Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials

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Fältnamn	Indikatorer	Metadata
000		16652naa a2201453 4500
001		oai:DiVA.org:uu-442888
003		SwePub
008		210521s2021 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
024	7	a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4428882 URI
024	7	a https://doi.org/10.1038/s41467-021-22446-z2 DOI
040		a (SwePub)uu
041		a engb eng
042		9 SwePub
072	7	a ref2 swepub-contenttype
072	7	a art2 swepub-publicationtype
100	1	a Axfors, Cathrineu Uppsala universitet,Obstetrisk och reproduktiv hälsoforskning,Stanford Univ, Meta Res Innovat Ctr Stanford METRICS, Stanford, CA 94305 USA.4 aut0 (Swepub:uu)catax386
245	1 0	a Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials
264		c 2021-04-15
264	1	b Springer Nature,c 2021
338		a electronic2 rdacarrier
500		a Correction in: Nature Communications, year: 2021, volume: 12, Article number: 3001, DOI: 10.1038/s41467-021-23559-1 Shared first authorship: Cathrine Axfors and Andreas M. Schmitt.
520		a Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We present a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality has been extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses include patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine is 1.11 (95% CI: 1.02, 1.20; I-2=0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I-2=0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine is associated with increased mortality in COVID-19 patients, and there is no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities. Hydroxychloroquine and chloroquine have been investigated as a potential treatment for Covid-19 in several clinical trials. Here the authors report a meta-analysis of published and unpublished trials, and show that treatment with hydroxychloroquine for patients with Covid-19 was associated with increased mortality, and there was no benefit from chloroquine.
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Hälsovetenskapx Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi0 (SwePub)303022 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Health Sciencesx Public Health, Global Health, Social Medicine and Epidemiology0 (SwePub)303022 hsv//eng
700	1	a Schmitt, Andreas M.u Univ Basel, Univ Hosp Basel, Dept Clin Res, Basel, Switzerland.;Univ Basel, Dept Med Oncol, Basel, Switzerland.4 aut
700	1	a Janiaud, Perrineu Univ Basel, Univ Hosp Basel, Dept Clin Res, Basel, Switzerland.4 aut
700	1	a van't Hooft, Jannekeu Stanford Univ, Meta Res Innovat Ctr Stanford METRICS, Stanford, CA 94305 USA.;Univ Amsterdam, Amsterdam Univ Med Ctr, Amsterdam, Netherlands.4 aut
700	1	a Abd-Elsalam, Sheriefu Tanta Univ, Fac Med, Trop Med & Infect Dis Dept, Tanta, Egypt.4 aut
700	1	a Abdo, Ehab F.u Assiut Univ, Fac Med, Trop Med & Gastroenterol Dept, Assiut, Egypt.4 aut
700	1	a Abella, Benjamin S.u Univ Penn, Dept Emergency Med, Philadelphia, PA 19104 USA.4 aut
700	1	a Akram, Javedu Univ Hlth Sci, Dept Internal Med, Lahore, Punjab, Pakistan.4 aut
700	1	a Amaravadi, Ravi K.u Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA.;Univ Penn, Dept Med, Philadelphia, PA 19104 USA.4 aut
