Death rates in HIV-positive antiretroviral-naive patients with CD4 count greater than 350 cells per μl in Europe and North America: A pooled cohort observational study

Lodwick, R.K.; Sabin, C.A.; Porter, K.; Ledergerber, B.; Van Sighem, A.; Cozzi-Lepri, A.; Khaykin, P.; Mocroft, A.; Jacobson, L.P.; De Wit, S.; Obel, N.; Castagna, A.; Wasmuth, J.-.; Gill, J.; Klein, M.B.; Gange, S.; Riera, M.; Mussini, C.; Gutierrez, F.; Touloumi, G.; Carrieri, P.; Guest, J.L.; Brockmeyer, N.H.; Phillips, A.N.; Antoniadou, A.; Gargalianos-Kakolyris, P.; Katsarou, O.; Kordossis, T.; Lazanas, M.; Panos, G.; Paparizos, V.; Paraskevis, D.; Petrikkos, G.; Sambatakou, H.; Skoutelis, A.; Pantazis, N.; Bakoyannis, G.; Gioukari, V.; de Wolf, F.; O Bezemer, D.; Gras, L.A.J.; Kesselring, A.M.; van Sighem, A.I.; Smit, C.; Zhang, S.; Zaheri, S.; Prins, J.M.; Schreij, G.; Bravenboer, B.; van der Ende, M.E.; Kauff mann, R.H.; ten Kate, R.W.; Kroon, F.P.; Bronsveld, W.; Vriesendorp, R.; van Houte, D.; ten Napel, C.H.H.; Brinkman, K.; van Eeden, A.; Mulder, J.W.; Juttmann, J.R.; Veenstra, J.; Koopmans, P.P.; Sprenger, H.G.; Hoepelman, I.M.; Danner, S.A.; Richter, C.; Tanis, A.A.; Van, A.; Delforge, M.; Necsoi, C.; Demeester, R.; Gennotte, A.; Gerard, M.; Guillaume, M.; Hermans, P.; Kabeya, K.; Konopnicki, D.; Martin, C.; Libois, A.; Payen, M.; Semaille, P.; Van Laethem, Y.; Del Amo, J.; Meyer, L.; Bucher, H.C.; Chene, G.; Pillay, D.; Prins, J.M.; Rosinska, M.; Sabin, C.A.; Touloumi, G.; Lodi, S.; Coughlin, K.; Walker, S.; Babiker, A.; de Luca, A.; Fisher, M.; Muga, R.; Fatkenheuer, G.; Rockstroh, J.; Vehreschild, J.; Hertenstein, C.; Berenguer, J.; Garcia, F.; Labarga, P.; Moreno, S.; Angeles Munoz, M.; Caro-Murillo, A.M.; Sobrino, P.; Perez-Cachafeiro, S.; Jarrin, I.; Alejos, B.; Garcia, I.; Gomez-Sirvent, J.; Soriano, V.; Pulido, F.; Iribarren, J.; Masia, M.; Vidal, F.; Sanz, J.; Blanco, J.A.; Sola, J.; Gerstoft, J.; Kronborg, G.; Roge, B.; Larsen, C.S.; Pedersen, G.; Laursen, A.L.; Nielsen, L.; Jensen, J.; Babacan, E.; Bickel, M.; Bodtlander, A.; Brodt, H.; Carlebach, A.; Gute, P.; Haberl, A.; Helm, E.; Klauke, S.; Knecht, G.; Lennemann, T.; Locher, L.; Lutz, T.; Mosch, M.; Muller, A.; Nisius, G.; Staszewski, S.; Stephan, C.; Sturmer, M.; von Hentig, N.; Wolf, T.; Rimland, D.; Moanna, A.; Moorfi eld, M.; Dorsey, M.; Desilva, K.; Schlueter