, OR 1.6, 95% CI 1.0 to 2.7, p = 0.05, I 2 = 87%). For conversion of mild cognitive impairment to dementia, one study showed a significant association with AF (OR 4.6, 95% CI 1.7 to 12.5). Conclusion: There is consistent evidence supporting an association between AF and increased incidence of dementia in patients with stroke whereas there remains considerable uncertainty about any link in the broader population. The potential association between AF and incident dementia in mild cognitive impairment merits further investigation.
Published: 2011

47. Long-term use of thiazolidinediones and the associated risk of pneumonia or lower respiratory tract infection: systematic review and meta-analysis

Author: Sonal Singh, Curt D. Furberg, and Yoon K. Loke
Subjects: Adult, Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Opportunistic Infections, Lower respiratory tract infection, Internal medicine, medicine, Humans, Hypoglycemic Agents, Risk factor, Intensive care medicine, Adverse effect, Respiratory Tract Infections, Aged, Randomized Controlled Trials as Topic, Respiratory tract infections, business.industry, Respiratory disease, Pneumonia, Middle Aged, medicine.disease, Diabetes Mellitus, Type 2, Female, Thiazolidinediones, business, Rosiglitazone, Publication Bias, Pioglitazone, medicine.drug
Abstract: Introduction The peroxisome proliferator-activated receptor-γ agonists rosiglitazone and pioglitazone activate glucocorticoid receptors and have an immunomodulatory effect. The authors aimed to systematically determine the risk of pneumonia or lower respiratory tract infections associated with thiazolidinediones. Methods Systematic searches of MEDLINE, EMBASE, regulatory documents and trial registries were carried out for randomised controlled trials of thiazolidinediones with no date restrictions through March 2010. The authors selected long-term (≥1 year) randomised controlled trials of thiazolidinediones versus a placebo, metformin or sulfonylurea control for prevention or treatment of type 2 diabetes that reported on pneumonia or lower respiratory tract infection adverse events or serious adverse events (hospitalisation, disability or death). Relative risks (RRs) were estimated using a fixed-effects meta-analysis, and statistical heterogeneity was assessed using the I 2 statistic. Results Thirteen trials (n=17 627, including 8163 patients receiving thiazolidinediones and 9464 patients receiving control therapy) with a duration of follow-up of 1–5.5 years were included after a detailed screening of 58 studies. Thiazolidinediones were associated with a statistically significantly increased risk for any pneumonia or lower respiratory tract infection (n=130/8163 vs 100/9464; RR 1.40; 95% CI 1.08 to 1.82; p=0.01; I 2 =0%) and serious pneumonia or lower respiratory tract infection (n=111/7391 vs 87/8692; RR 1.39; 95% CI 1.05 to 1.83; p=0.02; I 2 =0%). Interpretation Long-term thiazolidinedione use is associated with a modestly increased risk of any pneumonia or lower respiratory tract infection and serious pneumonia or lower respiratory tract infection in patients with type 2 diabetes.
Published: 2011

48. Risk of pneumonia associated with long-term use of inhaled corticosteroids in chronic obstructive pulmonary disease: a critical review and update

Author: Yoon K. Loke and Sonal Singh
Subjects: Pulmonary and Respiratory Medicine, COPD, medicine.medical_specialty, Inhalation, medicine.drug_class, business.industry, medicine.disease, law.invention, Pneumonia, Systematic review, Pharmacotherapy, Randomized controlled trial, law, Meta-analysis, Internal medicine, medicine, Corticosteroid, business, Intensive care medicine
Abstract: Purpose of Review—To determine the effects of long-term inhaled corticosteroid use on pneumonia in patients with Chronic Obstructive Pulmonary Disease via systematic searches of MEDLINE, EMBASE, ISI, regulatory documents and manufacturers’ trial registries. Recent findings—Our updated meta-analysis of 24 long term randomized controlled trials involving 23, 096 participants shows a significantly increased risk of pneumonia with the use of inhaled corticosteroids in Chronic Obstructive Pulmonary Disease (RR 1.57, 95% CI 1.41–1.75, P
Published: 2010

49. Risk of myocardial infarction and cardiovascular death associated with inhaled corticosteroids in COPD

Author: Sonal Singh, Yoon K. Loke, and Chun Shing Kwok
Subjects: Risk, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Funnel plot, COPD, business.industry, Myocardial Infarction, Publication bias, medicine.disease, Respiratory Function Tests, Surgery, Pulmonary Disease, Chronic Obstructive, Adrenal Cortex Hormones, Cardiovascular Diseases, Internal medicine, Relative risk, Meta-analysis, Administration, Inhalation, medicine, Humans, Observational study, Myocardial infarction, Risk factor, business, Randomized Controlled Trials as Topic
Abstract: The effect of long-term inhaled corticosteroid (ICS) use on myocardial infarction (MI) and cardiovascular (CV) death in chronic obstructive pulmonary disease (COPD) remains uncertain. We conducted a systematic search of MEDLINE, EMBASE, ISI, regulatory documents and manufacturers' trial registries for long-term (>24 weeks duration) randomised controlled trials (RCTs) or controlled observational studies reporting on CV outcomes or death with ICS use in COPD. A fixed effects model was used to calculate the relative risks (RRs) and 95% CIs. 23 RCTs with 24-160 weeks of follow-up were included. In the RCTs, ICS were not associated with a significantly reduced risk of MI (RR 0.95, 95% CI 0.73-1.23; p = 0.68, I(2) = 0%), CV death (RR 1.02; 95% CI 0.81-1.27; p = 0.89, I(2) = 0%), or mortality (RR 0.96, 95% CI 0.86-1.07; p = 0.43, I(2) = 0%). In the observational studies, ICS use was associated with a significant reduction in CV death (two studies: RR 0.79, 95% CI 0.72-0, 86; p
Published: 2009

50. Homocysteine and Peripheral Arterial Disease: Systematic Review and Meta-analysis

Author: Yoon K. Loke, Matthew P. Armon, Felicity J. Meyer, Nader Khandanpour, and Barbara A. Jennings
Subjects: Male, medicine.medical_specialty, Homocysteine, Folic acid, MEDLINE, Hyperhomocysteinemia, Gastroenterology, Intermittent claudication, chemistry.chemical_compound, Internal medicine, medicine, Humans, Aged, Aged, 80 and over, Peripheral Vascular Diseases, Medicine(all), Evidence-Based Medicine, Peripheral arterial diseases, business.industry, Middle Aged, Atherosclerosis, Peripheral, Surgery, Up-Regulation, Clinical trial, Pooled variance, Treatment Outcome, chemistry, Meta-analysis, Dietary Supplements, Observational study, Female, medicine.symptom, Cardiology and Cardiovascular Medicine, business, Homocysteine-lowering therapy, Biomarkers
Abstract: ObjectiveTo evaluate homocysteine (Hcy) levels in patients with peripheral arterial disease (PAD) as compared to unaffected controls, and to review the clinical effects of therapy aimed at lowering homocysteine in PAD patients.MethodsMEDLINE, EMBASE and Cochrane databases were searched from 1950 to December 2007. We selected observational studies and trials that evaluated Hcy levels in patients with PAD compared to unaffected controls. We also included trials on the effect of Hcy-lowering therapy (folate supplementation) in PAD patients. Continuous outcomes were pooled in a random effects meta-analysis of the weighted mean difference between comparator groups.ResultsWe retrieved 33 potentially suitable articles from our search. Meta-analysis of 14 relevant studies showed that Hcy was significantly elevated (pooled mean difference +4.31μmoll; 95% C.I. 1.71, 6.31, p
Published: 2009
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