New insights into acute-on-chronic kidney disease in nephrology patients: the CKD-REIN study
BACKGROUNDAcute-on-chronic kidney disease (ACKD) is poorly understood and often overlooked. We studied its incidence, circumstances, determinants and outcomes in patients with CKD. METHODSWe used the Kidney Disease: Improving Global Outcomes criteria to identify all-stage acute kidney injury (AKI) e...
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| Veröffentlicht in: | Nephrology, dialysis, transplantation dialysis, transplantation, 2022-08, Vol.37 (9), p.1700-1709 |
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| creator | Hamroun, Aghilès Frimat, Luc Laville, Maurice Metzger, Marie Combe, Christian Fouque, Denis Jacquelinet, Christian Ayav, Carole Liabeuf, Sophie Lange, Céline Herpe, Yves-Edouard Zee, Jarcy Glowacki, François Massy, Ziad A Robinson, Bruce Stengel, Bénédicte Ayav, Carole Briançon, Serge Cannet, Dorothée Combe, Christian Fouque, Denis Frimat, Luc Herpe, Yves-Edouard Jacquelinet, Christian Laville, Maurice Massy, Ziad A Pascal, Christophe Robinson, Bruce M Stengel, Bénédicte Lange, Céline Legrand, Karine Liabeuf, Sophie Metzger, Marie Speyer, Elodie Hannedouche, Prs Thierry Moulin, Bruno Mailliez, Sébastien Lebrun, Gaétan Magnant, Eric Choukroun, Gabriel Deroure, Benjamin Lacraz, Adeline Lambrey, Guy Bourdenx, Jean Philippe Essig, Marie Lobbedez, Thierry Azar, Raymond Sekhri, Hacène Smati, Mustafa Jamali, Mohamed Klein, Alexandre Delahousse, Michel Martin, Séverine Landru, Isabelle Thervet, Eric Lang, Philippe Belenfant, Xavier Urena, Pablo Vela, Carlos Kamar, Nassim Chauveau, Dominique Panescu, Viktor Noel, Christian Glowacki, François Hoffmann, Maxime Hourmant, Maryvonne Besnier, Dominique Testa, Angelo Kuentz, François Zaoui, Philippe Chazot, Charles Juillard, Laurent Burtey, Stéphane Keller, Adrien Maisonneuve, Nathalie |
| description | BACKGROUNDAcute-on-chronic kidney disease (ACKD) is poorly understood and often overlooked. We studied its incidence, circumstances, determinants and outcomes in patients with CKD. METHODSWe used the Kidney Disease: Improving Global Outcomes criteria to identify all-stage acute kidney injury (AKI) events in 3033 nephrology outpatients with CKD Stages 3-5 participating in the CKD-Renal Epidemiology and Information Network cohort study (2013-20), and cause-specific Cox models to estimate hazard ratios [HRs; 95% confidence intervals (CIs)] of AKI-associated risk factors. RESULTSAt baseline, 22% of the patients [mean age 67 years, 65% men, mean estimated glomerular filtration rate (eGFR) 32 mL/min/1.73 m2] had a history of AKI. Over a 3-year follow-up, 443 had at least one AKI event: 27% were Stage 2 or 3 and 11% required dialysis; 74% involved hospitalization including 47% acquired as hospital inpatients; and a third were not reported in hospital discharge reports. Incidence rates were 10.1 and 4.8/100 person-years in patients with and without an AKI history, respectively. In 2375 patients without this history, male sex, diabetes, cardiovascular disease, cirrhosis, several drugs, low eGFR and serum albumin levels were significantly associated with a higher risk of AKI, as were low birth weight ( |
| doi_str_mv | 10.1093/ndt/gfab249 |
| format | Article |
