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1. Heart failure in younger patients: the Meta-analysis Global Group in Chronic Heart Failure (MAGGIC)

Author

Wong, Chih M., Hawkins, Nathaniel M., Petrie, Mark C., Jhund, Pardeep S., Gardner, Roy S., Ariti, Cono A., Poppe, Katrina K., Earle, Nikki, Whalley, Gillian A., Squire, Iain B., Doughty, Robert N., McMurray, John J.V., Berry, C., Doughty, R., Granger, C., Køber, L., Massie, B., McAlister, F., McMurray, J., Pocock, S., Poppe, K., Swedberg, K., Somaratne, J., Whalley, G., Ahmed, A., Andersson, B., Bayes-Genis, A., Berry, C., Cowie, M., Cubbon, R., Doughty, R., Ezekowitz, J., Gonzalez-Juanatey, J., Gorini, M., Gotsman, I., Grigorian-Shamagian, L., Guazzi, M., Kearney, M., Køber, L., Komajda, M., di Lenarda, A., Lenzen, M., Lucci, D., Macín, S., Madsen, B., Maggioni, A., Martínez-Sellés, M., McAlister, F., Oliva, F., Poppe, K., Rich, M., Richards, M., Senni, M., Squire, I., Taffet, G., Tarantini, L., Tribouilloy, C., Troughton, R., Tsutsui, H., Whalley, G., Doughty, R., Earle, N., Gamble, G.D., Poppe, K., Whalley, G., Ariti, C., Dobson, J., Pocock, S., Poppe, K., Doughty, R.N., Whalley, G., Andersson, B., Hall, C., Richards, A.M., Troughton, R., Lainchbury, J., Berry, C., Hogg, K., Norrie, J., Stevenson, K., Brett, M., McMurray, J., Pfeffer, M.A., Swedberg, K., Granger, C.B., Held, P., McMurray, J.J.V., Michelson, E.L., Olofsson, B., Östergren, J., Yusuf, S., Køber, L., Torp-Pedersen, C., Ahmed, Ali, Lenzen, M.J., Scholte op Reimer, W.J.M., Boersma, E., Vantrimpont, P.J.M.J., Follath, F., Swedberg, K., Cleland, J., Komajda, M., Gotsman, I., Zwas, D., Planer, D., Azaz-Livshits, T., Admon, D., Lotan, C., Keren, A., Grigorian-Shamagian, L., Varela-Roman, A., Mazón-Ramos, P., Rigeiro-Veloso, P., Bandin-Dieguez, M.A., Gonzalez-Juanatey, J.R., Guazzi, M., Myers, J., Arena, R., McAlister, F.A., Ezekowitz, J., Armstrong, P.W., Cujec, Bibiana, Paterson, Ian, Cowie, M.R., Wood, D.A., Coats, A.J.S., Thompson, S.G., Suresh, V., Poole-Wilson, P.A., Sutton, G.C., Martínez-Sellés, M., Robles, J.A.G., Prieto, L., Muñoa, M.D., Frades, E., Díaz-Castro, O., Almendral, J., Tarantini, L., Faggiano, P., Senni, M., Lucci, D., Bertoli, D., Porcu, M., Opasich, C., Tavazzi, L., Maggioni, A.P., Kirk, V., Bay, M., Parner, J., Krogsgaard, K., Herzog, T.M., Boesgaard, S., Hassager, C., Nielsen, O.W., Aldershvile, J., Nielsen, H., Kober, L., Macín, S.M., Perna, E.R., Cimbaro Canella, J.P., Alvarenga, P., Pantich, R., Ríos, N., Farias, E.F., Badaracco, J.R., Madsen, B.K., Hansen, J.F., Stokholm, K.H., Brons, J., Husum, D., Mortensen, L.S., Bayes-Genis, A., Vazquez, R., Puig, T., Fernandez-Palomeque, C., Bardají, A., Pascual-Figal, D., Ordoñez-Llanos, J., Valdes, M., Gabarrus, A., Pavon, R., Pastor, L., Gonzalez-Juanatey, J.R., Almendral, J., Fiol, M., Nieto, V., Macaya, C., Cinca, J., Bayes de Luna, A., Newton, J.D., Blackledge, H.M., Squire, I.B., Wright, S.P., Whalley, G.A., Doughty, R.N., Kerzner, R., Gage, B.F., Freedland, K.E., Rich, M.W., Huynh, B.C., Rovner, A, Freedland, KE, Carney, RM, Rich, MW, Taffet, GE, Teasdale, T.A., Bleyer, A.J., Kutka, N.J., Luchi, R.J., Tribouilloy, C., Rusinaru, D., Mahjoub, H., Soulière, V., Lévy, F., Peltier, M., Tsutsui, H., Tsuchihashi, M., Takeshita, A., MacCarthy, P.A., Kearney, M.T., Nolan, J., Lee, A.J., Prescott, R.J., Shah, A.M., Brooksby, W.P., Fox, K.A.A., Varela-Roman, A., Gonzalez-Juanatey, J.R., Basante, P., Trillo, R., Garcia-Seara, J., Martinez-Sande, J.L., and Gude, F.

Published
2014
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3. Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates A beta, tau, immunity and lipid processing (vol 51, pg 414, 2019)

Author

Kunkle, BW, Grenier-Boley, B, Sims, R, Bis, JC, Damotte, V, Naj, AC, Boland, A, Vronskaya, M, van der Lee, SJ, Amlie-Wolf, A, Bellenguez, C, Frizatti, A, Chouraki, V, Martin, ER, Sleegers, K, Badarinarayan, N, Jakobsdottir, J, Hamilton-Nelson, KL, Moreno-Grau, S, Olaso, R, Raybould, R, Chen, YN, Kuzma, AB, Hiltunen, M, Morgan, T, Ahmad, S, Vardarajan, BN, Epelbaum, J, Hoffmann, P, Boada, M, Beecham, GW, Garnier, JG, Harold, D, Fitzpatrick, AL, Valladares, O, Moutet, ML, Gerrish, A, Smith, AV, Qu, LM, Bacq, D, Denning, N, Jian, XQ, Zhao, Y, Del Zompo, M, Fox, NC, Choi, SH, Mateo, I, Hughes, JT, Adams, HH, Malamon, J, Sanchez-Garcia, F, Patel, Y, Brody, JA, Dombroski, BA, Naranjo, MCD, Daniilidou, M, Eiriksdottir, G, Mukherjee, S, Wallon, D, Uphill, J, Aspelund, T, Cantwell, LB, Garzia, F, Galimberti, D, Hofer, E, Butkiewicz, M, Fin, B, Scarpini, E, Sarnowski, C, Bush, WS, Meslage, S, Kornhuber, J, White, CC, Song, Y, Barber, RC, Engelborghs, S, Sordon, S, Voijnovic, D, Adams, PM, Vandenberghe, R, Mayhaus, M, Cupples, LA, Albert, MS, De Deyn, PP, Gu, W, Himali, JJ, Beekly, D, Squassina, A, Hartmann, AM, Orellana, A, Blacker, D, Rodriguez-Rodriguez, E, Lovestone, S, Garcia, ME, Doody, RS, Munoz-Fernadez, C, Sussams, R, Lin, HH, Fairchild, TJ, Benito, YA, Holmes, C, Karamujic-Comic, H, Frosch, MP, Thonberg, H, Maier, W, Roshchupkin, G, Ghetti, B, Giedraitis, V, Kawalia, A, Li, S, Huebinger, RM, Kilander, L, Moebus, S, Hernandez, I, Kamboh, MI, Brundin, R, Turton, J, Yang, Q, Katz, MJ, Concari, L, Lord, J, Beiser, AS, Keene, CD, Helisalmi, S, Kloszewska, I, Kukull, WA, Koivisto, AM, Lynch, A, Tarraga, L, Larson, EB, Haapasalo, A, Lawlor, B, Mosley, TH, Lipton, RB, Solfrizzi, V, Gill, M, Longstreth, WT, Montine, TJ, Frisardi, V, Diez-Fairen, M, Rivadeneira, F, Petersen, RC, Deramecourt, V, Alvarez, I, Salani, F, Ciaramella, A, Boerwinkle, E, Reiman, EM, Fievet, N, Rotter, JI, Reisch, JS, Hanon, O, Cupidi, C, Uitterlinden, AGA, Royall, DR, Dufouil, C, Maletta, RG, de Rojas, I, Sano, M, Brice, A, Cecchetti, R, St George-Hyslop, P, Ritchie, K, Tsolaki, M, Tsuang, DW, Dubois, B, Craig, D, Wu, CK, Soininen, H, Avramidou, D, Albin, RL, Fratiglioni, L, Germanou, A, Apostolova, LG, Keller, L, Koutroumani, M, Arnold, SE, Panza, F, Gkatzima, O, Asthana, S, Hannequin, D, Whitehead, P, Atwood, CS, Caffarra, P, Hampel, H, Quintela, I, Carracedo, A, Lannfelt, L, Rubinsztein, DC, Barnes, LL, Pasquier, F, Frolich, L, Barral, S, McGuinness, B, Beach, TG, Johnston, JA, Becker, JT, Passmore, P, Bigio, EH, Schott, JM, Bird, TD, Warren, JD, Boeve, BF, Lupton, MK, Bowen, JD, Proitsi, P, Boxer, A, Powell, JF, Burke, JR, Kauwe, JSK, Burns, JM, Mancuso, M, Buxbaum, JD, Bonuccelli, U, Cairns, NJ, McQuillin, A, Cao, CH, Livingston, G, Carlson, CS, Bass, NJ, Carlsson, CM, Hardy, J, Carney, RM, Bras, J, Carrasquillo, MM, Guerreiro, R, Allen, M, Chui, HC, Fisher, E, Masullo, C, Crocco, EA, DeCarli, C, Bisceglio, G, Dick, M, Ma, L, Duara, R, Graff-Radford, NR, Evans, DA, Hodges, A, Faber, KM, Scherer, M, Fallon, KB, Riemenschneider, M, Fardo, DW, Heun, R, Farlow, MR, Kolsch, H, Ferris, S, Leber, M, Foroud, TM, Heuser, I, Galasko, DR, Giegling, I, Gearing, M, Hull, M, Geschwind, DH, Gilbert, JR, Morris, J, Green, RC, Mayo, K, Growdon, JH, Feulner, T, Hamilton, RL, Harrell, LE, Drichel, D, Honig, LS, Cushion, TD, Huentelman, MJ, Hollingworth, P, Hulette, CM, Hyman, BT, Marshall, R, Jarvik, GP, Meggy, A, Abner, E, Menzies, GE, Jin, LW, Leonenko, G, Real, LM, Jun, GR, Baldwin, CT, Grozeva, D, Karydas, A, Russo, G, Kaye, JA, Kim, R, Jessen, F, Kowall, NW, Vellas, B, Kramer, JH, Vardy, E, LaFerla, FM, Jockel, KH, Lah, JJ, Dichgans, M, Leverenz, JB, Mann, D, Levey, AI, Pickering-Brown, S, Lieberman, AP, Klopp, N, Lunetta, KL, Wichmann, HE, Lyketsos, CG, Morgan, K, Marson, DC, Brown, K, Martiniuk, F, Medway, C, Mash, DC, Nothen, MM, Masliah, E, Hooper, NM, McCormick, WC, Daniele, A, McCurry, SM, Bayer, A, McDavid, AN, Gallacher, J, Mckee, AC, van den Bussche, H, Mesulam, M, Brayne, C, Miller, BL, Riedel-Heller, S, Miller, CA, Miller, JW, Al-Chalabi, A, Morris, JC, Shaw, CE, Myers, AJ, Wiltfang, J, O'Bryant, S, Olichney, JM, Alvarez, V, Parisi, JE, Singleton, AB, Paulson, HL, Collinge, J, Perry, WR, Mead, S, Peskind, E, Cribbs, DH, Rossor, M, Pierce, A, Ryan, NS, Poon, WW, Nacmias, B, Potter, H, Sorbi, S, Quinn, JF, Sacchinelli, E, Raj, A, Spalletta, G, Raskind, M, Caltagirone, C, Bossu, P, Orfei, MD, Reisberg, B, Clarke, R, Reitz, C, Smith, AD, Ringman, JM, Warden, D, Roberson, ED, Wilcock, G, Rogaeva, E, Bruni, AC, Rosen, HJ, Gallo, M, Rosenberg, RN, Ben-Shlomo, Y, Sager, MA, Mecocci, P, Saykin, AJ, Pastor, P, Cuccaro, ML, Vance, JM, Schneider, JA, Schneider, LS, Slifer, S, Seeley, WW, Smith, AG, Sonnen, JA, Spina, S, Stern, RA, Swerdlow, RH, Tang, M, Tanzi, RE, Trojanowski, JQ, Troncoso, JC, Van Deerlin, VM, Van Eldik, LJ, Vinters, HV, Vonsattel, JP, Weintraub, S, Welsh-Bohmer, KA, Wilhelmsen, KC, Williamson, J, Wingo, TS, Woltjer, RL, Wright, CB, Yu, CE, Yu, L, Saba, Y, Pilotto, A, Bullido, MJ, Peters, O, Crane, PK, Bennett, D, Bosco, P, Coto, E, Boccardi, V, De Jager, PL, Lleo, A, Warner, N, Lopez, OL, Ingelsson, M, Deloukas, P, Cruchaga, C, Graff, C, Gwilliam, R, Fornage, M, Goate, AM, Sanchez-Juan, P, Kehoe, PG, Amin, N, Ertekin-Taner, N, Berr, C, Debette, S, Love, S, Launer, LJ, Younkin, SG, Dartigues, JF, Corcoran, C, Ikram, MA, Dickson, DW, Nicolas, G, Campion, D, Tschanz, J, Schmidt, H, Hakonarson, H, Clarimon, J, Munger, R, Schmidt, R, Farrer, LA, Van Broeckhoven, C, O'Donovan, MC, DeStefano, AL, Jones, L, Haines, JL, Deleuze, JF, Owen, MJ, Gudnason, V, Mayeux, R, Escott-Price, V, Psaty, BM, Ramirez, A, Wang, LS, Ruiz, A, van Duijn, CM, Holmans, PA, Seshadri, S, Williams, J, Amouyel, P, Schellenberg, GD, Lambert, JC, Pericak-Vance, MA, ADGC, EADI, Cohorts Heart Aging Res Genomic, and Genetic Environm Risk AD Defining

