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2. Effect of SGLT2 Inhibitors on Stroke and Atrial Fibrillation in Diabetic Kidney Disease: Results From the CREDENCE Trial and Meta-Analysis
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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. 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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. 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., Groningen Kidney Center (GKC), Zhou, Z, Jardine, M, Li, Q, Neuen, B, Cannon, C, De Zeeuw, D, Edwards, R, 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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, 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, Arauz-Pacheco, C, Arfeen, S, Arif, A, Arvind, M, Atray, N, Awad, A, Bakris, G, Barnhill, P, Barranco, E, 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Moreda, R, Moustafa, M, Trenche, S, Narayanan, M, Narvarte, J, Nassar, T, Newman, G, Nichol, B, Nicol, P, Nisnisan, J, Nossuli, A, 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, and Zaniewski-Singh, M
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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 (
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- 2021
3. Effect of SGLT2 inhibitors on stroke and atrial fibrillation in diabetic kidney disease: Results from the CREDENCE trial and meta-analysis
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Zhou, Z, Jardine, M, Li, Q, Neuen, B, Cannon, C, De Zeeuw, D, Edwards, R, Levin, A, Mahaffey, K, Perkovic, V, Neal, B, Lindley, R, Guerrero, R, Aizenberg, D, Albisu, J, Alvarisqueta, A, Bartolacci, I, Berli, M, Bordonava, A, Calella, P, Cantero, M, Cartasegna, L, Cercos, E, Coloma, G, Colombo, H, Commendatore, V, Cuadrado, J, Cuneo, C, Cusumano, A, Douthat, W, Dran, R, Farias, E, Fernandez, M, Finkelstein, H, Fragale, G, Fretes, J, Garcia, N, Gastaldi, A, Gelersztein, E, Glenny, J, Gonzalez, J, Del Carmen Gonzalez Colaso, P, Goycoa, C, Greloni, G, Guinsburg, A, Hermida, S, Juncos, L, Klyver, M, Kraft, F, Krynski, F, Lanchiotti, P, De La Fuente, R, Marchetta, N, Mele, P, Nicolai, S, Novoa, P, Orio, S, Otreras, F, Oviedo, A, Raffaele, P, Resk, J, Rista, L, Papini, N, Sala, J, Santos, J, Schiavi, L, Sessa, H, Casabella, T, Ulla, M, Valdez, M, Vallejos, A, Villarino, A, Visco, V, Wassermann, A, Zaidman, C, Cheung, N, Droste, C, Fraser, I, Johnson, D, Mah, P, Nicholls, K, Packham, D, Proietto, J, Roberts, A, Roger, S, Tsang, V, Raduan, R, Da Costa, F, Amodeo, C, Turatti, L, Bregman, R, Sanches, F, Canani, L, Chacra, A, Borges, J, Vencio, S, Da Silva Franco, R, D'Avila, D, De Souza Portes, E, De Souza, P, Deboni, L, Filho, F, Neto, B, Gomes, M, Kohara, S, Keitel, E, Saraiva, J, Lisboa, H, De Carvalho Contieri, F, Milagres, R, Junior, R, De Brito, C, Hissa, M, Sabbag, A, Noronha, I, Panarotto, D, Filho, R, Pereira, M, Saporito, W, Scotton, A, Schuch, T, De Almeida, R, Ramos, C, Felicio, J, Thome, F, Hachmann, J, Yamada, S, Hayashida, C, Petry, T, Zanella, M, 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, Jorquera, J, Farina, M, Gajardo, V, 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, Arcos, E, Avendano, J, Ruiz, J, Ortiz, L, Gonzalez, A, Triana, E, Higuera, J, Malaver, N, De Salazar, D, Rosero, R, Lozano, M, Cometa, L, Valenzuela, A, Alonso, R, 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, Gourdy, P, Klein, A, Le Meur, Y, Penfornis, A, Roussel, R, Saulnier, P, 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, Haase, F, Diaz, J, Roca, L, Arenales, J, Polo, J, Juarez, E, 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, Dewan, D, Fernando, M, Gopalakrishnan, N, Gracious, N, Alva, H, Jain, D, Keshavamurthy, C, Khullar, D, Sahay, M, Peringat, J, Prasad, N, Rao, K, Reddy, S, Melemadathil, S, Sudhakar, B, Vyasam, R, Bonadonna, R, Castellino, P, Ceriello, A, Chiovato, L, De Cosmo, S, De Nicola, L, Derosa, G, Carlo, A, Cianni, G, Frasca, G, Fuiano, G, Gambaro, G, Garibotto, G, Giorda, C, Malberti, F, Mandreoli, M, Mannucci, E, Orsi, E, Piatti, P, Santoro, D, Sasso, F, Serviddio, G, Stella, A, Trevisan, R, Veronelli, A, 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, Kadir, K, Ali, N, Yusof, M, Gan, C, Ismail, M, Kong, W, Lam, S, Lee, L, Lim, S, Loh, C, Manocha, A, Ng, K, Ahmad, N, Ratnasingam, V, Shudim, S, Vengadasalam, P, Munoz, L, Salazar, M, Cruz, J, Soto, M, Ramos, J, Wong, A, Rotter, J, Escalante, T, Sosa, F, Lozano, F, Cervera, L, Baron, P, Ballesteros, C, Rangel, J, Jimenez, L, Santana, S, Flores, F, Molina, H, Ceballos, R, Del Campo Blanco, B, Franco, G, Loza, O, Rocha, C, Vera, G, Castellanos, R, Calcaneo, J, Rosano, M, Pattzi, H, Guzman, J, Joerg, I, Sanchez, S, Mijangos, J, Sanson, P, Tamayo Y Orozco, J, Chavez, E, Cepeda, A, Carrillo, L, Mesa, J, Escobedo, R, Baker, J, Noonan, P, Scott, R, Walker, R, Watson, E, Williams, M, Young, S, Abejuela, Z, Agra, J, Aquitania, G, Caringal, C, Comia, R, Santos, L, Gomez, O, Jimeno, C, Santos, F, Tan, G, Tolentino, M, Yao, C, Yap, Y, Ygpuara, M, 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, Anghel, V, Avram, R, Busegeanu, M, Cif, A, Cosma, D, Crisan, C, Demian, L, Ferariu, I, Halmagyi, I, Hancu, N, Munteanu, M, Negru, D, Onaca, A, Petrica, L, Popa, A, Ranetti, A, 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, Cho, Y, Jeong, I, Kim, S, Kim, Y, Kwon, H, Kwon, M, Lee, B, Lee, J, Lee, M, Nam, M, Oh, K, Park, C, Park, S, Yoon, K, Garcia, P, Mercadal, L, Barrios, C, Castro, F, Guldris, S, Lopez, M, De Los Rios, J, Fresnedo, G, Serrano, A, Garcia, I, Martinez, F, Gimeno, J, Mendoza, M, Marin, T, Portillo, C, Vila, M, Torres, M, Iglesias, J, Perez, J, Vera, M, Simon, M, Canonge, R, Riera, M, Madueno, F, Plaza, M, Chang, C, Chuang, L, Hsia, T, Hsieh, C, Hwang, S, Lin, C, Lu, Y, Sheu, W, Barna, O, Bilyk, S, 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, 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, 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, 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, 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, Narayanan, M, Narvarte, J, Nassar, T, Newman, G, Nichol, B, Nicol, P, Nisnisan, J, Nossuli, A, 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. 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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. 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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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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., and Zaniewski-Singh M.
- Abstract
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 (45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]). CONCLUSIONS: Although we found no clear effect
- Published
- 2021
4. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy
- Author
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Perkovic, V., Jardine, M. J., Neal, B., Bompoint, S., Heerspink, H. J. L., Charytan, D. M., Edwards, R., Agarwal, R., Bakris, G., Bull, S., Cannon, C. P., Capuano, G., Chu, P. -L., De Zeeuw, D., Greene, T., Levin, A., Pollock, C., Wheeler, D. C., Yavin, Y., Zhang, H., Zinman, B., Meininger, G., Brenner, B. M., Mahaffey, K. 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- Subjects
Aged ,Canagliflozin ,Cardiovascular Diseases ,Creatinine ,Diabetes Mellitus, Type 2 ,Diabetic Nephropathies ,Double-Blind Method ,Female ,Follow-Up Studies ,Glomerular Filtration Rate ,Humans ,Kidney Failure, Chronic ,Male ,Middle Aged ,Sodium-Glucose Transporter 2 Inhibitors ,Type 2 diabetes ,030204 cardiovascular system & hematology ,Diabetic nephropathy ,Kidney Failure ,chemistry.chemical_compound ,0302 clinical medicine ,030212 general & internal medicine ,03.02. Klinikai orvostan ,Dapagliflozin ,Chronic ,11 Medical and Health Sciences ,EMPAGLIFLOZIN ,General Medicine ,Life Sciences & Biomedicine ,Type 2 ,medicine.drug ,medicine.medical_specialty ,Nephropathy ,03 medical and health sciences ,Medicine, General & Internal ,Internal medicine ,Diabetes mellitus ,General & Internal Medicine ,CREDENCE Trial Investigators ,medicine ,Diabetes Mellitus ,Science & Technology ,business.industry ,urogenital system ,diabetic nephropathy ,Type 2 Diabetes Mellitus ,KIDNEY-DISEASE ,medicine.disease ,chemistry ,business ,Kidney disease - Abstract
BACKGROUND: Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium-glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS: In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin-angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of
- Published
- 2019
5. Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial
- Author
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M., Holman R., DeMets D., Riddle M., Goodman S., McGuire D., Alexander K., Devore A., Melloni C., Patel C., Kong D., Bloomfield G., Roe M., Tricoci P., Harrison R., Lopes R., Mathews R., Mehta R., Schuyler Jones W., Vemulapalli S., Povsic T., Eapen Z., Dombrowski K., Kolls B., Jordan D., Ambrosy A., Greene S., Mandawat A., Shavadia J., Cooper L., Sharma A., Guimaraes P., Friedman D., Wilson M., Endsley P., Gentry T., Collier J., Perez K., James K., Roush J., Pope C., Howell C., Johnson M., Bailey M., Cole J., Akers T., Vandyne B., Thomas B., Rich J., Bartone S., Beaulieu G., Brown K., Chau T., Christian T., Coker R., Greene D., Haddock T., Jenkins W., Haque G., Marquess M., Pesarchick J., Rethaford R., Stone A., Al Kawas F., Anderson M., Enns R., Sinay I., Mathieu C., Yordanov V., Hramiak I., Haluzik M., Galatius S., Guerci B., Nauck M., Migdalis I., Tan C. B. K., Kocsis G., Giaccari A., Lee M. K., Munoz E. G. 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M., Dauber I., Davila W., De Armas L., Dean J., Detweiler R., Diaz E., Di Giovanna M., Dor I., Drummond W., Eagerton D., Earl J., Eaton C., Ellison H., Farris N., Fiel T., Firek A., First B., Forgosh L., French W., Gandy W., Garcia R., Gill S., Gordon M., Guice M., Gummadi S., Hackenyos J., Hairston K., Hanson L., Harrison L., Hartman I., Heitner J., Hejeebu S., Hermany P., Hernandez-Cassis C., Hidalgo H., Higgins A., Ibrahim H., Jacobs S., Johnson D., Joshi P., Kaster S., Kellum D., Kim C., Kim E., Kirby W., Knouse A., Kulback S., Kumar M., Kuruvanka T., Labroo A., Lasswell W., Lentz J., Lenzmeier T., Lewis D., Li Z., Lillestol M., Little R., Lorraine R., McKeown-Biagas C., McNeill R., Mehta A., Miller A., Moran J., Morawski E., Nadar V., O'Connor T., Odio A., Parker R., Patel R., Phillips L., Raad G., Rahman A., Raikhel M., Raisinghani A., Rajan R., Rasouli N., Rauzi F., Rohr K., Roseman H., Rovner S., Saba F., Sachson R., Schabauer A., Schneider R., Schuchard T., Sensenbrenner J., Shlesinger Y., Singh N., Sivalingam K., Stonesifer L., Storey D., Suh D., Tahir M., Tan A., Tan M., Taylon A., Thakkar M., Tripathy D., Uwaifo G., Vedere A., Venugopal C., Vo A., Welch M., Welker J., White A., Willis J., Wynne A., Yazdani S., Price L., Lokhngina Y., Xing W., Overton R., Stewart M., Stead J., Lindsay A., Patel V., Ross J., Soffer J., Daga S., Sowell M., Patel P., Garvey L., Ackert J., Abraham S., Sabol M. B., Altobelli D., Ha J., Kulkarni M., Noronha D., Casson E., Zang E., Sandhu C., Kumar R., Chen D., Taft L., Ye J., Shannon J., Wilson T., Babi C., Miller D., Russell R., Bull G., Hereghty B., Fernandez-Salazar E., Longley T., Donaldson J., Jarosz M., Murphy K., Adams P., James R., Richards J., Sedani S., Althouse D., Watson D., Lorimer J., Lauder S., Schultheis R., Womer T., Wraight E., Li W., Price-Olsen E., Watson A., Kelly A., McLaughlin P., Fleming J., Schubert J., Schleiden D., Harris T., Prakash R., Breneman J., Deshpande S., Saswadkar A., Kumari A., Shitut A., Raorane A., Karmalkar A., Mhambrey A., Bhosale A., Vaphare A., Patil A. 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Bartolo, P, Dotta, F, Frontoni, S, Galetta, M, Gambineri, A, Gazzaruso, C, Giorgino, F, Lauro, D, Orsi, E, Paolisso, G, Perriello, G, Piatti, P, Pontiroli, A, Ponzani, P, Rivellese, A, Sesti, G, Tonolo, G, Trevisan, R, Ahn, C, Baik, S, Cha, B, Chung, C, Jang, H, Kim, C, Kim, H, Kim, I, Lee, E, Lee, H, Lee, K, Moon, K, Namgung, J, Park, K, Yoo, S, Yu, J, Llamas, E, Cervantes-Escarcega, J, Flota-Cervera, L, Gonzalez-Gonzalez, J, Pascoe-Gonzalez, S, Pelayo-Orozco, E, Ramirez-Diaz, S, Saldana-Mendoza, A, Jerjes-Diaz, C, Torres-Colores, J, Vidrio-Velazquez, M, Villagordoa-Mesa, J, Beijerbacht, H, Groutars, R, Hoek, B, Hoogslag, P, Kooy, A, Kragten, J, Lieverse, A, Swart, H, Viergever, E, Ahlqvist, J, Cooper, J, Gulseth, H, Guttormsen, G, Wium, C, Arbanil, H, Calderon, J, Camacho, L, Espinoza, A, Garrido, E, Luna, A, Manrique, H, Revoredo, F, Gonzales, R, Rincon, L, Zubiate, C, Ebo, G, Morales-Palomares, E, Arciszewska, M, Banach, M, Bijata-Bronisz, R, Derezinski, T, Gadzinski, W, Gajek, J, 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Uwaifo, G, Vedere, A, Venugopal, C, Vo, A, Welch, M, Welker, J, White, A, Willis, J, Wynne, A, Yazdani, S, Price, L, Lokhngina, Y, Xing, W, Overton, R, Stewart, M, Stead, J, Lindsay, A, Patel, V, Ross, J, Soffer, J, Daga, S, Sowell, M, Patel, P, Garvey, L, Ackert, J, Abraham, S, Sabol, M, Altobelli, D, Ha, J, Kulkarni, M, Noronha, D, Casson, E, Zang, E, Sandhu, C, Kumar, R, Chen, D, Taft, L, Ye, J, Shannon, J, Wilson, T, Babi, C, Miller, D, Russell, R, Bull, G, Hereghty, B, Fernandez-Salazar, E, Longley, T, Donaldson, J, Jarosz, M, Murphy, K, Adams, P, James, R, Richards, J, Sedani, S, Althouse, D, Watson, D, Lorimer, J, Lauder, S, Schultheis, R, Womer, T, Wraight, E, Li, W, Price-Olsen, E, Watson, A, Kelly, A, Mclaughlin, P, Fleming, J, Schubert, J, Schleiden, D, Harris, T, Prakash, R, Breneman, J, Deshpande, S, Saswadkar, A, Kumari, A, Shitut, A, Raorane, A, Karmalkar, A, Mhambrey, A, Bhosale, A, Vaphare, A, Patil, A, Khandelwal, C, Shaik, F, Nadar, M, Karka, M, Kadgaonkar, N, Gupta, 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F., Green J. B., Janmohamed S., D'Agostino R. B., Granger C. B., Jones N. P., Leiter L. A., Rosenberg A. E., Sigmon K. N., Somerville M. C., Thorpe K. M., McMurray J. J. V., Del Prato S., Califf R. M., Holman R., DeMets D., Riddle M., Goodman S., McGuire D., Alexander K., Devore A., Melloni C., Patel C., Kong D., Bloomfield G., Roe M., Tricoci P., Harrison R., Lopes R., Mathews R., Mehta R., Schuyler Jones W., Vemulapalli S., Povsic T., Eapen Z., Dombrowski K., Kolls B., Jordan D., Ambrosy A., Greene S., Mandawat A., Shavadia J., Cooper L., Sharma A., Guimaraes P., Friedman D., Wilson M., Endsley P., Gentry T., Collier J., Perez K., James K., Roush J., Pope C., Howell C., Johnson M., Bailey M., Cole J., Akers T., Vandyne B., Thomas B., Rich J., Bartone S., Beaulieu G., Brown K., Chau T., Christian T., Coker R., Greene D., Haddock T., Jenkins W., Haque G., Marquess M., Pesarchick J., Rethaford R., Stone A., Al Kawas F., Anderson M., Enns R., Sinay I., Mathieu C., Yordanov V., Hramiak I., Haluzik M., Galatius S., Guerci B., Nauck M., Migdalis I., Tan C. B. K., Kocsis G., Giaccari A., Lee M. K., Munoz E. G. C., Cornel J., Birkeland K., Pinto M., Tirador L., Olesinska-Mader M., Shestakova M., Distiller L., Lopez-Sendon J., Eliasson B., Chiang C. -E., Srimahachota S., Mankovsky B., Bethel M. A., Dungan K., Kosiborod M., Alvarisqueta A., Baldovino J., Besada D., Calella P., Cantero M. C., Castano P., Chertkoff A., Cuadrado J., De Loredo L., Dominguez A., Espanol M. V., Finkelstein H., Frechtel G., Fretes J., Garrido Santos N., Gonzalez J., Litvak M., Loureyro J., Maffei L., Maldonado N., Mohr Gasparini D., Orio S., Perez Manghi F., Rodriguez Papini N., Sala J., Schygiel P., Sposetti G., Ulla M., Verra F., Zabalua S., Zaidman C., Crenier L., Debroye C., Duyck F., Scheen A., Van Gaal L., Vercammen C., Damyanova V., Dimitrov S., Kovacheva S., Lozanov L., Margaritov V., Mihaylova-Shumkova R., Nikolaeva A., Stoyanova Z., Akhras R., Beaudry Y., Bedard J., Berlingieri J., Chehayeb R., Cheung S., Conway J., Cusson J., Della Siega A., Dumas R., Dzongowski P., Ferguson M., Gaudet D., Grondin F., Gupta A., Gupta M., Halperin F., Houle P. -A., Jones M., Kouz S., Kovacs C., Landry D., Lonn E., O'Mahony W., Peterson S., Reich D., Rosenbloom A., St-Maurice F., Tugwell B., Vizel S., Woo V., Brychta T., Cech V., Dvorakova E., Edelsberger T., Halciakova K., Krizova J., Lastuvka J., Piperek M., Prymkova V., Raclavska L., Silhova E., Urbanek R., Vrkoc J., Andersen U., Bronnum-Schou J., Hove J., Jensen J. 