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We studied its incidence, circumstances, determinants and outcomes in patients with CKD. METHODSWe used the Kidney Disease: Improving Global Outcomes criteria to identify all-stage acute kidney injury (AKI) events in 3033 nephrology outpatients with CKD Stages 3-5 participating in the CKD-Renal Epidemiology and Information Network cohort study (2013-20), and cause-specific Cox models to estimate hazard ratios [HRs; 95% confidence intervals (CIs)] of AKI-associated risk factors. RESULTSAt baseline, 22% of the patients [mean age 67 years, 65% men, mean estimated glomerular filtration rate (eGFR) 32 mL/min/1.73 m2] had a history of AKI. Over a 3-year follow-up, 443 had at least one AKI event: 27% were Stage 2 or 3 and 11% required dialysis; 74% involved hospitalization including 47% acquired as hospital inpatients; and a third were not reported in hospital discharge reports. Incidence rates were 10.1 and 4.8/100 person-years in patients with and without an AKI history, respectively. In 2375 patients without this history, male sex, diabetes, cardiovascular disease, cirrhosis, several drugs, low eGFR and serum albumin levels were significantly associated with a higher risk of AKI, as were low birth weight (<2500 g) (adjusted HR 1.98; 95% CI 1.35-2.91) and haemoglobin level (HR 1.21; 1.12-1.32 per 1 g/dL decrease). Within 1 year, only 63% of the patients had recovered their previous kidney function, 13.7% had started kidney replacement therapy and 12.7% had died. CONCLUSIONSThe study highlights the high rate of hospital-acquired AKI events in patients with CKD, and their underreporting at hospital discharge. It also reveals low birth weight and anaemia as possible new risk factors in CKD patients.</description><identifier>ISSN: 0931-0509</identifier><identifier>EISSN: 1460-2385</identifier><identifier>DOI: 10.1093/ndt/gfab249</identifier><language>eng</language><publisher>Oxford University Press</publisher><subject>Human health and pathology ; Life Sciences</subject><ispartof>Nephrology, dialysis, transplantation, 2022-08, Vol.37 (9), p.1700-1709</ispartof><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c300t-c6a7818a6794b955d61fe3aa19cbac854d8ebee6cc89c05ff751ce456cf11fcb3</citedby><cites>FETCH-LOGICAL-c300t-c6a7818a6794b955d61fe3aa19cbac854d8ebee6cc89c05ff751ce456cf11fcb3</cites><orcidid>0000-0001-5384-9006 ; 0000-0002-0360-573X ; 0000-0002-1490-7549 ; 0000-0001-5771-5996 ; 0000-0002-9707-7199 ; 0000-0002-0570-0917</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://u-picardie.hal.science/hal-03760907$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Hamroun, Aghilès</creatorcontrib><creatorcontrib>Frimat, Luc</creatorcontrib><creatorcontrib>Laville, Maurice</creatorcontrib><creatorcontrib>Metzger, Marie</creatorcontrib><creatorcontrib>Combe, Christian</creatorcontrib><creatorcontrib>Fouque, Denis</creatorcontrib><creatorcontrib>Jacquelinet, Christian</creatorcontrib><creatorcontrib>Ayav, Carole</creatorcontrib><creatorcontrib>Liabeuf, Sophie</creatorcontrib><creatorcontrib>Lange, Céline</creatorcontrib><creatorcontrib>Herpe, Yves-Edouard</creatorcontrib><creatorcontrib>Zee, Jarcy</creatorcontrib><creatorcontrib>Glowacki, François</creatorcontrib><creatorcontrib>Massy, Ziad