700	1	a Angus, Derek C.u Univ Pittsburgh, Clin Res Invest & Syst Modeling Acute Illness CRI, Dept Crit Care Med, Pittsburgh, PA USA.;Univ Pittsburgh, UPMC Hlth Syst Off Healthcare Innovat, Med Ctr, Pittsburgh, PA USA.4 aut
700	1	a Arabi, Yaseen M.u King Saud Bin Abdulaziz Univ Hlth Sci, Intens Care Dept, Riyadh, Saudi Arabia.;King Abdullah Int Med Res Ctr, Riyadh, Saudi Arabia.4 aut
700	1	a Azhar, Shehnooru Univ Hlth Sci, Dept Publ Hlth, Lahore, Punjab, Pakistan.4 aut
700	1	a Baden, Lindsey R.u Brigham & Womens Hosp, Div Infect Dis, 75 Francis St, Boston, MA 02115 USA.4 aut
700	1	a Baker, Arthur W.u Duke Univ, Med Ctr, Dept Med, Div Infect Dis & Int Hlth, Durham, NC 27710 USA.4 aut
700	1	a Belkhir, Leilau Catholic Univ Louvain, Infect Dis Dept, Clin Univ St Luc, Brussels, Belgium.4 aut
700	1	a Benfield, Thomasu Copenhagen Univ Hosp, Ctr Res & Disrupt Infect Dis, Dept Infect Dis, Hvidovre, Denmark.4 aut
700	1	a Berrevoets, Marvin A. H.u Elisabeth Tweesteden Hosp, Dept Internal Med, Tilburg, Netherlands.4 aut
700	1	a Chen, Cheng-Pinu Minist Hlth & Welf, Dept Infect Dis, Taoyuan Gen Hosp, Taoyuan, Taiwan.4 aut
700	1	a Chen, Tsung-Chiau Minist Hlth & Welf, Dept Internal Med, Taichung Hosp, Taichung, Taiwan.4 aut
700	1	a Cheng, Shu-Hsingu Minist Hlth & Welf, Dept Infect Dis, Taoyuan Gen Hosp, Taoyuan, Taiwan.4 aut
700	1	a Cheng, Chien-Yuu Minist Hlth & Welf, Dept Infect Dis, Taoyuan Gen Hosp, Taoyuan, Taiwan.4 aut
700	1	a Chung, Wei-Shengu Minist Hlth & Welf, Dept Internal Med, Taichung Hosp, Taichung, Taiwan.4 aut
700	1	a Cohen, Yehuda Z.u Sanofi, Bridgewater, NJ USA.4 aut
700	1	a Cowan, Lisa N.u Sanofi, Bridgewater, NJ USA.4 aut
700	1	a Dalgard, Olavu Akershus Univ Hosp, Dept Infect Dis, Div Med, Lorenskog, Norway.;Univ Oslo, Fac Med, Inst Clin Med, Oslo, Norway.4 aut
700	1	a de Almeida e Val, Fernando F.u Fundacao Med Trop Dr Heitor Vieira Dourado, Manaus, Amazonas, Brazil.4 aut
700	1	a de Lacerda, Marcus V. G.u Fundacao Med Trop Dr Heitor Vieira Dourado, Manaus, Amazonas, Brazil.;FIOCRUZ AM, Inst Leonidas & Maria Deane ILMD, Manaus, Amazonas, Brazil.4 aut
700	1	a de Melo, Gisely C.u Fundacao Med Trop Dr Heitor Vieira Dourado, Manaus, Amazonas, Brazil.;Univ Estado Amazonas, Manaus, Amazonas, Brazil.4 aut
700	1	a Derde, Lennieu Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.;Univ Med Ctr Utrecht, Intens Care Ctr, Utrecht, Netherlands.4 aut
700	1	a Dubee, Vincentu Angers Univ Hosp, Infect & Trop Dis Dept, Angers, France.4 aut
700	1	a Elfakir, Anissau Ividata Life Sci, Levallois Perret, France.4 aut
700	1	a Gordon, Anthony C.u Imperial Coll London, Dept Surg & Canc Anaesthet Pain Med & Intens Care, London, England.;Imperial Coll Healthcare NHS Trust, London, England.4 aut
700	1	a Hernandez-Cardenas, Carmen M.u Inst Nacl Enfermedades Resp Ismael Cosio Villegas, Crit Care Dept, Ciudad De Mexico, Mexico.4 aut
700	1	a Hills, Thomasu Med Res Inst New Zealand, Wellington, New Zealand.;Auckland City Hosp, Auckland, New Zealand.4 aut
700	1	a Hoepelman, Andy I. M.u Univ Med Ctr Utrecht, Dept Infect Dis, Utrecht, Netherlands.4 aut
700	1	a Huang, Yi-Wenu Minist Hlth & Welf, Dept Internal Med, Chang Hua Hosp, Changhua, Taiwan.4 aut
700	1	a Igau, Brunou Sanofi, Bridgewater, NJ USA.4 aut