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P., Lund P., Melchior T., Nyvad O., Schou M., Boye A., Cadinot D., Gouet D., Henry P., Kessler L., Lalau J. -D., Petit C., Thuan J. -F., Voinot C., Vouillarmet J., Axthelm C., Berger D., Bieler T., Birkenfeld A., Bott J., Busch K., Caca K., Chevts J., Donaubauer T., Erlinger R., Funke K., Grosskopf J., Hagenow A., Hamann M., Hartard M., Heymer P., Huppertz W., Illies G., Jacob S., Jung T., Kahrmann G., Kast P., Kellerer M., Kempe H. -P., Khariouzov A., Klausmann G., Klein C., Kleinecke-Pohl U., Kleinertz K., Koch T., Kosch C., Lorra B., Luedemann J., Luttermann M., Maxeiner S., Milek K., Moelle A., Neumann G., Nischik R., Oehrig-Pohl E., Plassmann G., Pohlmeier L., Proepper F., Regner S., Rieker W., Rose L., Samer H., Sauter J., Schaper F., Schiffer C., Schmidt J., Scholz B. -M., Schulze J., Segner A., Seufert J., Sigal H., Steindorf J., Stockhausen J., Stuebler P., Taeschner H., Tews D., Tschoepe D., Wilhelm K., Zeller-Stefan H., Avramidis I., Bousboulas S., Bristianou M., Dimitriadis G., Elisaf M., Kotsa K., Melidonis A., Mitrakou A., Pagkalos E., Papanas N., Pappas A., Sampanis C., Tentolouris N., Tsapas A., Tzatzagou G., Ozaki R., Hajdu C., Harcsa E., Konyves L., Mucsi J., Pauker Z., Petro G., Ples Z., Revesz K., Sandor V., Vass V., Avogaro A., Boemi M., Bonadonna R., Consoli A., De Cosmo S., Di Bartolo P., Dotta F., Frontoni S., Galetta M., Gambineri A., Gazzaruso C., Giorgino F., Lauro D., Orsi E., Paolisso G., Perriello G., Piatti P., Pontiroli A., Ponzani P., Rivellese A. 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Z., Zubiate C., Ebo G., Morales-Palomares E., Arciszewska M., Banach M., Bijata-Bronisz R., Derezinski T., Gadzinski W., Gajek J., Klodawska K., Krzyzagorska E., Madej A., Miekus P., Opiela J., Romanczuk P., Siegel A., Skokowska E., Stankiewicz A., Stasinska T., Trznadel-Morawska I., Witek R., Aksentyev S., Bondar I., Demidova I., Dreval A., Ershova O., Galstyan G., Garganeeva A., Izmozherova N., Karetnikova V., Kharakhulakh M., Khokhlov A., Kobalava Z., Koshelskaya O., Kosmacheva E., Kostin V., Koziolova N., Kuzin A., Lesnov V., Lysenko T., Markov V., Mayorov A., Moiseev S., Myasoedova S., Petunina N., Rebrov A., Ruyatkina L., Samoylova J., Sazonova O., Shilkina N., Sokolova N., Vasilevskaya O., Verbovaya N., Vishneva E., Vorobyev S., Vorokhobina N., Zanozina O., Zhdanova E., Zykova T., Burgess L., Coetzee K., Dawood S., Lombard L., Makotoko E., Moodley R., Oosthuysen W., Sarvan M., Calvo Gomez C., Cano Rodriguez I., Castro Conde A., Cequier Fillat A., Cuatrecasas Cambra G., de Alvaro Moreno F., De Teresa Parreno L., Delgado Lista J., Dominguez Escribano J. R., Duran Garcia S., Elvira Gonzalez J., Fernandez Rodriguez J. M., Goday Arno A., Gomez Huelgas R., Gonzalez Juanatey J. R., Hernandez Mijares A., Jimenez Diaz V. A., Jodar Gimeno E., Lucas Morante T., Marazuela M., Martell Claros N., Mauricio Puente D., Mena Ribas E., Merino Torres J. F., Mezquita Raya P., Nubiola Calonge A., Ordonez Sanchez X., Pascual Izuel J. M., Perea Castilla V., Perez Perez A., Perez Soto I., Quesada Charneco M., Quesada Simon A., Redon Mas J., Rego Iraeta A., Rodriguez Alvarez M., Rodriguez Rodriguez I., Saban Ruiz J., Soto Gonzalez A., Tinahones Madueno F., Trescoli Serrano C., Ulied Arminana A., Bachus E., Berndtsson Blom K., Eliasson K., Koskinen P., Larnefeldt H., Lif-Tiberg C., Linderfalk C., Lund G., Lundman P., Moris L., Olsson A., Salmonsson S., Sanmartin Berglund J., Sjoberg F., Soderberg S., Torstensson I., Chen J. -F., Tien K. J., Tseng S. -T., Tu S. -T., Wang C. -Y., Wang J. -H., Phrommintikul A., Yamwong S., Jintapakorn W., Hutayanon P., Sansanayudh N., Bazhan L., Fushtey I., Grachova M., Katerenchuk V., Korpachev V., Kravchun N., Larin O., Mykhalchyshyn G., Myshanych H., Oleksyk O., Orlenko V., Pashkovska N., Pertseva N., Petrosyan O., Smirnov I., Vlasenko M., Zlova T., Aye M., Baksi A., Balasubramani M., Beboso R., Blagden M., Bundy C., Cookson T., Copland A., Emslie-Smith A., Green F., Gunstone A., Issa B., Jackson-Voyzey E., Johnson A., Maclean M., McKnight J., Muzulu S., O'Connell I., Oyesile B., Patterson C., Pearson E., Philip S., Smith P., Sukumaran U., Abbas J., Aggarwala G., Akhter F., Andersen J., Anglade M., Argoud G., Ariani M., Ashdji R., Bakhtari L., Banerjee S., Bartlett A., Baum H., Bays H., Beasley R., Belfort de Aguiar R., Benjamin S., Bhagwat R., Bhargava A., Bode B., Bratcher C., Briskin T., Brockmyre A., Broughton R., Brown J., Budhraja M., Cannon K., Carr J., Cathcart H., Cavale A., Chaykin L., Cheung D., Childress R., Cohen A., Condit J., Cooksey E., Cornett G. M., Dauber I., Davila W., De Armas L., Dean J., Detweiler R., Diaz E., Di Giovanna M., Dor I., Drummond W., Eagerton D., Earl J., Eaton C., Ellison H., Farris N., Fiel T., Firek A., First B., Forgosh L., French W., Gandy W., Garcia R., Gill S., Gordon M., Guice M., Gummadi S., Hackenyos J., Hairston K., Hanson L., Harrison L., Hartman I., Heitner J., Hejeebu S., Hermany P., Hernandez-Cassis C., Hidalgo H., Higgins A., Ibrahim H., Jacobs S., Johnson D., Joshi P., Kaster S., Kellum D., Kim C., Kim E., Kirby W., Knouse A., Kulback S., Kumar M., Kuruvanka T., Labroo A., Lasswell W., Lentz J., Lenzmeier T., Lewis D., Li Z., Lillestol M., Little R., Lorraine R., McKeown-Biagas C., McNeill R., Mehta A., Miller A., Moran J., Morawski E., Nadar V., O'Connor T., Odio A., Parker R., Patel R., Phillips L., Raad G., Rahman A., Raikhel M., Raisinghani A., Rajan R., Rasouli N., Rauzi F., Rohr K., Roseman H., Rovner S., Saba F., Sachson R., Schabauer A., Schneider R., Schuchard T., Sensenbrenner J., Shlesinger Y., Singh N., Sivalingam K., Stonesifer L., Storey D., Suh D., Tahir M., Tan A., Tan M., Taylon A., Thakkar M., Tripathy D., Uwaifo G., Vedere A., Venugopal C., Vo A., Welch M., Welker J., White A., Willis J., Wynne A., Yazdani S., Price L., Lokhngina Y., Xing W., Overton R., Stewart M., Stead J., Lindsay A., Patel V., Ross J., Soffer J., Daga S., Sowell M., Patel P., Garvey L., Ackert J., Abraham S., Sabol M. B., Altobelli D., Ha J., Kulkarni M., Noronha D., Casson E., Zang E., Sandhu C., Kumar R., Chen D., Taft L., Ye J., Shannon J., Wilson T., Babi C., Miller D., Russell R., Bull G., Hereghty B., Fernandez-Salazar E., Longley T., Donaldson J., Jarosz M., Murphy K., Adams P., James R., Richards J., Sedani S., Althouse D., Watson D., Lorimer J., Lauder S., Schultheis R., Womer T., Wraight E., Li W., Price-Olsen E., Watson A., Kelly A., McLaughlin P., Fleming J., Schubert J., Schleiden D., Harris T., Prakash R., Breneman J., Deshpande S., Saswadkar A., Kumari A., Shitut A., Raorane A., Karmalkar A., Mhambrey A., Bhosale A., Vaphare A., Patil A. P., Khandelwal C., Shaik F., Nadar M., Karka M., Kadgaonkar N., Gupta N., Aher N., Potnis O., Naicker P., Shinde R., Sharma R., Godse R., Solanki S., Sahu S., Dumbre S., Kumar S., Patil S., and Mandal T.
- Abstract
Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were
- Published
- 2018
6. Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups
- Author
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Mahaffey, Kw, Jardine, Mj, Bompoint, S, Cannon, Cp, Neal, B, Heerspink, Hjl, Charytan, Dm, Edwards, R, Agarwal, R, Bakris, G, Bull, S, Capuano, G, de Zeeuw, D, Greene, T, Levin, A, Pollock, C, Sun, T, Wheeler, Dc, Yavin, Y, Zhang, H, Zinman, B, Rosenthal, N, Brenner, Bm, Perkovic, V, Guerrero, Raa, Aizenberg, D, Albisu, Jp, Alvarisqueta, A, Bartolacci, I, Berli, Ma, Bordonava, A, Calella, P, Cantero, Mc, Cartasegna, Lr, Cercos, E, Coloma, Gc, Colombo, H, Commendatore, V, Cuadrado, J, Cuneo, Ca, Cusumano, Am, Douthat, Wg, Dran, Rd, Farias, E, Fernandez, Mf, Finkelstein, H, Fragale, G, Fretes, Jo, Garcia, Nh, Gastaldi, A, Gelersztein, E, Glenny, Ja, Gonzalez, Jp, Colaso, Pdg, Goycoa, C, Greloni, Gc, Guinsburg, A, Hermida, S, Juncos, Li, Klyver, Mi, Kraft, F, Krynski, F, Lanchiotti, Pv, de la Fuente, Ral, Marchetta, N, Mele, P, Nicolai, S., Novoa, Pa, Orio, Si, Otreras, F, Oviedo, A, Raffaele, P, Resk, Jh, Rista, L, Papini, Nr, Sala, J, Santos, Jc, Schiavi, Lb, Sessa, H, Casabella, Ts, Ulla, Mr, Valdez, M, Vallejos, A, Villarino, A, Visco, Ve, Wassermann, A, Zaidman, Cj, Cheung, Nw, Droste, C, Fraser, I, Johnson, D, Mah, Pm, Nicholls, K, Packham, D, Proietto, J, Roberts, A, Roger, S, Tsang, V, Raduan, Ra, da Costa, Faa, Amodeo, C, Turatti, Laa, Bregman, R, Sanches, Fcc, Canani, Lh, Chacra, Ar, Cunha Borges, Jl, Vencio, Sac, Franco, Rjd, D'Avila, D, Portes, Ed, de Souza, P, Deboni, Lm, Fraige, F, Neto, Bg, Gomes, M, Kohara, Sk, Keitel, E, Saraiva, Jfk, Lisboa, Hrk, Contieri, Fld, Milagres, R, Montenegro, R, de Brito, Cm, Hissa, Mn, Sabbag, Arn, Noronha, I, Panarotto, D, Pecoits, R, Pereira, Ma, Saporito, W, Scotton, As, Schuch, T, de Almeida, Rs, Ramos, Cs, Felicio, Js, Thome, F, Hachmann, Jct, Yamada, S, Hayashida, Cy, Petry, Tbz, Zanella, Mt, 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, Mcmahon, A, Muirhead, N, Pichette, V, Rabasa-Lhoret, R, Steele, A, Tangri, N, Torshizi, A, Woo, V, Zalunardo, Nadia, Fernandez Montenegro, Maria Alicia, Godoy Jorquera, Juan Gonzalo, Medina Farina, Marcelo, Saavedra Gajardo, Victor, Vejar, Margarita, Chen, Nan, Chen, Qinkai, Gan, Shenglian, Kong, Yaozhong, Detian, Li, Wenge, Li, Xuemei, Li, Lin, Hongli, Liu, Jian, Weiping, Lu, Mao, Hong, Ren, Yan, Song, Weihong, Sun, Jiao, Sun, Lin, Ping, Tu, Wang, Guixia, Yang, Jinkui, Yin, Aiping, Xueqing, Yu, Zhao, Minghui, Zheng, Hongguang, Accini Mendoza, Jose Luis, Arcos, Edgar, Avendano, Jorge, Diaz Ruiz, Jorge Ernesto Andres, Garcia Ortiz, Luis Hernando, Gonzalez, Alexander, Hernandez Triana, Eric, Diego Higuera, Juan, Malaver, Natalia, Ines Molina de Salazar, Dora, Rosero, Ricardo, Terront Lozano, Monica Alexandra, Valderrama Cometa, Luis, Valenzuela, Alex, Vargas Alonso, Ruben Dario, Villegas, Ivan, Yupanqui, Hernan, Bartaskova, Dagmar, Barton, Petr, Belobradkova, Jana, Dohnalova, Lenka, Drasnar, Tomas, Ferkl, Richard, Halciakova, Katarina, Klokocnikova, Vera, Kovar, Richard, Lastuvka, Jiri, Lukac, Martin, Pesickova, Satu, Peterka, Karel, Pumprla, Jiri, Rychlik, Ivan, Saudek, Frantisek, Tesar, Vladimir, Valis, Martin, Weiner, Pavel, Zemek, Stanislav, Alamartine, Eric, Borot, Sophie, Cariou, Bertrand, Dussol, Bertrand, Fauvel, Jean-Pierre, Gourdy, Pierre, Klein, Alexandre, Le Meur, Yannick, Penfornis, Alfred, Roussel, Ronan, Saulnier, Pierre-Jean, Thervet, Eric, Zaoui, Philippe, Burst, Volker, Faghih, Markus, Faulmann, Grit, Haller, Hermann, Jerwan-Keim, Reinhold, Maxeiner, Stephan, Paschen, Bjoern, Plassmann, Georg, Rose, Ludger, Gonzalez Orellana, Ronaldo Arturo, Paul Haase, Franklin, Moreira Diaz, Juan Pablo, Ramirez Roca, Luis Alberto, Sanchez Arenales, Jose Antonio, Sanchez Polo, Jose Vicente, Turcios Juarez, Erick, Csecsei, Gyongyi, Csiky, Botond, Danos, Peter, Deak, Laszlo, Dudas, Mihaly, Harcsa, Eleonora, Keltai, Katalin, Keresztesi, Sandor, Kiss, Konyves, Laszlo, Major, Lajos, Mileder, Margit, Molnar, Marta, Mucsi, Janos, Oroszlan, Tamas, Ory, Ivan, Paragh, Gyorgy, Peterfai, Eva, Petro, Gizella, Revesz, Katalin, Takacs, Robert, Vangel, Sandor, Vasas, Szilard, Zsom, Marianna, Abraham, Oomman, Bhushan, Raju Sree, Deepak, Dewan, Edwin, Fernando M., Gopalakrishnan, Natarajan, Gracious, Noble, Hansraj, Alva, Jain, Dinesh, Keshavamurthy, C. B., Khullar, Dinesh, Manisha, Sahay, Peringat, Jayameena, Prasad, Narayan, Satyanarayana, Rao K., Sreedhar, Reddy, Sreelatha, Melemadathil, Sudhakar, Bhimavarapu, Vyasam, Ramesh Chandra, Bonadonna, Riccardo, Castellino, Pietro, Ceriello, Antonio, Chiovato, Luca, De Cosmo, Salvatore, De Nicola, Luca, Derosa, Giuseppe, Di Carlo, Alberto, Di Cianni, Graziano, Frasca, Giovanni, Fuiano, Giorgio, Gambaro, Giovanni, Garibotto, Giacomo, Giorda, Carlo, Malberti, Fabio, Mandreoli, Marcora, Mannucci, Edoardo, Orsi, Emanuela, Piatti, Piermarco, Santoro, Domenico, Sasso, Ferdinando Carlo, Serviddio, Gaetano, Stella, Andrea, Trevisan, Roberto, Veronelli, Anna Maria, Zanoli, Luca, Akiyama, Hitoshi, Aoki, Hiromi, Asano, Akimichi, Iitsuka, Tadashi, Kajiyama, Shizuo, Kashine, Susumu, Kawada, Toshio, Kodera, Takamoto, Kono, Hiroshi, Koyama, Kazunori, Kumeda, Yasuro, Miyauchi, Shozo, Mizuyama, Kazuyuki, Niiya, Tetsuji, Oishi, Hiroko, Ota, Satoshi, Sakakibara, Terue, Takai, Masahiko, Tomonaga, Osamu, Tsujimoto, Mitsuru, Wada, Takashi, Wakasugi, Masakiyo, Wakida, Yasushi, Watanabe, Takayuki, Yamada, Masayo, Yanagida, Kazuhiro, Yanase, Toshihiko, and Yumita, Wataru
- Subjects
Male ,Risk ,primary prevention ,canagliflozin ,clinical trial ,diabetes mellitus ,renal insufficiency, chronic ,secondary prevention ,renal insufficiency ,Double-Blind Method ,Original Research Articles ,Humans ,Sodium-Glucose Transporter 2 Inhibitors ,Proportional Hazards Models ,canagliflozin, clinical trial, diabetes mellitus, primary prevention, renal insufficiency, chronic, secondary prevention ,Middle Aged ,Placebo Effect ,chronic ,Treatment Outcome ,Diabetes Mellitus, Type 2 ,Cardiovascular Diseases ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,Kidney Failure, Chronic ,Female - Abstract
Supplemental Digital Content is available in the text., Background: Canagliflozin reduces the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, but effects on specific cardiovascular outcomes are uncertain, as are effects in people without previous cardiovascular disease (primary prevention). Methods: In CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation), 4401 participants with type 2 diabetes mellitus and chronic kidney disease were randomly assigned to canagliflozin or placebo on a background of optimized standard of care. Results: Primary prevention participants (n=2181, 49.6%) were younger (61 versus 65 years), were more often female (37% versus 31%), and had shorter duration of diabetes mellitus (15 years versus 16 years) compared with secondary prevention participants (n=2220, 50.4%). Canagliflozin reduced the risk of major cardiovascular events overall (hazard ratio [HR], 0.80 [95% CI, 0.67–0.95]; P=0.01), with consistent reductions in both the primary (HR, 0.68 [95% CI, 0.49–0.94]) and secondary (HR, 0.85 [95% CI, 0.69–1.06]) prevention groups (P for interaction=0.25). Effects were also similar for the components of the composite including cardiovascular death (HR, 0.78 [95% CI, 0.61–1.00]), nonfatal myocardial infarction (HR, 0.81 [95% CI, 0.59–1.10]), and nonfatal stroke (HR, 0.80 [95% CI, 0.56–1.15]). The risk of the primary composite renal outcome and the composite of cardiovascular death or hospitalization for heart failure were also consistently reduced in both the primary and secondary prevention groups (P for interaction >0.5 for each outcome). Conclusions: Canagliflozin significantly reduced major cardiovascular events and kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, including in participants who did not have previous cardiovascular disease. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02065791.