A</creatorcontrib><creatorcontrib>Robinson, Bruce</creatorcontrib><creatorcontrib>Stengel, Bénédicte</creatorcontrib><creatorcontrib>Ayav, Carole</creatorcontrib><creatorcontrib>Briançon, Serge</creatorcontrib><creatorcontrib>Cannet, Dorothée</creatorcontrib><creatorcontrib>Combe, Christian</creatorcontrib><creatorcontrib>Fouque, Denis</creatorcontrib><creatorcontrib>Frimat, Luc</creatorcontrib><creatorcontrib>Herpe, Yves-Edouard</creatorcontrib><creatorcontrib>Jacquelinet, Christian</creatorcontrib><creatorcontrib>Laville, Maurice</creatorcontrib><creatorcontrib>Massy, Ziad A</creatorcontrib><creatorcontrib>Pascal, Christophe</creatorcontrib><creatorcontrib>Robinson, Bruce M</creatorcontrib><creatorcontrib>Stengel, Bénédicte</creatorcontrib><creatorcontrib>Lange, Céline</creatorcontrib><creatorcontrib>Legrand, Karine</creatorcontrib><creatorcontrib>Liabeuf, Sophie</creatorcontrib><creatorcontrib>Metzger, Marie</creatorcontrib><creatorcontrib>Speyer, Elodie</creatorcontrib><creatorcontrib>Hannedouche, Prs Thierry</creatorcontrib><creatorcontrib>Moulin, Bruno</creatorcontrib><creatorcontrib>Mailliez, Sébastien</creatorcontrib><creatorcontrib>Lebrun, Gaétan</creatorcontrib><creatorcontrib>Magnant, Eric</creatorcontrib><creatorcontrib>Choukroun, Gabriel</creatorcontrib><creatorcontrib>Deroure, Benjamin</creatorcontrib><creatorcontrib>Lacraz, Adeline</creatorcontrib><creatorcontrib>Lambrey, Guy</creatorcontrib><creatorcontrib>Bourdenx, Jean Philippe</creatorcontrib><creatorcontrib>Essig, Marie</creatorcontrib><creatorcontrib>Lobbedez, Thierry</creatorcontrib><creatorcontrib>Azar, Raymond</creatorcontrib><creatorcontrib>Sekhri, Hacène</creatorcontrib><creatorcontrib>Smati, Mustafa</creatorcontrib><creatorcontrib>Jamali, Mohamed</creatorcontrib><creatorcontrib>Klein, Alexandre</creatorcontrib><creatorcontrib>Delahousse, Michel</creatorcontrib><creatorcontrib>Martin, Séverine</creatorcontrib><creatorcontrib>Landru, Isabelle</creatorcontrib><creatorcontrib>Thervet, Eric</creatorcontrib><creatorcontrib>Lang, Philippe</creatorcontrib><creatorcontrib>Belenfant, Xavier</creatorcontrib><creatorcontrib>Urena, Pablo</creatorcontrib><creatorcontrib>Vela, Carlos</creatorcontrib><creatorcontrib>Kamar, Nassim</creatorcontrib><creatorcontrib>Chauveau, Dominique</creatorcontrib><creatorcontrib>Panescu, Viktor</creatorcontrib><creatorcontrib>Noel, Christian</creatorcontrib><creatorcontrib>Glowacki, François</creatorcontrib><creatorcontrib>Hoffmann, Maxime</creatorcontrib><creatorcontrib>Hourmant, Maryvonne</creatorcontrib><creatorcontrib>Besnier, Dominique</creatorcontrib><creatorcontrib>Testa, Angelo</creatorcontrib><creatorcontrib>Kuentz, François</creatorcontrib><creatorcontrib>Zaoui, Philippe</creatorcontrib><creatorcontrib>Chazot, Charles</creatorcontrib><creatorcontrib>Juillard, Laurent</creatorcontrib><creatorcontrib>Burtey, Stéphane</creatorcontrib><creatorcontrib>Keller, Adrien</creatorcontrib><creatorcontrib>Maisonneuve, Nathalie</creatorcontrib><creatorcontrib>Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) study group</creatorcontrib><title>New insights into acute-on-chronic kidney disease in nephrology patients: the CKD-REIN study</title><title>Nephrology, dialysis, transplantation</title><description>BACKGROUNDAcute-on-chronic kidney disease (ACKD) is poorly understood and often overlooked. We studied its incidence, circumstances, determinants and outcomes in patients with CKD. METHODSWe used the Kidney Disease: Improving Global Outcomes criteria to identify all-stage acute kidney injury (AKI) events in 3033 nephrology outpatients with CKD Stages 3-5 participating in the CKD-Renal Epidemiology and Information Network cohort study (2013-20), and cause-specific Cox models to estimate hazard ratios [HRs; 95% confidence intervals (CIs)] of AKI-associated risk factors. RESULTSAt baseline, 22% of the patients [mean age 67 years, 65% men, mean estimated glomerular filtration rate (eGFR) 32 mL/min/1.73 m2] had a history of AKI. Over a 3-year follow-up, 443 had at least one AKI event: 27% were Stage 2 or 3 and 11% required dialysis; 74% involved hospitalization including 47% acquired as hospital inpatients; and a third were not reported in hospital discharge reports. Incidence rates were 10.1 and 4.8/100 person-years in patients with and without an AKI history, respectively. In 2375 patients without this history, male sex, diabetes, cardiovascular disease, cirrhosis, several drugs, low eGFR and serum albumin levels were significantly associated with a higher risk of AKI, as were low birth weight (<2500 g) (adjusted HR 1.98; 95% CI 1.35-2.91) and haemoglobin level (HR 1.21; 1.12-1.32 per 1 g/dL decrease). Within 1 year, only 63% of the patients had recovered their previous kidney function, 13.7% had started kidney replacement therapy and 12.7% had died. CONCLUSIONSThe study highlights the high rate of hospital-acquired AKI events in patients with CKD, and their underreporting at hospital discharge. It also reveals low birth weight and anaemia as possible new risk factors in CKD patients.</description><subject>Human health and pathology</subject><subject>Life Sciences</subject><issn>0931-0509</issn><issn>1460-2385</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><recordid>eNo9kFFLwzAUhYMoOKdP_oE8KlKXNE3a-CZzuuGYIPomhDS92aJdW5tU6b-3Y8One7jn4zx8CF1SckuJZJOqCJO11XmcyCM0ookgUcwyfoxGQ0sjwok8RWfefxJCZJymI_Sxgl_sKu_Wm-CHEGqsTRcgqqvIbNq6cgZ_uaKCHhfOg_YwQLiCZujKet3jRgcHVfB3OGwAT58fotfZYoV96Ir-HJ1YXXq4ONwxen-cvU3n0fLlaTG9X0aGERIiI3Sa0UyLVCa55LwQ1ALTmkqTa5PxpMggBxDGZNIQbm3KqYGEC2MptSZnY3S9393oUjWt2-q2V7V2an6_VLsfYakgkqQ_dGCv9mzT1t8d-KC2zhsoS11B3XkVc5FxyWImBvRmj5q29r4F-79Nidr5VoNvdfDN_gAPS3Tl</recordid><startdate>20220822</startdate><enddate>20220822</enddate><creator>Hamroun, Aghilès</creator><creator>Frimat, Luc</creator><creator>Laville, Maurice</creator><creator>Metzger, Marie</creator><creator>Combe, 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Guy</creatorcontrib><creatorcontrib>Bourdenx, Jean Philippe</creatorcontrib><creatorcontrib>Essig, Marie</creatorcontrib><creatorcontrib>Lobbedez, Thierry</creatorcontrib><creatorcontrib>Azar, Raymond</creatorcontrib><creatorcontrib>Sekhri, Hacène</creatorcontrib><creatorcontrib>Smati, Mustafa</creatorcontrib><creatorcontrib>Jamali, Mohamed</creatorcontrib><creatorcontrib>Klein, Alexandre</creatorcontrib><creatorcontrib>Delahousse, Michel</creatorcontrib><creatorcontrib>Martin, Séverine</creatorcontrib><creatorcontrib>Landru, Isabelle</creatorcontrib><creatorcontrib>Thervet, Eric</creatorcontrib><creatorcontrib>Lang, Philippe</creatorcontrib><creatorcontrib>Belenfant, Xavier</creatorcontrib><creatorcontrib>Urena, Pablo</creatorcontrib><creatorcontrib>Vela, Carlos</creatorcontrib><creatorcontrib>Kamar, Nassim</creatorcontrib><creatorcontrib>Chauveau, Dominique</creatorcontrib><creatorcontrib>Panescu, Viktor</creatorcontrib><creatorcontrib>Noel, Christian</creatorcontrib><creatorcontrib>Glowacki, François</creatorcontrib><creatorcontrib>Hoffmann, Maxime</creatorcontrib><creatorcontrib>Hourmant, Maryvonne</creatorcontrib><creatorcontrib>Besnier, Dominique</creatorcontrib><creatorcontrib>Testa, Angelo</creatorcontrib><creatorcontrib>Kuentz, François</creatorcontrib><creatorcontrib>Zaoui, Philippe</creatorcontrib><creatorcontrib>Chazot, Charles</creatorcontrib><creatorcontrib>Juillard, Laurent</creatorcontrib><creatorcontrib>Burtey, Stéphane</creatorcontrib><creatorcontrib>Keller, Adrien</creatorcontrib><creatorcontrib>Maisonneuve, Nathalie</creatorcontrib><creatorcontrib>Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) study group</creatorcontrib><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Nephrology, dialysis, transplantation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hamroun, Aghilès</au><au>Frimat, Luc</au><au>Laville, Maurice</au><au>Metzger, Marie</au><au>Combe, Christian</au><au>Fouque, Denis</au><au>Jacquelinet, Christian</au><au>Ayav, Carole</au><au>Liabeuf, Sophie</au><au>Lange, Céline</au><au>Herpe, Yves-Edouard</au><au>Zee, Jarcy</au><au>Glowacki, François</au><au>Massy, Ziad A</au><au>Robinson, Bruce</au><au>Stengel, Bénédicte</au><au>Ayav, Carole</au><au>Briançon, Serge</au><au>Cannet, Dorothée</au><au>Combe, Christian</au><au>Fouque, Denis</au><au>Frimat, Luc</au><au>Herpe, Yves-Edouard</au><au>Jacquelinet, Christian</au><au>Laville, Maurice</au><au>Massy, Ziad A</au><au>Pascal, Christophe</au><au>Robinson, Bruce M</au><au>Stengel, Bénédicte</au><au>Lange, Céline</au><au>Legrand, Karine</au><au>Liabeuf, Sophie</au><au>Metzger, Marie</au><au>Speyer, Elodie</au><au>Hannedouche, Prs Thierry</au><au>Moulin, Bruno</au><au>Mailliez, Sébastien</au><au>Lebrun, Gaétan</au><au>Magnant, Eric</au><au>Choukroun, Gabriel</au><au>Deroure, Benjamin</au><au>Lacraz, Adeline</au><au>Lambrey, Guy</au><au>Bourdenx, Jean Philippe</au><au>Essig, Marie</au><au>Lobbedez, Thierry</au><au>Azar, Raymond</au><au>Sekhri, Hacène</au><au>Smati, Mustafa</au><au>Jamali, Mohamed</au><au>Klein, Alexandre</au><au>Delahousse, Michel</au><au>Martin, Séverine</au><au>Landru, Isabelle</au><au>Thervet, Eric</au><au>Lang, Philippe</au><au>Belenfant, Xavier</au><au>Urena, Pablo</au><au>Vela, Carlos</au><au>Kamar, Nassim</au><au>Chauveau, Dominique</au><au>Panescu, Viktor</au><au>Noel, Christian</au><au>Glowacki, François</au><au>Hoffmann, Maxime</au><au>Hourmant, Maryvonne</au><au>Besnier, Dominique</au><au>Testa, Angelo</au><au>Kuentz, François</au><au>Zaoui, Philippe</au><au>Chazot, Charles</au><au>Juillard, Laurent</au><au>Burtey, Stéphane</au><au>Keller, Adrien</au><au>Maisonneuve, Nathalie</au><aucorp>Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) study group</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>New insights into acute-on-chronic kidney disease in nephrology patients: the CKD-REIN study</atitle><jtitle>Nephrology, dialysis, transplantation</jtitle><date>2022-08-22</date><risdate>2022</risdate><volume>37</volume><issue>9</issue><spage>1700</spage><epage>1709</epage><pages>1700-1709</pages><issn>0931-0509</issn><eissn>1460-2385</eissn><abstract>BACKGROUNDAcute-on-chronic kidney disease (ACKD) is poorly understood and often overlooked. We studied its incidence, circumstances, determinants and outcomes in patients with CKD. METHODSWe used the Kidney