Validation of the geriatric vulnerability score in older patients with ovarian cancer: an analysis from the GCIG-ENGOT-GINECO EWOC-1 study
Older patients with ovarian cancer represent a heterogeneous population. The French National Group of Investigators for the Study of Ovarian and Breast Cancer developed the geriatric vulnerability score (GVS) to identify geriatric parameters predictive of poor outcomes. A prospective validation of t...
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| creator | Falandry, Claire Pommeret, Fanny Gladieff, Laurence Tinquaut, Fabien Lorusso, Domenica Mouret-Reynier, Marie-Ange D'Hondt, Véronique Mollon-Grange, Delphine Floquet, Anne Abadie-Lacourtoisie, Sophie Brachet, Pierre-Emmanuel Stefani, Laetitia Rousseau, Frédérique Frenel, Jean-Sébastien Del Piano, Francesco Komulainen, Marja Warkus, Thomas Trédan, Olivier Pujade-Lauraine, Eric Freyer, Gilles |
| description | Older patients with ovarian cancer represent a heterogeneous population. The French National Group of Investigators for the Study of Ovarian and Breast Cancer developed the geriatric vulnerability score (GVS) to identify geriatric parameters predictive of poor outcomes. A prospective validation of the GVS was needed.
The EWOC-1 study (NCT02001272) was an international, open-label, phase 2, three-arm trial designed according to a two-step process. Patients aged 70 years or older with newly diagnosed stage III or IV ovarian cancer were identified and the GVS determined. Those with a GVS of 3 or greater were randomly assigned to the EWOC-1 trial, stratified by country and surgical outcome, to receive three different carboplatin with or without paclitaxel regimens; those not included in the EWOC-1 trial were followed up in the EWOC-1 registry. External validation of the GVS was a secondary endpoint of the trial. Three validation cohorts were identified: the total population (validation cohort 1 [V1], n=447), the registry-only population (validation cohort 2 [V2], n=327), and the carboplatin–paclitaxel-treated population (validation cohort 3 [V3], n=320).
From Dec 11, 2013, to Nov 16, 2018, 447 patients were included in 48 academic centres in six countries; 120 in the EWOC-1 trial and 327 in the EWOC-1 registry. Median follow-up was 19·7 (95% CI 8·5–29·7) months for the total cohort; missing values were low ( |
| doi_str_mv | 10.1016/S2666-7568(22)00002-2 |
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The EWOC-1 study (NCT02001272) was an international, open-label, phase 2, three-arm trial designed according to a two-step process. Patients aged 70 years or older with newly diagnosed stage III or IV ovarian cancer were identified and the GVS determined. Those with a GVS of 3 or greater were randomly assigned to the EWOC-1 trial, stratified by country and surgical outcome, to receive three different carboplatin with or without paclitaxel regimens; those not included in the EWOC-1 trial were followed up in the EWOC-1 registry. External validation of the GVS was a secondary endpoint of the trial. Three validation cohorts were identified: the total population (validation cohort 1 [V1], n=447), the registry-only population (validation cohort 2 [V2], n=327), and the carboplatin–paclitaxel-treated population (validation cohort 3 [V3], n=320).
From Dec 11, 2013, to Nov 16, 2018, 447 patients were included in 48 academic centres in six countries; 120 in the EWOC-1 trial and 327 in the EWOC-1 registry. Median follow-up was 19·7 (95% CI 8·5–29·7) months for the total cohort; missing values were low (<2%). According to the maximum likelihood analysis, the hazard ratio (HR) of death in V1 was 1·8 (95% CI 1·1–3·1, p=0·029) for those with a GVS of 1; 2·4 (1·4–4·0, p=0·0009) with a GVS of 2; 4·1 (2·5–7·0, p<0·0001) for a GVS of 3; 5·5 (3·3–9·3, p<0·0001) for a GVS of 4; and 9·1 (4·7–17·5, p<0·0001) for a GVS of 5 compared with a score of 0. Whatever the validation cohort, GVS of 3 or more significantly segregated two groups with different overall survival: V1 (median 13·2 [95% CI: 10·8–18·7] vs 40·8 [32·0–45·6] months; HR 2·8 [95% CI 2·2–3·7]; p<0·0001); V2 (11·9 [95% CI 8·8–18·1] vs 40·8 [32·0–45·6] months, HR 3·5 [2·5–4·9]; p<0·0001); and V3 (18·1 [95% CI 15·8–31·8] vs 43·0 [40·6–49·7] months, HR 2·6 [1·9 to 3·7]; p<0·0001).