- Published
- 2019
7. Linagliptin Effects on Heart Failure and Related Outcomes in Individuals With Type 2 Diabetes Mellitus at High Cardiovascular and Renal Risk in CARMELINA
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McGuire D, Alexander J, Johansen O, Perkovic V, Rosenstock J, Cooper M, Wanner C, Kahn S, Toto R, Zinman B, Baanstra D, Pfarr E, Schnaidt S, Meinicke T, George J, von Eynatten M, Marx N, Aizenberg D, Fiorella A, Edgardo N, Belen C, Alonso P, Walter M, Maia K, Guillermo S, Leandro B, Constanza R, Alejandra N, Melina C, Ariel I, Rodrigo C, Alvarez C, Jorge M, Gabriel C, German S, Bartolacci I, Bolobanich G, Tale T, Meritano M, Echeverria M, Gerrini S, Alvarez M, Torrijos N, Berli M, Coggiola J, Castaneda G, Rode R, Milessi R, Roude A, Bono J, Caresani J, Arias V, Westberg J, Allende G, Liberman A, Bordonava A, Almagro S, Gerbaudo C, Schiavi L, Budassi N, Cecilia M, Buncuga M, Carlos S, Osvaldo T, Mercedes S, Calella P, Agustina V, Aljandro M, Alberto D, Fiorella M, Cantero M, Cariganano M, Anadon P, Cartasegna L, Gabriela M, Fernanda A, Alberto R, Chacon C, Jazmin F, Colombo H, Coni E, Mattausch S, Thomsenhall K, della Torre M, Morandini M, Berra F, Margarita H, Commendatore V, Tedesco J, Bolzan P, Cuneo C, Narcisa G, Caputi V, Pablo S, Sandra G, Pacora F, Tinari M, Jure H, Parody M, Toranzo A, Frechtel G, Yohena S, Lovecchio S, Muller C, Martin S, Olivera C, Breyaui M, Bianchi G, Garcia C, Luciana V, Florencia F, Ruben G, Gelersztein E, Rey G, Sanchez C, Fornasari L, Di Pierro L, Giacomi G, Miguel S, Laura T, Gonzalo C, Ramon C, Glenny J, Koretzky M, Porto A, Tiberio O, Ellenberg A, Saurral R, Igarzabal C, Vilamajo O, Matkovich J, de Lapertosa S, Villagra M, Cuzziol G, de la Cruz M, Pinchetti R, Mierez M, Lopez C, Gorosito V, Gabito A, Kleiban A, Grosembacher L, Adrian P, Paula R, Javier G, Kraft F, Andres F, Krynski F, Nicolas P, Marcelo F, Alfredo F, de la Fuente R, Natalia C, Luquez H, Recuero Y, Becchetti N, Ruiz M, Costantino M, Vazquez G, Guzman C, Pelatia P, Maffei L, Sassone S, Yantorno M, Prado G, Khron B, Maldonado N, Gustavo L, Veronica V, Marino J, Elizabeth A, Alejandra C, Oscar R, Azize G, Gallardo M, Escudero M, Vargas E, Ramos H, Lucero C, Najenson M, Crocci I, Chiesa A, Nardone L, Dominguez S, Zanini A, Manghi F, Grossman M, Giudice G, Romeo A, Piskorz D, Miguel C, Susana D, Noeli U, Rosa S, Martin V, Soledad A, Virginia M, Lorena G, Prado A, Veronica L, Eduardo H, Adolfo P, Florencia W, Rista L, Scolari C, Rojas N, Bertolio V, Zarandon R, Jair S, Orlando C, Sanabria H, Ignacio D, Viviana C, Marina R, Sarjanovich R, Scaro G, Huerta C, Mana M, Gutierrez M, Dain A, Gavicola R, Sessa H, Sacripanti J, Felman R, Vilarino P, Sicer M, Lagrutta M, Sala J, Casabella T, Cecilia H, Carlos B, Vines G, Javier R, Vico M, Lanchiotti P, Martella C, Torres L, Villarino A, Molina M, Martinez J, Farias C, Bertola S, Rojas M, Guzman P, Nisi J, Martinez D, Barrionuevo M, Vita N, Lopez A, Vottero E, Giuliano M, Paron L, Vogel D, Mele P, Imposti H, Dominguez A, Zaidman C, Fernando G, Beck M, Beltrame P, Chemello D, Junior R, Abreu A, Fernandes V, Saboia J, Rodrigues L, Carvalho M, Gurgel M, Gadelha D, Ramos C, Borba V, Golbert M, Pitthan M, Golbert L, Valentini R, Canani L, Gross J, Valenti A, Sartori C, Dutra O, Azevedo E, Azevedo A, Vaz R, Vaz H, da Costa F, da Costa L, Panarotto D, Lain F, Camazzola F, Dellomea B, Rech R, Pizzato P, Nunes C, Jaeger C, Silveira D, Wagner L, Machado L, Rea R, de Bem A, Alves J, Jonasson T, Malucelli F, Betti R, Lerario A, Lisboa H, Bem J, Tres G, Tavares C, Nardi A, Pozzatto M, Backes L, Reolao J, Scariot E, Ziguer E, Baldissera D, Griz L, Antunes D, Victor F, Freire K, Barros A, Costi B, Sa M, Carneiro A, Felicio J, Felicio K, Penha P, Ferreira J, Melo F, Alves A, Souza A, Costa L, Pinheiro D, Turatti L, Augusto G, Leanca C, Santomauro A, Forti A, Sena R, Marinho A, Facanha C, de Souza K, de Souza A, de Queiroz W, Leite S, Vieira S, Gubert L, Olsen A, Piazzetta G, Fuck A, Ferreira M, Fortes J, Brandao T, Alves F, Radice E, dos Santos J, de Almeida R, Franco D, Saporito W, Eliaschewitz F, de Siqueira K, Bona R, Genestreti P, de Castro D, Visconti G, Sampaio C, Palhares F, Konigsfeld H, Alves E, Feder C, Leao B, Saraiva J, Rodovalho S, Costa M, Pires N, Figueiredo E, Werner G, Garcia J, de Paiva I, Quirino B, Botelho R, da Silva R, Navarro A, Lourenco C, Pereira A, Arantes F, Boner D, Saad J, Falchetto E, Washizu E, Mandil A, Pimenta N, Tofani F, Fonseca T, Teixeira L, Maia L, Lemos M, Mouco O, Nakazone M, Weiand L, Bohn J, Hissa M, Araripe F, Carvalho F, Cancado G, Wang R, Chacra A, Fusaro A, de Mendonca E, Cercato C, Halpern A, Alves B, Braile M, Sestito R, Mustafa E, Ferreira V, Sbardellini B, de Almeida P, Guimaraes F, Piedade M, Bienert I, Braga J, Daher R, Hirakawa T, Terra E, Farias E, Figueiredo M, Lima L, Moraes K, Avelino I, Flato U, Plavnik F, Portes E, Moreira M, Vendramini M, Veloso R, Padilha M, Rodrigues A, Adam R, Santos S, Sayeg N, Guerrero D, Madeira M, Siqueira J, Pinheiro R, Villacorta A, Mellazi A, Braga T, Kaiser S, Paolino B, Lefterov I, Marinchev A, Angelova S, Klyuchkova N, Lybomirova Z, Kerekovski Y, Kuneva T, Penkova D, Levterov G, Videnova E, Georgieva P, Shinkov A, Borissova A, Vlahov J, Dakovska-Dekova L, Lucheva M, Luchev P, Temelkova M, Borisova K, Tsenov S, Andreeva V, Margaritov V, Arasheva G, Lozanov L, Borisov R, Gorcheva D, Henein S, Whatley S, Boutros M, Kalyniuk N, Berlingieri J, Nisker W, Hoag G, Hepburn D, Harvey M, Manjoo P, Yale J, Sherman M, Tsoukas M, Rehman W, Mason M, Santerre M, De Kock J, Barkhuizen F, Rooke C, Gill C, Kooy J, Burgoyne G, de Kock J, Degen G, Hockman L, Invik R, Roberts P, Ward K, Alasaad H, Susan A, Davies V, Gupta N, Milhalidis J, Grossman L, Agawal N, Yared Z, Rwaheed, Nouhad S, Nahla A, Khandwala H, Warwick A, Wadehra D, Manan A, Vecchiarelli J, Aslam N, Ferrao A, St-Maurice F, Collette R, Davey B, Nawaz S, Coutu B, Costi P, Greiss I, Mansour F, Raymond J, St-Phard W, Nadra I, Della Siega A, Barahona L, Klinke P, Contractor H, Fryer M, Chandra N, Conti B, Telzer L, Sorensen S, Lounsbury N, Martin E, Mitchell L, Pelzer E, Nelson S, Jones M, Cox J, Luco G, Trhoughton T, Labonte R, Chouinard G, Frechette A, Rheaume M, Cusson J, Faucher J, Dery V, Kelly A, Miranda B, Al-Kayssi N, Malette P, Rheault P, Fredette P, Dumas R, Palardy J, Belanger A, Boucher P, Doyon B, Charbonneau J, Bailey G, Odendaal M, Stephan K, Badenhorst J, Knight D, Thurgood A, Johnston M, Cooper-Rosen E, Jagger R, Green M, Weisnagel S, Gangloff A, Bergeron J, Pesant Y, Chevalier P, Woo V, Hurd C, Ruckert G, Lira J, Navarro G, Venegas M, Gonzalez P, Montecinos H, Vidal G, Fernandez M, Varas J, Fernandez C, Aguilar J, Marin R, Kindel C, Yovaniniz P, Gherman O, Aravena M, Carvajal J, Macias E, Corrado P, Lazcano M, Garrido B, Charme G, Carrasco J, Vignolo P, Saavedra S, Gajardo V, Saavedra C, Santamaria D, del Castillo B, Balda I, Zurvarra V, Fu G, Jiang D, Huang H, Wang M, Song J, Lu W, Lin Y, Lu Z, Shi Y, Zhong M, Zhao X, Chen D, Zhang G, He Y, Shi P, Chu K, Gao Q, Deng W, Zhang J, Zhang Y, Chen H, Liu E, Xie Y, Lin R, Tan W, Yuan Z, Wang Y, Ren J, Yu H, Luo M, Ma W, Shi W, Xu H, Xu M, Liu G, 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Kitamura H, Toriumi Y, Ishiguro H, Naganuma T, Shu S, Suzuki K, Hirota Y, Hayashi T, Hozawa K, Fukui T, Abe Y, Yamauchi K, Maruyama M, Matsumura S, Kozuma R, Nagai Y, Kihara Y, Maeda H, Nakanishi K, Iitsuka T, Hatori M, Shinozaki Y, Akiyama D, Kawabe M, Takei M, Sato A, Kawai Y, Kitajima K, Ide M, Sato N, Morisaki H, Nakashima K, Takayanagi H, Watanabe H, Iwahashi N, Tsujimoto M, Hibuse K, Hata T, Ueno K, Tatsuma H, Wakida Y, Ito T, Mizuno R, Fujita H, Konishi N, Kanehira T, Watanabe R, Miyaoka H, Okada T, Yamamoto M, Okita S, Murakami H, Todo Y, Umeoka F, Hori K, Shiraishi K, Tada F, Shimizu T, Tamai J, Sasaki C, Okuzima Y, Yasuda M, Iwaita Y, Tanaka K, Rha S, Na J, Cho D, Cho Y, Hwang E, Choi T, Won K, Kim H, Kim S, Oh D, Lee J, Choi H, Chung H, Park H, Suh Y, Kim Y, Kim N, Kim K, An J, Kim J, Park K, Kwak S, Kim M, Hwangbo Y, Lee D, Hong A, Kim L, Oh C, Moon S, Jung C, Jin J, Hyun B, Yang Y, Kong S, Yoon K, Yang H, Hong T, Oh J, Park J, Lee H, Choi J, Ahn J, Han S, Park W, Jo S, Suh S, An W, Park M, Lee S, Kim D, Jin H, Seo J, Chung C, Lim J, Huh J, Park I, Yu S, Sim N, Khan S, Albakari N, Sivaraman J, Manaf K, Maharuddin I, Nagendram S, Ali N, Abdul Latiff N, Othman N, Sarip S, Chew E, Mohamed S, Aziz N, Hui K, Lin L, Velaiutham S, Khir A, Lee L, Manikam S, Chooi K, Chang M, Ooi C, Anthony J, Seganathirajah M, Ng O, Ismail N, Cheah C, Ramanathan G, Mui N, Wen F, Choo T, Bin Ruhani A, Jamaludin S, Abidin S, Nor F, Abu Hassan M, Hanari N, Ahmad N, Suan M, Zainul N, Ali S, Sridhar G, Han C, Chin A, Vin L, Kadir K, Zain A, Hussain N, Pusparajah P, Lozano F, Gomez A, Zaccari E, Vigil A, Preciado C, de Leon M, Parra M, Cervantes A, Aguirre E, Orozco E, Gonzalez S, Elizondo R, Flores E, Guerrero M, Flores F, Sanchez J, Perez F, Rodriguez J, Martinez L, Marquez D, Gutierrez B, Flores M, Real M, Campos P, Garcia P, Rios M, Romero E, Perez Z, Tarabay C, Munoz L, Farias J, Gonzalez J, Palestino N, Sanchez L, Carrillo G, Ordonez N, Pech C, Andrade M, Euan J, Ortegon M, Garcia S, Orozco J, Vazquez H, Herrera R, Perez E, Arango A, Ibarra M, Gonzales L, Esperano J, Quintana L, Salazar I, Ruiz L, Barron C, Ballesteros C, Cervera L, Hercilla E, Gomez H, Mesa J, Herrera P, Rodriguez M, Ochoa R, Mora E, Charles C, Silva R, Mijangos J, Diaz C, Zavala C, Baron P, Bernal A, Martinez F, Tlapale M, Ramirez E, Basila A, Munguia R, Tello M, Martinez M, Mulder H, van der Graaff P, Nawaz A, Keller I, Schoofs M, Smak-Gregoor P, Al-Windy N, Bulut S, de Jong J, Maas A, Schaardenburgh P, Imholz B, Heijster J, Hoogenberg K, Smit C, Kooy A, Huvers F, Landewe-Cleuren S, Kars M, van Moorsel D, Wolffenbuttel B, Lutgens H, Schutte E, Gansevoort R, Idzerda N, Westerink J, Weijmans M, Berg J, van Kleef M, Slob M, Jaspers N, Hovens M, Monajemi H, Kobielusz-Gembala I, Zmuda W, Adamczyk M, Konieczny M, Strzelecka-Sosik A, Nowacka E, Krzyzagorska E, Sekulska M, CzajkowskaKaczmarek E, Kaczmarek B, Opawska K, Dabrowska M, Kus W, Wrzesien-Kus A, Piotrowski G, Hotlos L, Ocicka-Kozakiewicz A, Jurowiecki J, Stasinska T, Karczewicz-Janowska J, Jaruga J, ZytkiewiczJaruga D, Krupinska E, Pupek-Musialik D, Bogdanski P, Szulinska M, Skrypnik D, Skokowska E, Bojarska-Los M, Giermkowska-Samek M, Pirog M, Wojnowski L, Jelinska A, Gradzka M, Danyluk A, Lysek R, Sliwinska T, Podrazka-Szczepaniak A, Barney M, Tomczyk A, Necki M, Malicka J, Dudzinska M, KiszczakBochynska E, Markiewicz A, Galbas K, Paciorkowski A, Mazur S, Mazur M, Chmielowski A, Swiatek A, Sobocka B, Wis J, Jozefowska M, Kaczmarek M, Timler M, Cieplucha Z, Lazuka L, Lazuka N, Wittek A, Spyra J, Jasiel-Wojculewicz H, Stefanski A, Wierucki L, Hanczuk A, Misiura M, Szmygel K, Kolcowa O, Orlowska-Kunikowska E, Rutkowski M, Ignaszewska-Wyrzykowska A, Popenda G, Maciejewska J, Mostowy A, WojteckaGrabka M, Grazyna M, Wieslaw K, Barbara K, Kramarczuk E, Wojciech C, Jaroslaw H, Ewa B, Karas P, Agnieszka S, Hanna C, Justyna S, Piotr K, Wozniak I, Mateusz W, Katarzyna W, Jacek F, Andrzej J, Cymerman K, Gmytrasiewicz M, Zambrzycki J, Krysiak-Kowaluk H, Klodawska K, Klszczewski Z, Zieleniewski J, Opadczuk P, Urbanska K, Faran-Grabowska K, Szczepanik T, Siegel A, Kleczek A, Kincel K, Nowak D, Slowik-Gomulka L, Watemborska-Matuszyk G, Lampart J, Strozik-Krecichwost A, Dziewit T, Broncel M, Wojcik-Odyniec J, Jakubczyk E, Wierzbicka K, Witowicz A, Jedrych B, Korczyk P, Socik-Pojawa M, Monteiro P, Monteiro S, Mendes P, Soares F, Mendes S, Leite L, Vicente J, Santos M, Ferreira A, Alves P, Rosario F, Garrao A, Duarte L, Rogado C, Duarte R, Laginha T, Matos P, Raposo J, Mariz J, Teixeira J, Capela C, Leitao A, Cardiga R, Alface M, Augusto S, Basto L, Cunha A, Rei D, Dantas J, Verdasca I, Andrade L, Silva A, Suarez M, Dias V, Silva J, Pereira N, Goncalves M, Goncalves A, Silveira A, Sampaio A, Dias A, Diogo M, Vilaca C, Cif A, Calin T, Elena S, Crisan C, Adina S, Ramona S, Anghel V, Simona C, Turcu L, Mihaela V, Cosma D, Cristina H, Marius-Calin H, Negrisanu G, Andreea-Andrada M, Maria-Mihaela V, Camelia T, Oana P, Monia A, Onaca A, Mircea O, Mot A, Stolea V, Elena N, Barbonta D, Cristian B, Oana S, Popescu A, Madalina M, Coman A, Anca C, Constantinescu S, Mircea C, Diaconu-Sotropa M, Ene D, Pintilei E, Mihai G, Delia R, Toarba I, Simona H, Negru D, Flaminzeanu F, Iulian C, Maria-Cristina C, Doros R, Cleo S, Sorin B, Demian L, Mihai S, Raul B, Ioana A, Nicolau A, Cosmin P, Isabela G, Elena C, Ileana T, Valuyskikh E, Miroshnichenko E, Klementyeva N, Zelman O, Chumakova G, Vigel A, Leonova N, Pergaeva Y, Stefanovskaya O, Pushkareva S, Antoshkina L, Zheleznova N, Iveitsman, Barbarash O, Zvereva T, Zhuravleva E, Zavyrylina I, Usoltceva E, Savostyanova Y, Kupriyanova T, Krivoshapova K, Kondyukova N, Inozemceva A, Argunova Y, Tsyba L, Belenky D, Mariich O, Terekhova A, Tsygankova O, Kuznetsova E, Nagibovich G, Ivchenko Y, Dobronravov V, Dobronravov A, Bush M, Trofimenko I, Vishnevsky A, Zikov V, Kositsyn D, Palzman Z, Spiridonova T, Rodina N, Polozhentsev S, Mamedova L, Panov A, Abesadze I, Alugishvili M, Ivashkin V, Drapkina O, Korneeva O, Zyatenkova E, Glinkina I, Poluboyarinova I, Gurova O, Raykhman A, Vertkin A, Rodykova I, Shamaeva K, Petrovskaya T, Uzueva E, Milovanov Y, Milovanova S, Milovanova L, Markina M, Dobrosmyslov I, Markov V, Afanasiev S, Babich E, Belokopytova N, Demyanov S, Maximov A, Maximov I, Rebrova T, Shtatolkina M, Masin A, Demko A, Chuyko O, Pronina A, Charf G, Akatova