700	1	a Jin, Ronghuau Capital Med Univ, Beijing Youan Hosp, Beijing, Peoples R China.4 aut
700	1	a Jurado-Camacho, Felipeu Inst Nacl Enfermedades Resp Ismael Cosio Villegas, Crit Care Dept, Ciudad De Mexico, Mexico.4 aut
700	1	a Khan, Khalid S.u Univ Granada, Hosp Real, Dept Prevent Med & Publ Hlth, Ave Hosp, Granada, Spain.4 aut
700	1	a Kremsner, Peter G.u Univ Tubingen, Inst Trop Med, Tubingen, Germany.;Ctr Rech Med Lambarene, Lambarene, Gabon.;German Ctr Infect Res, Partner Site Tubingen, Tubingen, Germany.4 aut
700	1	a Kreuels, Bennou Univ Med Ctr Hamburg Eppendorf, Dept Med, Div Trop Med, Hamburg, Germany.;Univ Med Ctr Hamburg Eppendorf, Div Infect Dis, Hamburg, Germany.;Bernhard Nocht Inst Trop Med, Dept Trop Med, Hamburg, Germany.4 aut
700	1	a Kuo, Cheng-Yuu Minist Hlth & Welf, Dept Internal Med, Pingtung Hosp, Pingtung, Taiwan.4 aut
700	1	a Le, Thuy4 aut
700	1	a Lin, Yi-Chunu Minist Hlth & Welf, Dept Infect Dis, Taoyuan Gen Hosp, Taoyuan, Taiwan.4 aut
700	1	a Lin, Wu-Puu Minist Hlth & Welf, Dept Internal Med, Taipei Hosp, New Taipei, Taiwan.4 aut
700	1	a Lin, Tse-Hungu Minist Hlth & Welf, Dept Internal Med, Chang Hua Hosp, Changhua, Taiwan.4 aut
700	1	a Lyngbakken, Magnus Nakremu Univ Oslo, Fac Med, Inst Clin Med, Oslo, Norway.;Akershus Univ Hosp, Div Med, Lorenskog, Norway.4 aut
700	1	a McArthur, Colinu Med Res Inst New Zealand, Wellington, New Zealand.;Auckland City Hosp, Auckland, New Zealand.;Monash Univ, Australian & New Zealand Intens Care Res Ctr, Sch Epidemiol & Prevent Med, Melbourne, Vic, Australia.4 aut
700	1	a McVerry, Bryan J.u Univ Pittsburgh, Dept Med, Pittsburgh, PA USA.4 aut
700	1	a Meza-Meneses, Patriciau Hosp Reg Alta Especialidad Ixtapaluca, Ixtapaluca, Mexico.4 aut
700	1	a Monteiro, Wuelton M.u Fundacao Med Trop Dr Heitor Vieira Dourado, Manaus, Amazonas, Brazil.;Univ Estado Amazonas, Manaus, Amazonas, Brazil.4 aut
700	1	a Morpeth, Susan C.u Middlemore Hosp, Auckland, New Zealand.4 aut
700	1	a Mourad, Ahmadu Duke Univ, Dept Med, Med Ctr, Durham, NC 27710 USA.4 aut
700	1	a Mulligan, Mark J.u NYU Grossman Sch Med, Dept Microbiol, New York, NY USA.;NYU Grossman Sch Med, Dept Internal Med, Div Infect Dis & Immunol, New York, NY USA.4 aut
700	1	a Murthy, Srinivasu Univ British Columbia, Sch Med, Vancouver, BC, Canada.4 aut
700	1	a Naggie, Susannau Duke Univ, Med Ctr, Dept Med, Div Infect Dis & Int Hlth, Durham, NC 27710 USA.4 aut
700	1	a Narayanasamy, Shantiu Duke Univ, Med Ctr, Dept Med, Div Infect Dis & Int Hlth, Durham, NC 27710 USA.4 aut
700	1	a Nichol, Alistairu Monash Univ, Australian & New Zealand Intens Care Res Ctr, Sch Epidemiol & Prevent Med, Melbourne, Vic, Australia.;Alfred Hlth, Dept Intens Care, Melbourne, Vic, Australia.;St Vincents Univ Hosp, Dept Anesthesia & Intens Care, Dublin, Ireland.;Univ Coll Dublin, Sch Med & Med Sci, Dublin, Ireland.4 aut
700	1	a Novack, Lewis A.u Harvard Med Sch, Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA.4 aut
700	1	a O'Brien, Sean M.u Duke Univ, Dept Biostat & Bioinformat, Med Ctr, Durham, NC USA.;Duke Clin Res Inst, Durham, NC USA.4 aut
700	1	a Okeke, Nwora Lanceu Duke Univ, Med Ctr, Dept Med, Div Infect Dis & Int Hlth, Durham, NC 27710 USA.4 aut
700	1	a Perez, Lenau Excelya, Montpellier, France.4 aut