Published
2019

4. Meta-analysis of genetic association with diagnosed Alzheimer's disease identifies novel risk loci and implicates Abeta, Tau, immunity and lipid processing

Author

Kunkle, BW, Grenier-Boley, B, Sims, R, Bis, JC, Naj, AC, Boland, A, Vronskaya, M, van der Lee, SJ, Amlie-Wolf, A, Bellenguez, C, Frizatti, A, Chouraki, V, Martin, ER, Sleegers, K, Badarinarayan, N, Jakobsdottir, J, Hamilton-Nelson, KL, Aloso, R, Raybould, R, Chen, Y, Kuzma, AB, Hiltunen, M, Morgan, T, Ahmad, S, Vardarajan, BN, Epelbaum, J, Hoffmann, P, Boada, M, Beecham, GW, Garnier, JG, Harold, D, Fitzpatrick, AL, Valladares, O, Moutet, ML, Gerrish, A, Smith, AV, Qu, L, Bacq, D, Denning, N, Jian, X, Zhao, Y, Zompo, MD, Fox, NC, Grove, ML, Choi, SH, Mateo, I, Hughes, JT, Adams, HH, Malamon, J, Garcia, FS, Patel, Y, Brody, JA, Dombroski, B, Naranjo, MCD, Daniilidou, M, Eiriksdottir, G, Mukherjee, S, Wallon, D, Uphill, J, Aspelund, T, Cantwell, LB, Garzia, F, Galimberti, D, Hofer, E, Butkiewics, M, Fin, B, Scarpini, E, Sarnowski, C, Bush, W, Meslage, S, Kornhuber, J, White, CC, Song, Y, Barber, RC, Engelborghs, S, Pichler, S, Voijnovic, D, Adams, PM, Vandenberghe, R, Mayhaus, M, Cupples, LA, Albert, MS, De Deyn, PP, Gu, W, Himali, JJ, Beekly, D, Squassina, A, Hartmann, AM, Orellana, A, Blacker, D, Rodriguez-Rodriguez, E, Lovestone, S, Garcia, ME, Doody, RS, Fernadez, CM, Sussams, R, Lin, H, Fairchild, TJ, Benito, YA, Holmes, C, Comic, H, Frosch, MP, Thonberg, H, Maier, W, Roschupkin, G, Ghetti, B, Giedraitis, V, Kawalia, A, Li, S, Huebinger, RM, Kilander, L, Moebus, S, Hernández, I, Kamboh, MI, Brundin, R, Turton, J, Yang, Q, Katz, MJ, Concari, L, Lord, J, Beiser, AS, Keene, CD, Helisalmi, S, Kloszewska, I, Kukull, WA, Koivisto, AM, Lynch, A, Tarraga, L, Larson, EB, Haapasalo, A, Lawlor, B, Mosley, TH, Lipton, RB, Solfrizzi, V, Gill, M, Longstreth Jr, WT, Montine, TJ, Frisardi, V, Ortega-Cubero, S, Rivadeneira, F, Petersen, RC, Deramecourt, V, Ciaramella, A, Boerwinkle, E, Reiman, EM, Fievet, N, Caltagirone, C, Rotter, JI, Reisch, JS, Hanon, O, Cupidi, C, Uitterlinden, AG, Royall, DR, Dufouil, C, Maletta, RG, Moreno-Grau, S, Sano, M, Brice, A, Cecchetti, R, St George-Hyslop, P, Ritchie, K, Tsolaki, M, Tsuang, DW, Dubois, B, Craig, D, Wu, CK, Soininen, H, Avramidou, D, Albin, RL, Fratiglioni, L, Germanou, A, Apostolova, LG, Keller, L, Koutroumani, M, Arnold, SE, Panza, F, Gkatzima, O, Asthana, S, Hannequin, D, Whitehead, P, Atwood, CS, Caffarra, P, Hampel, H, Baldwin, CT, Lannfelt, L, Rubinsztein, DC, Barnes, LL, Pasquier, F, Frölich, L, Barral, S, McGuinness, B, Beach, TG, Johnston, JI, Becker, JT, Passmore, P, Bigio, EH, Schott, JM, Bird, TD, Warren, JD, Boeve, BF, Lupton, MK, Bowen, JD, Proitsi, P, Boxer, A, Powell, JF, Burke, JR, Kauwe, JK, Burns, JM, Mancuso, M, Buxbaum, JD, Bonuccelli, U, Cairns, NJ, McQuillin, A, Cao, C, Livingston, G, Carlson, CS, Bass, NJ, Carlsson, CM, Hardy, J, Carney, RM, Bras, J, Carrasquillo, MM, Guerreiro, R, Allen, M, Chui, HC, Fisher, E, Cribbs, DH, Masullo, C, Crocco, EA, DeCarli, C, Bisceglio, G, Dick, M, Ma, L, Duara, R, Graff-Radford, NR, Evans, DA, Hodges, A, Faber, KM, Scherer, M, Fallon, KB, Riemenschneider, M, Fardo, DW, Heun, R, Farlow, MR, Ferris, S, Leber, M, Foroud, TM, Heuser, I, Galasko, DR, Giegling, I, Gearing, M, Hüll, M, Geschwind, DH, Gilbert, JR, Morris, J, Green, RC, Mayo, K, Growdon, JH, Feulner, T, Hamilton, RL, Harrell, LE, Drichel, D, Honig, LS, Cushion, TD, Huentelman, MJ, Hollingworth, P, Hulette, CM, Hyman, BT, Marshall, R, Jarvik, GP, Meggy, A, Abner, E, Menzies, G, Jin, LW, Leonenko, G, Jun, G, Grozeva, D, Karydas, A, Russo, G, Kaye, JA, Kim, R, Jessen, F, Kowall, NW, Vellas, B, Kramer, JH, Vardy, E, LaFerla, FM, Jöckel, KH, Lah, JJ, Dichgans, M, Leverenz, JB, Mann, D, Levey, AI, Pickering-Brown, S, Lieberman, AP, Klopp, N, Lunetta, KL, Wichmann, HE, Lyketsos, CG, Morgan, K, Marson, DC, Brown, K, Martiniuk, F, Medway, C, Mash, DC, Nöthen, MM, Masliah, E, Hooper, NM, McCormick, WC, Daniele, A, McCurry, SM, Bayer, A, McDavid, AN, Gallacher, J, McKee, AC, van den Bussche, H, Mesulam, M, Brayne, C, Miller, BL, Riedel-Heller, S, Miller, CA, Miller, JW, Al-Chalabi, A, Morris, JC, Shaw, CE, Myers, AJ, Wiltfang, J, O’Bryant, S, Coto, E, Olichney, JM, Alvarez, V, Parisi, JE, Singleton, AB, Paulson, HL, Collinge, J, Perry, W, Mead, S, Peskind, E, Rosser, M, Pierce, A, Ryan, N, Poon, WW, Nacmias, B, Potter, H, Sorbi, S, Quinn, JF, Sacchinelli, E, Raj, A, Spalletta, G, Raskind, M, Bossù, P, Reisberg, B, Clarke, R, Reitz, C, Smith, AD, Ringman, JM, Warden, D, Roberson, ED, Wilcock, G, Rogaeva, E, Bruni, AC, Rosen, HJ, Gallo, M, Rosenberg, RN, Ben-Shlomo, Y, Sager, MA, Mecocci, P, Saykin, AJ, Pastor, P, Cuccaro, ML, Vance, JM, Schneider, JA, Schneider, LS, Seeley, WW, Smith, AG, Sonnen, JA, Spina, S, Stern, RA, Swerdlow, RH, Tanzi, RE, Trojanowski, JQ, Troncoso, JC, Van Deerlin, VM, Van Eldik, LJ, Vinters, HV, Vonsattel, JP, Weintraub, S, Welsh-Bohmer, KA, Wilhelmsen, KC, Williamson, J, Wingo, TS, Woltjer, RL, Wright, CB, Yu, CE, Yu, L, Crane, PK, Bennett, DA, Boccardi, V, De Jager, PL, Warner, N, Lopez, OL, McDonough, S, Ingelsson, M, Deloukas, P, Cruchaga, C, Graff, C, Gwilliam, R, Fornage, M, Goate, AM, Sanchez-Juan, P, Kehoe, PG, Amin, N, Ertekin-Taner, N, Berr, C, Debette, S, Love, S, Launer, LJ, Younkin, SG, Dartigues, JF, Corcoran, C, Ikram, MA, Dickson, DW, Campion, D, Tschanz, J, Schmidt, H, Hakonarson, H, Munger, R, Schmidt, R, Farrer, LA, Van Broeckhoven, C, O’Donovan, MC, DeStefano, AL, Jones, L, Haines, JL, Deleuze, JF, Owen, MJ, Gudnason, V, Mayeux, R, Escott-Price, V, Psaty, BM, Ruiz, A, Ramirez, A, Wang, LS, van Duijn, CM, Holmans, PA, Seshadri, S, Williams, J, Amouyel, P, Schellenberg, GD, Lambert, JC, Pericak-Vance, MA, Bis, JC [0000-0002-3409-1110], Garnier, JG [0000-0003-4991-763X], Smith, AV [0000-0001-9088-234X], Denning, N [0000-0001-8467-7382], Vandenberghe, R [0000-0001-6237-2502], Himali, JJ [0000-0003-1391-9481], Rodriguez-Rodriguez, E [0000-0001-7742-677X], Frisardi, V [0000-0003-0764-7387], Ortega-Cubero, S [0000-0003-0520-9439], Hanon, O [0000-0002-4697-122X], Brice, A [0000-0002-0941-3990], Albin, RL [0000-0002-0629-608X], Buxbaum, JD [0000-0001-8898-8313], Bass, NJ [0000-0002-4481-778X], Fisher, E [0000-0003-2850-9936], Bayer, A [0000-0002-7514-248X], Gallacher, J [0000-0002-2394-5299], Brayne, C [0000-0001-5307-663X], Riedel-Heller, S [0000-0003-4321-6090], Al-Chalabi, A [0000-0002-4924-7712], and Apollo - University of Cambridge Repository

Subjects
Aging, 4202 Epidemiology, Genome-wide association study, Disease, Neurodegenerative, Biology, 3101 Biochemistry and Cell Biology, Alzheimer's Disease, 3105 Genetics, 03 medical and health sciences, 0302 clinical medicine, Clinical Research, Acquired Cognitive Impairment, Genetics, medicine, 2.1 Biological and endogenous factors, Dementia, Gene, 030304 developmental biology, Genetic association, 2 Aetiology, 0303 health sciences, Prevention, Human Genome, 42 Health Sciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Lipid metabolism, medicine.disease, Brain Disorders, 3. Good health, Meta-analysis, Neurological, Alzheimer's disease, 030217 neurology & neurosurgery, 31 Biological Sciences
Abstract

IntroductionLate-onset Alzheimer’s disease (LOAD, onset age > 60 years) is the most prevalent dementia in the elderly1, and risk is partially driven by genetics2. Many of the loci responsible for this genetic risk were identified by genome-wide association studies (GWAS)3–8. To identify additional LOAD risk loci, the we performed the largest GWAS to date (89,769 individuals), analyzing both common and rare variants. We confirm 20 previous LOAD risk loci and identify four new genome-wide loci (IQCK, ACE, ADAM10, and ADAMTS1). Pathway analysis of these data implicates the immune system and lipid metabolism, and for the first time tau binding proteins and APP metabolism. These findings show that genetic variants affecting APP and Aβ processing are not only associated with early-onset autosomal dominant AD but also with LOAD. Analysis of AD risk genes and pathways show enrichment for rare variants (P = 1.32 × 10−7) indicating that additional rare variants remain to be identified.