E, Urlaeva I, Nikolin O, Khovaeva Y, Ermachkova L, Burdina E, Shvalb P, Suchkov I, Pshennikov A, Gryaznov S, Rymar O, Dolinskaya Y, Bahareva Y, Mustafina S, Sherbakova L, Ovsyannikova A, Bolshakova O, Polunicheva E, Dora S, Agafyina A, Yashina A, Vasilieva I, Yakhontova P, Selivanova S, Kargapoltseva O, Shilina N, Bayramova G, Sorokin I, Astamirova K, Kuchuk P, Koniushenko D, Malykh N, Dvorkin M, Krovelets T, Konovalova K, Seeber M, van Niekerk F, Siebert H, Steenkamp W, Wiid S, Noeth M, Siebert R, Breedt J, Bouwer J, Kapp C, Venter T, Rayner B, Trinder Y, Rheeder P, Delport E, Mathijs S, Soma P, van Zyl D, Strydom M, Marais A, Badat A, Hansa S, Fourie D, Walton T, Engelbrecht J, Jansen J, Roos J, du Toit S, Lehloenya K, van Zyl L, van Zyl F, Naude M, Mookadam M, van der Merwe A, Trokis J, Lombard L, Coetzee K, Ismail S, Bruning H, Latiff G, Yasmin O, Pillay T, Mohamed Z, Dawood S, Stapelberg A, Abrahams P, Jurgens J, van Heerden P, Swart E, Botha C, Meeding J, Hemus A, Oosthuysen W, Visagie G, Fourie N, Hutton P, van der Merwe N, Chelin N, Everton T, Duki M, Ghila N, Joshi M, Hira M, Madueno F, Martinez B, Sebastian N, Mercadal L, Isbert S, Gonzalez I, Asencio J, Figueras M, Rivas M, Garcia H, Fusalba A, Geat D, Cambra G, Sastre J, Castro F, Mas A, Portillo C, Serrano I, Hernandez S, Fajardo F, Juan C, Ferrer J, Peralta F, Padin C, Mauricio D, Madorell B, San Miguel F, Pedrol N, Trescoli C, Montanana C, Gonzalo M, Capellan J, Estrella A, Martinez C, Montesinos I, Loscos A, Coronado J, Perez J, Castillo B, Alonso C, Quesada V, Teruel J, Perez S, Lama M, del Rio E, Zlova T, Ponomarenko K, Karpenko O, Bezuglova S, Mitskevych L, Kizim S, Nevolina I, Katerenchuk V, Liudmyla B, Ivan K, Rudyk I, Olena M, Anna I, Ganna B, Topchii I, Semenovykh P, Yulia Y, Mykhalchyshyn G, Kirienko D, Kobiliak N, Bodnar, Mykhalchyshyn, Pertseva N, Olena G, Tomashkevych H, Korpachev V, Prybyla O, Kovalchuk A, Kushnarova N, Zinych O, Tseluyko V, Andriy Z, Olga R, Mankovskyy B, Zherdova N, Lykhoshapko O, Logoida P, Godlevska O, Olena V, Olga C, Gyrina O, Alifer O, Dozhuk K, Pekhenko V, Gorobets N, Korneichuk A, Makarenko E, Martynyuk L, Martynuyk O, Stanislavchuk M, Larysa P, Natalia S, Botsyurko V, Kostitska I, Dzeman O, Ablitsov Y, Ivaseiko S, Konovart O, Sandurska S, Vendzilovych Y, Samoylov O, Iryna C, Rozhkivska L, Ulyanchenko I, Kateryna V, Orlenko V, Ivaskina K, Tronko M, Tronko K, Pashkovska N, Stankova N, Vynnychenko L, Bolotnikova N, Demokhova N, Reshotko D, Popova A, Dr Bogdana, Tetiana S, Svitlana D, Oksana R, Vlasenko M, Litvinova S, Semenyuk I, Fishchuk O, Mostovoy Y, Tkachenko T, Ovcharuk M, Rasputina L, Vakaliuk I, Tymochko N, Drapchak I, Petrovska L, Lai W, Yen H, Voon W, Lin T, Cheng K, Chiu C, Chu C, Hsu P, Chiang C, Li Y, Kuo C, Lin S, Chao T, Yu W, Sung S, Wang K, Lu T, Shih K, Wu C, Chiang F, Hwang J, Tsai C, Juang J, Jeng J, Tang S, Lai C, Cheng C, Hsieh I, Hsieh M, Chen C, Lee C, Pai P, Ko P, Wang T, Chen T, Wu H, Chang S, Chen K, Hsieh L, Chou C, Jiang J, Lee M, Huang J, Chen J, Chiu K, Tsai L, Chen P, Saxena M, Collier D, Vaidya B, Harman S, Ramell M, Davies M, Chatterjee S, Meakin L, Quinn M, Bain S, Mallipedhi A, Min T, Bashir J, Blagden M, Ali J, McCrimmon R, Brennan G, Malcolm E, McDonald D, Pearson E, Illsley G, Darzy K, Winocour P, Hanif W, Cockwell P, Charlton M, Thekkepat S, Howat I, Devers M, Patrick J, Wyatt N, Smith C, Singh B, Nicholas J, Gillani S, Green F, Bell E, Boyle J, MacKin S, Livingstone R, Arif A, Syed M, Hammoud J, Sparks J, Anderson M, Tumey R, Condit J, Reddy M, Abalos-Galito M, Rebecca J, Barker T, Seaton B, Campbell E, Kompanik H, Jayson L, Huffman C, Bialow M, McDonnell G, McCaffrey J, Manis C, DeLuca E, Levins J, Bartlett M, Anorga K, Franco M, Gentry P, Hodge D, Pohil R, Rschultz, Leggett R, Blair L, Gisler J, Niegos F, Osburn M, Parma K, Schendel S, Stines L, Winnie M, Wu P, Canales J, Yu J, Cornett G, Beavins J, Hyde D, Zapinski D, Johnson T, Levinson D, Ahmed A, Kenny B, Kuehl A, Bates C, Jantzi C, Ananthula P, Shafer J, Louthan J, Bays A, Stapleton A, Staton P, Strum D, Taylor P, Smith A, Rapp R, Bao S, Randolph C, MacGillivray B, Schuster R, Harden T, Barnella C, Dunnam T, Whiles R, Bolick C, Brockmyre A, Plucker S, Marshall C, Poteet C, Morin D, Tavel E, Averill N, McFann A, Purcell D, Dixon T, Corey E, Goss J, Drescher R, Irfan M, Naeem M, Egelhof R, Mehta P, Koehler T, Walia J, Fernandez J, Bedel G, Preet R, Bhuchar S, Ahmed F, Onyema D, Benchabbat A, Kohanbash L, Miller P, Lalinde M, Carrithers E, Patterson R, Raube-Miceli A, Martinez A, Harris B, Levy R, Siev E, Berlin H, DiMattia M, Sugimoto D, Dugas J, Benson M, Stegemoller R, Schmoll M, Kinnaman S, O'Connor T, Powel T, Rudolph L, Lewiecki M, Best E, Chavez J, Garcia M, Cohen R, Colman D, Ocampo M, Heaney L, Rappley G, Quezada I, Santos V, Nikfarjam A, Reyes M, Rodriguez R, Josephs L, Hernandez R, Flores P, Espinoza L, Mejia W, Pedraza Z, Castaneda R, Laguerre J, Cook R, Patel R, Werner H, Blank R, Small S, Andersen J, Holmes D, Farmer M, Wiener V, Pharr W, Bray B, Beekman J, Anderson A, Andrawis N, Gabra N, Moche T, Marty S, Galvez O, Reyes R, Garcia R, Lerma G, Pliquin B, Mayfield R, Durham N, Phillips R, Baran A, Kondo N, Dempsey S, Kufs W, Laddis T, Zimmer K, Van Depol M, Dweck L, Kestler M, Werner N, Ashraf M, Quick A, Schallert G, Sligh T, Trueba P, Batista J, Martinez T, Moya J, Amarales V, Santos E, Torres P, Diaz T, Diaz J, Hodish I, Else T, Buras E, Moratis A, Valika S, Rahman A, Malalis W, Box E, Box P, Kerwood B, Nagaeva J, Metz C, Hinnant J, Griswell D, 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Colfer H, Kane L, Teklinski A, Gadowski G, Levanovich P, Saba F, Confident L, Hossain S, Steinberg B, Philippe B, Choroenthkongtrakal S, Boccalano F, Anand R, Syam V, Manohar A, Suresh P, Madhusudhan P, Patel P, Cambier P, Klonaris J, Cheng W, Fisher S, Schelle M, Reese L, McLean S, Poock J, Hoens J, Rosie A, Welshons R, Dean J, Kuhlman P, Luke R, Lohrbauer L, Cunningham M, Buday P, Lehmann M, Chrzanowski K, Fletcher A, Hargrove J, Harris F, Debs-Perez G, Maiquez A, Cordoves L, Georgescu M, Tayoun H, Munoz F, Ortiz D, Munoz G, Hamzeh I, Misra A, Zhang L, Forgosh L, Loria K, Roncari C, Hommerding J, Morris G, Lebron C, Blake K, LaVenture K, Lange C, Levinson L, Baungarten T, Edevante S, Shawley S, Moyer H, Elliott K, Iachini K, Rajan R, Davis C, Shattuck A, Simon W, Lakin G, Secrist N, Buth D, Steere D, Talbot K, Singh N, Mascolo R, Sloan S, Kmetzo J, Brown J, Carter L, Lawrence M, Arauz-Pacheco C, Lender D, Kozlow W, Cavanaugh L, Wilson J, Gujja P, Akhter F, Khan M, Mohammed A, Satyavolu S, Dev D, Yalamanchili H, Sumeyye C, Fernandes H, Chaleff F, Jancko M, Trenche S, Kaplan W, Wilcox S, Goisse M, Rua M, Black J, Chapman K, Suh D, Yan L, Song D, Chanara S, Houchin V, McKeinness A, Sotolongo R, Gutierrez K, Miranda-Palma B, Solano M, Jain M, Needell J, Banerjee A, Jarratt M, Hantel S, Lees K, Welty F, Freedman S, Parhofer K, Birkeland K, McGill J, Tijssen J, Clemmensen P, Pehrson S, Grande P, Januzzi J, Wood M, Petrie M, Sairanen T, Tatlisumak T, Soinne L, Kase C, Turan T, Mann J, Agarwal R, Fogarty D, Navaneethan S, Srinivas T, Forsmark C, Frossard J, Gelrud A, Mayerle J, Lee R, Heist R, Sullivan R, Buchbinder E, Chodak G, Edelman M, Thompson V, Coles A, and CARMELINA Investigators
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cardiovascular disease ,type 2 diabetes mellitus ,heart failure ,chronic kidney diseases - Abstract
Background: Individuals with type 2 diabetes mellitus are at increased risk for heart failure (HF), particularly those with coexisting atherosclerotic cardiovascular disease and/or kidney disease. Some but not all dipeptidyl peptidase-4 inhibitors have been associated with increased HF risk. We performed secondary analyses of HF and related outcomes with the dipeptidyl peptidase-4 inhibitor linagliptin versus placebo in CARMELINA (The Cardiovascular and Renal Microvascular Outcome Study With Linagliptin), a cardiovascular outcomes trial that enrolled participants with type 2 diabetes mellitus and atherosclerotic cardiovascular disease and/or kidney disease. Methods: Participants in 27 countries with type 2 diabetes mellitus and concomitant atherosclerotic cardiovascular disease and/or kidney disease were randomized 1:1 to receive once daily oral linagliptin 5 mg or placebo, on top of standard of care. All hospitalization for HF (hHF), cardiovascular outcomes, and deaths were prospectively captured and centrally adjudicated. In prespecified and post hoc analyses of HF and related events, Cox proportional hazards models adjusting for region and baseline history of HF were used. Recurrent hHF events were analyzed using a negative binomial model. In a subset of participants with left ventricular ejection fraction captured within the year before randomization, HF-related outcomes were assessed in subgroups stratified by left ventricular ejection fraction > or 50%. Results: CARMELINA enrolled 6979 participants (mean age, 65.9 years; estimated glomerular filtration rate, mL/min per 1.73m(2); hemoglobin A1c, 8.0%; 62.9% men; diabetes mellitus duration, 14.8 years), including 1873 (26.8%) with a history of HF at baseline. Median follow-up was 2.2 years. Linagliptin versus placebo did not affect the incidence of hHF (209/3494 [6.0%] versus 226/3485 [6.5%], respectively; hazard ratio [HR], 0.90; 95% CI, 0.74-1.08), the composite of cardiovascular death/hHF (HR, 0.94; 95% CI, 0.82-1.08), or risk for recurrent hHF events (326 versus 359 events, respectively; rate ratio, 0.94; 95% CI, 0.75-1.20). There was no heterogeneity of linagliptin effects on hHF by history of HF at baseline, baseline estimated glomerular filtration rate or urine albumin-creatinine ratio, or prerandomization left ventricular ejection fraction. Conclusions: In a large, international cardiovascular outcome trial in participants with type 2 diabetes mellitus and concomitant atherosclerotic cardiovascular disease and/or kidney disease, linagliptin did not affect the risk of hHF or other selected HF-related outcomes, including among participants with and without a history of HF, across the spectrum of kidney disease, and independent of previous left ventricular ejection fraction. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01897532.
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- 2019
8. Effect of Linagliptin vs Placebo on Major Cardiovascular Events in Adults With Type 2 Diabetes and High Cardiovascular and Renal Risk The CARMELINA Randomized Clinical Trial
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Satyavolu S, Dev D, Yalamanchili H, Sumeyye C, Fernandes H, Chaleff F, Jancko M, Trenche S, Kaplan W, Wilcox S, Goisse M, Rua M, Black J, Chapman K, Suh D, Yan L, Song D, Chanara S, Houchin V, McKeinness A, Sotolongo R, Gutierrez K, Miranda-Palma B, Solano M, Jain M, Needell J, Banerjee A, Jarratt M, Hantel S, Lees K, Welty F, Freedman S, Parhofer K, Birkeland K, McGill J, Tijssen J, Clemmensen P, Pehrson S, Grande P, Januzzi J, Wood M, Petrie M, Sairanen T, Tatlisumak T, Soinne L, Kase C, Turan T, Mann J, Agarwal R, Fogarty D, Navaneethan S, Srinivas T, Forsmark C, Frossard J, Gelrud A, Mayerle J, Lee R, Heist R, Sullivan R, Buchbinder E, Chodak G, Edelman M, Thompson V, Coles A, and CARMELINA Investigators
- Abstract
IMPORTANCE Type 2 diabetes is associated with increased cardiovascular (CV) risk. Prior trials have demonstrated CV safety of 3 dipeptidyl peptidase 4 (DPP-4) inhibitors but have included limited numbers of patients with high CV risk and chronic kidney disease. OBJECTIVE To evaluate the effect of linagliptin, a selective DPP-4 inhibitor, on CV outcomes and kidney outcomes in patients with type 2 diabetes at high risk of CV and kidney events. DESIGN, SETTING, AND PARTICIPANTS Randomized, placebo-controlled, multicenter noninferiority trial conducted from August 2013 to August 2016 at 605 clinic sites in 27 countries among adults with type 2 diabetes, hemoglobin A(1c) of 6.5% to 10.0%, high CV risk (history of vascular disease and urine-albumin creatinine ratio [UACR] > 200mg/g), and high renal risk (reduced eGFR and micro-or macroalbuminuria). Participants with end-stage renal disease (ESRD) were excluded. Final follow-up occurred on January 18, 2018. INTERVENTIONS Patients were randomized to receive linagliptin, 5 mg once daily (n = 3494), or placebo once daily (n = 3485) added to usual care. Other glucose-lowering medications or insulin could be added based on clinical need and local clinical guidelines. MAIN OUTCOMES AND MEASURES Primary outcomewas time to first occurrence of the composite of CV death, nonfatalmyocardial infarction, or nonfatal stroke. Criteria for noninferiority of linagliptin vs placebo was defined by the upper limit of the 2-sided 95% CI for the hazard ratio (HR) of linagliptin relative to placebo being less than 1.3. Secondary outcome was time to first occurrence of adjudicated death due to renal failure, ESRD, or sustained 40% or higher decrease in eGFR from baseline. RESULTS Of 6991 enrollees, 6979 (mean age, 65.9 years; eGFR, 54.6 mL/min/1.73m2; 80.1% with UACR > 30mg/g) received at least 1 dose of study medication and 98.7% completed the study. During a median follow-up of 2.2 years, the primary outcome occurred in 434 of 3494 (12.4%) and 420 of 3485 (12.1%) in the linagliptin and placebo groups, respectively, (absolute incidence rate difference, 0.13 [95% CI,-0.63 to 0.90] per 100 person-years) (HR, 1.02; 95% CI, 0.89-1.17; P
- Published
- 2019
9. THYROID FUNCTION AND THE BRAIN.
- Author
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Lozanov, L.