Wirtz, S.; Mindley, R.; Dozier, R.; Robinson, Y.; Brown, P.; Moroni, M.; Angarano, G.; Antinori, A.; Carosi, G.; Cauda, R.; d'Arminio Monforte, A.; Di Perri, G.; Galli, M.; Ghinelli, F.; Iardino, R.; Ippolito, G.; Lazzarin, A.; Mazzotta, F.; Perno, C.; Viale, P.; Von Schlosser, F.; Ammassari, A.; Balotta, C.; Bonfanti, P.; Capobianchi, M.; Ceccherini-Silberstein, F.; Gervasoni, C.; Girardi, E.; Lo Caputo, S.; Maggiolo, F.; Murri, R.; Puoti, M.; Torti, C.; Salpietro, S.; Marangione, M.; Galli, L.; Gianotti, N.; Cossarini, F.; Spagnuolo, V.; Arendt, G.; Esser, S.; Jager, H.; Schwarze, S.; Stoll, M.; Wolf, H.; Jansen, K.; Michalik, C.; Skaletzrorowski, A.; Konigs, C.; Gingelmaier, A.; Margolick, J.B.; Phair, J.P.; Wolinsky, S.M.; Detels, R.; Rinaldo, C.R.; Boirot, C.; Bouhnik, A.D.; Carrieri, M.P.; Cassuto, J.P.; Chesney, M.; Cohen, J.; Dellamonica, P.; Dujardin, P.; Gallais, H.; Gastaut, J.A.; Kurkdji, P.; Lepeu, G.; Mechali, D.; Moatti, J.P.; Moreau, J.; Negre, M.; Obadia, Y.; Poizot-Martin, I.; Pradier, C.; Preau, M.; Rey, D.; Roux, P.; Rouzioux, C.; Sobel, A.; Spire, B.; Tremolieres, F.; Villes, V.; Vincent, E.; Vlahov, D.; Borghi, V.; Casabona, J.; Miro, J.M.; Gatell, J.M.; Lopez-Dieguez-Puerta, M.; Tural, C.; Clotet, B.; Podzamczer, D.; Ferrer, E.; Murillas, J.; Segura, F.; Navarro, G.; Force, L.; Vilaro, J.; Masabeu, A.; Guadarrama, M.; Betancourt, A.J.; Romero, A.; Agusti, C.; Battegay, M.; Bernasconi, E.; Boni, J.; Burgisser, P.; Calmy, A.; Cavassini, M.; Dubs, R.; Egger, M.; Elzi, L.; Fischer, M.; Flepp, M.; Fontana, A.; Francioli, P.; Furrer, H.; Fux, C.A.; Gorgievski, M.; Gunthard, H.F.; Hirsch, H.H.; Hirschel, B.; Hosli, I.; Kahlert, C.; Kaiser, L.; Karrer, U.; Kind, C.; Klimkait, T.; Martinetti, G.; Martinez, B.; Muller, N.; Nadal, D.; Paccaud, F.; Pantaleo, G.; Rauch, A.; Regenass, S.; Rickenbach, M.; Rudin, C.; Schmid, P.; Schultze, D.; Schoni, F.; Schupbach, J.; Speck, R.; Taff e, P.; Telenti, A.; Trkola, A.; Vernazza, P.; Weber, R.; Yerl, Y.U.C.S.C.J.A.S.; Anderson, J.; Delpech, V.; Dunn, D.; Easterbrook, P.; Gazzard, B.; Gilson, R.; Gompels, M.; Hill, T.; Johnson, M.; Leen, C.; Nelson, M.; Orkin, C.; Palfreeman, A.; Pillay, D.; Post, F.; Schwenk, A.; Walsh, J.; Bansi, L.; Huntington, S.; Glabay, A.; Anastos, K.; Minkoff, H.; Young, M.; Greenblatt, R.; Levine, A.; Cohen, M.