Published
2018
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5. Prognostic significance of anaemia in patients with heart failure with preserved and reduced ejection fraction: Results from the MAGGIC individual patient data meta-analysis

Author

Berry, C, Poppe, K, Gamble, G, Earle, N, Ezekowitz, J, Squire, I, Mcmurray, J, Mcalister, F, Komajda, M, Swedberg, K, Maggioni, A, Ahmed, A, Whalley, G, Doughty, R, Tarantini, L, Granger, C, Køber, L, Massie, B, Pocock, S, Somaratne, J, Andersson, B, Bayes-Genis, A, Cowie, M, Cubbon, R, Gonzalez-Juanatey, J, Gorini, M, Gotsman, I, Grigorian-Shamagian, L, Guazzi, M, Kearney, M, Di Lenarda, A, Lenzen, M, Lucci, D, Macín, S, Madsen, B, Martínez-Sellés, M, Oliva, F, Rich, M, Richards, M, Senni, M, Taffet, G, Tribouilloy, C, Troughton, R, Tsutsui, H, Ariti, C, Dobson, J, Hall, C, Lainchbury, J, Hogg, K, Norrie, J, Stevenson, K, Brett, M, Pfeffer, M, Held, P, Michelson, E, Olofsson, B, Östergren, J, Yusuf, S, Torp-Pedersen, C, Scholte op Reimer, W, Boersma, E, Vantrimpont, P, Follath, F, Cleland, J, Zwas, D, Planer, D, Azaz-Livshits, T, Admon, D, Lotan, C, Keren, A, Varela-Roman, A, Mazón-Ramos, P, Rigeiro-Veloso, P, Bandin-Dieguez, M, Myers, J, Arena, R, Armstrong, P, Cujec, B, Paterson, I, Wood, D, Coats, A, Thompson, S, Suresh, V, Poole-Wilson, P, Sutton, G, Robles, J, Prieto, L, Muñoa, M, Frades, E, Díaz-Castro, O, Almendral, J, Faggiano, P, Bertoli, D, Porcu, M, Opasich, C, Tavazzi, L, Kirk, V, Bay, M, Parner, J, Krogsgaard, K, Herzog, T, Boesgaard, S, Hassager, C, Nielsen, O, Aldershvile, J, Nielsen, H, Kober, L, Perna, E, Cimbaro Canella, J, Alvarenga, P, Pantich, R, Ríos, N, Farias, E, Badaracco, J, Hansen, J, Stokholm, K, Brons, J, Husum, D, Mortensen, L, Vazquez, R, Puig, T, Fernandez-Palomeque, C, Bardají, A, Pascual-Figal, D, Ordoñez-Llanos, J, Valdes, M, Gabarrus, A, Pavon, R, Pastor, L, Fiol, M, Nieto, V, Macaya, C, Cinca, J, Cygankiewitz, I, Bayes De Luna, A, Newton, J, Blackledge, H, Wright, S, Kerzner, R, Gage, B, Freedland, K, Huynh, B, Rovner, A, Carney, R, Teasdale, T, Bleyer, A, Kutka, N, Luchi, R, Rusinaru, D, Mahjoub, H, Soulière, V, Lévy, F, Peltier, M, Tsuchihashi, M, Takeshita, A, Maccarthy, P, Nolan, J, Lee, A, Prescott, R, Shah, A, Brooksby, W, Fox, K, Basante, P, Trillo, R, Garcia-Seara, J, Martinez-Sande, J, Gude, F, Berry C, Poppe KK, Gamble GD, Earle NJ, Ezekowitz JA, Squire IB, McMurray JJV, McAlister FA, Komajda M, Swedberg K, Maggioni AP, Ahmed A, Whalley GA, Doughty RN, Tarantini L, Granger C, Køber L, Massie B, Pocock S, Somaratne J, Andersson B, Bayes-Genis A, Cowie M, Cubbon R, Gonzalez-Juanatey J, Gorini M, Gotsman I, Grigorian-Shamagian L, Guazzi M, Kearney M, Di Lenarda A, Lenzen M, Lucci D, Macín S, Madsen B, Martínez-Sellés M, Oliva F, Rich M, Richards M, Senni M, Taffet G, Tribouilloy C, Troughton R, Tsutsui H, Ariti C, Dobson J, Hall C, Lainchbury J, Hogg K, Norrie J, Stevenson K, Brett M, Pfeffer MA, Held P, Michelson EL, Olofsson B, Östergren J, Yusuf S, Torp-Pedersen C, Scholte op Reimer W, Boersma E, Vantrimpont PJMJ, Follath F, Cleland J, Zwas D, Planer D, Azaz-Livshits T, Admon D, Lotan C, Keren A, Varela-Roman A, Mazón-Ramos P, Rigeiro-Veloso P, Bandin-Dieguez MA, Myers J, Arena R, Armstrong PW, Cujec B, Paterson I, Wood DA, Coats AJS, Thompson SG, Suresh V, Poole-Wilson PA, Sutton GC, Robles JAG, Prieto L, Muñoa MD, Frades E, Díaz-Castro O, Almendral J, Faggiano P, Bertoli D, Porcu M, Opasich C, Tavazzi L, Kirk V, Bay M, Parner J, Krogsgaard K, Herzog TM, Boesgaard S, Hassager C, Nielsen OW, Aldershvile J, Nielsen H, Kober L, Perna ER, Cimbaro Canella JP, Alvarenga P, Pantich R, Ríos N, Farias EF, Badaracco JR, Hansen JF, Stokholm KH, Brons J, Husum D, Mortensen LS, Vazquez R, Puig T, Fernandez-Palomeque C, Bardají A, Pascual-Figal D, Ordoñez-Llanos J, Valdes M, Gabarrus A, Pavon R, Pastor L, Fiol M, Nieto V, Macaya C, Cinca J, Cygankiewitz I, Bayes De Luna A, Newton JD, Blackledge HM, Wright SP, Kerzner R, Gage BF, Freedland KE, Huynh BC, Rovner A, Carney RM, Teasdale TA, Bleyer AJ, Kutka NJ, Luchi RJ, Rusinaru D, Mahjoub H, Soulière V, Lévy F, Peltier M, Tsuchihashi M, Takeshita A, MacCarthy PA, Nolan J, Lee AJ, Prescott RJ, Shah AM, Brooksby WP, Fox KAA, Basante P, Trillo R, Garcia-Seara J, Martinez-Sande JL, Gude F, Berry, C, Poppe, K, Gamble, G, Earle, N, Ezekowitz, J, Squire, I, Mcmurray, J, Mcalister, F, Komajda, M, Swedberg, K, Maggioni, A, Ahmed, A, Whalley, G, Doughty, R, Tarantini, L, Granger, C, Køber, L, Massie, B, Pocock, S, Somaratne, J, Andersson, B, Bayes-Genis, A, Cowie, M, Cubbon, R, Gonzalez-Juanatey, J, Gorini, M, Gotsman, I, Grigorian-Shamagian, L, Guazzi, M, Kearney, M, Di Lenarda, A, Lenzen, M, Lucci, D, Macín, S, Madsen, B, Martínez-Sellés, M, Oliva, F, Rich, M, Richards, M, Senni, M, Taffet, G, Tribouilloy, C, Troughton, R, Tsutsui, H, Ariti, C, Dobson, J, Hall, C, Lainchbury, J, Hogg, K, Norrie, J, Stevenson, K, Brett, M, Pfeffer, M, Held, P, Michelson, E, Olofsson, B, Östergren, J, Yusuf, S, Torp-Pedersen, C, Scholte op Reimer, W, Boersma, E, Vantrimpont, P, Follath, F, Cleland, J, Zwas, D, Planer, D, Azaz-Livshits, T, Admon, D, Lotan, C, Keren, A, Varela-Roman, A, Mazón-Ramos, P, Rigeiro-Veloso, P, Bandin-Dieguez, M, Myers, J, Arena, R, Armstrong, P, Cujec, B, Paterson, I, Wood, D, Coats, A, Thompson, S, Suresh, V, Poole-Wilson, P, Sutton, G, Robles, J, Prieto, L, Muñoa, M, Frades, E, Díaz-Castro, O, Almendral, J, Faggiano, P, Bertoli, D, Porcu, M, Opasich, C, Tavazzi, L, Kirk, V, Bay, M, Parner, J, Krogsgaard, K, Herzog, T, Boesgaard, S, Hassager, C, Nielsen, O, Aldershvile, J, Nielsen, H, Kober, L, Perna, E, Cimbaro Canella, J, Alvarenga, P, Pantich, R, Ríos, N, Farias, E, Badaracco, J, Hansen, J, Stokholm, K, Brons, J, Husum, D, Mortensen, L, Vazquez, R, Puig, T, Fernandez-Palomeque, C, Bardají, A, Pascual-Figal, D, Ordoñez-Llanos, J, Valdes, M, Gabarrus, A, Pavon, R, Pastor, L, Fiol, M, Nieto, V, Macaya, C, Cinca, J, Cygankiewitz, I, Bayes De Luna, A, Newton, J, Blackledge, H, Wright, S, Kerzner, R, Gage, B, Freedland, K, Huynh, B, Rovner, A, Carney, R, Teasdale, T, Bleyer, A, Kutka, N, Luchi, R, Rusinaru, D, Mahjoub, H, Soulière, V, Lévy, F, Peltier, M, Tsuchihashi, M, Takeshita, A, Maccarthy, P, Nolan, J, Lee, A, Prescott, R, Shah, A, Brooksby, W, Fox, K, Basante, P, Trillo, R, Garcia-Seara, J, Martinez-Sande, J, Gude, F, Berry C, Poppe KK, Gamble GD, Earle NJ, Ezekowitz JA, Squire IB, McMurray JJV, McAlister FA, Komajda M, Swedberg K, Maggioni AP, Ahmed A, Whalley GA, Doughty RN, Tarantini L, Granger C, Køber L, Massie B, Pocock S, Somaratne J, Andersson B, Bayes-Genis A, Cowie M, Cubbon R, Gonzalez-Juanatey J, Gorini M, Gotsman I, Grigorian-Shamagian L, Guazzi M, Kearney M, Di Lenarda A, Lenzen M, Lucci D, Macín S, Madsen B, Martínez-Sellés M, Oliva F, Rich M, Richards M, Senni M, Taffet G, Tribouilloy C, Troughton R, Tsutsui H, Ariti C, Dobson J, Hall C, Lainchbury J, Hogg K, Norrie J, Stevenson K, Brett M, Pfeffer MA, Held P, Michelson EL, Olofsson B, Östergren J, Yusuf S, Torp-Pedersen C, Scholte op Reimer W, Boersma E, Vantrimpont PJMJ, Follath F, Cleland J, Zwas D, Planer D, Azaz-Livshits T, Admon D, Lotan C, Keren A, Varela-Roman A, Mazón-Ramos P, Rigeiro-Veloso P, Bandin-Dieguez MA, Myers J, Arena R, Armstrong PW, Cujec B, Paterson I, Wood DA, Coats AJS, Thompson SG, Suresh V, Poole-Wilson PA, Sutton GC, Robles JAG, Prieto L, Muñoa MD, Frades E, Díaz-Castro O, Almendral J, Faggiano P, Bertoli D, Porcu M, Opasich C, Tavazzi L, Kirk V, Bay M, Parner J, Krogsgaard K, Herzog TM, Boesgaard S, Hassager C, Nielsen OW, Aldershvile J, Nielsen H, Kober L, Perna ER, Cimbaro Canella JP, Alvarenga P, Pantich R, Ríos N, Farias EF, Badaracco JR, Hansen JF, Stokholm KH, Brons J, Husum D, Mortensen LS, Vazquez R, Puig T, Fernandez-Palomeque C, Bardají A, Pascual-Figal D, Ordoñez-Llanos J, Valdes M, Gabarrus A, Pavon R, Pastor L, Fiol M, Nieto V, Macaya C, Cinca J, Cygankiewitz I, Bayes De Luna A, Newton JD, Blackledge HM, Wright SP, Kerzner R, Gage BF, Freedland KE, Huynh BC, Rovner A, Carney RM, Teasdale TA, Bleyer AJ, Kutka NJ, Luchi RJ, Rusinaru D, Mahjoub H, Soulière V, Lévy F, Peltier M, Tsuchihashi M, Takeshita A, MacCarthy PA, Nolan J, Lee AJ, Prescott RJ, Shah AM, Brooksby WP, Fox KAA, Basante P, Trillo R, Garcia-Seara J, Martinez-Sande JL, and Gude F

Abstract

Background: Anaemia is common among patients with heart failure (HF) and is an important prognostic marker. Aim: We sought to determine the prognostic importance of anaemia in a large multinational pooled dataset of prospectively enrolled HF patients, with the specific aim to determine the prognostic role of anaemia in HF with preserved and reduced ejection fraction (HF-PEF and HF-REF, respectively). Design: Individual person data meta-analysis. Methods: Patients with haemoglobin (Hb) data fromthe MAGGIC dataset were used. Anaemia was defined as Hb < 120 g/l in women and <130 g/l inmen. HF-PEF was defined as EF ≥ 50%; HF-REF was EF < 50%. Cox proportional hazardmodelling, with adjustment for clinically relevant variables, was undertaken to investigate factors associated with 3-year all-causemortality. Results: Thirteen thousand two hundred and ninety-five patients with HF from 19 studies (9887 with HF-REF and 3408 with HF-PEF). The prevalence of anaemia was similar among those with HF-REF and HF-PEF (42.8 and 41.6% respectively). Compared with patients with normal Hb values, those with anaemia were older, were more likely to have diabetes, ischaemic aetiology, New York Heart Association class IV symptoms, lower estimated glomerular filtration rate and were more likely to be taking diuretic and less likely to be taking a beta-blocker. Patients with anaemia had higher all-cause mortality (adjusted hazard ratio [aHR] 1.38, 95% confidence interval [CI] 1.25-1.51), independent of EF group: aHR 1.67 (1.39-1.99) in HFPEF and aHR 2.49 (2.13-2.90) in HF-REF. Conclusions: Anaemia is an adverse prognostic factor in HF irrespective of EF. The prognostic importance of anaemia was greatest in patients with HF-REF.