- Subjects
THYROID gland ,THYROID hormones ,HYPOTHYROIDISM ,HORMONE deficiencies ,SYMPTOMS - Abstract
Thyroid hormones are essential for brain maturation and functioning throughout life. In adults, functional disorders of the thyroid gland can lead to various clinical manifestations, and most of these disorders are usually reversible with appropriate treatment. Neurological manifestations are nonspecific, which often leads to a delay in diagnosis. Conversely, in the fetal period and early childhood, thyroid hormone deficiency, even of short duration, can lead to irreversible brain damage, the consequences of which depend not only on the severity, but also on the specific moment of its appearance. The importance of thyroid hormones to the brain requires tightly controlled mechanisms of hormone delivery and specific cellular interactions in their metabolism. Disruption of these mechanisms leads to various syndromes of neurological damage. A challenge in the near future will be a deeper understanding of the pathophysiology of thyroid hormone action in the brain. [ABSTRACT FROM AUTHOR]
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- 2024
10. Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups Results From the Randomized CREDENCE Trial
- Author
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Mahaffey, KW, Jardine, MJ, Bompoint, S, Cannon, CP, Neal, B, Heerspink, HJL, Charytan, DM, Edwards, R, Agarwal, R, Bakris, G, Bull, S, Capuano, G, de Zeeuw, D, Greene, T, Levin, A, Pollock, C, Sun, T, Wheeler, DC, Yavin, Y, Zhang, H, Zinman, B, Rosenthal, N, Brenner, BM, Perkovic, V, Ahuad Guerrero, RA, Aizenberg, D, Pablo Albisu, J, Alvarisqueta, A, Bartolacci, I, Alberto Berli, M, Bordonava, A, Calella, P, Cecilia Cantero, M, Rodolfo Cartasegna, L, Cercos, E, Cecilia Coloma, G, Colombo, H, Commendatore, V, Cuadrado, J, Alberto Cuneo, C, Maria Cusumano, A, Guillermo Douthat, W, Dario Dran, R, Farias, E, Florencia Fernandez, M, Finkelstein, H, Fragale, G, Osvaldo Fretes, J, Horacio Garcia, N, Gastaldi, A, Gelersztein, E, Archibaldo Glenny, J, Pablo Gonzalez, J, Gonzalez Colaso, PDC, Goycoa, C, Cristian Greloni, G, Guinsburg, A, Hermida, S, Isaias Juncos, L, Isabel Klyver, M, Kraft, F, Krynski, F, Virginia Lanchiotti, P, Alfonso Leon de la Fuente, R, Marchetta, N, Mele, P, Nicolai, S, 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- Abstract
BACKGROUND: Canagliflozin reduces the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, but effects on specific cardiovascular outcomes are uncertain, as are effects in people without previous cardiovascular disease (primary prevention). METHODS: In CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation), 4401 participants with type 2 diabetes mellitus and chronic kidney disease were randomly assigned to canagliflozin or placebo on a background of optimized standard of care. RESULTS: Primary prevention participants (n=2181, 49.6%) were younger (61 versus 65 years), were more often female (37% versus 31%), and had shorter duration of diabetes mellitus (15 years versus 16 years) compared with secondary prevention participants (n=2220, 50.4%). Canagliflozin reduced the risk of major cardiovascular events overall (hazard ratio [HR], 0.80 [95% CI, 0.67-0.95]; P=0.01), with consistent reductions in both the primary (HR, 0.68 [95% CI, 0.49-0.94]) and secondary (HR, 0.85 [95% CI, 0.69-1.06]) prevention groups (P for interaction=0.25). Effects were also similar for the components of the composite including cardiovascular death (HR, 0.78 [95% CI, 0.61-1.00]), nonfatal myocardial infarction (HR, 0.81 [95% CI, 0.59-1.10]), and nonfatal stroke (HR, 0.80 [95% CI, 0.56-1.15]). The risk of the primary composite renal outcome and the composite of cardiovascular death or hospitalization for heart failure were also consistently reduced in both the primary and secondary prevention groups (P for interaction >0.5 for each outcome). CONCLUSIONS: Canagliflozin significantly reduced major cardiovascular events and kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, including in participants who did not have previous cardiovascular disease. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02065791.
- Published
- 2019
11. INSUFFICIENCY OF LEVOTHYROXINE THERAPY IN AUTOIMMUNE HYPOTHYROIDISM: EFFECT OF GLUCOCORTICOID ADMINISTRATION.
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Lozanov, B., Gorcheva, D., Lozanov, L. B., Koleva, V., and Refetoff, S.
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LEVOTHYROXINE , *THYROID hormones , *THERAPEUTICS ,THERAPEUTIC use of glucocorticoids - Abstract
Objective. The non-effectiveness of levothyroxine administration in hypothyroidism depends on many factors and mechanisms influencing its absorption in small intestins or bounding of circulating hormone with different active molecules. Methods. Thyroid hormones, TSH, rT3, TGl, TPOAb, TG-Ab, were measured using commercially available assays. For anti-T4ab, radioiodine-labeled T4 was added to the patient's serum and the IgG fraction subsequently precipitated by addition of 15% polyethylene glycol. Background was determined by testing 100 control sera from individuals without autoimmune thyroid disease. Results. A 42-year old woman (71.5 kg) with Hashimoto thyroiditis receiving levothyroxine (L-T4) 150 µg and liothyronine (L-T3) 37.5 µg was admitted to the hospital with clinical data of hypothyroidism, TSH-23.8 mU/L, FT4-6.18 pmol/L (n.range 9-19 pmol/L), TPO-Ab 696 IU/mL, TGAb 818 IU/mL, circulating T4-antibodies positive. She has a good adherence to medication, malabsorption or administration of other drugs were excluded. L-T4 absorption test revealed 44% increase of serum FT4 at 120 min after ingestion of 150 mcg L-T4 (2.1 mcg/kg). Methylprednisolone pulses of 500 mg i.v. administered in three consecutive days at equal doses of L-T4/L-T3 resulted in a rapid increase of FT4 to 14.5 pmol/L, fall of TSH to 0.18 mU/L and decrease of anti-T4 antibodies to referent range; TPO-Ab and TG-Ab also decreased significantly. Monotherapy by 150 mcg L-T4 was continued in the next three months. A recurrence of hypothyroidism with increase of circulating T4-Ab was observed 100 days later. New administrations of methylprednisolone two pulses of 500 mg revealed a similar normalization of thyroid hormones and anti-T4 antibodies. Conclusion. The data showed that T4-antibodies might be a cause of insufficient effects of levothyroxine therapy in autoimmune hypothyroidism. This could be overcome by glucocorticoid administration probably resulting in FT4 release from circulating immune complexes. [ABSTRACT FROM AUTHOR]
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- 2017
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12. Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial
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Adrian F Hernandez, Jennifer B Green, Salim Janmohamed, Ralph B D'Agostino, Christopher B Granger, Nigel P Jones, Lawrence A Leiter, Anne E Rosenberg, Kristina N Sigmon, Matthew C Somerville, Karl M Thorpe, John J V McMurray, Stefano Del Prato, John J.V. McMurray, Ralph B. D'Agostino, Christopher B. Granger, Adrian F. Hernandez, Lawrence A. Leiter, Robert M Califf, Rury Holman, David DeMets, Matthew Riddle, Shaun Goodman, Darren McGuire, Karen Alexander, Adam Devore, Chiara Melloni, Chetan Patel, David Kong, Gerald Bloomfield, Matthew Roe, Pierluigi Tricoci, Rob Harrison, Renato Lopes, Robin Mathews, Rajendra Mehta, William Schuyler Jones, Sreekanth Vemulapalli, Thomas Povsic, Zubin Eapen, Keith Dombrowski, Brad Kolls, Dedrick Jordan, Andrew Ambrosy, Stephen Greene, Aditya Mandawat, Jay Shavadia, Lauren Cooper, Abhinav Sharma, Patricia Guimaraes, Daniel Friedman, Matt Wilson, Patricia Endsley, Tracy Gentry, Jeannie Collier, Kathleen Perez, Kourtnei James, Jennifer Roush, Connie Pope, Christina Howell, Megan Johnson, Matt Bailey, Joanna Cole, Teresa Akers, Beth Vandyne, Betsy Thomas, Jenny Rich, Susan Bartone, Gail Beaulieu, Kim Brown, Tuan Chau, Tamra Christian, Rebecca Coker, Deb Greene, Trevorlyn Haddock, Wendy Jenkins, Ghazala Haque, Marsha Marquess, Jean Pesarchick, Renee Rethaford, Allegra Stone, Firas Al Kawas, Michelle Anderson, Robert Enns, Isaac Sinay, Chantal Mathieu, Victor Yordanov, Irene Hramiak, Martin Haluzik, Søren Galatius, Bruno Guerci, Michael Nauck, Ilias Migdalis, Choon Beng Kathryn Tan, Gyozo Kocsis, Andrea Giaccari, Moon Kyu Lee, Ernesto German Cardona Muñoz, Jan Cornel, Kare Birkeland, Miguel Pinto, Louie Tirador, Martyna Olesinska-Mader, Marina Shestakova, Larry Distiller, Jose Lopez-Sendon, Bjorn Eliasson, Chern-En Chiang, Suphot Srimahachota, Boris Mankovsky, M Angelyn Bethel, Kathleen Dungan, Mikhail Kosiborod, Andres Alvarisqueta, Jorge Baldovino, Diego Besada, Pedro Calella, Maria Cecilia Cantero, Patricia Castaño, Alejandro Chertkoff, Jesus Cuadrado, Luis De Loredo, Andrea Dominguez, Maria Vanesa Español, Hernan Finkelstein, Gustavo Frechtel, Jose Fretes, Natalia Garrido Santos, Joaquin Gonzalez, Marcos Litvak, Juan Loureyro, Laura Maffei, Natacha Maldonado, Diego Mohr Gasparini, Silvia Orio, Federico Perez Manghi, Nelson Rodriguez Papini, Jorgelina Sala, Pablo Schygiel, Georgina Sposetti, Maria Ulla, Fernando Verra, Silvina Zabalua, Cesar Zaidman, Laurent Crenier, Corinne Debroye, Francis Duyck, André Scheen, Luc Van Gaal, Chris Vercammen, Velichka Damyanova, Stefan Dimitrov, Snezhina Kovacheva, Lachezar Lozanov, Viktor Margaritov, Rositsa Mihaylova-Shumkova, Antoaneta Nikolaeva, Zhasmina Stoyanova, Ronald Akhras, Yves Beaudry, Jacques Bedard, Joseph Berlingieri, Raja Chehayeb, Stephen Cheung, James Conway, Jean Cusson, Anthony Della Siega, Richard Dumas, Peter Dzongowski, Murdo Ferguson, Daniel Gaudet, Francois Grondin, Anil Gupta, Milan Gupta, Frank Halperin, Pierre-Alain Houle, Michael Jones, Simon Kouz, Christopher Kovacs, Daniel Landry, Eva Lonn, William O'Mahony, Sean Peterson, Dennis Reich, Alan Rosenbloom, Francois St-Maurice, Barna Tugwell, Saul Vizel, Vincent Woo, Tomas Brychta, Vladimir Cech, Eva Dvorakova, Tomas Edelsberger, Katarina Halciakova, Jarmila Krizova, Jiri Lastuvka, Martin Piperek, Vera Prymkova, Lea Raclavska, Elena Silhova, Robin Urbanek, Jan Vrkoc, Ulla Andersen, Jens Brønnum-Schou, Jens Hove, Jan Skov Jensen, Lars Kober, Ole Peter Kristiansen, Per Lund, Thomas Melchior, Ole Nyvad, Morten Schou, Alain Boye, Didier Cadinot, Didier Gouet, Patrick Henry, Laurence Kessler, Jean-Daniel Lalau, Catherine Petit, Jean-Francois Thuan, Christel Voinot, Julien Vouillarmet, Christoph Axthelm, Dirk Berger, Tasso Bieler, Andreas Birkenfeld, Jochen Bott, Klaus Busch, Karel Caca, Julia Chevts, Torsten Donaubauer, Rudolf Erlinger, Klaus Funke, Josef Grosskopf, Andreas Hagenow, Monika Hamann, Manfred Hartard, Peter Heymer, Wolfgang Huppertz, Gabriele Illies, Stephan Jacob, Thomas Jung, Gerd Kahrmann, Petra Kast, Monika Kellerer, Hans-Peter Kempe, Andrei Khariouzov, Gerhard Klausmann, Christiane Klein, Uwe Kleinecke-Pohl, Klaus Kleinertz, Thorsten Koch, Christine Kosch, Babette Lorra, Joerg Luedemann, Matthias Luttermann, Stephan Maxeiner, Karsten Milek, Andrea Moelle, Gerhard Neumann, Ruth Nischik, Edith Oehrig-Pohl, Georg Plassmann, Lars Pohlmeier, Felix Proepper, Stefan Regner, Werner Rieker, Ludger Rose, Holger Samer, Joachim Sauter, Frank Schaper, Clemens Schiffer, Juergen Schmidt, Bernd-M. Scholz, Joerg Schulze, Alexander Segner, Jochen Seufert, Helena Sigal, Joerg Steindorf, Juergen Stockhausen, Petra Stuebler, Heidrun Taeschner, Dietrich Tews, Diethelm Tschoepe, Karl Wilhelm, Helga Zeller-Stefan, Iakovos Avramidis, Stavros Bousboulas, Magdalini Bristianou, Georgios Dimitriadis, Moses Elisaf, Kalliopi Kotsa, Andreas Melidonis, Asimina Mitrakou, Emmanouil Pagkalos, Nikolaos Papanas, Angelos Pappas, Christos Sampanis, Nikolaos Tentolouris, Apostolos Tsapas, Glykeria Tzatzagou, Risa Ozaki, Csaba Hajdú, Eleonóra Harcsa, Laszlo Konyves, János Mucsi, Zsolt Pauker, Gizella Petró, Zsolt Plés, Katalin Revesz, Vangel Sándor, Viktor Vass, Angelo Avogaro, Massimo Boemi, Riccardo Bonadonna, Agostino Consoli, Salvatore De Cosmo, Paolo Di Bartolo, Francesco Dotta, Simona Frontoni, Marianna Galetta, Alessandra Gambineri, Carmine Gazzaruso, Francesco Giorgino, Davide Lauro, Emanuela Orsi, Giuseppe Paolisso, Gabriele Perriello, Piermarco Piatti, Antonio Pontiroli, Paola Ponzani, Angela Albarosa Rivellese, Giorgio Sesti, Giancarlo Tonolo, Roberto Trevisan, Chul Woo Ahn, Sei-Hyun Baik, Bong-Soo Cha, Choon-Hee Chung, Hak Chul Jang, Chong-Jin Kim, Hye Soon Kim, In Joo Kim, Eun Young Lee, Hyoung Woo Lee, Kwan-Woo Lee, Keon-Woong Moon, June Namgung, Kyong Soo Park, Soon Jib Yoo, Jaemyung Yu, Edmundo-Alfredo Bayram Llamas, Jose-Luis Cervantes-Escárcega, Luis Fernando Flota-Cervera, José Gerardo González-González, Sara Pascoe-Gonzalez, Emilia Susana Pelayo-Orozco, Santiago-Paulino Ramirez-Diaz, Arturo Saldana-Mendoza, Carlos Sánchez Jerjes-Díaz, Jose Juan Torres-Colores, Maricela Vidrio-Velázquez, Juan Villagordoa-Mesa, Hugo Peter Beijerbacht, Reginald G.E.J. Groutars, Boudewijn A Hoek, Pieter A.M. Hoogslag, Adriaan Kooy, Johannes A. Kragten, Aloysius G. Lieverse, Hendrik P. Swart, Eric P. Viergever, Jørn Ahlqvist, John Cooper, Hanne Gulseth, Gaute Guttormsen, Cecilie Wium, Hugo Arbañil, Jorge Calderon, Luis Camacho, Augusto Dextre Espinoza, Elizabeth Garrido, Alejandro Luna, Helard Manrique, Frederick Massucco Revoredo, Rolando Vargas Gonzales, Luis Zapata Rincon, Carlos Zubiate, Geraldine Ebo, Ellen Morales-Palomares, Malgorzata Arciszewska, Marek Banach, Renata Bijata-Bronisz, Tadeusz Derezinski, Waldemar Gadzinski, Jacek Gajek, Katarzyna Klodawska, Ewa Krzyzagorska, Andrzej Madej, Pawel Miekus, Jaroslaw Opiela, Piotr Romanczuk, Anna Siegel, Ewa Skokowska, Andrzej Stankiewicz, Teresa