Disease: Improving Global Outcomes criteria to identify all-stage acute kidney injury (AKI) events in 3033 nephrology outpatients with CKD Stages 3-5 participating in the CKD-Renal Epidemiology and Information Network cohort study (2013-20), and cause-specific Cox models to estimate hazard ratios [HRs; 95% confidence intervals (CIs)] of AKI-associated risk factors. RESULTSAt baseline, 22% of the patients [mean age 67 years, 65% men, mean estimated glomerular filtration rate (eGFR) 32 mL/min/1.73 m2] had a history of AKI. Over a 3-year follow-up, 443 had at least one AKI event: 27% were Stage 2 or 3 and 11% required dialysis; 74% involved hospitalization including 47% acquired as hospital inpatients; and a third were not reported in hospital discharge reports. Incidence rates were 10.1 and 4.8/100 person-years in patients with and without an AKI history, respectively. In 2375 patients without this history, male sex, diabetes, cardiovascular disease, cirrhosis, several drugs, low eGFR and serum albumin levels were significantly associated with a higher risk of AKI, as were low birth weight (<2500 g) (adjusted HR 1.98; 95% CI 1.35-2.91) and haemoglobin level (HR 1.21; 1.12-1.32 per 1 g/dL decrease). Within 1 year, only 63% of the patients had recovered their previous kidney function, 13.7% had started kidney replacement therapy and 12.7% had died. CONCLUSIONSThe study highlights the high rate of hospital-acquired AKI events in patients with CKD, and their underreporting at hospital discharge. It also reveals low birth weight and anaemia as possible new risk factors in CKD patients.</abstract><pub>Oxford University Press</pub><doi>10.1093/ndt/gfab249</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0001-5384-9006</orcidid><orcidid>https://orcid.org/0000-0002-0360-573X</orcidid><orcidid>https://orcid.org/0000-0002-1490-7549</orcidid><orcidid>https://orcid.org/0000-0001-5771-5996</orcidid><orcidid>https://orcid.org/0000-0002-9707-7199</orcidid><orcidid>https://orcid.org/0000-0002-0570-0917</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0931-0509 |
| ispartof | Nephrology, dialysis, transplantation, 2022-08, Vol.37 (9), p.1700-1709 |
| issn | 0931-0509 1460-2385 |
| language | eng |
| recordid | cdi_hal_primary_oai_HAL_hal_03760907v1 |
| source | Oxford Academic Journals (OUP); Alma/SFX Local Collection; EZB Electronic Journals Library |
| subjects | Human health and pathology Life Sciences |
| title | New insights into acute-on-chronic kidney disease in nephrology patients: the CKD-REIN study |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-14T13%3A52%3A49IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_hal_p&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=New%20insights%20into%20acute-on-chronic%20kidney%20disease%20in%20nephrology%20patients:%20the%20CKD-REIN%20study&rft.jtitle=Nephrology,%20dialysis,%20transplantation&rft.au=Hamroun,%20Aghil%C3%A8s&rft.aucorp=Chronic%20Kidney%20Disease-Renal%20Epidemiology%20and%20Information%20Network%20(CKD-REIN)%20study%20group&rft.date=2022-08-22&rft.volume=37&rft.issue=9&rft.spage=1700&rft.epage=1709&rft.pages=1700-1709&rft.issn=0931-0509&rft.eissn=1460-2385&rft_id=info:doi/10.1093/ndt/gfab249&rft_dat=%3Cproquest_hal_p%3E2568593236%3C/proquest_hal_p%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2568593236&rft_id=info:pmid/&rfr_iscdi=true |