Published
2016

6. Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitis

Author

Whitcomb, DC, LaRusch, J, Krasinskas, AM, Klei, L, Smith, JP, Brand, RE, Neoptolemos, JP, Lerch, MM, Tector, M, Sandhu, BS, Guda, NM, Orlichenko, L, Alkaade, S, Amann, ST, Anderson, MA, Baillie, J, Banks, PA, Conwell, D, Coté, GA, Cotton, PB, DiSario, J, Farrer, LA, Forsmark, CE, Johnstone, M, Gardner, TB, Gelrud, A, Greenhalf, W, Haines, JL, Hartman, DJ, Hawes, RA, Lawrence, C, Lewis, M, Mayerle, J, Mayeux, R, Melhem, NM, Money, ME, Muniraj, T, Papachristou, GI, Pericak-Vance, MA, Romagnuolo, J, Schellenberg, GD, Sherman, S, Simon, P, Singh, VP, Slivka, A, Stolz, D, Sutton, R, Weiss, FU, Wilcox, CM, Zarnescu, NO, Wisniewski, SR, O'Connell, MR, Kienholz, ML, Roeder, K, Barmada, MM, Yadav, D, Devlin, B, Albert, MS, Albin, RL, Apostolova, LG, Arnold, SE, Baldwin, CT, Barber, R, Barnes, LL, Beach, TG, Beecham, GW, Beekly, D, Bennett, DA, Bigio, EH, Bird, TD, Blacker, D, Boxer, A, Burke, JR, Buxbaum, JD, Cairns, NJ, Cantwell, LB, Cao, C, Carney, RM, Carroll, SL, Chui, HC, Clark, DG, Cribbs, DH, Crocco, EA, and Cruchaga, C

Abstract

Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR and SPINK1 variants were associated with pancreatitis risk. We now report two associations at genome-wide significance identified and replicated at PRSS1-PRSS2 (P < 1 × 10-12) and X-linked CLDN2 (P < 1 × 10-21) through a two-stage genome-wide study (stage 1: 676 cases and 4,507 controls; stage 2: 910 cases and 4,170 controls). The PRSS1 variant likely affects disease susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous (or hemizygous in males) CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men (male hemizygote frequency is 0.26, whereas female homozygote frequency is 0.07). © 2012 Nature America, Inc. All rights reserved.

Published
2012

7. The survival of patients with heart failure with preserved or reduced left ventricular ejection fraction: an individual patient data meta-analysis

Author

Granger, C, Massie, B, Somaratne, J, Ahmed, A, Cowie, M, Gonzalez-Juanatey, J, Gorini, M, Kearney, M, di Lenarda, A, Lenzen, M, Macin, S, Madsen, B, Maggioni, A, McAlister, F, Oliva, F, Rich, M, Richards, M, Squire, I, Taffet, G, Earle, N, Perera, K, Dobson, J, Pocock, S, Poppe, K, Whalley, G, Andersson, B, Hall, C, Richards, AM, Troughton, R, Lainchbury, J, Berry, C, Hogg, K, Norrie, J, Stevenson, K, Brett, M, McMurray, J, Pfeffer, MA, Granger, CB, Held, P, McMurray, JJV, Michelson, EL, Olofsson, B, Ostergren, J, Yusuf, S, Torp-Pedersen, C, Lenzen, MJ, Reimer, WJMS, Boersma, E, Vantrimpont, PJMJ, Follath, F, Swedberg, K, Cleland, J, Komajda, M, Gotsman, I, Zwas, D, Planer, D, Azaz-Livshits, T, Admon, D, Lotan, C, Keren, A, Grigorian-Shamagian, L, Mazon-Ramos, P, Rigeiro-Veloso, P, Bandin-Dieguez, MA, Guazzi, M, Myers, J, Arena, R, McAlister, FA, Ezekowitz, J, Armstrong, PW, Cujec, B, Paterson, I, Cowie, MR, Wood, DA, Coats, AJS, Thompson, SG, Suresh, V, Poole-Wilson, PA, Sutton, GC, Martinez-Selles, M, Robles, JAG, Prieto, L, Munoa, MD, Frades, E, Diaz-Castro, O, Tarantini, L, Faggiano, P, Senni, M, Lucci, D, Bertoli, D, Porcu, M, Opasich, C, Tavazzi, L, Maggioni, AP, Kirk, V, Bay, M, Parner, J, Krogsgaard, K, Herzog, TM, Boesgaard, S, Hassager, C, Nielsen, OW, Aldershvile, J, Nielsen, H, Kober, L, Macin, SM, Perna, ER, Canella, JPC, Alvarenga, P, Pantich, R, Rios, N, Farias, EF, Badaracco, JR, Madsen, BK, Hansen, JF, Stokholm, KH, Brons, J, Husum, D, Mortensen, LS, Bayes-Genis, A, Vazquez, R, Puig, T, Fernandez-Palomeque, C, Bardaji, A, Pascual-Figal, D, Ordonez-Llanos, J, Valdes, M, Gabarrus, A, Pavon, R, Pastor, L, Almendral, J, Fiol, M, Nieto, V, Macaya, C, Cinca, J, de Luna, AB, Newton, JD, Blackledge, HM, Squire, IB, Wright, SP, Whalley, GA, Doughty, RN, Kerzner, R, Gage, BF, Huynh, BC, Rovner, A, Freedland, KE, Carney, RM, Rich, MW, Taffet, GE, Teasdale, TA, Bleyer, AJ, Kutka, NJ, Luchi, RJ, Tribouilloy, C, Rusinaru, D, Mahjoub, H, Souliere, V, Levy, F, Peltier, M, Tsutsui, H, Tsuchihashi, M, Takeshita, A, MacCarthy, PA, Kearney, MT, Cubbon, R, Nolan, J, Lee, AJ, Prescott, RJ, Shah, AM, Brooksby, WP, Fox, KAA, Varela-Roman, A, Gonzalez-Juanatey, JR, Basante, P, Trillo, R, Garcia-Seara, J, Martinez-Sande, JL, and Gude, F

Subjects
Meta-analysis, Heart failure, Prognosis
Abstract

A substantial proportion of patients with heart failure have preserved left ventricular ejection fraction (HF-PEF). Previous studies have reported mixed results whether survival is similar to those patients with heart failure and reduced EF (HF-REF). We compared survival in patients with HF-PEF with that in patients with HF-REF in a meta-analysis using individual patient data. Preserved EF was defined as an EF epsilon 50. The 31 studies included 41 972 patients: 10 347 with HF-PEF and 31 625 with HF-REF. Compared with patients with HF-REF, those with HF-PEF were older (mean age 71 vs. 66 years), were more often women (50 vs. 28), and have a history of hypertension (51 vs. 41). Ischaemic aetiology was less common (43 vs. 59) in patients with HF-PEF. There were 121 [95 confidence interval (CI): 117, 126] deaths per 1000 patient-years in those with HF-PEF and 141 (95 CI: 138, 144) deaths per 1000 patient-years in those with HF-REF. Patients with HF-PEF had lower mortality than those with HF-REF (adjusted for age, gender, aetiology, and history of hypertension, diabetes, and atrial fibrillation); hazard ratio 0.68 (95 CI: 0.64, 0.71). The risk of death did not increase notably until EF fell below 40. Patients with HF-PEF have a lower risk of death than patients with HF-REF, and this difference is seen regardless of age, gender, and aetiology of HF. However, absolute mortality is still high in patients with HF-PEF highlighting the need for a treatment to improve prognosis.

Published
2012

8. The survival of patients with heart failure with preserved or reduced left ventricular ejection fraction: an individual patient data meta-analysis

Author

Berry C, Doughty RN, Granger C, Kober L, Massie B, McAlister F, McMurray J, Pocock S, Poppe K, Swedberg K, Somaratne J, Whalley GA, Ahmed A, Andersson B, Bayes-Genis A, Cowie M, Cubbon R, Ezekowitz J, Gonzalez-Juanatey J, Gorini M, Gotsman I, Grigorian-Shamagian L, Guazzi M, Kearney M, Komajda M, di Lenarda A, Lenzen M, Lucci D, Macin S, Madsen B, Maggioni A, Martinez-Selles M, Oliva F, Rich M, Richards M, Senni M, Squire I, Taffet G, Tarantini L, Tribouilloy C, Troughton R, Tsutsui H, Earle N, Perera K, Dobson J, Whalley G, Hall C, Richards AM, Lainchbury J, Hogg K, Norrie J, Stevenson K, Brett M, Pfeffer MA, Granger CB, Held P, McMurray JJV, Michelson EL, Olofsson B, Ostergren J, Yusuf S, Torp-Pedersen C, Lenzen MJ, Reimer WJMS, Boersma E, Vantrimpont PJMJ, Follath F, Cleland J, Zwas D, Planer D, Azaz-Livshits T, Admon D, Lotan C, Keren A, Varela-Roman A, Mazon-Ramos P, Rigeiro-Veloso P, Bandin-Dieguez MA, Gonzalez-Juanatey JR, Myers J, Arena R, McAlister FA, Armstrong PW, Cujec B, Paterson I, Cowie MR, Wood DA, Coats AJS, Thompson SG, Suresh V, Poole-Wilson PA, Sutton GC, Robles JAG, Prieto L, Munoa MD, Frades E, Diaz-Castro O, Almendral J, Faggiano P, Bertoli D, Porcu M, Opasich C, Tavazzi L, Maggioni AP, Kirk V, Bay M, Parner J, Krogsgaard K, Herzog TM, Boesgaard S, Hassager C, Nielsen OW, Aldershvile J, Nielsen H, Macin SM, Perna ER, Canella JPC, Alvarenga P, Pantich R, Rios N, Farias EF, Badaracco JR, Madsen BK, Hansen JF, Stokholm KH, Brons J, Husum D, Mortensen LS, Vazquez R, Puig T, Fernandez-Palomeque C, Bardaji A, Pascual-Figal D, Ordonez-Llanos J, Valdes M, Gabarrus A, Pavon R, Pastor L, Fiol M, Nieto V, Macaya C, Cinca J, de Luna AB, Newton JD, Blackledge HM, Squire IB, Wright SP, Kerzner R, Gage BF, Freedland KE, Rich MW, Huynh BC, Rovner A, Carney RM, Taffet GE, Teasdale TA, Bleyer AJ, Kutka NJ, Luchi RJ, Rusinaru D, Mahjoub H, Souliere V, Levy F, Peltier M, Tsuchihashi M, Takeshita A, MacCarthy PA, Kearney MT, Nolan J, Lee AJ, Prescott RJ, Shah AM, Brooksby WP, Fox KAA, Basante P, Trillo R, Garcia-Seara J, Martinez-Sande JL, Gude F, Berry, C, Doughty, R, Granger, C, Kober, L, Massie, B, Mcalister, F, Mcmurray, J, Pocock, S, Poppe, K, Swedberg, K, Somaratne, J, Whalley, G, Ahmed, A, Andersson, B, Bayes-Genis, A, Cowie, M, Cubbon, R, Ezekowitz, J, Gonzalez-Juanatey, J, Gorini, M, Gotsman, I, Grigorian-Shamagian, L, Guazzi, M, Kearney, M, Komajda, M, di Lenarda, A, Lenzen, M, Lucci, D, Macin, S, Madsen, B, Maggioni, A, Martinez-Selles, M, Oliva, F, Rich, M, Richards, M, Senni, M, Squire, I, Taffet, G, Tarantini, L, Tribouilloy, C, Troughton, R, Tsutsui, H, Earle, N, Perera, K, Dobson, J, Hall, C, Richards, A, Lainchbury, J, Hogg, K, Norrie, J, Stevenson, K, Brett, M, Pfeffer, M, Held, P, Michelson, E, Olofsson, B, Ostergren, J, Yusuf, S, Torp-Pedersen, C, Reimer, W, Boersma, E, Vantrimpont, P, Follath, F, Cleland, J, Zwas, D, Planer, D, Azaz-Livshits, T, Admon, D, Lotan, C, Keren, A, Varela-Roman, A, Mazon-Ramos, P, Rigeiro-Veloso, P, Bandin-Dieguez, M, Myers, J, Arena, R, Armstrong, P, Cujec, B, Paterson, I, Wood, D, Coats, A, Thompson, S, Suresh, V, Poole-Wilson, P, Sutton, G, Robles, J, Prieto, L, Munoa, M, Frades, E, Diaz-Castro, O, Almendral, J, Faggiano, P, Bertoli, D, Porcu, M, Opasich, C, Tavazzi, L, Kirk, V, Bay, M, Parner, J, Krogsgaard, K, Herzog, T, Boesgaard, S, Hassager, C, Nielsen, O, Aldershvile, J, Nielsen, H, Perna, E, Canella, J, Alvarenga, P, Pantich, R, Rios, N, Farias, E, Badaracco, J, Hansen, J, Stokholm, K, Brons, J, Husum, D, Mortensen, L, Vazquez, R, Puig, T, Fernandez-Palomeque, C, Bardaji, A, Pascual-Figal, D, Ordonez-Llanos, J, Valdes, M, Gabarrus, A, Pavon, R, Pastor, L, Fiol, M, Nieto, V, Macaya, C, Cinca, J, de Luna, A, Newton, J, Blackledge, H, Wright, S, Kerzner, R, Gage, B, Freedland, K, Huynh, B, Rovner, A, Carney, R, Teasdale, T, Bleyer, A, Kutka, N, Luchi, R, Rusinaru, D, Mahjoub, H, Souliere, V, Levy, F, Peltier, M, Tsuchihashi, M, Takeshita, A, Maccarthy, P, Nolan, J, Lee, A, Prescott, R, Shah, A, Brooksby, W, Fox, K, Basante, P, Trillo, R, Garcia-Seara, J, Martinez-Sande, J, and Gude, F