Stasinska, Iwona Trznadel-Morawska, Robert Witek, Sergey Aksentyev, Irina Bondar, Irina Demidova, Alexander Dreval, Olga Ershova, Gagik Galstyan, Alla Garganeeva, Nadezhda Izmozherova, Victoria Karetnikova, Marina Kharakhulakh, Aleksandr Khokhlov, Zhanna Kobalava, Olga Koshelskaya, Elena Kosmacheva, Vladimir Kostin, Natalia Koziolova, Anatoly Kuzin, Victor Lesnov, Tatyana Lysenko, Valentin Markov, Alexander Mayorov, Sergey Moiseev, Svetlana Myasoedova, Nina Petunina, Andrey Rebrov, Ludmila Ruyatkina, Julia Samoylova, Olga Sazonova, Natalia Shilkina, Nadezhda Sokolova, Olga Vasilevskaya, Nelli Verbovaya, Elena Vishneva, Sergey Vorobyev, Natalya Vorokhobina, Olga Zanozina, Elena Zhdanova, Tatyana Zykova, Lesley Burgess, Kathleen Coetzee, Saleem Dawood, Landman Lombard, Ellen Makotoko, Rajendran Moodley, Wessels Oosthuysen, Mohamed Sarvan, Carlos Calvo Gómez, Isidoro Cano Rodríguez, Almudena Castro Conde, Angel Cequier Fillat, Guillem Cuatrecasas Cambra, Fernando de Álvaro Moreno, Luis De Teresa Parreño, Javier Delgado Lista, José Ramón Domínguez Escribano, Santiago Durán García, Javier Elvira González, José María Fernández Rodríguez, Alberto Goday Arno, Ricardo Gomez Huelgas, José Ramón González Juanatey, Antonio Hernandez Mijares, Víctor Alfonso Jiménez Díaz, Esteban Jodar Gimeno, Tomás Lucas Morante, Monica Marazuela, Nieves Martell Claros, Didac Mauricio Puente, Elena Mena Ribas, Juan Francisco Merino Torres, Pedro Mezquita Raya, Andreu Nubiola Calonge, Xavier Ordoñez Sánchez, Jose Maria Pascual Izuel, Verónica Perea Castilla, Antonio Pérez Pérez, Isabel Perez Soto, Miguel Quesada Charneco, Angustias Quesada Simón, Josep Redón Mas, Antonia Rego Iraeta, Maria Rodriguez Alvarez, Irene Rodríguez Rodríguez, José Sabán Ruiz, Alfonso Soto González, Francisco Tinahones Madueno, Carlos Trescoli Serrano, Angels Ulied Armiñana, Erasmus Bachus, Katarina Berndtsson Blom, Ken Eliasson, Pekka Koskinen, Hans Larnefeldt, Cornelia Lif-Tiberg, Carina Linderfalk, Gustav Lund, Pia Lundman, Linda Moris, Åke Olsson, Staffan Salmonsson, Johan Sanmartin Berglund, Folke Sjöberg, Stefan Söderberg, Ingemar Torstensson, Jung-Fu Chen, Kai Jen Tien, Shih-Ting Tseng, Shih-Te Tu, Chih-Yuan Wang, Ji-Hung Wang, Arintaya Phrommintikul, Sukit Yamwong, Woravut Jintapakorn, Pisit Hutayanon, Nakarin Sansanayudh, Larysa Bazhan, Ivan Fushtey, Mariya Grachova, Vitaliy Katerenchuk, Vadym Korpachev, Nonna Kravchun, Oleksandr Larin, Galyna Mykhalchyshyn, Halyna Myshanych, Olga Oleksyk, Valeriia Orlenko, Nataliia Pashkovska, Nataliia Pertseva, Olena Petrosyan, Ivan Smirnov, Maryna Vlasenko, Tetiana Zlova, Myint Aye, Arun Baksi, Mathangi Balasubramani, Ronnie Beboso, Mark Blagden, Charles Bundy, Tobias Cookson, Allan Copland, Alistair Emslie-Smith, Fiona Green, Anthony Gunstone, Basil Issa, Ewart Jackson-Voyzey, Andrew Johnson, Malcolm Maclean, John McKnight, Solomon Muzulu, Ian O'Connell, Babatunde Oyesile, Catherine Patterson, Ewan Pearson, Sam Philip, Paul Smith, Usha Sukumaran, Jalal Abbas, Gaurav Aggarwala, Faiq Akhter, James Andersen, Moise Anglade, Georges Argoud, Mehrdad Ariani, Reswan Ashdji, Ladan Bakhtari, Subhash Banerjee, Andrew Bartlett, Howard Baum, Harold Bays, Richard Beasley, Renata Belfort de Aguiar, Sabrina Benjamin, Ravi Bhagwat, Anuj Bhargava, Bruce Bode, Christina Bratcher, Toby Briskin, Andrew Brockmyre, Raymond Broughton, Judith Brown, Madhusudan Budhraja, Kevin Cannon, Jewell Carr, Harold Cathcart, Arvind Cavale, Louis Chaykin, Deanna Cheung, Richard Childress, Allan Cohen, Jonathan Condit, Erin Cooksey, George Mitchell Cornett, Ira Dauber, William Davila, Luis De Armas, Julius Dean, Robert Detweiler, Ernesto Diaz, Michael Di Giovanna, Isaac Dor, Waymon Drummond, Donald Eagerton, John Earl, Charles Eaton, Howard Ellison, Neil Farris, Thomas Fiel, Anthony Firek, Brian First, Les Forgosh, William French, Winston Gandy, Ronald Garcia, Santosh Gill, Murray Gordon, Michael Guice, Siva Gummadi, Jonathan Hackenyos, Kristen Hairston, Lenita Hanson, Lindsay Harrison, Israel Hartman, John Heitner, Srini Hejeebu, Paul Hermany, Carlos Hernandez-Cassis, Horacio Hidalgo, Alexander Higgins, Hassan Ibrahim, Shahram Jacobs, David Johnson, Parag Joshi, Steven Kaster, Daniel Kellum, Christopher Kim, Ellen Kim, William Kirby, Albert Knouse, Steven Kulback, Mariananda Kumar, Tulsidas Kuruvanka, Ajay Labroo, William Lasswell, John Lentz, Thomas Lenzmeier, David Lewis, Zhaoping Li, Michael Lillestol, Raymond Little, Richard Lorraine, Cecilia McKeown-Biagas, Robert McNeill, Anand Mehta, Alan Miller, Joseph Moran, Emily Morawski, Venkatesh Nadar, Thomas O'Connor, Alberto Odio, Reginald Parker, Rajesh Patel, Lawrence Phillips, George Raad, Aref Rahman, Marina Raikhel, Ajit Raisinghani, Raj Rajan, Neda Rasouli, Frank Rauzi, Kathryn Rohr, Hal Roseman, Sergio Rovner, Fadi Saba, Richard Sachson, Alex Schabauer, Ricky Schneider, Timothy Schuchard, John Sensenbrenner, Yshay Shlesinger, Narendra Singh, Kanagaratnam Sivalingam, Larry Stonesifer, Daniel Storey, David Suh, Mohammed Tahir, Anjanette Tan, Marilyn Tan, Alain Taylon, Maitreya Thakkar, Devjit Tripathy, Gabriel Uwaifo, Amarnath Vedere, Chandra Venugopal, Anthony Vo, Michelle Welch, James Welker, Alexander White, John Willis, Alan Wynne, Shahram Yazdani, Anne Rosenberg, Lauren Price, Kristina Sigmon, Yuliya Lokhngina, Weibing Xing, Robert Overton, Murray Stewart, Janet Stead, Alistair Lindsay, Vickas Patel, Jorge Ross, Joseph Soffer, Shruti Daga, Margaret Sowell, Prashant Patel, Louisa Garvey, Jessica Ackert, Sybil Abraham, Mary Beth Sabol, Desma Altobelli, JuYoung Ha, Mangesh Kulkarni, Matthew Somerville, Drusilla Noronha, Ed Casson, Eddie Zang, Chamandeep Sandhu, Rakesh Kumar, David Chen, Lin Taft, Rajivkumar Patel, June Ye, Jennifer Shannon, Tim Wilson, Charleen Babi, Diane Miller, Karl Thorpe, Rachael Russell, Georgina Bull, Belinda Hereghty, Eva Fernandez-Salazar, Troy Longley, Jill Donaldson, Marie Jarosz, Karen Murphy, Patricia Adams, Peter Smith, Rachel James, Jackie Richards, Sangeeta Sedani, Denise Althouse, David Watson, Jamie Lorimer, Steven Lauder, Ron Schultheis, Terese Womer, Ella Wraight, Wenyan Li, Emma Price-Olsen, Anthony Watson, Aoife Kelly, Patricia McLaughlin, John Fleming, Jessica Schubert, Debra Schleiden, Tara Harris, Rahul Prakash, Jody Breneman, Sameer Deshpande, Aarti Saswadkar, Aditi Kumari, Aditi Shitut, Amruta Raorane, Anisha Karmalkar, Ankita Mhambrey, Archana Bhosale, Ashok Vaphare, Ashwini P Patil, Chaitali Khandelwal, Fayaz Shaik, Madhumitha Nadar, Mounika Karka, Neha Kadgaonkar, Nikita Gupta, Nutan Aher, Omkar Potnis, Pallavi Naicker, Rakesh Shinde, Richa Sharma, Rupali Godse, Sheetal Solanki, Shruti Sahu, Snehal Dumbre, Somesh Kumar, Suradnya Patil, Trisha Mandal, Hernandez, Adrian F, Green, Jennifer B, Janmohamed, Salim, D'Agostino, Ralph B, Granger, Christopher B, Jones, Nigel P, Leiter, Lawrence A, Rosenberg, Anne E, Sigmon, Kristina N, Somerville, Matthew C, Thorpe, Karl M, Mcmurray, John J V, Del Prato, Stefano, Mcmurray, John J. V., D'Agostino, Ralph B., Granger, Christopher B., Hernandez, Adrian F., Leiter, Lawrence A., Califf, Robert M, Holman, Rury, Demets, David, Riddle, Matthew, Goodman, Shaun, Mcguire, Darren, Alexander, Karen, Devore, Adam, Melloni, Chiara, Patel, Chetan, Kong, David, Bloomfield, Gerald, Roe, Matthew, Tricoci, Pierluigi, Harrison, Rob, Lopes, Renato, Mathews, Robin, Mehta, Rajendra, Schuyler Jones, William, Vemulapalli, Sreekanth, Povsic, Thoma, Eapen, Zubin, Dombrowski, Keith, Kolls, Brad, Jordan, Dedrick, Ambrosy, Andrew, Greene, Stephen, Mandawat, Aditya, Shavadia, Jay, Cooper, Lauren, Sharma, Abhinav, Guimaraes, Patricia, Friedman, Daniel, Wilson, Matt, Endsley, Patricia, Gentry, Tracy, Collier, Jeannie, Perez, Kathleen, James, Kourtnei, Roush, Jennifer, Pope, Connie, Howell, Christina, Johnson, Megan, Bailey, Matt, Cole, Joanna, Akers, Teresa, Vandyne, Beth, Thomas, Betsy, Rich, Jenny, Bartone, Susan, Beaulieu, Gail, Brown, Kim, Chau, Tuan, Christian, Tamra, Coker, Rebecca, Greene, Deb, Haddock, Trevorlyn, Jenkins, Wendy, Haque, Ghazala, Marquess, Marsha, Pesarchick, Jean, Rethaford, Renee, Stone, Allegra, Al Kawas, Fira, Anderson, Michelle, Enns, Robert, Sinay, Isaac, Mathieu, Chantal, Yordanov, Victor, Hramiak, Irene, Haluzik, Martin, Galatius, Søren, Guerci, Bruno, Nauck, Michael, Migdalis, Ilia, Tan, Choon Beng Kathryn, Kocsis, Gyozo, Giaccari, Andrea, Lee, Moon Kyu, Muñoz, Ernesto German Cardona, Cornel, Jan, Birkeland, Kare, Pinto, Miguel, Tirador, Louie, Olesinska-Mader, Martyna, Shestakova, Marina, Distiller, Larry, Lopez-Sendon, Jose, Eliasson, Bjorn, Chiang, Chern-En, Srimahachota, Suphot, Mankovsky, Bori, Bethel, M Angelyn, Dungan, Kathleen, Kosiborod, Mikhail, Alvarisqueta, Andre, Baldovino, Jorge, Besada, Diego, Calella, Pedro, Cantero, Maria Cecilia, Castaño, Patricia, Chertkoff, Alejandro, Cuadrado, Jesu, De Loredo, Lui, Dominguez, Andrea, Español, Maria Vanesa, Finkelstein, Hernan, Frechtel, Gustavo, Fretes, Jose, Garrido Santos, Natalia, Gonzalez, Joaquin, Litvak, Marco, Loureyro, Juan, Maffei, Laura, Maldonado, Natacha, Mohr Gasparini, Diego, Orio, Silvia, Perez Manghi, Federico, Rodriguez Papini, Nelson, Sala, Jorgelina, Schygiel, Pablo, Sposetti, Georgina, Ulla, Maria, Verra, Fernando, Zabalua, Silvina, Zaidman, Cesar, Crenier, Laurent, Debroye, Corinne, Duyck, Franci, Scheen, André, Van Gaal, Luc, Vercammen, Chri, Damyanova, Velichka, Dimitrov, Stefan, Kovacheva, Snezhina, Lozanov, Lachezar, Margaritov, Viktor, Mihaylova-Shumkova, Rositsa, Nikolaeva, Antoaneta, Stoyanova, Zhasmina, Akhras, Ronald, Beaudry, Yve, Bedard, Jacque, Berlingieri, Joseph, Chehayeb, Raja, Cheung, Stephen, Conway, Jame, Cusson, Jean, Della Siega, Anthony, Dumas, Richard, Dzongowski, Peter, Ferguson, Murdo, Gaudet, Daniel, Grondin, Francoi, Gupta, Anil, Gupta, Milan, Halperin, Frank, Houle, Pierre-Alain, Jones, Michael, Kouz, Simon, Kovacs, Christopher, Landry, Daniel, Lonn, Eva, O'Mahony, William, Peterson, Sean, Reich, Denni, Rosenbloom, Alan, St-Maurice, Francoi, Tugwell, Barna, Vizel, Saul, Woo, Vincent, Brychta, Toma, Cech, Vladimir, Dvorakova, Eva, Edelsberger, Toma, Halciakova, Katarina, Krizova, Jarmila, Lastuvka, Jiri, Piperek, Martin, Prymkova, Vera, Raclavska, Lea, Silhova, Elena, Urbanek, Robin, Vrkoc, Jan, Andersen, Ulla, Brønnum-Schou, Jen, Hove, Jen, Jensen, Jan Skov, Kober, Lar, Kristiansen, Ole Peter, Lund, Per, Melchior, Thoma, Nyvad, Ole, Schou, Morten, Boye, Alain, Cadinot, Didier, Gouet, Didier, Henry, Patrick, Kessler, Laurence, Lalau, Jean-Daniel, Petit, Catherine, Thuan, Jean-Francoi, Voinot, Christel, Vouillarmet, Julien, Axthelm, Christoph, Berger, Dirk, Bieler, Tasso, Birkenfeld, Andrea, Bott, Jochen, Busch, Klau, Caca, Karel, Chevts, Julia, Donaubauer, Torsten, Erlinger, Rudolf, Funke, Klau, Grosskopf, Josef, Hagenow, Andrea, Hamann, Monika, Hartard, Manfred, Heymer, Peter, Huppertz, Wolfgang, Illies, Gabriele, Jacob, Stephan, Jung, Thoma, Kahrmann, Gerd, Kast, Petra, Kellerer, Monika, Kempe, Hans-Peter, Khariouzov, Andrei, Klausmann, Gerhard, Klein, Christiane, Kleinecke-Pohl, Uwe, Kleinertz, Klau, Koch, Thorsten, Kosch, Christine, Lorra, Babette, Luedemann, Joerg, Luttermann, Matthia, Maxeiner, Stephan, Milek, Karsten, Moelle, Andrea, Neumann, Gerhard, Nischik, Ruth, Oehrig-Pohl, Edith, Plassmann, Georg, Pohlmeier, Lar, Proepper, Felix, Regner, Stefan, Rieker, Werner, Rose, Ludger, Samer, Holger, Sauter, Joachim, Schaper, Frank, Schiffer, Clemen, Schmidt, Juergen, Scholz, Bernd-M., Schulze, Joerg, Segner, Alexander, Seufert, Jochen, Sigal, Helena, Steindorf, Joerg, Stockhausen, Juergen, Stuebler, Petra, Taeschner, Heidrun, Tews, Dietrich, Tschoepe, Diethelm, Wilhelm, Karl, Zeller-Stefan, Helga, Avramidis, Iakovo, Bousboulas, Stavro, Bristianou, Magdalini, Dimitriadis, Georgio, Elisaf, Mose, Kotsa, Kalliopi, Melidonis, Andrea, Mitrakou, Asimina, Pagkalos, Emmanouil, Papanas, Nikolao, Pappas, Angelo, Sampanis, Christo, Tentolouris, Nikolao, Tsapas, Apostolo, Tzatzagou, Glykeria, Ozaki, Risa, Hajdú, Csaba, Harcsa, Eleonóra, Konyves, Laszlo, Mucsi, Jáno, Pauker, Zsolt, Petró, Gizella, Plés, Zsolt, Revesz, Katalin, Sándor, Vangel, Vass, Viktor, Avogaro, Angelo, Boemi, Massimo, Bonadonna, Riccardo, Consoli, Agostino, De Cosmo, Salvatore, Di Bartolo, Paolo, Dotta, Francesco, Frontoni, Simona, Galetta, Marianna, Gambineri, Alessandra, Gazzaruso, Carmine, Giorgino, Francesco, Lauro, Davide, Orsi, Emanuela, Paolisso, Giuseppe, Perriello, Gabriele, Piatti, Piermarco, Pontiroli, Antonio, Ponzani, Paola, Rivellese, Angela Albarosa, Sesti, Giorgio, Tonolo, Giancarlo, Trevisan, Roberto, Ahn, Chul Woo, Baik, Sei-Hyun, Cha, Bong-Soo, Chung, Choon-Hee, Jang, Hak Chul, Kim, Chong-Jin, Kim, Hye Soon, Kim, In Joo, Lee, Eun Young, Lee, Hyoung Woo, Lee, Kwan-Woo, Moon, Keon-Woong, Namgung, June, Park, Kyong Soo, Yoo, Soon Jib, Yu, Jaemyung, Llamas, Edmundo-Alfredo Bayram, Cervantes-Escárcega, Jose-Lui, Flota-Cervera, Luis Fernando, González-González, José Gerardo, Pascoe-Gonzalez, Sara, Pelayo-Orozco, Emilia Susana, Ramirez-Diaz, Santiago-Paulino, Saldana-Mendoza, Arturo, Jerjes-Díaz, Carlos Sánchez, Torres-Colores, Jose Juan, Vidrio-Velázquez, Maricela, Villagordoa-Mesa, Juan, Beijerbacht, Hugo Peter, Groutars, Reginald G. E. J., Hoek, Boudewijn A, Hoogslag, Pieter A. M., Kooy, Adriaan, Kragten, Johannes A., Lieverse, Aloysius G., Swart, Hendrik P., Viergever, Eric P., Ahlqvist, Jørn, Cooper, John, Gulseth, Hanne, Guttormsen, Gaute, Wium, Cecilie, Arbañil, Hugo, Calderon, Jorge, Camacho, Lui, Espinoza, Augusto Dextre, Garrido, Elizabeth, Luna, Alejandro, Manrique, Helard, Revoredo, Frederick Massucco, Gonzales, Rolando Varga, Rincon, Luis