The GVS has high prognostic performance for overall survival in patients with advanced ovarian cancer, independently of geographic and historic effect (V1), as well as treatment patterns (V3), validated in an international population. Even though the GVS is time consuming it will allow the stratification of populations for clinical research and might permit the orientation of the geriatric intervention to specific domains.
French National Cancer Institute.
For the French translation of the abstract see Supplementary Materials section.]]></description><identifier>ISSN: 2666-7568</identifier><identifier>EISSN: 2666-7568</identifier><identifier>DOI: 10.1016/S2666-7568(22)00002-2</identifier><identifier>PMID: 36098291</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Aged ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Cancer ; Carboplatin - therapeutic use ; Carcinoma, Ovarian Epithelial - drug therapy ; Female ; Humans ; Life Sciences ; Ovarian Neoplasms - drug therapy ; Paclitaxel - therapeutic use</subject><ispartof>The Lancet. Healthy longevity, 2022-03, Vol.3 (3), p.e176-e185</ispartof><rights>2022 The Authors. Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license</rights><rights>Copyright © 2022 The Authors. Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c399t-6e437803f67b8fd9d1181f3de349513a13ac74957f11bbc81286fa8a5c4dd64b3</citedby><cites>FETCH-LOGICAL-c399t-6e437803f67b8fd9d1181f3de349513a13ac74957f11bbc81286fa8a5c4dd64b3</cites><orcidid>0000-0001-5881-9383</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,781,785,865,886,27929,27930</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36098291$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-04768782$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Falandry, Claire</creatorcontrib><creatorcontrib>Pommeret, Fanny</creatorcontrib><creatorcontrib>Gladieff, Laurence</creatorcontrib><creatorcontrib>Tinquaut, Fabien</creatorcontrib><creatorcontrib>Lorusso, Domenica</creatorcontrib><creatorcontrib>Mouret-Reynier, Marie-Ange</creatorcontrib><creatorcontrib>D'Hondt, Véronique</creatorcontrib><creatorcontrib>Mollon-Grange, Delphine</creatorcontrib><creatorcontrib>Floquet, Anne</creatorcontrib><creatorcontrib>Abadie-Lacourtoisie, Sophie</creatorcontrib><creatorcontrib>Brachet, Pierre-Emmanuel</creatorcontrib><creatorcontrib>Stefani, Laetitia</creatorcontrib><creatorcontrib>Rousseau, Frédérique</creatorcontrib><creatorcontrib>Frenel, Jean-Sébastien</creatorcontrib><creatorcontrib>Del Piano, Francesco</creatorcontrib><creatorcontrib>Komulainen, Marja</creatorcontrib><creatorcontrib>Warkus, Thomas</creatorcontrib><creatorcontrib>Trédan, Olivier</creatorcontrib><creatorcontrib>Pujade-Lauraine, Eric</creatorcontrib><creatorcontrib>Freyer, Gilles</creatorcontrib><title>Validation of the geriatric vulnerability score in older patients with ovarian cancer: an analysis from the GCIG-ENGOT-GINECO EWOC-1 study</title><title>The Lancet. Healthy longevity</title><addtitle>Lancet Healthy Longev</addtitle><description><![CDATA[Older patients with ovarian cancer represent a heterogeneous population. The French National Group of Investigators for the Study of Ovarian and Breast Cancer developed the geriatric vulnerability score (GVS) to identify geriatric parameters predictive of poor outcomes. A prospective validation of the GVS was needed.