700	1	a Perez-Padilla, Rogeliou Inst Nacl Enfermedades Resp Ismael Casio Villegas, Dept Smoking & COPD, Ciudad De Mexico, Mexico.4 aut
700	1	a Perrin, Laurentu Sanofi, Montpellier, France.4 aut
700	1	a Remigio-Luna, Arantxau Inst Nacl Enfermedades Resp Ismael Casio Villegas, Dept Smoking & COPD, Ciudad De Mexico, Mexico.4 aut
700	1	a Rivera-Martinez, Norma E.u Hosp Reg Alta Especialidad Oaxaca, Oaxaca, Oaxaca, Mexico.4 aut
700	1	a Rockhold, Frank W.u Duke Univ, Dept Biostat & Bioinformat, Med Ctr, Durham, NC USA.;Duke Clin Res Inst, Durham, NC USA.4 aut
700	1	a Rodriguez-Llamazares, Sebastianu Inst Nacl Enfermedades Resp Ismael Casio Villegas, Dept Smoking & COPD, Ciudad De Mexico, Mexico.4 aut
700	1	a Rolfe, Robertu Duke Univ, Med Ctr, Dept Med, Div Infect Dis & Int Hlth, Durham, NC 27710 USA.4 aut
700	1	a Rosa, Rossanau UnityPoint Hlth, Des Moines, IA USA.4 aut
700	1	a Rosjo, Helgeu Univ Oslo, Fac Med, Inst Clin Med, Oslo, Norway.;Akershus Univ Hosp, Div Res & Innovat, Lorenskog, Norway.4 aut
700	1	a Sampaio, Vanderson S.u Fundacao Med Trop Dr Heitor Vieira Dourado, Manaus, Amazonas, Brazil.;Fundacao Vigilancia Saude Amazonas, Manaus, Amazonas, Brazil.4 aut
700	1	a Seto, Todd B.u Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA.;Queens Med Ctr, Honolulu, HI USA.4 aut
700	1	a Shahzad, Muhammadu Univ Hlth Sci, Dept Pharmacol, Lahore, Punjab, Pakistan.4 aut
700	1	a Soliman, Shaimaau Menoufia Univ, Publ Hlth & Community Med, Menoufia, Egypt.4 aut
700	1	a Stout, Jason E.u Duke Univ, Med Ctr, Dept Med, Div Infect Dis & Int Hlth, Durham, NC 27710 USA.4 aut
700	1	a Thirion-Romero, Ireriu Inst Nacl Enfermedades Resp Ismael Casio Villegas, Dept Smoking & COPD, Ciudad De Mexico, Mexico.4 aut
700	1	a Troxel, Andrea B.u NYU Grossman Sch Med, Dept Populat Hlth, Div Biostat, New York, NY USA.4 aut
700	1	a Tseng, Ting-Yuu Minist Hlth & Welf, Dept Internal Med, Taichung Hosp, Taichung, Taiwan.4 aut
700	1	a Turner, Nicholas A.u Duke Univ, Med Ctr, Dept Med, Div Infect Dis & Int Hlth, Durham, NC 27710 USA.4 aut
700	1	a Ulrich, Robert J.u NYU Grossman Sch Med, Dept Med, Div Infect Dis & Immunol, New York, NY USA.4 aut
700	1	a Walsh, Stephen R.u Brigham & Womens Hosp, Div Infect Dis, 75 Francis St, Boston, MA 02115 USA.4 aut
700	1	a Webb, Steve A.u Monash Univ, Australian & New Zealand Intens Care Res Ctr, Sch Epidemiol & Prevent Med, Melbourne, Vic, Australia.;St John God Hosp, Subiaco, WA, Australia.4 aut
700	1	a Weehuizen, Jesper M.u Univ Med Ctr Utrecht, Dept Infect Dis, Utrecht, Netherlands.4 aut
700	1	a Velinova, Mariau PRA Hlth Sci, Groningen, Netherlands.4 aut
700	1	a Wong, Hon-Laiu Minist Hlth & Welf, Dept Internal Med, Keelung Hosp, Keelung, Taiwan.4 aut
700	1	a Wrenn, Rebekahu Duke Univ, Med Ctr, Dept Med, Div Infect Dis & Int Hlth, Durham, NC 27710 USA.4 aut
700	1	a Zampieri, Fernando G.u HCor Hosp Coracao, Res Inst, Sao Paulo, Brazil.;BRICNet Brazilian Res Intens Care Network, Res Inst, Sao Paulo, Brazil.;IDor Res Inst, Sao Paulo, Brazil.4 aut
700	1	a Zhong, Wuu Beijing Inst Pharmacol & Toxicol, Natl Engn Res Ctr Emergency Drug, Beijing, Peoples R China.4 aut
700	1	a Moher, Davidu Ottawa Hosp Res Inst, Ctr Journalol, Clin Epidemiol Program, Ottawa, ON, Canada.4 aut