Zapata, Zubiate, Carlo, Ebo, Geraldine, Morales-Palomares, Ellen, Arciszewska, Malgorzata, Banach, Marek, Bijata-Bronisz, Renata, Derezinski, Tadeusz, Gadzinski, Waldemar, Gajek, Jacek, Klodawska, Katarzyna, Krzyzagorska, Ewa, Madej, Andrzej, Miekus, Pawel, Opiela, Jaroslaw, Romanczuk, Piotr, Siegel, Anna, Skokowska, Ewa, Stankiewicz, Andrzej, Stasinska, Teresa, Trznadel-Morawska, Iwona, Witek, Robert, Aksentyev, Sergey, Bondar, Irina, Demidova, Irina, Dreval, Alexander, Ershova, Olga, Galstyan, Gagik, Garganeeva, Alla, Izmozherova, Nadezhda, Karetnikova, Victoria, Kharakhulakh, Marina, Khokhlov, Aleksandr, Kobalava, Zhanna, Koshelskaya, Olga, Kosmacheva, Elena, Kostin, Vladimir, Koziolova, Natalia, Kuzin, Anatoly, Lesnov, Victor, Lysenko, Tatyana, Markov, Valentin, Mayorov, Alexander, Moiseev, Sergey, Myasoedova, Svetlana, Petunina, Nina, Rebrov, Andrey, Ruyatkina, Ludmila, Samoylova, Julia, Sazonova, Olga, Shilkina, Natalia, Sokolova, Nadezhda, Vasilevskaya, Olga, Verbovaya, Nelli, Vishneva, Elena, Vorobyev, Sergey, Vorokhobina, Natalya, Zanozina, Olga, Zhdanova, Elena, Zykova, Tatyana, Burgess, Lesley, Coetzee, Kathleen, Dawood, Saleem, Lombard, Landman, Makotoko, Ellen, Moodley, Rajendran, Oosthuysen, Wessel, Sarvan, Mohamed, Calvo Gómez, Carlo, Cano Rodríguez, Isidoro, Castro Conde, Almudena, Cequier Fillat, Angel, Cuatrecasas Cambra, Guillem, de Álvaro Moreno, Fernando, De Teresa Parreño, Lui, Delgado Lista, Javier, Domínguez Escribano, José Ramón, Durán García, Santiago, Elvira González, Javier, Fernández Rodríguez, José María, Goday Arno, Alberto, Gomez Huelgas, Ricardo, González 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B., Altobelli, D., Ha, J., Kulkarni, M., Noronha, D., Casson, E., Zang, E., Sandhu, C., Kumar, R., Chen, D., Taft, L., Ye, J., Shannon, J., Wilson, T., Babi, C., Miller, D., Russell, R., Bull, G., Hereghty, B., Fernandez-Salazar, E., Longley, T., Donaldson, J., Jarosz, M., Murphy, K., Adams, P., James, R., Richards, J., Sedani, S., Althouse, D., Watson, D., Lorimer, J., Lauder, S., Schultheis, R., Womer, T., Wraight, E., Li, W., Price-Olsen, E., Watson, A., Kelly, A., Mclaughlin, P., Fleming, J., Schubert, J., Schleiden, D., Harris, T., Prakash, R., Breneman, J., Deshpande, S., Saswadkar, A., Kumari, A., Shitut, A., Raorane, A., Karmalkar, A., Mhambrey, A., Bhosale, A., Vaphare, A., Patil, A. P., Khandelwal, C., Shaik, F., Nadar, M., Karka, M., Kadgaonkar, N., Gupta, N., Aher, N., Potnis, O., Naicker, P., Shinde, R., Sharma, R., Godse, R., Solanki, S., Sahu, S., Dumbre, S., Kumar, S., Patil, S., Mandal, T., Skin function and permeability, Dermatology, Hernandez, A, Green, J, Janmohamed, S, D'Agostino, R, Granger, C, Jones, N, Leiter, L, Rosenberg, A, Sigmon, K, Somerville, M, Thorpe, K, Mcmurray, J, Del Prato, S, Califf, R, Holman, R, Demets, D, Riddle, M, Goodman, S, Mcguire, D, Alexander, K, Devore, A, Melloni, C, Patel, C, Kong, D, Bloomfield, G, Roe, M, Tricoci, P, Harrison, R, Lopes, R, Mathews, R, Mehta, R, Schuyler Jones, W, Vemulapalli, S, Povsic, T, Eapen, Z, Dombrowski, K, Kolls, B, Jordan, D, Ambrosy, A, Greene, S, Mandawat, A, Shavadia, J, Cooper, L, Sharma, A, Guimaraes, P, Friedman, D, Wilson, M, Endsley, P, Gentry, T, Collier, J, Perez, K, James, K, Roush, J, Pope, C, Howell, C, Johnson, M, Bailey, M, Cole, J, Akers, T, Vandyne, B, Thomas, B, Rich, J, Bartone, S, Beaulieu, G, Brown, K, Chau, T, Christian, T, Coker, R, Greene, D, Haddock, T, Jenkins, W, Haque, G, Marquess, M, Pesarchick, J, Rethaford, R, Stone, A, Al Kawas, F, Anderson, M, Enns, R, Sinay, I, Mathieu, C, Yordanov, V, Hramiak, I, Haluzik, M, Galatius, S, Guerci, B, Nauck, M, Migdalis, I, Tan, C, Kocsis, G, Giaccari, A, Lee, M, Munoz, E, Cornel, J, Birkeland, K, Pinto, M, Tirador, L, Olesinska-Mader, M, Shestakova, M, Distiller, L, Lopez-Sendon, J, Eliasson, B, Chiang, C, Srimahachota, S, Mankovsky, B, Bethel, M, Dungan, K, Kosiborod, M, Alvarisqueta, A, Baldovino, J, Besada, D, Calella, P, Cantero, M, Castano, P, Chertkoff, A, Cuadrado, J, De Loredo, L, Dominguez, A, Espanol, M, Finkelstein, H, Frechtel, G, Fretes, J, Garrido Santos, N, Gonzalez, J, Litvak, M, Loureyro, J, Maffei, L, Maldonado, N, Mohr Gasparini, D, Orio, S, Perez Manghi, F, Rodriguez Papini, N, Sala, J, Schygiel, P, Sposetti, G, Ulla, M, Verra, F, Zabalua, S, Zaidman, C, Crenier, L, Debroye, C, Duyck, F, Scheen, A, Van Gaal, L, Vercammen, C, Damyanova, V, Dimitrov, S, Kovacheva, S, Lozanov, L, Margaritov, V, Mihaylova-Shumkova, R, Nikolaeva, A, Stoyanova, Z, Akhras, R, Beaudry, Y, Bedard, J, Berlingieri, J, Chehayeb, R, Cheung, S, Conway, J, Cusson, J, Della Siega, A, Dumas, R, Dzongowski, P, Ferguson, M, Gaudet, D, Grondin, F, Gupta, A, Gupta, M, Halperin, F, Houle, P, Jones, M, Kouz, S, Kovacs, C, Landry, D, Lonn, E, O'Mahony, W, Peterson, S, Reich, D, Rosenbloom, A, St-Maurice, F, Tugwell, B, Vizel, S, Woo, V, Brychta, T, Cech, V, Dvorakova, E, Edelsberger, T, Halciakova, K, Krizova, J, Lastuvka, J, Piperek, M, Prymkova, V, Raclavska, L, Silhova, E, Urbanek, R, Vrkoc, J, Andersen, U, Bronnum-Schou, J, Hove, J, Jensen, J, Kober, L, Kristiansen, O, Lund, P, Melchior, T, Nyvad, O, Schou, M, Boye, A, Cadinot, D, Gouet, D, Henry, P, Kessler, L, Lalau, J, Petit, C, Thuan, J, Voinot, C, Vouillarmet, J, Axthelm, C, Berger, D, Bieler, T, Birkenfeld, A, Bott, J, Busch, K, Caca, K, Chevts, J, Donaubauer, T, Erlinger, R, Funke, K, Grosskopf, J, Hagenow, A, Hamann, M, Hartard, M, Heymer, P, Huppertz, W, Illies, G, Jacob, S, Jung, T, Kahrmann, G, Kast, P, Kellerer, M, Kempe, H, Khariouzov, A, Klausmann, G, Klein, C, Kleinecke-Pohl, U, Kleinertz, K, Koch, T, Kosch, C, Lorra, B, Luedemann, J, Luttermann, M, Maxeiner, S, Milek, K, Moelle, A, Neumann, G, Nischik, R, Oehrig-Pohl, E, Plassmann, G, Pohlmeier, L, Proepper, F, Regner, S, Rieker, W, Rose, L, Samer, H, Sauter, J, Schaper, F, Schiffer, C, Schmidt, J, Scholz, B, Schulze, J, Segner, A, Seufert, J, Sigal, H, Steindorf, J, Stockhausen, J, Stuebler, P, Taeschner, H, Tews, D, Tschoepe, D, Wilhelm, K, Zeller-Stefan, H, Avramidis, I, Bousboulas, S, Bristianou, M, Dimitriadis, G, Elisaf, M, Kotsa, K, Melidonis, A, Mitrakou, A, Pagkalos, E, Papanas, N, Pappas, A, Sampanis, C, Tentolouris, N, Tsapas, A, Tzatzagou, G, Ozaki, R, Hajdu, C, Harcsa, E, Konyves, L, Mucsi, J, Pauker, Z, Petro, G, Ples, Z, Revesz, K, Sandor, V, Vass, V, Avogaro, A, Boemi, M, Bonadonna, R, Consoli, A, De Cosmo, S, Di Bartolo, P, Dotta, F, Frontoni, S, Galetta, M, Gambineri, A, Gazzaruso, C, Giorgino, F, Lauro, D, Orsi, E, Paolisso, G, Perriello, G, Piatti, P, Pontiroli, A, Ponzani, P, Rivellese, A, Sesti, G, Tonolo, G, Trevisan, R, Ahn, C, Baik, S, Cha, B, Chung, C, Jang, H, Kim, C, Kim, H, Kim, I, Lee, E, Lee, H, Lee, K, Moon, K, Namgung, J, Park, K, Yoo, S, Yu, J, Llamas, E, Cervantes-Escarcega, J, Flota-Cervera, L, Gonzalez-Gonzalez, J, Pascoe-Gonzalez, S, Pelayo-Orozco, E, Ramirez-Diaz, S, Saldana-Mendoza, A, Jerjes-Diaz, C, Torres-Colores, J, Vidrio-Velazquez, M, Villagordoa-Mesa, J, Beijerbacht, H, Groutars, R, Hoek, B, Hoogslag, P, Kooy, A, Kragten, J, Lieverse, A, Swart, H, Viergever, E, Ahlqvist, J, Cooper, J, Gulseth, H, Guttormsen, G, Wium, C, Arbanil, H, Calderon, J, Camacho, L, Espinoza, A, Garrido, E, Luna, A, Manrique, H, Revoredo, F, Gonzales, R, Rincon, L, Zubiate, C, Ebo, G, Morales-Palomares, E, Arciszewska, M, Banach, M, Bijata-Bronisz, R, Derezinski, T, Gadzinski, W, Gajek, J, Klodawska, K, Krzyzagorska, E, Madej, A, Miekus, P, Opiela, J, Romanczuk, P, Siegel, A, Skokowska, E, Stankiewicz, A, Stasinska, T, Trznadel-Morawska, I, Witek, R, Aksentyev, S, Bondar, I, Demidova, I, Dreval, A, Ershova, O, Galstyan, G, Garganeeva, A, Izmozherova, N, Karetnikova, V, Kharakhulakh, M, Khokhlov, A, Kobalava, Z, Koshelskaya, O, Kosmacheva, E, Kostin, V, Koziolova, N, Kuzin, A, Lesnov, V, Lysenko, T, Markov, V, Mayorov, A, Moiseev, S, Myasoedova, S, Petunina, N, Rebrov, A, Ruyatkina, L, Samoylova, J, Sazonova, O, Shilkina, N, Sokolova, N, Vasilevskaya, O, Verbovaya, N, Vishneva, E, Vorobyev, S, Vorokhobina, N, Zanozina, O, Zhdanova, E, Zykova, T, Burgess, L, Coetzee, K, Dawood, S, Lombard, L, Makotoko, E, Moodley, R, Oosthuysen, W, Sarvan, M, Calvo Gomez, C, Cano Rodriguez, I, Castro Conde, A, Cequier Fillat, A, Cuatrecasas Cambra, G, de Alvaro Moreno, F, De Teresa Parreno, L, Delgado Lista, J, Dominguez Escribano, J, Duran Garcia, S, Elvira Gonzalez, J, Fernandez Rodriguez, J, Goday Arno, A, Gomez Huelgas, R, Gonzalez Juanatey, J, Hernandez Mijares, A, Jimenez Diaz, V, Jodar Gimeno, E, Lucas Morante, T, Marazuela, M, Martell Claros, N, Mauricio Puente, D, Mena Ribas, E, Merino Torres, J, Mezquita Raya, P, Nubiola Calonge, A, Ordonez Sanchez, X, Pascual Izuel, J, Perea Castilla, V, Perez Perez, A, Perez Soto, I, Quesada Charneco, M, Quesada Simon, A, Redon Mas, J, Rego Iraeta, A, Rodriguez Alvarez, M, Rodriguez Rodriguez, I, Saban Ruiz, J, Soto Gonzalez, A, Tinahones Madueno, F, Trescoli Serrano, C, Ulied Arminana, A, Bachus, E, Berndtsson Blom, K, Eliasson, K, Koskinen, P, Larnefeldt, H, Lif-Tiberg, C, Linderfalk, C, Lund, G, Lundman, P, Moris, L, Olsson, A, Salmonsson, S, Sanmartin Berglund, J, Sjoberg, F, Soderberg, S, Torstensson, I, Chen, J, Tien, K, Tseng, S, Tu, S, Wang, C, Wang, J, Phrommintikul, A, Yamwong, S, Jintapakorn, W, Hutayanon, P, Sansanayudh, N, Bazhan, L, Fushtey, I, Grachova, M, Katerenchuk, V, Korpachev, V, Kravchun, N, Larin, O, Mykhalchyshyn, G, Myshanych, H, Oleksyk, O, Orlenko, V, Pashkovska, N, Pertseva, N, Petrosyan, O, Smirnov, I, Vlasenko, M, Zlova, T, Aye, M, Baksi, A, Balasubramani, M, Beboso, R, Blagden, M, Bundy, C, Cookson, T, Copland, A, Emslie-Smith, A, Green, F, Gunstone, A, Issa, B, Jackson-Voyzey, E, Johnson, A, Maclean, M, Mcknight, J, Muzulu, S, O'Connell, I, Oyesile, B, Patterson, C, Pearson, E, Philip, S, Smith, P, Sukumaran, U, Abbas, J, Aggarwala, G, Akhter, F, Andersen, J, Anglade, M, Argoud, G, Ariani, M, Ashdji, R, Bakhtari, L, Banerjee, S, Bartlett, A, Baum, H, Bays, H, Beasley, R, Belfort de Aguiar, R, Benjamin, S, Bhagwat, R, Bhargava, A, Bode, B, Bratcher, C, Briskin, T, Brockmyre, A, Broughton, R, Brown, J, Budhraja, M, Cannon, K, Carr, J, Cathcart, H, Cavale, A, Chaykin, L, Cheung, D, Childress, R, Cohen, A, Condit, J, Cooksey, E, Cornett, G, Dauber, I, Davila, W, De Armas, L, Dean, J, Detweiler, R, Diaz, E, Di Giovanna, M, Dor, I, Drummond, W, Eagerton, D, Earl, J, Eaton, C, Ellison, H, Farris, N, Fiel, T, Firek, A, First, B, Forgosh, L, French, W, Gandy, W, Garcia, R, Gill, S, Gordon, M, Guice, M, Gummadi, S, Hackenyos, J, Hairston, K, Hanson, L, Harrison, L, Hartman, I, Heitner, J, Hejeebu, S, Hermany, P, Hernandez-Cassis, C, Hidalgo, H, Higgins, A, Ibrahim, H, Jacobs, S, Johnson, D, Joshi, P, Kaster, S, Kellum, D, Kim, E, Kirby, W, Knouse, A, Kulback, S, Kumar, M, Kuruvanka, T, Labroo, A, Lasswell, W, Lentz, J, Lenzmeier, T, Lewis, D, Li, Z, Lillestol, M, Little, R, Lorraine, R, McKeown-Biagas, C, Mcneill, R, Mehta, A, Miller, A, Moran, J, Morawski, E, Nadar, V, O'Connor, T, Odio, A, Parker, R, Patel, R, Phillips, L, Raad, G, Rahman, A, Raikhel, M, Raisinghani, A, Rajan, R, Rasouli, N, Rauzi, F, Rohr, K, Roseman, H, Rovner, S, Saba, F, Sachson, R, Schabauer, A, Schneider, R, Schuchard, T, Sensenbrenner, J, Shlesinger, Y, Singh, N, Sivalingam, K, Stonesifer, L, Storey, D, Suh, D, Tahir, M, Tan, A, Tan, M, Taylon, A, Thakkar, M, Tripathy, D, Uwaifo, G, Vedere, A, Venugopal, C, Vo, A, Welch, M, Welker, J, White, A, Willis, J, Wynne, A, Yazdani, S, Price, L, Lokhngina, Y, Xing, W, Overton, R, Stewart, M, Stead, J, Lindsay, A, Patel, V, Ross, J, Soffer, J, Daga, S, Sowell, M, Patel, P, Garvey, L, Ackert, J, Abraham, S, Sabol, M, Altobelli, D, Ha, J, Kulkarni, M, Noronha, D, Casson, E, Zang, E, Sandhu, C, Kumar, R, Chen, D, Taft, L, Ye, J, Shannon, J, Wilson, T, Babi, C, Miller, D, Russell, R, Bull, G, Hereghty, B, Fernandez-Salazar, E, Longley, T, Donaldson, J, Jarosz, M, Murphy, K, Adams, P, James, R, Richards, J, Sedani, S, Althouse, D, Watson, D, Lorimer, J, Lauder, S, Schultheis, R, Womer, T, Wraight, E, Li, W, Price-Olsen, E, Watson, A, Kelly, A, Mclaughlin, P, Fleming, J, Schubert, J, Schleiden, D, Harris, T, Prakash, R, Breneman, J, Deshpande, S, Saswadkar, A, Kumari, A, Shitut, A, Raorane, A, Karmalkar, A, Mhambrey, A, Bhosale, A, Vaphare, A, Patil, A, Khandelwal, C, Shaik, F, Nadar, M, Karka, M, Kadgaonkar, N, Gupta, N, Aher, N, Potnis, O, Naicker, P, Shinde, R, Sharma, R, Godse, R, Solanki, S, Sahu, S, Dumbre, S, Kumar, S, Patil, S, and Mandal, T
- Subjects
Male ,Placebo-controlled study ,Myocardial Infarction ,alanine aminotransferase, albiglutide, bilirubin, placebo, antidiabetic agent, glucagon like peptide 1, rGLP-1 protein ,Kaplan-Meier Estimate ,030204 cardiovascular system & hematology ,law.invention ,0302 clinical medicine ,Randomized controlled trial ,law ,Glucagon-Like Peptide 1 ,Cardiovascular Disease ,Medicine(all) ,education.field_of_study ,Subcutaneous ,Medicine (all) ,albigutide ,Hazard ratio ,General Medicine ,Middle Aged ,Albiglutide ,Stroke ,Treatment Outcome ,Tolerability ,Cardiovascular Diseases ,Female ,type 2 diabetes ,Type 2 ,Human ,Adult ,medicine.medical_specialty ,Injections, Subcutaneous ,Population ,030209 endocrinology & metabolism ,Placebo ,Injections, Subcutaneou ,Drug Administration Schedule ,Injections ,03 medical and health sciences ,Double-Blind Method ,Internal medicine ,Diabetes Mellitus ,medicine ,Humans ,Hypoglycemic Agents ,education ,Aged ,Diabetes Mellitus, Type 2 ,Hypoglycemic Agent ,business.industry ,Semaglutide ,Settore MED/13 - ENDOCRINOLOGIA ,Harmony ,business - Abstract
Background: \ud Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke.\ud \ud Methods: \ud We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515.\ud \ud Findings: \ud Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p
- Published
- 2018
13. [Study of 6 cases with retroperitoneal primary neoplasms].