The EWOC-1 study (NCT02001272) was an international, open-label, phase 2, three-arm trial designed according to a two-step process. Patients aged 70 years or older with newly diagnosed stage III or IV ovarian cancer were identified and the GVS determined. Those with a GVS of 3 or greater were randomly assigned to the EWOC-1 trial, stratified by country and surgical outcome, to receive three different carboplatin with or without paclitaxel regimens; those not included in the EWOC-1 trial were followed up in the EWOC-1 registry. External validation of the GVS was a secondary endpoint of the trial. Three validation cohorts were identified: the total population (validation cohort 1 [V1], n=447), the registry-only population (validation cohort 2 [V2], n=327), and the carboplatin–paclitaxel-treated population (validation cohort 3 [V3], n=320).
From Dec 11, 2013, to Nov 16, 2018, 447 patients were included in 48 academic centres in six countries; 120 in the EWOC-1 trial and 327 in the EWOC-1 registry. Median follow-up was 19·7 (95% CI 8·5–29·7) months for the total cohort; missing values were low (<2%). According to the maximum likelihood analysis, the hazard ratio (HR) of death in V1 was 1·8 (95% CI 1·1–3·1, p=0·029) for those with a GVS of 1; 2·4 (1·4–4·0, p=0·0009) with a GVS of 2; 4·1 (2·5–7·0, p<0·0001) for a GVS of 3; 5·5 (3·3–9·3, p<0·0001) for a GVS of 4; and 9·1 (4·7–17·5, p<0·0001) for a GVS of 5 compared with a score of 0. Whatever the validation cohort, GVS of 3 or more significantly segregated two groups with different overall survival: V1 (median 13·2 [95% CI: 10·8–18·7] vs 40·8 [32·0–45·6] months; HR 2·8 [95% CI 2·2–3·7]; p<0·0001); V2 (11·9 [95% CI 8·8–18·1] vs 40·8 [32·0–45·6] months, HR 3·5 [2·5–4·9]; p<0·0001); and V3 (18·1 [95% CI 15·8–31·8] vs 43·0 [40·6–49·7] months, HR 2·6 [1·9 to 3·7]; p<0·0001).
The GVS has high prognostic performance for overall survival in patients with advanced ovarian cancer, independently of geographic and historic effect (V1), as well as treatment patterns (V3), validated in an international population. Even though the GVS is time consuming it will allow the stratification of populations for clinical research and might permit the orientation of the geriatric intervention to specific domains.
French National Cancer Institute.