700	1	a Goodman, Steven N.u Stanford Univ, Meta Res Innovat Ctr Stanford METRICS, Stanford, CA 94305 USA.;Stanford Univ, Sch Med, Stanford, CA 94305 USA.;Stanford Univ, Dept Epidemiol & Populat Hlth, Sch Med, Stanford, CA 94305 USA.4 aut
700	1	a Ioannidis, John P. A.u Stanford Univ, Meta Res Innovat Ctr Stanford METRICS, Stanford, CA 94305 USA.;Stanford Univ, Sch Med, Stanford, CA 94305 USA.;Stanford Univ, Dept Epidemiol & Populat Hlth, Sch Med, Stanford, CA 94305 USA.;Stanford Univ, Dept Med, Stanford Prevent Res Ctr, Stanford, CA 94305 USA.;Berlin Inst Hlth, Meta Res Innovat Ctr Berlin METRIC B, Berlin, Germany.4 aut
700	1	a Hemkens, Lars G.u Stanford Univ, Meta Res Innovat Ctr Stanford METRICS, Stanford, CA 94305 USA.;Univ Basel, Univ Hosp Basel, Dept Clin Res, Basel, Switzerland.;Berlin Inst Hlth, Meta Res Innovat Ctr Berlin METRIC B, Berlin, Germany.4 aut
710	2	a Uppsala universitetb Obstetrisk och reproduktiv hälsoforskning4 org
773	0	t Nature Communicationsd : Springer Natureg 12:1q 12:1x 2041-1723
856	4	u https://doi.org/10.1038/s41467-021-22446-zy Fulltext
856	4	u https://uu.diva-portal.org/smash/get/diva2:1556288/FULLTEXT01.pdfx primaryx Raw objecty fulltext:print
856	4	u https://www.nature.com/articles/s41467-021-22446-z.pdf
856	4 8	u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-442888
856	4 8	u https://doi.org/10.1038/s41467-021-22446-z

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By the author/editor: Axfors, Cathrine; Schmitt, Andreas ...; Janiaud, Perrine; van't Hooft, Jan ...; Abd-Elsalam, She ...; Abdo, Ehab F.; show more...; Abella, Benjamin ...; Akram, Javed; Amaravadi, Ravi ...; Angus, Derek C.; Arabi, Yaseen M.; Azhar, Shehnoor; Baden, Lindsey R ...; Baker, Arthur W.; Belkhir, Leila; Benfield, Thomas; Berrevoets, Marv ...; Chen, Cheng-Pin; Chen, Tsung-Chia; Cheng, Shu-Hsing; Cheng, Chien-Yu; Chung, Wei-Sheng; Cohen, Yehuda Z.; Cowan, Lisa N.; Dalgard, Olav; de Almeida e Val ...; de Lacerda, Marc ...; de Melo, Gisely ...; Derde, Lennie; Dubee, Vincent; Elfakir, Anissa; Gordon, Anthony ...; Hernandez-Carden ...; Hills, Thomas; Hoepelman, Andy ...; Huang, Yi-Wen; Igau, Bruno; Jin, Ronghua; Jurado-Camacho, ...; Khan, Khalid S.; Kremsner, Peter ...; Kreuels, Benno; Kuo, Cheng-Yu; Le, Thuy; Lin, Yi-Chun; Lin, Wu-Pu; Lin, Tse-Hung; Lyngbakken, Magn ...; McArthur, Colin; McVerry, Bryan J ...; Meza-Meneses, Pa ...; Monteiro, Wuelto ...; Morpeth, Susan C ...; Mourad, Ahmad; Mulligan, Mark J ...; Murthy, Srinivas; Naggie, Susanna; Narayanasamy, Sh ...; Nichol, Alistair; Novack, Lewis A.; O'Brien, Sean M.; Okeke, Nwora Lan ...; Perez, Lena; Perez-Padilla, R ...; Perrin, Laurent; Remigio-Luna, Ar ...; Rivera-Martinez, ...; Rockhold, Frank ...; Rodriguez-Llamaz ...; Rolfe, Robert; Rosa, Rossana; Rosjo, Helge; Sampaio, Vanders ...; Seto, Todd B.; Shahzad, Muhamma ...; Soliman, Shaimaa; Stout, Jason E.; Thirion-Romero, ...; Troxel, Andrea B ...; Tseng, Ting-Yu; Turner, Nicholas ...; Ulrich, Robert J ...; Walsh, Stephen R ...; Webb, Steve A.; Weehuizen, Jespe ...; Velinova, Maria; Wong, Hon-Lai; Wrenn, Rebekah; Zampieri, Fernan ...; Zhong, Wu; Moher, David; Goodman, Steven ...; Ioannidis, John ...; Hemkens, Lars G.; show less...

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