- Author
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Lozanov L
- Subjects
- Adult, Carcinoma surgery, Female, Humans, Leiomyoma surgery, Lipoma surgery, Middle Aged, Teratoma surgery, Retroperitoneal Neoplasms surgery
- Published
- 1979
14. [Freund's complete adjuvant and the infectiousness of Eimeria tenella oocysts for chickens].
- Author
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Penev P, Ivanov P, and Lozanov L
- Subjects
- Animals, Coccidiosis immunology, Coccidiosis veterinary, Poultry Diseases immunology, Spores pathogenicity, Chickens immunology, Eimeria pathogenicity, Freund's Adjuvant administration & dosage
- Published
- 1982
15. [Pneumoperitoneum after laparotomy and the diagnostic difficulties which it may create].
- Author
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Lozanov L
- Subjects
- Humans, Male, Middle Aged, Pneumoperitoneum diagnosis, Postoperative Complications diagnosis, Laparotomy adverse effects, Pneumoperitoneum etiology, Postoperative Complications etiology
- Published
- 1980
16. [Clinical aspects, pathomorphology and histokinetics in experimental Eimeria acervulina infection in chickens].
- Author
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Lozanov L
- Subjects
- Animals, Coccidiosis diagnosis, Coccidiosis pathology, Enteritis diagnosis, Enteritis pathology, Enteritis veterinary, Histocytochemistry, Intestinal Mucosa pathology, Kinetics, Poultry Diseases metabolism, Poultry Diseases pathology, Time Factors, Chickens, Coccidiosis veterinary, Poultry Diseases diagnosis
- Abstract
Experiments were carried out with birds experimentally infected with Eimeria acervulina. It was found that this causative agent was responsible for catarrhal to hemorrhagic enteritis, however, the feces did not contain blood despite their becoming watery. In the duodenum it was shown to accomplish schizogony three times: the first schizogony took place up to the 72nd hour, the second one--up to the 120th hour, and the third one--up to the 168 th hour. On the other hand, gametogony started at the 168 th hr. Most severe lesions in the mucosa were found on the 7th-8th day following infection. They coincided in time with the third generation of schizonts and the gametogony. The alteration processes in the mucous membrane affected the villi to a larger extent than the propria mucosae. Villi regeneration proceeded from the 9 th to the 12 th day. The prepatent period lasted 144 hours. Macrophages were not found to carry the sporozoites to the glands. Dystrophic and necrobiotic changes in the viscera predominated over the proliferation processes, and this made it reasonable to believe that the basic moment in the pathogenesis of the disease was the mechanical destruction of the epithelial cells of the villi as well as the adsorption of toxic products from the decomposition of the necrotic cell mass in the intestinal lumen. Eimeria acervulina was said to produce pathogenic, but not lethal effects.
- Published
- 1983
17. [Hygienic evaluation of the effectiveness of short-term suburban recreation from the viewpoint of natural climatic and demographic factors].
- Author
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Mechkuev R, Lozanov L, Chuchkova M, Iotov L, and Toshkov S
- Subjects
- Bulgaria, Humans, Leisure Activities, Time Factors, Climate, Health, Recreation, Suburban Population, Urban Health, Urban Population
- Abstract
The importance of recreation grew considerably with the increase of leisure time and cultural level of the workers. In our country, on the other hand, there are no complete hygienic studies on the problems of organization and necessary equipment for recreation. In that connection, hygienic-urbanization, hygienic-sociological, microclimatic and physiological studies, as well as investigations on ultraviolet radiation, level of noise and extent of air pollution in some typical recreation places (Sofia and Varna) were carried out. Better conditions were established in nature - town ourskirts environment (as regard ultraviolet radiation, noise level, degree of air pollution, temperature-humidity and radiation microclimate) and their favourable effect on the physiological functions of organism (particularly as regards thermoregulation and cardiovascular system). A dependence was also established between the population recreation needs and social-demographic and nature - climatic factors. Tangible recommendations for the improvement of the state of short-term town outskirts recreation in Sofia and Varna are proposed on the base of the results.
- Published
- 1981
18. [Hygiene research in solving the health aspects of urban development].
- Author
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Efremov E, Chuchkova M, Lozanov L, Iotov L, and Toshkov S
- Subjects
- Bulgaria, Ecology, Environment, Humans, Hygiene, Research, Health, Urban Health, Urbanization
- Abstract
The urban development and the problems it raises at present, are in direct relation with the conditions, which affect considerably the health of the population. The territorial and settlement system, the urban planning on ecological basis, the new methods of building in applying polymeric materials, the conditions of the environment in health establishments, the regulations of the physical factors, noise and electromagnetic energy are subject to the hygienic studies, in which the Institute of Hygiene and Occupational Health is engaged. The connective unit in the variety of the mentioned fields of investigation is the health of the inhabitants and finding the right way in its protection and keeping. The attitudes of prophylaxis, the creation and establishing of urban environment, corresponding to the conflict-free existence and potentiation of the health development of the inhabitants, are clarified, as they are related to the basic trends of the world Health Organization, whose targets are "Health for All by the year 2000".
- Published
- 1988
19. [Changes in the physical environmental factors in modern buildings related to the use of polymeric construction materials].
- Author
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Lozanov L
- Subjects
- Chemical Phenomena, Chemistry, Physical, Electricity, Heating, Humans, Hygiene, Temperature, Climate, Construction Materials adverse effects, Housing, Microclimate, Polymers adverse effects
- Abstract
The polymeric materials are used on a large scale in building and furnishing of modern edifices. However, in spite of the doubtless positive effect there are a number of important hygienic problems, related to the ability of these new materials, at unregulated and not controlled usage, to cause unfavourable changes in the parameters of the environment and through them to affect the health and spirits of the inhabitants. The basic hygienic problems in the application of polymeric building materials /PBM/ are derived from the elimination of harmful chemical substances from the latter. Besides of great importance are the changes in the physical parameters of the environment in the premises of the edifices, arising from the accumulation of static electricity on the surface of the PBM, the aggravated thermal technical characteristics of some materials, etc. The results of the hygiene investigations for thermal protective properties of different types of PBM, used as floor covering and their effect on the thermal metabolic processes and colds of the inhabitants are pointed out. The biological effect of static electricity and the dependence of the electrification of the materials on the composition and the physico-chemical nature of the materials and some microclimatic parameters and other exploitation conditions are clarified. Recommendations are given for the preliminary hygienic control of these materials, in order to avoid the aggravation of the parameters of the environment in the modern buildings.
- Published
- 1985
20. [Pathomorphology and histokinesis of the changes due to Eimeria in turkey poults experimentally infected with Eimeria adenoeides].
- Author
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Lozanov L and Koĭnarski V
- Subjects
- Animals, Cecum pathology, Coccidiosis pathology, Kinetics, Necrosis, Time Factors, Coccidiosis veterinary, Poultry Diseases pathology, Turkeys
- Abstract
Studied were the morphologic changes in an experimental Eimeria adenoeides infection in turkey-poults. The birds were killed daily from the 1st to the 10th day of infection, keeping records of the gross lesions and the microscopic changes in the internal organs. It was found that Eimeria adenoeides performs two cycles of shisogony in the caeca. Most severe were the changes on the 4th and 5th day of infection, which corresponded to the second shisogony and the gametogonia. At the same time there were in the liver, kidneys, and heart granular protein dystrophy which was believed to be a second one, being the result or resorption of toxic cell detritus products in the intestines.
- Published
- 1985
21. [Histokinesis in experimental ovine cysticercosis].
- Author
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Lozanov L, Georgieva D, and Kamburov P
- Subjects
- Animals, Cysticercosis parasitology, Cysticercosis pathology, Heart parasitology, Liver parasitology, Liver pathology, Lung parasitology, Lung pathology, Muscles parasitology, Muscles pathology, Myocardium pathology, Sheep, Sheep Diseases parasitology, Time Factors, Cysticercosis veterinary, Sheep Diseases pathology
- Abstract
The dynamic of the morphologic changes taking place in the viscera of lambs was followed up in lambs with an experimental Cysticercus ovis infection. The tests were carried out with 6 two-month-old lambs infected with 30,000 ova of Taenia ovis each. The animals were killed on the 2nd, 4th, 12th, 54th, and 70th day of infection, taking notes on the gross and microscopic changes in the internal organs. It was found that in the predilection sites of localization the migrating oncospheres were transformed into cysticerci around which specific granuloma were formed from the center to the periphery, consisting of eosinophile leukocytes, epitheloid and gigantic cells, lymphocytes, lymphoid cells, and outermost--a connective tissue capsule. As the result of the abundant leukocyte infiltration the cysticerci quickly perished and a suppurant was formed instead that later on was replaced by connective tissue.
- Published
- 1984
22. [Several current hygienic problems in residential and recreational environments--results of studies during the 7th five-year-plan].
- Author
-
Efremov E, Mechkuev R, Chuchkova M, Lozanov L, and Iotov L
- Subjects
- Bulgaria, Environment Design standards, Housing standards, Humans, Rest, Urban Health standards, Urban Health trends, Environment Design trends, Housing trends, Hygiene, Recreation
- Abstract
Dwelling and rest - two of the basic elements of life activity, draw now-a-days the attention of state, political, economic and scientific bodies and organizations in our country. The care of man in our society is expressed in such a formation and protection of the environment that could guarantee adequate conditions for dwelling and rest at present and in the future. The hygienic problems, associated with that type activity, include planning and construction of new settlement systems studies on the deleterious and favourable physical factors (noise, vibration, electromagnetic fields, natural solar radiation), mode of construction, equipment and exploitation of residential and administrative buildings. They are the object of the present paper, which presents, in a summarized way, the experience of the research work at the laboratory "Physical factors of the environment, planning and construction in settlements", at the RIHOD, carried out during the seventh 5-year period. Some results are presented that have an essential share in the new approach to the hygienic standardization and regulation of the qualities of the environment for dwelling and rest.
- Published
- 1983
23. [Inhibitory effect of oil emulsions on the oocyst infectiveness of Eimeria tenella].
- Author
-
Penev P, Ivanov P, and Lozanov L
- Subjects
- Animals, Chickens, Coccidiosis drug therapy, Coccidiosis parasitology, Drug Evaluation, Preclinical veterinary, Eimeria pathogenicity, Emulsions, Freund's Adjuvant therapeutic use, Poultry Diseases drug therapy, Poultry Diseases parasitology, Coccidiosis veterinary, Eimeria drug effects, Oils therapeutic use
- Abstract
Comparative studies were carried out on the inhibitory effect of some oleoemulsions on the acute course of an experimental coccidial infection caused by Eimeria tenella. Such effect was demonstrated with the oral application of sporulated oocysts both with the complete and incomplete Freund's adjuvant and with oleum ricini and oleum helianthi in combination. The results of histopathologic investigations showed that the two types of Freund's adjuvant inhibited the rapid and joint excysting of a large number of oocysts. Inhibited was the invasion of sporozoits in the epithelial cells of the mucous membrane and thus the acute course of the coccidial infection caused by Eimeria tenella.
- Published
- 1984
24. [Hygienic evaluation of the planning and construction of housing complexes].
- Author
-
Mechkuev R, Chuchkova M, Iotov L, Lozanov L, and Kurchatova G
- Subjects
- Bulgaria, Facility Design and Construction, Microclimate, Sanitation, Ultraviolet Rays, City Planning, Health, Housing, Urban Health
- Abstract
Three blocks of flats were the subject of this study. They have been projected and built at different periods and the study covers the following principal aspects: sanitary urbanization analysis, assay of some of the basic environmental physical factors and physiologic reactions of the human organism and atmosphere contamination. These blocks of flats are still unable to provide wholy adequate sanitary conditions, in conformity with the urbanization setup, edifice situating, planning and organization of public services on the territory and anthropogenic factors. For an optimal environment one should take into consideration all sanitary requirements early in the process of projecting blocks of flats.
- Published
- 1980
25. [Our experience with a Billroth I resection with preservation of the pylorus after Maki].
- Author
-
Lozanov L
- Subjects
- Adult, Aged, Female, Humans, Male, Middle Aged, Stomach Ulcer surgery, Gastrectomy methods, Pylorus surgery
- Published
- 1979
26. [Changes in the chemical properties of environmental air in contact with polymeric construction materials used in modern buildings].
- Author
-
Lozanov L and Popivanova I
- Subjects
- Air Pollutants analysis, Bulgaria, Construction Materials analysis, Humans, Maximum Allowable Concentration, Microclimate, Polymers analysis, Time Factors, Volatilization, Air Pollutants adverse effects, Construction Materials adverse effects, Polymers adverse effects
- Abstract
Sanitary and chemical studies of 15 types of polymeric building materials, used in the construction of modern establishments as floor coverings, lining and roofing materials, isolating materials and pastes. Elimination of chemical substances of the polymeric building materials is established. In the first days after their production or use the concentrations of the eliminated substances are considerably above the MAC--with some of the tens and hundreds times above the hygienic norm. MAC of the eliminated polymeric building materials is reached for different periods of time, as the latter define also the quarantine dates for permitting the usage of the materials. For materials which point out to considerable deviations of the norms on the first days after production or use a new instruction for technical safety is required. The diffused floor coverings on epoxide basis, paste "Pirolik" and some types of ligneous surfaces on the basis of carbamide-formaldehyde pitch, received unfavourable hygienic assessment. They show elimination of chemical substances considerably above MAC, even after more than 9 months of their production.
- Published
- 1987
27. [Action of sodium sulfachlorpyrazine (ESB3) on the endogenous development of Eimeria tenella in the experimental infestation of chickens].
- Author
-
Penev PM and Lozanov L
- Subjects
- Animals, Coccidiosis drug therapy, Coccidiosis parasitology, Drug Evaluation, Preclinical veterinary, Eimeria growth & development, Poultry Diseases parasitology, Time Factors, Chickens parasitology, Coccidiosis veterinary, Coccidiostats therapeutic use, Eimeria drug effects, Poultry Diseases drug therapy, Sulfachlorpyridazine therapeutic use, Sulfanilamides therapeutic use
- Abstract
Studies were carried out on the action of sulfachlorpyrisine-Na (ESB3) on the endogenic development of Eimeria tenella in the case of experimental infection in birds. Most sensitive to the preparation were the endogenic forms between the 48 h and the 72 nd following the act of infection. Given to birds on the day of infection and 24 hours later it produced no harmful effect on the further endogenic development of E. tenella. When the preparation was applied at the 72 nd hour it led to the degeneration of most of the II generation schizonts and inhibited their further development. As a result no oocysts were found in the feces of birds up to the 10 th-11 th day after infection. When applied at the 92 nd and the 120 th hour sulfachlorpyrisine-Na interfered with the development of the already finite forms of gametogony without concurrent degenerative effects.
- Published
- 1983
28. [Improvement in public health management in the People's Republic of Bulgaria].
- Author
-
Grigorov G and Lozanov L
- Subjects
- Bulgaria, Efficiency, Government Agencies, Health Services Administration, Workforce, Public Health Administration standards
- Published
- 1978
29. [Paget-Schroetter syndrome and superior vena cava syndrome].
- Author
-
Lozanov L
- Subjects
- Axillary Vein, Female, Humans, Middle Aged, Intermittent Claudication, Thrombophlebitis, Vena Cava, Superior
- Published
- 1971
30. [Pyloric stenosis caused by calculosis of the gallbladder].
- Author
-
Lozanov L
- Subjects
- Aged, Cholecystectomy, Female, Humans, Cholelithiasis complications, Pyloric Stenosis etiology
- Published
- 1967
31. [A new modification of the surgical treatment of inguinal hernia].
- Author
-
Lozanov L
- Subjects
- Humans, Methods, Hernia, Inguinal surgery, Suture Techniques
- Published
- 1968
32. [On the extension of surgical intervention in rectal cancer].
- Author
-
Lozanov L
- Subjects
- Adult, Aged, Colostomy, Female, Humans, Male, Middle Aged, Rectal Neoplasms surgery
- Published
- 1968
33. [Stomach resection and anomalies of the small intestine].
- Author
-
Lozanov L
- Subjects
- Humans, Methods, Stomach Neoplasms surgery, Stomach Ulcer surgery, Gastrectomy, Jejunum abnormalities
- Published
- 1970
34. [Hematuria consecutive to extraurinary disease of unknown etiology].
- Author
-
LOZANOV L
- Subjects
- Humans, Hematuria etiology
- Published
- 1956
35. [On ileus following hepatobiliary operations].
- Author
-
Lozanov L
- Subjects
- Cholecystectomy adverse effects, Hepatectomy adverse effects, Humans, Postoperative Complications, Intestinal Obstruction etiology
- Published
- 1966
36. [A case of extensive resection of the small intestine in adults].
- Author
-
Lozanov L
- Subjects
- Aged, Female, Humans, Ileostomy, Intestinal Neoplasms surgery, Intestine, Small surgery
- Published
- 1965
37. [On bilious pancreatitis based on the experiences at the 1st City Hospital in Sofia].
- Author
-
Lozanov L
- Subjects
- Bulgaria, Humans, Pancreatitis surgery, Biliary Tract Diseases complications, Pancreatitis complications
- Published
- 1967
38. [Modification of the closure of the duodenal stump].
- Author
-
Lozanov L
- Subjects
- Humans, Duodenal Ulcer surgery, Duodenum surgery, Gastrectomy, Suture Techniques
- Published
- 1973
39. [Abnormal dilatation of the extra-hepatic bile ducts associated with an unusual anomaly].
- Author
-
Lozanov L
- Subjects
- Biliary Tract Diseases diagnostic imaging, Common Bile Duct surgery, Dilatation, Female, Humans, Middle Aged, Radiography, Common Bile Duct abnormalities
- Published
- 1973
40. [A rare form of urachus persistens].
- Author
-
Lozanov L and Marinova M
- Subjects
- Adult, Female, Humans, Male, Urachus surgery
- Published
- 1971
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