Subjects
Male, medicine.medical_specialty, Prognosi, Heart failure, Lower risk, Risk Factors, Cause of Death, Internal medicine, medicine, Humans, Meta-analysi, Aged, Randomized Controlled Trials as Topic, Ejection fraction, business.industry, Hazard ratio, Stroke Volume, Atrial fibrillation, medicine.disease, Confidence interval, Meta-analysis, Cardiology, Etiology, Female, Cardiology and Cardiovascular Medicine, business
Abstract

Aims A substantial proportion of patients with heart failure have preserved left ventricular ejection fraction (HF-PEF). Previous studies have reported mixed results whether survival is similar to those patients with heart failure and reduced EF (HF-REF). Methods and results We compared survival in patients with HF-PEF with that in patients with HF-REF in a meta-analysis using individual patient data. Preserved EF was defined as an EF ≥ 50%. The 31 studies included 41 972 patients: 10 347 with HF-PEF and 31 625 with HF-REF. Compared with patients with HF-REF, those with HF-PEF were older (mean age 71 vs. 66 years), were more often women (50 vs. 28%), and have a history of hypertension (51 vs. 41%). Ischaemic aetiology was less common (43 vs. 59%) in patients with HF-PEF. There were 121 [95% confidence interval (CI): 117, 126] deaths per 1000 patient-years in those with HF-PEF and 141 (95% CI: 138, 144) deaths per 1000 patient-years in those with HF-REF. Patients with HF-PEF had lower mortality than those with HF-REF (adjusted for age, gender, aetiology, and history of hypertension, diabetes, and atrial fibrillation); hazard ratio 0.68 (95% CI: 0.64, 0.71). The risk of death did not increase notably until EF fell below 40%. Conclusion Patients with HF-PEF have a lower risk of death than patients with HF-REF, and this difference is seen regardless of age, gender, and aetiology of HF. However, absolute mortality is still high in patients with HF-PEF highlighting the need for a treatment to improve prognosis.

Published
2012

9. Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease

Author

Naj, AC, Jun, G, Beecham, GW, Wang, LS, Vardarajan, BN, Buros, J, Gallins, PJ, Buxbaum, JD, Jarvik, GP, Crane, PK, Larson, EB, Bird, TD, Boeve, BF, Graff-Radford, NR, De Jager, PL, Evans, D, Schneider, JA, Carrasquillo, MM, Ertekin-Taner, N, Younkin, SG, Cruchaga, C, Kauwe, JSK, Nowotny, P, Kramer, P, Hardy, J, Huentelman, MJ, Myers, AJ, Barmada, MM, Demirci, FY, Baldwin, CT, Green, RC, Rogaeva, E, George-Hyslop, PS, Arnold, SE, Barber, R, Beach, T, Bigio, EH, Bowen, JD, Boxer, A, Burke, JR, Cairns, NJ, Carlson, CS, Carney, RM, Carroll, SL, Chui, HC, Clark, DG, Corneveaux, J, Cotman, CW, Cummings, JL, Decarli, C, Dekosky, ST, Diaz-Arrastia, R, Dick, M, Dickson, DW, Ellis, WG, Faber, KM, Fallon, KB, Farlow, MR, Ferris, S, Frosch, MP, Galasko, DR, Ganguli, M, Gearing, M, Geschwind, DH, Ghetti, B, Gilbert, JR, Gilman, S, Giordani, B, Glass, JD, Growdon, JH, Hamilton, RL, Harrell, LE, Head, E, Honig, LS, Hulette, CM, Hyman, BT, Jicha, GA, Jin, LW, Johnson, N, Karlawish, J, Karydas, A, Kaye, JA, and Kim, R

Abstract

The Alzheimer Disease Genetics Consortium (ADGC) performed a genome-wide association study of late-onset Alzheimer disease using a three-stage design consisting of a discovery stage (stage 1) and two replication stages (stages 2 and 3). Both joint analysis and meta-analysis approaches were used. We obtained genome-wide significant results at MS4A4A (rs4938933; stages 1 and 2, meta-analysis P (P M) = 1.7 × 10 -9, joint analysis P (P J) = 1.7 × 10 -9; stages 1, 2 and 3, P M = 8.2 × 10 -12), CD2AP (rs9349407; stages 1, 2 and 3, P M = 8.6 × 10 -9), EPHA1 (rs11767557; stages 1, 2 and 3, P M = 6.0 × 10 -10) and CD33 (rs3865444; stages 1, 2 and 3, P M = 1.6 × 10 -9). We also replicated previous associations at CR1 (rs6701713; P M = 4.6 × 10 -10, P J = 5.2 × 10 -11), CLU (rs1532278; P M = 8.3 × 10 -8, P J = 1.9 × 10 -8), BIN1 (rs7561528; P M = 4.0 × 10 -14, P J = 5.2 × 10 -14) and PICALM (rs561655; P M = 7.0 × 10 -11, P J = 1.0 × 10 -10), but not at EXOC3L2, to late-onset Alzheimer's disease susceptibility. © 2011 Nature America, Inc. All rights reserved.

Published
2011

10. The survival of patients with heart failure with preserved or reduced left ventricular ejection fraction: an individual patient data meta-analysis

Author

Berry, C, Doughty, R, Granger, C, Kober, L, Massie, B, Mcalister, F, Mcmurray, J, Pocock, S, Poppe, K, Swedberg, K, Somaratne, J, Whalley, G, Ahmed, A, Andersson, B, Bayes-Genis, A, Cowie, M, Cubbon, R, Ezekowitz, J, Gonzalez-Juanatey, J, Gorini, M, Gotsman, I, Grigorian-Shamagian, L, Guazzi, M, Kearney, M, Komajda, M, di Lenarda, A, Lenzen, M, Lucci, D, Macin, S, Madsen, B, Maggioni, A, Martinez-Selles, M, Oliva, F, Rich, M, Richards, M, Senni, M, Squire, I, Taffet, G, Tarantini, L, Tribouilloy, C, Troughton, R, Tsutsui, H, Earle, N, Perera, K, Dobson, J, Hall, C, Richards, A, Lainchbury, J, Hogg, K, Norrie, J, Stevenson, K, Brett, M, Pfeffer, M, Held, P, Michelson, E, Olofsson, B, Ostergren, J, Yusuf, S, Torp-Pedersen, C, Reimer, W, Boersma, E, Vantrimpont, P, Follath, F, Cleland, J, Zwas, D, Planer, D, Azaz-Livshits, T, Admon, D, Lotan, C, Keren, A, Varela-Roman, A, Mazon-Ramos, P, Rigeiro-Veloso, P, Bandin-Dieguez, M, Myers, J, Arena, R, Armstrong, P, Cujec, B, Paterson, I, Wood, D, Coats, A, Thompson, S, Suresh, V, Poole-Wilson, P, Sutton, G, Robles, J, Prieto, L, Munoa, M, Frades, E, Diaz-Castro, O, Almendral, J, Faggiano, P, Bertoli, D, Porcu, M, Opasich, C, Tavazzi, L, Kirk, V, Bay, M, Parner, J, Krogsgaard, K, Herzog, T, Boesgaard, S, Hassager, C, Nielsen, O, Aldershvile, J, Nielsen, H, Perna, E, Canella, J, Alvarenga, P, Pantich, R, Rios, N, Farias, E, Badaracco, J, Hansen, J, Stokholm, K, Brons, J, Husum, D, Mortensen, L, Vazquez, R, Puig, T, Fernandez-Palomeque, C, Bardaji, A, Pascual-Figal, D, Ordonez-Llanos, J, Valdes, M, Gabarrus, A, Pavon, R, Pastor, L, Fiol, M, Nieto, V, Macaya, C, Cinca, J, de Luna, A, Newton, J, Blackledge, H, Wright, S, Kerzner, R, Gage, B, Freedland, K, Huynh, B, Rovner, A, Carney, R, Teasdale, T, Bleyer, A, Kutka, N, Luchi, R, Rusinaru, D, Mahjoub, H, Souliere, V, Levy, F, Peltier, M, Tsuchihashi, M, Takeshita, A, Maccarthy, P, Nolan, J, Lee, A, Prescott, R, Shah, A, Brooksby, W, Fox, K, Basante, P, Trillo, R, Garcia-Seara, J, Martinez-Sande, J, Gude, F, Berry C, Doughty RN, Granger C, Kober L, Massie B, McAlister F, McMurray J, Pocock S, Poppe K, Swedberg K, Somaratne J, Whalley GA, Ahmed A, Andersson B, Bayes-Genis A, Cowie M, Cubbon R, Ezekowitz J, Gonzalez-Juanatey J, Gorini M, Gotsman I, Grigorian-Shamagian L, Guazzi M, Kearney M, Komajda M, di Lenarda A, Lenzen M, Lucci D, Macin S, Madsen B, Maggioni A, Martinez-Selles M, Oliva F, Rich M, Richards M, Senni M, Squire I, Taffet G, Tarantini L, Tribouilloy C, Troughton R, Tsutsui H, Earle N, Perera K, Dobson J, Whalley G, Hall C, Richards AM, Lainchbury J, Hogg K, Norrie J, Stevenson K, Brett M, Pfeffer MA, Granger CB, Held P, McMurray JJV, Michelson EL, Olofsson B, Ostergren J, Yusuf S, Torp-Pedersen C, Lenzen MJ, Reimer WJMS, Boersma E, Vantrimpont PJMJ, Follath F, Cleland J, Zwas D, Planer D, Azaz-Livshits T, Admon D, Lotan C, Keren A, Varela-Roman A, Mazon-Ramos P, Rigeiro-Veloso P, Bandin-Dieguez MA, Gonzalez-Juanatey JR, Myers J, Arena R, McAlister FA, Armstrong PW, Cujec B, Paterson I, Cowie MR, Wood DA, Coats AJS, Thompson SG, Suresh V, Poole-Wilson PA, Sutton GC, Robles JAG, Prieto L, Munoa MD, Frades E, Diaz-Castro O, Almendral J, Faggiano P, Bertoli D, Porcu M, Opasich C, Tavazzi L, Maggioni AP, Kirk V, Bay M, Parner J, Krogsgaard K, Herzog TM, Boesgaard S, Hassager C, Nielsen OW, Aldershvile J, Nielsen H, Macin SM, Perna ER, Canella JPC, Alvarenga P, Pantich R, Rios N, Farias EF, Badaracco JR, Madsen BK, Hansen JF, Stokholm KH, Brons J, Husum D, Mortensen LS, Vazquez R, Puig T, Fernandez-Palomeque C, Bardaji A, Pascual-Figal D, Ordonez-Llanos J, Valdes M, Gabarrus A, Pavon R, Pastor L, Fiol M, Nieto V, Macaya C, Cinca J, de Luna AB, Newton JD, Blackledge HM, Squire IB, Wright SP, Kerzner R, Gage BF, Freedland KE, Rich MW, Huynh BC, Rovner A, Carney RM, Taffet GE, Teasdale TA, Bleyer AJ, Kutka NJ, Luchi RJ, Rusinaru D, Mahjoub H, Souliere V, Levy F, Peltier M, Tsuchihashi M, Takeshita A, MacCarthy PA, Kearney MT, Nolan J, Lee AJ, Prescott RJ, Shah AM, Brooksby WP, Fox KAA, Basante P, Trillo R, Garcia-Seara J, Martinez-Sande JL, Gude F, Berry, C, Doughty, R, Granger, C, Kober, L, Massie, B, Mcalister, F, Mcmurray, J, Pocock, S, Poppe, K, Swedberg, K, Somaratne, J, Whalley, G, Ahmed, A, Andersson, B, Bayes-Genis, A, Cowie, M, Cubbon, R, Ezekowitz, J, Gonzalez-Juanatey, J, Gorini, M, Gotsman, I, Grigorian-Shamagian, L, Guazzi, M, Kearney, M, Komajda, M, di Lenarda, A, Lenzen, M, Lucci, D, Macin, S, Madsen, B, Maggioni, A, Martinez-Selles, M, Oliva, F, Rich, M, Richards, M, Senni, M, Squire, I, Taffet, G, Tarantini, L, Tribouilloy, C, Troughton, R, Tsutsui, H, Earle, N, Perera, K, Dobson, J, Hall, C, Richards, A, Lainchbury, J, Hogg, K, Norrie, J, Stevenson, K, Brett, M, Pfeffer, M, Held, P, Michelson, E, Olofsson, B, Ostergren, J, Yusuf, S, Torp-Pedersen, C, Reimer, W, Boersma, E, Vantrimpont, P, Follath, F, Cleland, J, Zwas, D, Planer, D, Azaz-Livshits, T, Admon, D, Lotan, C, Keren, A, Varela-Roman, A, Mazon-Ramos, P, Rigeiro-Veloso, P, Bandin-Dieguez, M, Myers, J, Arena, R, Armstrong, P, Cujec, B, Paterson, I, Wood, D, Coats, A, Thompson, S, Suresh, V, Poole-Wilson, P, Sutton, G, Robles, J, Prieto, L, Munoa, M, Frades, E, Diaz-Castro, O, Almendral, J, Faggiano, P, Bertoli, D, Porcu, M, Opasich, C, Tavazzi, L, Kirk, V, Bay, M, Parner, J, Krogsgaard, K, Herzog, T, Boesgaard, S, Hassager, C, Nielsen, O, Aldershvile, J, Nielsen, H, Perna, E, Canella, J, Alvarenga, P, Pantich, R, Rios, N, Farias, E, Badaracco, J, Hansen, J, Stokholm, K, Brons, J, Husum, D, Mortensen, L, Vazquez, R, Puig, T, Fernandez-Palomeque, C, Bardaji, A, Pascual-Figal, D, Ordonez-Llanos, J, Valdes, M, Gabarrus, A, Pavon, R, Pastor, L, Fiol, M, Nieto, V, Macaya, C, Cinca, J, de Luna, A, Newton, J, Blackledge, H, Wright, S, Kerzner, R, Gage, B, Freedland, K, Huynh, B, Rovner, A, Carney, R, Teasdale, T, Bleyer, A, Kutka, N, Luchi, R, Rusinaru, D, Mahjoub, H, Souliere, V, Levy, F, Peltier, M, Tsuchihashi, M, Takeshita, A, Maccarthy, P, Nolan, J, Lee, A, Prescott, R, Shah, A, Brooksby, W, Fox, K, Basante, P, Trillo, R, Garcia-Seara, J, Martinez-Sande, J, Gude, F, Berry C, Doughty RN, Granger C, Kober L, Massie B, McAlister F, McMurray J, Pocock S, Poppe K, Swedberg K, Somaratne J, Whalley GA, Ahmed A, Andersson B, Bayes-Genis A, Cowie M, Cubbon R, Ezekowitz J, Gonzalez-Juanatey J, Gorini M, Gotsman I, Grigorian-Shamagian L, Guazzi M, Kearney M, Komajda M, di Lenarda A, Lenzen M, Lucci D, Macin S, Madsen B, Maggioni A, Martinez-Selles M, Oliva F, Rich M, Richards M, Senni M, Squire I, Taffet G, Tarantini L, Tribouilloy C, Troughton R, Tsutsui H, Earle N, Perera K, Dobson J, Whalley G, Hall C, Richards AM, Lainchbury J, Hogg K, Norrie J, Stevenson K, Brett M, Pfeffer MA, Granger CB, Held P, McMurray JJV, Michelson EL, Olofsson B, Ostergren J, Yusuf S, Torp-Pedersen C, Lenzen MJ, Reimer WJMS, Boersma E, Vantrimpont PJMJ, Follath F, Cleland J, Zwas D, Planer D, Azaz-Livshits T, Admon D, Lotan C, Keren A, Varela-Roman A, Mazon-Ramos P, Rigeiro-Veloso P, Bandin-Dieguez MA, Gonzalez-Juanatey JR, Myers J, Arena R, McAlister FA, Armstrong PW, Cujec B, Paterson I, Cowie MR, Wood DA, Coats AJS, Thompson SG, Suresh V, Poole-Wilson PA, Sutton GC, Robles JAG, Prieto L, Munoa MD, Frades E, Diaz-Castro O, Almendral J, Faggiano P, Bertoli D, Porcu M, Opasich C, Tavazzi L, Maggioni AP, Kirk V, Bay M, Parner J, Krogsgaard K, Herzog TM, Boesgaard S, Hassager C, Nielsen OW, Aldershvile J, Nielsen H, Macin SM, Perna ER, Canella JPC, Alvarenga P, Pantich R, Rios N, Farias EF, Badaracco JR, Madsen BK, Hansen JF, Stokholm KH, Brons J, Husum D, Mortensen LS, Vazquez R, Puig T, Fernandez-Palomeque C, Bardaji A, Pascual-Figal D, Ordonez-Llanos J, Valdes M, Gabarrus A, Pavon R, Pastor L, Fiol M, Nieto V, Macaya C, Cinca J, de Luna AB, Newton JD, Blackledge HM, Squire IB, Wright SP, Kerzner R, Gage BF, Freedland KE, Rich MW, Huynh BC, Rovner A, Carney RM, Taffet GE, Teasdale TA, Bleyer AJ, Kutka NJ, Luchi RJ, Rusinaru D, Mahjoub H, Souliere V, Levy F, Peltier M, Tsuchihashi M, Takeshita A, MacCarthy PA, Kearney MT, Nolan J, Lee AJ, Prescott RJ, Shah AM, Brooksby WP, Fox KAA, Basante P, Trillo R, Garcia-Seara J, Martinez-Sande JL, and Gude F