doi:10.1016/S0140-6736(10)60932-4

Summary Background Whether people living with HIV who have not received antiretroviral therapy (ART) and have high CD4 cell counts have higher mortality than the general population is unknown. We aimed to examine this by analysis of pooled data from industrialised countries. We merged data on demographics, CD4 cell counts, viral-load measurements, hepatitis C co-infection status, smoking status, date of death, and whether death was AIDS-related or not from 23 European and North American cohorts. We calculated standardised mortality ratios (SMRs) standardised by age, sex, and year, stratifying by risk group. Data were included for patients aged 20-59 years who had at least one CD4 count greater than 350 cells per μL while ART naive. All pre-ART CD4 counts greater than 350 cells per μL from January, 1990, to December, 2004, were included. We investigated mortality for four risk groups - men who have sex with men, heterosexual people, injecting drug users, and those at other or unknown risk. The association between CD4 cell count and death rate was investigated by use of Poisson regression methods. Data were analysed for 40 830 patients contributing 80 682 person-years of follow-up. Of 419 deaths, 401 were used in the SMR analysis: 100 men who have sex with men (SMR 1·30, 95 CI 1·06-1·58); 68 heterosexual people (2·94, 2·28-3·73); 203 injecting drug users (9·37, 8·13-10·75); and 30 in the other or unknown risk category (4·57, 3·09-6·53). Compared with CD4 counts of 350-499 cells per μL, death rate was lower in patients with counts of 500-699 cells per μL (adjusted rate ratio 0·77, 95 CI 0·61-0·95) and counts of 700 cells per μL (0·66, 0·52-0·85). In HIV-infected ART-naive patients with high CD4 cell counts, death rates were raised compared with the general population. In men who have sex with men this was modest, suggesting that a substantial proportion of the increased risk in other groups is due to confounding by other factors. Even though the increased risk is small, new studies of potential benefits of ART in this group are merited. European Commission, FP6. European AIDS Treatment Network (NEAT).