For the French translation of the abstract see Supplementary Materials section.]]></description><subject>Aged</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Cancer</subject><subject>Carboplatin - therapeutic use</subject><subject>Carcinoma, Ovarian Epithelial - drug therapy</subject><subject>Female</subject><subject>Humans</subject><subject>Life Sciences</subject><subject>Ovarian Neoplasms - drug therapy</subject><subject>Paclitaxel - therapeutic use</subject><issn>2666-7568</issn><issn>2666-7568</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkdFq2zAUhs3YaEvXR-jQZXvhzZIdSd7NKCZzA6G5aLtdClk6XjQUK5PklLzCnnpy0oXdTQh0OHz_f9D5s-waFx9xgemnR0IpzdmM8htCbot0SE7eZBen9tt_6vPsKoSfEzPDJeb1WXZe0qLmpMYX2e9v0hoto3EDcj2Ka0A_wBsZvVFoN9oBvOyMNXGPgnIekEmc1eDRNolgiAG9mLhGbieTakBKDgr8Z5RKOUi7Dyag3rvNwbltFm0-f2hXT3m7eJg3KzT_vmpyjEIc9f599q6XNsDV63uZPX-dPzX3-XLVLpq7Za7Kuo45hapkvCh7yjre61pjzHFfaiirOn1QpqtYKlmPcdcpjgmnveRypiqtadWVl9nt0Xctrdh6s5F-L5w04v5uKaZeUTHKGSc7nNibI7v17tcIIYqNCQqslQO4MQjCcFXQqmIkobMjqrwLwUN_8saFmFITh9TEFIkgRBxSE5Puw-uIsduAPqn-ZpSAL0cA0lJ2BrwIKm1egTYeVBTamf-M-AORuaU_</recordid><startdate>202203</startdate><enddate>202203</enddate><creator>Falandry, Claire</creator><creator>Pommeret, Fanny</creator><creator>Gladieff, Laurence</creator><creator>Tinquaut, Fabien</creator><creator>Lorusso, Domenica</creator><creator>Mouret-Reynier, Marie-Ange</creator><creator>D'Hondt, Véronique</creator><creator>Mollon-Grange, Delphine</creator><creator>Floquet, Anne</creator><creator>Abadie-Lacourtoisie, Sophie</creator><creator>Brachet, Pierre-Emmanuel</creator><creator>Stefani, Laetitia</creator><creator>Rousseau, Frédérique</creator><creator>Frenel, Jean-Sébastien</creator><creator>Del Piano, Francesco</creator><creator>Komulainen, Marja</creator><creator>Warkus, Thomas</creator><creator>Trédan, Olivier</creator><creator>Pujade-Lauraine, Eric</creator><creator>Freyer, Gilles</creator><general>Elsevier Ltd</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0001-5881-9383</orcidid></search><sort><creationdate>202203</creationdate><title>Validation of the geriatric vulnerability score in older patients with ovarian cancer: an analysis from the GCIG-ENGOT-GINECO EWOC-1 study</title><author>Falandry, Claire ; Pommeret, Fanny ; Gladieff, Laurence ; Tinquaut, Fabien ; Lorusso, Domenica ; Mouret-Reynier, Marie-Ange ; D'Hondt, Véronique ; Mollon-Grange, Delphine ; Floquet, Anne ; Abadie-Lacourtoisie, Sophie ; Brachet, Pierre-Emmanuel ; Stefani, Laetitia ; Rousseau, Frédérique ; Frenel, Jean-Sébastien ; Del Piano, Francesco ; Komulainen, Marja ; Warkus, Thomas ; Trédan, Olivier ; Pujade-Lauraine, Eric ; Freyer, Gilles</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c399t-6e437803f67b8fd9d1181f3de349513a13ac74957f11bbc81286fa8a5c4dd64b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Aged</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Cancer</topic><topic>Carboplatin - therapeutic use</topic><topic>Carcinoma, Ovarian Epithelial - drug therapy</topic><topic>Female</topic><topic>Humans</topic><topic>Life Sciences</topic><topic>Ovarian Neoplasms - drug therapy</topic><topic>Paclitaxel - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Falandry, Claire</creatorcontrib><creatorcontrib>Pommeret, Fanny</creatorcontrib><creatorcontrib>Gladieff, Laurence</creatorcontrib><creatorcontrib>Tinquaut, Fabien</creatorcontrib><creatorcontrib>Lorusso, Domenica</creatorcontrib><creatorcontrib>Mouret-Reynier, Marie-Ange</creatorcontrib><creatorcontrib>D'Hondt, Véronique</creatorcontrib><creatorcontrib>Mollon-Grange, Delphine</creatorcontrib><creatorcontrib>Floquet, Anne</creatorcontrib><creatorcontrib>Abadie-Lacourtoisie, Sophie</creatorcontrib><creatorcontrib>Brachet, Pierre-Emmanuel</creatorcontrib><creatorcontrib>Stefani, Laetitia</creatorcontrib><creatorcontrib>Rousseau, Frédérique</creatorcontrib><creatorcontrib>Frenel, Jean-Sébastien</creatorcontrib><creatorcontrib>Del