Abstract

Aims: A substantial proportion of patients with heart failure have preserved left ventricular ejection fraction (HF-PEF). Previous studies have reportedmixed resultswhether survival is similar to those patientswith heart failure and reduced EF (HF-REF). Methods and results: We compared survival in patients with HF-PEF with that in patients with HF-REF in a meta-analysis using individual patient data. Preserved EF was defined as an EF ≥ 50%. The 31 studies included 41 972 patients: 10 347 with HF-PEF and 31 625 with HF-REF. Compared with patients with HF-REF, those with HF-PEF were older (mean age 71 vs. 66 years), were more often women (50 vs. 28%), and have a history of hypertension (51 vs. 41%). Ischaemic aetiology was less common (43 vs. 59%) in patients with HF-PEF. There were 121 [95% confidence interval (CI): 117, 126] deaths per 1000 patient-years in those with HF-PEF and 141 (95% CI: 138, 144) deaths per 1000 patient-years in those with HF-REF. Patients with HF-PEF had lower mortality than those with HF-REF (adjusted for age, gender, aetiology, and history of hypertension, diabetes, and atrial fibrillation); hazard ratio 0.68 (95% CI: 0.64, 0.71). The risk of death did not increase notably until EF fell below 40%. Conclusion: Patients with HF-PEF have a lower risk of death than patients with HF-REF, and this difference is seen regardless of age, gender, and aetiology of HF. However, absolute mortality is still high in patients with HF-PEF highlighting the need for a treatment to improve prognosis.

Published
2012

16. Omega-3 augmentation of sertraline in treatment of depression in patients with coronary heart disease: a randomized controlled trial.

Author

Carney RM, Freedland KE, Rubin EH, Rich MW, Steinmeyer BC, Harris WS, Carney, Robert M, Freedland, Kenneth E, Rubin, Eugene H, Rich, Michael W, Steinmeyer, Brian C, and Harris, William S

Abstract

Context: Studies of depressed psychiatric patients have shown that antidepressant efficacy can be increased by augmentation with omega-3 fatty acids.Objective: To determine whether omega-3 improves the response to sertraline in patients with major depression and coronary heart disease (CHD).Design, Setting, and Participants: Randomized controlled trial. Between May 2005 and December 2008, 122 patients in St Louis, Missouri, with major depression and CHD were randomized.Interventions: After a 2-week run-in period, all patients were given 50 mg/d of sertraline and randomized in double-blind fashion to receive 2 g/d of omega-3 acid ethyl esters (930 mg of eicosapentaenoic acid [EPA] and 750 mg of docosahexaenoic acid [DHA]) (n=62) or to corn oil placebo capsules (n=60) for 10 weeks.Main Outcome Measures: Scores on the Beck Depression Inventory (BDI-II) and the Hamilton Rating Scale for Depression (HAM-D).Results: Adherence to the medication regimen was 97% or more in both groups for both medications. There were no differences in weekly BDI-II scores (treatment x time interaction = 0.02; 95% confidence interval [CI], -0.33 to 0.36; t(112) = 0.11; P = .91), pre-post BDI-II scores (placebo, 14.8 vs omega-3, 16.1; 95% difference-in-means CI, -4.5 to 2.0; t(116) = -0.77; P = .44), or HAM-D scores (placebo, 9.4 vs omega-3, 9.3; 95% difference-in-means CI, -2.2 to 2.4; t(115) = 0.12; P = .90). The groups did not differ on predefined indicators of depression remission (BDI-II < or = 8: placebo, 27.4% vs omega-3, 28.3%; odds ratio [OR], 0.96; 95% CI, 0.43-2.15; t(113) = -0.11; P = .91) or response (> 50% reduction in BDI-II from baseline: placebo, 49.0% vs omega-3, 47.7%; OR, 1.06; 95% CI, 0.51-2.19; t(112) = 0.15; P = .88).Conclusions: Treatment of patients with CHD and major depression with sertraline and omega-3 fatty acids did not result in superior depression outcomes at 10 weeks, compared with sertraline and placebo. Whether higher doses of omega-3 or sertraline, a different ratio of EPA to DHA, longer treatment, or omega-3 monotherapy can improve depression in patients with CHD remains to be determined.Trial Registration: clinicaltrials.gov Identifier: NCT00116857. [ABSTRACT FROM AUTHOR]

Published
2009
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25. Effects of anxiety and depression on heart disease attributions.

Author

Day RC, Freedland KE, and Carney RM

Abstract

Cardiac patients' beliefs about the causes of their illness may influence their receptivity to psychosocial interventions. The purpose of this study was to determine whether depression or anxiety influence patients' attributions about the causes of their heart disease. The primary hypothesis was that depressed or anxious patients are more likely to endorse negative emotions as among the causes of their heart disease than are patients who are not depressed or anxious. Sixty-nine patients with documented ischemic heart disease recruited from an exercise stress testing laboratory completed the Beck Depression and Anxiety Inventories and a heart disease attribution checklist. Univariate analyses confirmed that patients who are depressed or anxious are more likely than other patients to endorse negative emotions as causes of their heart disease. Anxiety but not depression was retained as an independent predictor of negative emotion attributions in a logistic regression analysis. We conclude that mood state influences cardiac patients' beliefs about the causes of their heart disease. [ABSTRACT FROM AUTHOR]

Published
2005
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34. Depression and poor glycemic control: a meta-analytic review of the literature.

Author

Lustman PJ, Anderson RJ, Freedland KE, de Groot M, Carney RM, Clouse RE, Lustman, P J, Anderson, R J, Freedland, K E, de Groot, M, Carney, R M, and Clouse, R E

Abstract

Objective: Depression is common among patients with diabetes, but its relationship to glycemic control has not been systematically reviewed. Our objective was to determine whether depression is associated with poor glycemic control.Research Design and Methods: Medline and PsycINFO databases and published reference lists were used to identify studies that measured the association of depression with glycemic control. Meta-analytic procedures were used to convert the findings to a common metric, calculate effect sizes (ESs), and statistically analyze the collective data.Results: A total of 24 studies satisfied the inclusion and exclusion criteria for the meta-analysis. Depression was significantly associated with hyperglycemia (Z = 5.4, P < 0.0001). The standardized ES was in the small-to-moderate range (0.17) and was consistent, as the 95% CI was narrow (0.13-0.21). The ES was similar in studies of either type 1 or type 2 diabetes (ES 0.19 vs. 0.16) and larger when standardized interviews and diagnostic criteria rather than self-report questionnaires were used to assess depression (ES 0.28 vs. 0.15).Conclusions: Depression is associated with hyperglycemia in patients with type 1 or type 2 diabetes. Additional studies are needed to establish the directional nature of this relationship and to determine the effects of depression treatment on glycemic control and the long-term course of diabetes. [ABSTRACT FROM AUTHOR]

Published
2000
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35. New CAD risk factors: interesting, but how useful?