Death rates in HIV-positive antiretroviral-naive patients with CD4 count greater than 350 cells per μl in Europe and North America: A pooled cohort observational study / R.K. Lodwick, C.A. Sabin, K. Porter, B. Ledergerber, A. Van Sighem, A. Cozzi-Lepri, P. Khaykin, A. Mocroft, L.P. Jacobson, S. De Wit, N. Obel, A. Castagna, J.-. Wasmuth, J. Gill, M.B. Klein, S. Gange, M. Riera, C. Mussini, F. Gutierrez, G. Touloumi, P. Carrieri, J.L. Guest, N.H. Brockmeyer, A.N. Phillips, A. Antoniadou, P. Gargalianos-Kakolyris, O. Katsarou, T. Kordossis, M. Lazanas, G. Panos, V. Paparizos, D. Paraskevis, G. Petrikkos, H. Sambatakou, A. Skoutelis, N. Pantazis, G. Bakoyannis, V. Gioukari, F. de Wolf, D. O Bezemer, L.A.J. Gras, A.M. Kesselring, A.I. van Sighem, C. Smit, S. Zhang, S. Zaheri, J.M. Prins, G. Schreij, B. Bravenboer, M.E. van der Ende, R.H. Kauff mann, R.W. ten Kate, F.P. Kroon, W. Bronsveld, R. Vriesendorp, D. van Houte, C.H.H. ten Napel, K. Brinkman, A. van Eeden, J.W. Mulder, J.R. Juttmann, J. Veenstra, P.P. Koopmans, H.G. Sprenger, I.M. Hoepelman, S.A. Danner, C. Richter, A.A. Tanis, A. Van, M. Delforge, C. Necsoi, R. Demeester, A. Gennotte, M. Gerard, M. Guillaume, P. Hermans, K. Kabeya, D. Konopnicki, C. Martin, A. Libois, M. Payen, P. Semaille, Y. Van Laethem, J. Del Amo, L. Meyer, H.C. Bucher, G. Chene, D. Pillay, J.M. Prins, M. Rosinska, C.A. Sabin, G. Touloumi, S. Lodi, K. Coughlin, S. Walker, A. Babiker, A. de Luca, M. Fisher, R. Muga, G. Fatkenheuer, J. Rockstroh, J. Vehreschild, C. Hertenstein, J. Berenguer, F. Garcia, P. Labarga, S. Moreno, M. Angeles Munoz, A.M. Caro-Murillo, P. Sobrino, S. Perez-Cachafeiro, I. Jarrin, B. Alejos, I. Garcia, J. Gomez-Sirvent, V. Soriano, F. Pulido, J. Iribarren, M. Masia, F. Vidal, J. Sanz, J.A. Blanco, J. Sola, J. Gerstoft, G. Kronborg, B. Roge, C.S. Larsen, G. Pedersen, A.L. Laursen, L. Nielsen, J. Jensen, E. Babacan, M. Bickel, A. Bodtlander, H. Brodt, A. Carlebach, P. Gute, A. Haberl, E. Helm, S. Klauke, G. Knecht, T. Lennemann, L. Locher, T. Lutz, M. Mosch, A. Muller, G. Nisius, S. Staszewski, C. Stephan, M. Sturmer, N. von Hentig, T. Wolf, D. Rimland, A. Moanna, M. Moorfi eld, M. Dorsey, K. Desilva, S. Schlueter Wirtz, R. Mindley, R. Dozier, Y. Robinson, P. Brown, M. Moroni, G. Angarano, A. Antinori, G. Carosi, R. Cauda, A. d'Arminio Monforte, G. Di Perri, M. Galli, F. Ghinelli, R. Iardino, G. Ippolito, A. Lazzarin, F. Mazzotta, C. Perno, P. Viale, F. Von Schlosser, A. Ammassari, C. Balotta, P. Bonfanti, M. Capobianchi, F. Ceccherini-Silberstein, C. Gervasoni, E. Girardi, S. Lo Caputo, F. Maggiolo, R. Murri, M. Puoti, C. Torti, S. Salpietro, M. Marangione, L. Galli, N. Gianotti, F. Cossarini, V. Spagnuolo, G. Arendt, S. Esser, H. Jager, S. Schwarze, M. Stoll, H. Wolf, K. Jansen, C. Michalik, A. SkaletzRorowski, C. Konigs, A. Gingelmaier, J.B. Margolick, J.P. Phair, S.M. Wolinsky, R. Detels, C.R. Rinaldo, C. Boirot, A.D. Bouhnik, M.P. Carrieri, J.P. Cassuto, M. Chesney, J. Cohen, P. Dellamonica, P. Dujardin, H. Gallais, J.A. Gastaut, P. Kurkdji, G. Lepeu, D. Mechali, J.P. Moatti, J. Moreau, M. Negre, Y. Obadia, I. Poizot-Martin, C. Pradier, M. Preau, D. Rey, P. Roux, C. Rouzioux, A. Sobel, B. Spire, F. Tremolieres, V. Villes, E. Vincent, D. Vlahov, V. Borghi, J. Casabona, J.M. Miro, J.M. Gatell, M. Lopez-Dieguez-Puerta, C. Tural, B. Clotet, D. Podzamczer, E. Ferrer, J. Murillas, F. Segura, G. Navarro, L. Force, J. Vilaro, A. Masabeu, M. Guadarrama, A.J. Betancourt, A. Romero, C. Agusti, M. Battegay, E. Bernasconi, J. Boni, P. Burgisser, A. Calmy, M. Cavassini, R. Dubs, M. Egger, L. Elzi, M. Fischer, M. Flepp, A. Fontana, P. Francioli, H. Furrer, C.A. Fux, M. Gorgievski, H.F. Gunthard, H.H. Hirsch, B. Hirschel, I. Hosli, C. Kahlert, L. Kaiser, U. Karrer, C. Kind, T. Klimkait, G. Martinetti, B. Martinez, N. Muller, D. Nadal, F. Paccaud, G. Pantaleo, A. Rauch, S. Regenass, M. Rickenbach, C. Rudin, P. Schmid, D. Schultze, F. Schoni, J. Schupbach, R. Speck, P. Taff e, A. Telenti, A. Trkola, P. Vernazza, R. Weber, y.U.C.S.c.J.A.S. Yerl, J. Anderson, V. Delpech, D. Dunn, P. Easterbrook, B. Gazzard, R. Gilson, M. Gompels, T. Hill, M. Johnson, C. Leen, M. Nelson, C. Orkin, A. Palfreeman, D. Pillay, F. Post, A. Schwenk, J. Walsh, L. Bansi, S. Huntington, A. Glabay, K. Anastos, H. Minkoff, M. Young, R. Greenblatt, A. Levine, M. Cohen. - In: THE LANCET. - ISSN 0140-6736. - 376:9738(2010), pp. 340-345. [10.1016/S0140-6736(10)60932-4]

Death rates in HIV-positive antiretroviral-naive patients with CD4 count greater than 350 cells per μl in Europe and North America: A pooled cohort observational study