Author

Carney RM, Cohen JD, and Rosenson R

Abstract

Homocysteine, Lp(a), infectious agents, emotional state--these and other factors have all been linked to an increased risk of coronary artery disease. Should you be screening patients for more than the traditional risk factors? If so, what can you do with this information? [ABSTRACT FROM AUTHOR]

Published
1998

38. Meta-analysis of genetic association with diagnosed Alzheimer’s disease identifies novel risk loci and implicates Abeta, Tau, immunity and lipid processing

Author

Kunkle, BW, Grenier-Boley, B, Sims, R, Bis, JC, Naj, AC, Boland, A, Vronskaya, M, Van Der Lee, SJ, Amlie-Wolf, A, Bellenguez, C, Frizatti, A, Chouraki, V, Martin, ER, Sleegers, K, Badarinarayan, N, Jakobsdottir, J, Hamilton-Nelson, KL, Aloso, R, Raybould, R, Chen, Y, Kuzma, AB, Hiltunen, M, Morgan, T, Ahmad, S, Vardarajan, BN, Epelbaum, J, Hoffmann, P, Boada, M, Beecham, GW, Garnier, JG, Harold, D, Fitzpatrick, AL, Valladares, O, Moutet, ML, Gerrish, A, Smith, AV, Qu, L, Bacq, D, Denning, N, Jian, X, Zhao, Y, Zompo, MD, Fox, NC, Grove, ML, Choi, SH, Mateo, I, Hughes, JT, Adams, HH, Malamon, J, Garcia, FS, Patel, Y, Brody, JA, Dombroski, B, Naranjo, MCD, Daniilidou, M, Eiriksdottir, G, Mukherjee, S, Wallon, D, Uphill, J, Aspelund, T, Cantwell, LB, Garzia, F, Galimberti, D, Hofer, E, Butkiewics, M, Fin, B, Scarpini, E, Sarnowski, C, Bush, W, Meslage, S, Kornhuber, J, White, CC, Song, Y, Barber, RC, Engelborghs, S, Pichler, S, Voijnovic, D, Adams, PM, Vandenberghe, R, Mayhaus, M, Cupples, LA, Albert, MS, De Deyn, PP, Gu, W, Himali, JJ, Beekly, D, Squassina, A, Hartmann, AM, Orellana, A, Blacker, D, Rodriguez-Rodriguez, E, Lovestone, S, Garcia, ME, Doody, RS, Fernadez, CM, Sussams, R, Lin, H, Fairchild, TJ, Benito, YA, Holmes, C, Comic, H, Frosch, MP, Thonberg, H, Maier, W, Roschupkin, G, Ghetti, B, Giedraitis, V, Kawalia, A, Li, S, Huebinger, RM, Kilander, L, Moebus, S, Hernández, I, Kamboh, MI, Brundin, R, Turton, J, Yang, Q, Katz, MJ, Concari, L, Lord, J, Beiser, AS, Keene, CD, Helisalmi, S, Kloszewska, I, Kukull, WA, Koivisto, AM, Lynch, A, Tarraga, L, Larson, EB, Haapasalo, A, Lawlor, B, Mosley, TH, Lipton, RB, Solfrizzi, V, Gill, M, Longstreth, WT, Montine, TJ, Frisardi, V, Ortega-Cubero, S, Rivadeneira, F, Petersen, RC, Deramecourt, V, Ciaramella, A, Boerwinkle, E, Reiman, EM, Fievet, N, Caltagirone, C, Rotter, JI, Reisch, JS, Hanon, O, Cupidi, C, Uitterlinden, AG, Royall, DR, Dufouil, C, Maletta, RG, Moreno-Grau, S, Sano, M, Brice, A, Cecchetti, R, St George-Hyslop, P, Ritchie, K, Tsolaki, M, Tsuang, DW, Dubois, B, Craig, D, Wu, CK, Soininen, H, Avramidou, D, Albin, RL, Fratiglioni, L, Germanou, A, Apostolova, LG, Keller, L, Koutroumani, M, Arnold, SE, Panza, F, Gkatzima, O, Asthana, S, Hannequin, D, Whitehead, P, Atwood, CS, Caffarra, P, Hampel, H, Baldwin, CT, Lannfelt, L, Rubinsztein, DC, Barnes, LL, Pasquier, F, Frölich, L, Barral, S, McGuinness, B, Beach, TG, Johnston, JI, Becker, JT, Passmore, P, Bigio, EH, Schott, JM, Bird, TD, Warren, JD, Boeve, BF, Lupton, MK, Bowen, JD, Proitsi, P, Boxer, A, Powell, JF, Burke, Kauwe, JK, Burns, JM, Mancuso, M, Buxbaum, JD, Bonuccelli, U, Cairns, NJ, McQuillin, A, Cao, C, Livingston, G, Carlson, CS, Bass, NJ, Carlsson, CM, Hardy, J, Carney, RM, Bras, J, Carrasquillo, MM, Guerreiro, R, Allen, M, Chui, HC, Fisher, E, Cribbs, DH, Masullo, C, Crocco, EA, DeCarli, C, Bisceglio, G, Dick, M, Ma, L, Duara, R, Graff-Radford, NR, Evans, DA, Hodges, A, Faber, KM, Scherer, M, Fallon, KB, Riemenschneider, M, Fardo, DW, Heun, R, Farlow, MR, Ferris, S, Leber, M, Foroud, TM, Heuser, I, Galasko, DR, Giegling, I, Gearing, M, Hüll, M, Geschwind, DH, Gilbert, Morris, J, Green, RC, Mayo, K, Growdon, JH, Feulner, T, Hamilton, RL, Harrell, LE, Drichel, D, Honig, LS, Cushion, TD, Huentelman, MJ, Hollingworth, P, Hulette, CM, Hyman, BT, Marshall, R, Jarvik, GP, Meggy, A, Abner, E, Menzies, G, Jin, LW, Leonenko, G, Jun, G, Grozeva, D, Karydas, A, Russo, G, Kaye, JA, Kim, R, Jessen, F, Kowall, NW, Vellas, B, Kramer, JH, Vardy, E, LaFerla, FM, Jöckel, KH, Lah, JJ, Dichgans, M, Leverenz, JB, Mann, D, Levey, AI, Pickering-Brown, S, Lieberman, AP, Klopp, N, Lunetta, KL, Wichmann, HE, Lyketsos, CG, Morgan, K, Marson, DC, Brown, K, Martiniuk, F, Medway, C, Mash, DC, Nöthen, MM, Masliah, E, Hooper, NM, McCormick, WC, Daniele, A, McCurry, SM, Bayer, A, McDavid, AN, Gallacher, J, McKee, AC, Van Den Bussche, H, Mesulam, M, Brayne, C, Miller, BL, Riedel-Heller, S, Miller, CA, Miller, JW, Al-Chalabi, A, Morris, JC, Shaw, CE, Myers, AJ, Wiltfang, J, O’Bryant, S, Coto, E, Olichney, JM, Alvarez, V, Parisi, JE, Singleton, AB, Paulson, HL, Collinge, J, Perry, W, Mead, S, Peskind, E, Rosser, M, Pierce, A, Ryan, N, Poon, WW, Nacmias, B, Potter, H, Sorbi, S, Quinn, JF, Sacchinelli, E, Raj, A, Spalletta, G, Raskind, M, Bossù, P, Reisberg, B, Clarke, R, Reitz, C, and S, AD

Subjects
2 Aetiology, Aging, Prevention, Human Genome, 4202 Epidemiology, 42 Health Sciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurodegenerative, 3101 Biochemistry and Cell Biology, Alzheimer's Disease, 3105 Genetics, 3. Good health, Brain Disorders, Clinical Research, FOS: Biological sciences, Neurological, Acquired Cognitive Impairment, Genetics, 2.1 Biological and endogenous factors, Dementia, 31 Biological Sciences
Abstract

Introduction Late-onset Alzheimer’s disease (LOAD, onset age > 60 years) is the most prevalent dementia in the elderly 1 , and risk is partially driven by genetics 2 . Many of the loci responsible for this genetic risk were identified by genome-wide association studies (GWAS) 3–8 . To identify additional LOAD risk loci, the we performed the largest GWAS to date (89,769 individuals), analyzing both common and rare variants. We confirm 20 previous LOAD risk loci and identify four new genome-wide loci ( IQCK , ACE , ADAM10 , and ADAMTS1 ). Pathway analysis of these data implicates the immune system and lipid metabolism, and for the first time tau binding proteins and APP metabolism. These findings show that genetic variants affecting APP and Aβ processing are not only associated with early-onset autosomal dominant AD but also with LOAD. Analysis of AD risk genes and pathways show enrichment for rare variants ( P = 1.32 × 10 −7 ) indicating that additional rare variants remain to be identified.

42. Sex dependent risk factors for mortality after myocardial infarction

Author

Matteo Anselmino, Louise Pilote, Chiara Rafanelli, Kenneth E. Freedland, Frank Doyle, Robert M. Carney, Seyed Hamzeh Hosseini, Ronald C. Kessler, Edwin R. van den Heuvel, Kapil Parakh, Hiroshi Sato, Hanna M. van Loo, Sherry L. Grace, Robert A. Schoevers, Richard P. Steeds, Peter de Jonge, Johan Denollet, Annelieke M. Roest, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Perceptual and Cognitive Neuroscience (PCN), Life Course Epidemiology (LCE), Stochastic Operations Research, Statistics, van Loo, Hm, van den Heuvel, Er, Schoevers, Ra, Anselmino, M, Carney, Rm, Denollet, J, Doyle, F, Freedland, Ke, Grace, Sl, Hosseini, Sh, Parakh, K, Pilote, L, Rafanelli, Chiara, Roest, Am, Sato, H, Steeds, Rp, Kessler, Rc, de Jonge, P., and Medical and Clinical Psychology

Subjects
Male, Interactions, Global Health, SDG 3 – Goede gezondheid en welzijn, ACUTE CORONARY EVENTS, Medicine, Prospective Studies, Myocardial infarction, COORDINATE DESCENT, Prospective cohort study, Medicine(all), Smoking, General Medicine, Middle Aged, All-cause mortality, DEPRESSION, REGULARIZATION PATHS, Meta-analysis, POPULATION TRENDS, Regression Analysis, HEART-FAILURE, Female, Sex, Risk assessment, GLOBAL REGISTRY, Research Article, medicine.medical_specialty, Interaction, Lower risk, Sex Factors, SDG 3 - Good Health and Well-being, Internal medicine, Diabetes Mellitus, Humans, Aged, Proportional Hazards Models, business.industry, Proportional hazards model, AGE INTERACTION, medicine.disease, Surgery, BODY-MASS INDEX, Risk factors, SYSTOLIC DYSFUNCTION, Myocardial infarction complications, Risk factor, business, Prediction, Body mass index
Abstract

Background Although a number of risk factors are known to predict mortality within the first years after myocardial infarction, little is known about interactions between risk factors, whereas these could contribute to accurate differentiation of patients with higher and lower risk for mortality. This study explored the effect of interactions of risk factors on all-cause mortality in patients with myocardial infarction based on individual patient data meta-analysis. Methods Prospective data for 10,512 patients hospitalized for myocardial infarction were derived from 16 observational studies (MINDMAPS). Baseline measures included a broad set of risk factors for mortality such as age, sex, heart failure, diabetes, depression, and smoking. All two-way and three-way interactions of these risk factors were included in Lasso regression analyses to predict time-to-event related all-cause mortality. The effect of selected interactions was investigated with multilevel Cox regression models. Results Lasso regression selected five two-way interactions, of which four included sex. The addition of these interactions to multilevel Cox models suggested differential risk patterns for males and females. Younger women (age

Published
2014

43. A regional One Health approach to the risk of invasion by Anopheles stephensi in Mauritius.

Author

Iyaloo DP, Zohdy S, Carney RM, Mosawa VR, Elahee KB, Munglee N, Latchooman N, Puryag S, Bheecarry A, Bhoobun H, Rasamoelina-Andriamanivo H, Bedja SA, Spear J, Baldet T, and Carter TE

Subjects
Animals, Mauritius, Humans, Aedes physiology, Aedes classification, Ecosystem, Introduced Species, Larva physiology, Anopheles physiology, Anopheles classification, Mosquito Vectors physiology, Mosquito Vectors classification, Malaria transmission, Malaria prevention & control, Malaria epidemiology, Mosquito Control methods, One Health
Abstract

Background: Anopheles stephensi is an invasive malaria vector in Africa that threatens to put an additional 126 million people at risk of malaria if it continues to spread. The island nation of Mauritius is highly connected to Asia and Africa and is at risk of introduction due to this connectivity. For early detection of An. stephensi, the Vector Biology and Control Division under the Ministry of Health in Mauritius, leveraged a well-established Aedes program, as An. stephensi is known to share Aedes habitats. These efforts triggered multisectoral coordination and cascading benefits of integrated vector and One Health approaches., Methods: Beginning June 2021, entomological surveys were conducted at points of entry (seaport, airport) and on ships transporting livestock in collaboration with the Civil Aviation Department, the Mauritian Port Authority and National Veterinary Services. A total of 18, 39, 723 mosquito larval surveys were respectively conducted in the airport, seaport, and other localities in Mauritius while two, 20, and 26 adult mosquito surveys were respectively conducted in the airport, seaport, and twenty-six animal assembly points. Alongside adult mosquito surveys, surveillance of vectors of veterinary importance (e.g.- Culicoides spp.) was also carried out in collaboration with National Parks and Conservation Service and land owners., Results: A total of 8,428 adult mosquitoes were collected and 1,844 larval habitats were positive for mosquitoes. All collected mosquitoes were morphologically identified and 151 Anopheles and 339 Aedes mosquitoes were also molecularly characterized. Mosquito species detected were Aedes albopictus, Anopheles arabiensis, An. coustani, An. merus, Culex quinquefasciatus, Cx. thalassius and Lutzia tigripes. Anopheles stephensi was not detected. The One Health approach was shared with the French Agricultural Research Centre for International Development (CIRAD), strengthening collaboration between Mauritius and Réunion Island on vector surveillance at entry points and insecticide resistance monitoring. The Indian Ocean Commission (IOC) was also alerted to the risk of An. stephensi, leading to regional efforts supporting trainings and development of a response strategy to An. stephensi bringing together stakeholders from Comoros, Madagascar, Mauritius, Réunion Island and Seychelles., Conclusions: Mauritius is a model system showing how existing public health entomology capabilities can be used to enhance vector surveillance and control and create multisectoral networks to respond to any emerging public and veterinary health vector-borne disease threat., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Published
2024
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44. Evaluating the psychometric structure of the Hamilton Rating Scale for Depression pre- and post-treatment in antidepressant randomised trials: Secondary analysis of 6843 individual participants from 20 trials.

Author

Byrne D, Doyle F, Brannick S, Carney RM, Cuijpers P, Dima AL, Freedland K, Guerin S, Hevey D, Kathuria B, Wallace E, and Boland F

Subjects
Humans, Male, Female, Middle Aged, Adult, Depression drug therapy, Aged, Factor Analysis, Statistical, Psychometrics standards, Antidepressive Agents therapeutic use, Psychiatric Status Rating Scales standards, Randomized Controlled Trials as Topic
Abstract

Background: The 17-item Hamilton Rating Scale for Depression (HRSD-17) is the most popular depression measure in antidepressant clinical trials. Prior evidence indicates poor replicability and inconsistent factorial structure. This has not been studied in pooled randomised trial data, nor has a psychometrically optimal model been developed., Aims: To examine the psychometric properties of the HRSD-17 for pre-treatment and post-treatment clinical trial data in a large pooled database of antidepressant randomised controlled trial participants, and to determine an optimal abbreviated version., Method: Data for 6843 participants were obtained from the data repository Vivli.org and randomly split into groups for exploratory (n = 3421) and confirmatory (n = 3422) factor analysis. Invariance methods were used to assess potential sex differences., Results: The HRSD-17 was psychometrically sub-optimal and non-invariant for all models. High item variances and low variance explained suggested redundancy in each model. EFA failed at baseline and produced four item models for outcome groups (five for placebo-outcome), which were metric but not scalar invariant., Conclusions: In antidepressant trial data, the HRSD-17 was psychometrically inadequate and scores were not sex invariant. Neither full nor abbreviated HRSD models are suitable for use in clinical trial settings and the HRSD's status as the gold standard should be reconsidered., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

Published
2024
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45. An exploratory graphical analysis of the Montgomery-Åsberg Depression Rating Scale pre- and post-treatment using pooled antidepressant trial secondary data.

Author

Byrne D, Ghoshal A, Boland F, Brannick S, Carney RM, Cuijpers P, Dima AL, Freedland KE, Guerin S, Hevey D, Kathuria B, McDarby V, Wallace E, and Doyle F

Subjects
Humans, Female, Male, Adult, Middle Aged, Depressive Disorder, Major drug therapy, Antidepressive Agents therapeutic use, Psychometrics, Psychiatric Status Rating Scales
Abstract

Background: The 10-item Montgomery-Åsberg Depression Rating Scale (MADRS) is a commonly used measure of depression in antidepressant clinical trials. Numerous studies have adopted classical test theory perspectives to assess the psychometric properties of this scale, finding generally positive results. However, its network configural structure and stability is unexplored across different time-points and treatment groups., Aims: To assess the network structure and stability of the MADRS in clinical settings pre- and post-treatment, and to determine a configurally invariant and stable model across time-points and treatment groups (placebo and intervention)., Method: Individual participant data for 6440 participants from 14 clinical trials of major depressive disorder was obtained from the data repository Vivli.org. Exploratory Graphical Analysis (EGA) was used to identify empirical models pre-treatment (baseline) and post-treatment (8-week outcome). Bootstrapping techniques were applied to obtain optimised configurally invariant models., Results: Empirical models presented with performance issues at baseline and for the placebo group at outcome. An abbreviated 8-item single-community model was found to be stable and configurally invariant across time-points and treatment groups. Symptoms such as low mood and lassitude showed most centrality across all models., Limitations: Metric invariance could not be explored due to research environment limitations., Conclusions: An 8-item one-community variant of the MADRS may provide optimal performance when conducting network analyses of antidepressant clinical trial outcomes. Findings suggest that interventions targeting low mood and lassitude might be most efficacious in treating depression among clinical trial participants. Further considerations of the potential impact on trial design and analysis should be explored., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Published
2025
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46. Treating Depression to Improve Survival in Coronary Heart Disease: What Have We Learned?

Author

Carney RM, Freedland KE, and Rich MW

Subjects
Humans, Depressive Disorder, Major psychology, Depressive Disorder, Major therapy, Antidepressive Agents therapeutic use, Depression therapy, Coronary Disease psychology, Coronary Disease mortality, Coronary Disease complications
Abstract

Major depressive disorder is a well-established risk factor for cardiac events in patients with coronary heart disease, but clinical trials have produced little evidence that treating depression reliably improves cardiac event-free survival in these patients. In this review, we offer evidence that certain symptoms that commonly remain after otherwise successful treatment of depression-insomnia, fatigue, and anhedonia-independently predict cardiac events. This may help to explain the failure of previous depression treatment trials to improve cardiac event-free survival even when other symptoms of depression improve. We thus propose that adverse cardiovascular effects that have long been attributed to syndromal depression may be instead caused by persistent fatigue, insomnia, and anhedonia, regardless of whether other symptoms of depression are present. We also identify interventions for these symptoms and call for more research to evaluate their effectiveness in depressed patients with coronary heart disease., Competing Interests: Funding Support and Author Disclosures This work was supported in part by Grant 5R01HL147862 from the National Heart, Lung, and Blood Institute of the National Institutes of Health, Bethesda, Maryland. The funding agency was not directly involved in the interpretation of the data or in the writing of the manuscript. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Published
2024
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47. Longitudinal Relationships Between Heart Failure Self-care and All-Cause Hospital Readmissions.

Author

Freedland KE, Skala JA, Steinmeyer BC, Chen L, Carney RM, and Rich MW

Subjects
Humans, Male, Female, Aged, Prospective Studies, Middle Aged, Longitudinal Studies, Aged, 80 and over, Heart Failure therapy, Patient Readmission statistics & numerical data, Self Care
Abstract

Background: Many patients with heart failure (HF) are repeatedly hospitalized. Heart failure self-care may reduce readmission rates. Hospitalizations may also affect self-care., Objective: The purpose of this secondary analysis was to test the hypotheses that better HF self-care is associated with a lower rate of all-cause readmissions and that readmissions motivate patients to improve their self-care., Methods: This was a prospective cohort study of patients with HF (N = 400) who were enrolled during a stay at an urban teaching hospital between 2014 and 2016. The Self-Care of Heart Failure Index v6.2 was administered during the hospital stay, along with other questionnaires, and repeated at 6-month intervals after discharge. All-cause readmissions and deaths were ascertained for 24 months., Results: A total of 333 (83.3%) were readmitted at least once, and 117 (29.3%) of the patients died during the follow-up period. A total of 1581 readmissions were ascertained. Higher Self-Care of Heart Failure Index Maintenance scores predicted more rather than fewer readmissions (adjusted hazard ratio, 1.09; 95% confidence interval, 1.01-1.17; P < .01). Conversely, more readmissions predicted higher Maintenance scores (b = 0.29; 95% confidence interval, 0.02-0.56; P < .05)., Conclusions: These findings do not support the hypothesis that HF self-care maintenance or management helps to reduce the rate of all-cause readmissions, but they do suggest that the experience of multiple readmissions may help to motivate improvements in HF self-care., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Published
2024
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48. Classifying stages in the gonotrophic cycle of mosquitoes from images using computer vision techniques.

Author

Azam FB, Carney RM, Kariev S, Nallan K, Subramanian M, Sampath G, Kumar A, and Chellappan S

Subjects
Animals, Female, Computers, Culex, Anopheles, Aedes
Abstract

The ability to distinguish between the abdominal conditions of adult female mosquitoes has important utility for the surveillance and control of mosquito-borne diseases. However, doing so requires entomological training and time-consuming manual effort. Here, we design computer vision techniques to determine stages in the gonotrophic cycle of female mosquitoes from images. Our dataset was collected from 139 adult female mosquitoes across three medically important species-Aedes aegypti, Anopheles stephensi, and Culex quinquefasciatus-and all four gonotrophic stages of the cycle (unfed, fully fed, semi-gravid, and gravid). From these mosquitoes and stages, a total of 1959 images were captured on a plain background via multiple smartphones. Subsequently, we trained four distinct AI model architectures (ResNet50, MobileNetV2, EfficientNet-B0, and ConvNeXtTiny), validated them using unseen data, and compared their overall classification accuracies. Additionally, we analyzed t-SNE plots to visualize the formation of decision boundaries in a lower-dimensional space. Notably, ResNet50 and EfficientNet-B0 demonstrated outstanding performance with an overall accuracy of 97.44% and 93.59%, respectively. EfficientNet-B0 demonstrated the best overall performance considering computational efficiency, model size, training speed, and t-SNE decision boundaries. We also assessed the explainability of this EfficientNet-B0 model, by implementing Grad-CAMs-a technique that highlights pixels in an image that were prioritized for classification. We observed that the highest weight was for those pixels representing the mosquito abdomen, demonstrating that our AI model has indeed learned correctly. Our work has significant practical impact. First, image datasets for gonotrophic stages of mosquitoes are not yet available. Second, our algorithms can be integrated with existing citizen science platforms that enable the public to record and upload biological observations. With such integration, our algorithms will enable the public to contribute to mosquito surveillance and gonotrophic stage identification. Finally, we are aware of work today that uses computer vision techniques for automated mosquito species identification, and our algorithms in this paper can augment these efforts by enabling the automated detection of gonotrophic stages of mosquitoes as well., (© 2023. The Author(s).)

Published
2023
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49. An Alzheimer's disease risk variant in TTC3 modifies the actin cytoskeleton organization and the PI3K-Akt signaling pathway in iPSC-derived forebrain neurons.

Author

Cukier HN, Duarte CL, Laverde-Paz MJ, Simon SA, Van Booven DJ, Miyares AT, Whitehead PL, Hamilton-Nelson KL, Adams LD, Carney RM, Cuccaro ML, Vance JM, Pericak-Vance MA, Griswold AJ, and Dykxhoorn DM

Subjects
Humans, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins c-akt, Neurons, Actin Cytoskeleton, Late Onset Disorders, Prosencephalon, Signal Transduction genetics, Ubiquitin-Protein Ligases, Induced Pluripotent Stem Cells, Alzheimer Disease genetics
Abstract

A missense variant in the tetratricopeptide repeat domain 3 (TTC3) gene (rs377155188, p.S1038C, NM&#95;003316.4:c 0.3113C>G) was found to segregate with disease in a multigenerational family with late-onset Alzheimer's disease. This variant was introduced into induced pluripotent stem cells (iPSCs) derived from a cognitively intact individual using CRISPR genome editing, and the resulting isogenic pair of iPSC lines was differentiated into cortical neurons. Transcriptome analysis showed an enrichment for genes involved in axon guidance, regulation of actin cytoskeleton, and GABAergic synapse. Functional analysis showed that the TTC3 p.S1038C iPSC-derived neuronal progenitor cells had altered 3-dimensional morphology and increased migration, while the corresponding neurons had longer neurites, increased branch points, and altered expression levels of synaptic proteins. Pharmacological treatment with small molecules that target the actin cytoskeleton could revert many of these cellular phenotypes, suggesting a central role for actin in mediating the cellular phenotypes associated with the TTC3 p.S1038C variant., Competing Interests: Disclosure statement The authors report no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2023
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50. Outcomes of a tailored self-care intervention for patients with heart failure and major depression: A secondary analysis of a randomized controlled trial.

Author

Freedland KE, Skala JA, Carney RM, Steinmeyer BC, and Rich MW

Subjects
Humans, Depression psychology, Self Care, Comorbidity, Quality of Life, Depressive Disorder, Major therapy, Heart Failure complications, Heart Failure therapy, Heart Failure psychology
Abstract

Background: Depression is a recognized barrier to heart failure self-care, but there has been little research on interventions to improve heart failure self-care in depressed patients., Objectives: To investigate the outcomes of an individually tailored self-care intervention for patients with heart failure and major depression, and to determine whether the adequacy of self-care at baseline, the severity of depression or anxiety, or other factors affect the outcomes of this intervention., Design: Secondary analysis of data from a pre-registered randomized controlled trial (NCT02997865)., Methods: Outpatients with heart failure and comorbid major depression (n = 139) were randomly assigned to cognitive behavior therapy or usual care for depression. In addition, an experienced cardiac nurse provided the tailored self-care intervention to all patients in both arms of the trial starting eight weeks after randomization. Weekly self-care intervention sessions were held between Weeks 8 and 16; the frequency was tapered to biweekly or monthly between Weeks 17 and 32. The Self-Care of Heart Failure Index (v6.2) was used to assess self-care outcomes, with scores ≥70 on each of its three scales (Maintenance, Management, and Confidence) being consistent with adequate self-care. The Week 16 Maintenance scale score was the primary outcome for this analysis., Results: At baseline, 107 (77%) of the patients scored in the inadequate self-care range on the Maintenance scale. Between Weeks 8 and 16, Maintenance scores improved more in patients with initially inadequate than initially adequate self-care (11.9 vs. 3.2 points, p = .003). Sixty-six (48%) of the patients with initially inadequate Maintenance scores achieved scores in the adequate range by Week 32 (p < .0001). Covariate-adjusted predictors of better Maintenance outcomes included adequate Maintenance at baseline (p < .0001), higher anxiety at baseline (p < .05), and higher dosages of the self-care intervention (p < .0001). Neither treatment with cognitive behavior therapy nor less severe major depression predicted better self-care outcomes., Conclusions: Depressed patients with inadequate heart failure self-care are able to achieve clinically significant improvements in self-care with the help of an individually tailored self-care intervention. Further refinement and testing are needed to increase the intervention's potential for clinical implementation., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Published
2023
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