Lodwick R. K.;Sabin C. A.;Porter K.;Ledergerber B.;Van Sighem A.;Cozzi-Lepri A.;Khaykin P.;Mocroft A.;Jacobson L. P.;De Wit S.;Obel N.;Castagna A.;Wasmuth J. -C.;Gill J.;Klein M. B.;Gange S.;Riera M.;Mussini C.;Gutierrez F.;Touloumi G.;Carrieri P.;Guest J. L.;Brockmeyer N. H.;Phillips A. N.;Antoniadou A.;Gargalianos-Kakolyris P.;Katsarou O.;Kordossis T.;Lazanas M.;Panos G.;Paparizos V.;Paraskevis D.;Petrikkos G.;Sambatakou H.;Skoutelis A.;Pantazis N.;Bakoyannis G.;Gioukari V.;de Wolf F.;O Bezemer D.;Gras L. A. J.;Kesselring A. M.;van Sighem A. I.;Smit C.;Zhang S.;Zaheri S.;Prins J. M.;Schreij G.;Bravenboer B.;van der Ende M. E.;Kauff mann R. H.;ten Kate R. W.;Kroon F. P.;Bronsveld W.;Vriesendorp R.;van Houte D.;ten Napel C. H. H.;Brinkman K.;van Eeden A.;Mulder J. W.;Juttmann J. R.;Veenstra J.;Koopmans P. P.;Sprenger H. G.;Hoepelman I. M.;Danner S. A.;Richter C.;Tanis A. A.;Van A.;Delforge M.;Necsoi C.;Demeester R.;Gennotte A-F.;Gerard M.;Guillaume M-P.;Hermans P.;Kabeya K.;Konopnicki D.;Martin C.;Libois A.;Payen M-C.;Semaille P.;Van Laethem Y.;Del Amo J.;Meyer L.;Bucher H. C.;Chene G.;Pillay D.;Prins J. M.;Rosinska M.;Sabin C. A.;Touloumi G.;Lodi S.;Coughlin K.;Walker S.;Babiker A.;de Luca A.;Fisher M.;Muga R.;Fatkenheuer G.;Rockstroh J.;Vehreschild J.;Hertenstein C.;Berenguer J.;Garcia F.;Labarga P.;Moreno S.;Angeles Munoz M.;Caro-Murillo A. M.;Sobrino P.;Perez-Cachafeiro S.;Jarrin I.;Alejos B.;Garcia I.;Gomez-Sirvent J.;Soriano V.;Pulido F.;Iribarren J.;Masia M.;Vidal F.;Sanz J.;Blanco J. A.;Sola J.;Gerstoft J.;Kronborg G.;Roge B.;Larsen C. S.;Pedersen G.;Laursen A. L.;Nielsen L.;Jensen J.;Babacan E.;Bickel M.;Bodtlander A.;Brodt H-R.;Carlebach A.;Gute P.;Haberl A.;Helm E.;Klauke S.;Knecht G.;Lennemann T.;Locher L.;Lutz T.;Mosch M.;Muller A.;Nisius G.;Staszewski S.;Stephan C.;Sturmer M.;von Hentig N.;Wolf T.;Rimland D.;Moanna A.;Moorfi eld M.;Dorsey M.;Desilva KE.;Schlueter Wirtz S.;Mindley R.;Dozier R.;Robinson Y.;Brown P.;Moroni M.;Angarano G.;Antinori A.;G. Carosi;Cauda R.;A. d'Arminio Monforte;Di Perri G.;M. Galli;Ghinelli F.;Iardino R.;G. Ippolito;A. Lazzarin;Mazzotta F.;C. Perno;Viale PL.;Von Schlosser F.;Ammassari A.;C. Balotta;P. Bonfanti;Capobianchi MR.;Ceccherini-Silberstein F.;Gervasoni C.;Girardi E.;Lo Caputo S.;Maggiolo F.;Murri R.;Puoti M.;Torti C.;Salpietro S.;Marangione M.;Galli L.;Gianotti N.;Cossarini F.;Spagnuolo V.;Arendt G.;Esser S.;Jager H.;Schwarze S.;Stoll M.;Wolf H.;Jansen K.;Michalik C.;SkaletzRorowski A.;Konigs C.;Gingelmaier A.;Margolick J. B.;Phair J. P.;Wolinsky S. M.;Detels R.;Rinaldo C. R.;Boirot C.;Bouhnik A. D.;Carrieri M. P.;Cassuto J. P.;Chesney M.;Cohen J.;Dellamonica P.;Dujardin P.;Gallais H.;Gastaut J. A.;Kurkdji P.;Lepeu G.;Mechali D.;Moatti J. P.;Moreau J.;Negre M.;Obadia Y.;Poizot-Martin I.;Pradier C.;Preau M.;D. Rey;Roux P.;Rouzioux C.;Sobel A.;Spire B.;Tremolieres F.;Villes V.;Vincent E.;Vlahov D.;Borghi V.;Casabona J.;Miro J. M.;Gatell J. M.;Lopez-Dieguez-Puerta M.;Tural C.;Clotet B.;Podzamczer D.;Ferrer E.;Murillas J.;Segura F.;Navarro G.;Force L.;Vilaro J.;Masabeu A.;Guadarrama M.;Betancourt A. J.;Romero A.;Agusti C.;Battegay M.;Bernasconi E.;Boni J.;Burgisser P.;Calmy A.;Cavassini M.;Dubs R.;Egger M.;Elzi L.;Fischer M.;Flepp M.;Fontana A.;Francioli P.;Furrer H.;Fux C. A.;Gorgievski M.;Gunthard H. F.;Hirsch H. H.;Hirschel B.;Hosli I.;Kahlert C.;Kaiser L.;Karrer U.;Kind C.;Klimkait T.;Martinetti G.;Martinez B.;Muller N.;Nadal D.;Paccaud F.;Pantaleo G.;Rauch A.;Regenass S.;Rickenbach M.;Rudin C.;Schmid P.;Schultze D.;Schoni F.;Schupbach J.;Speck R.;Taff e P.;Telenti A.;Trkola A.;Vernazza P.;Weber R.;Anderson J.;Delpech V.;Dunn D.;Easterbrook P.;Gazzard B.;Gilson R.;Gompels M.;Hill T.;Johnson M.;Leen C.;Nelson M.;Orkin C.;Palfreeman A.;Pillay D.;Post F.;Schwenk A.;Walsh J.;Bansi L.;Huntington S.;Glabay A.;Anastos K.;Minkoff H.;Young M.;Greenblatt R.;Levine A.;Cohen M.

2010

Abstract

Summary Background Whether people living with HIV who have not received antiretroviral therapy (ART) and have high CD4 cell counts have higher mortality than the general population is unknown. We aimed to examine this by analysis of pooled data from industrialised countries. We merged data on demographics, CD4 cell counts, viral-load measurements, hepatitis C co-infection status, smoking status, date of death, and whether death was AIDS-related or not from 23 European and North American cohorts. We calculated standardised mortality ratios (SMRs) standardised by age, sex, and year, stratifying by risk group. Data were included for patients aged 20-59 years who had at least one CD4 count greater than 350 cells per μL while ART naive. All pre-ART CD4 counts greater than 350 cells per μL from January, 1990, to December, 2004, were included. We investigated mortality for four risk groups - men who have sex with men, heterosexual people, injecting drug users, and those at other or unknown risk. The association between CD4 cell count and death rate was investigated by use of Poisson regression methods. Data were analysed for 40 830 patients contributing 80 682 person-years of follow-up. Of 419 deaths, 401 were used in the SMR analysis: 100 men who have sex with men (SMR 1·30, 95 CI 1·06-1·58); 68 heterosexual people (2·94, 2·28-3·73); 203 injecting drug users (9·37, 8·13-10·75); and 30 in the other or unknown risk category (4·57, 3·09-6·53). Compared with CD4 counts of 350-499 cells per μL, death rate was lower in patients with counts of 500-699 cells per μL (adjusted rate ratio 0·77, 95 CI 0·61-0·95) and counts of 700 cells per μL (0·66, 0·52-0·85). In HIV-infected ART-naive patients with high CD4 cell counts, death rates were raised compared with the general population. In men who have sex with men this was modest, suggesting that a substantial proportion of the increased risk in other groups is due to confounding by other factors. Even though the increased risk is small, new studies of potential benefits of ART in this group are merited. European Commission, FP6. European AIDS Treatment Network (NEAT).

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	Settori scientifico-disciplinari dell'articolo
	
			Settore MED/17 - Malattie Infettive
Settore MED/07 - Microbiologia e Microbiologia Clinica
		
	Data di pubblicazione
	
			2010
		
	Rivista in ANCE
	
			THE LANCET
		
	DOI
	
			https://dx.doi.org/10.1016/S0140-6736(10)60932-4
		
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