Piano, Francesco</creatorcontrib><creatorcontrib>Komulainen, Marja</creatorcontrib><creatorcontrib>Warkus, Thomas</creatorcontrib><creatorcontrib>Trédan, Olivier</creatorcontrib><creatorcontrib>Pujade-Lauraine, Eric</creatorcontrib><creatorcontrib>Freyer, Gilles</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>The Lancet. Healthy longevity</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Falandry, Claire</au><au>Pommeret, Fanny</au><au>Gladieff, Laurence</au><au>Tinquaut, Fabien</au><au>Lorusso, Domenica</au><au>Mouret-Reynier, Marie-Ange</au><au>D'Hondt, Véronique</au><au>Mollon-Grange, Delphine</au><au>Floquet, Anne</au><au>Abadie-Lacourtoisie, Sophie</au><au>Brachet, Pierre-Emmanuel</au><au>Stefani, Laetitia</au><au>Rousseau, Frédérique</au><au>Frenel, Jean-Sébastien</au><au>Del Piano, Francesco</au><au>Komulainen, Marja</au><au>Warkus, Thomas</au><au>Trédan, Olivier</au><au>Pujade-Lauraine, Eric</au><au>Freyer, Gilles</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Validation of the geriatric vulnerability score in older patients with ovarian cancer: an analysis from the GCIG-ENGOT-GINECO EWOC-1 study</atitle><jtitle>The Lancet. Healthy longevity</jtitle><addtitle>Lancet Healthy Longev</addtitle><date>2022-03</date><risdate>2022</risdate><volume>3</volume><issue>3</issue><spage>e176</spage><epage>e185</epage><pages>e176-e185</pages><issn>2666-7568</issn><eissn>2666-7568</eissn><abstract><![CDATA[Older patients with ovarian cancer represent a heterogeneous population. The French National Group of Investigators for the Study of Ovarian and Breast Cancer developed the geriatric vulnerability score (GVS) to identify geriatric parameters predictive of poor outcomes. A prospective validation of the GVS was needed.
The EWOC-1 study (NCT02001272) was an international, open-label, phase 2, three-arm trial designed according to a two-step process. Patients aged 70 years or older with newly diagnosed stage III or IV ovarian cancer were identified and the GVS determined. Those with a GVS of 3 or greater were randomly assigned to the EWOC-1 trial, stratified by country and surgical outcome, to receive three different carboplatin with or without paclitaxel regimens; those not included in the EWOC-1 trial were followed up in the EWOC-1 registry. External validation of the GVS was a secondary endpoint of the trial. Three validation cohorts were identified: the total population (validation cohort 1 [V1], n=447), the registry-only population (validation cohort 2 [V2], n=327), and the carboplatin–paclitaxel-treated population (validation cohort 3 [V3], n=320).
From Dec 11, 2013, to Nov 16, 2018, 447 patients were included in 48 academic centres in six countries; 120 in the EWOC-1 trial and 327 in the EWOC-1 registry. Median follow-up was 19·7 (95% CI 8·5–29·7) months for the total cohort; missing values were low (<2%). According to the maximum likelihood analysis, the hazard ratio (HR) of death in V1 was 1·8 (95% CI 1·1–3·1, p=0·029) for those with a GVS of 1; 2·4 (1·4–4·0, p=0·0009) with a GVS of 2; 4·1 (2·5–7·0, p<0·0001) for a GVS of 3; 5·5 (3·3–9·3, p<0·0001) for a GVS of 4; and 9·1 (4·7–17·5, p<0·0001) for a GVS of 5 compared with a score of 0. Whatever the validation cohort, GVS of 3 or more significantly segregated two groups with different overall survival: V1 (median 13·2 [95% CI: 10·8–18·7] vs 40·8 [32·0–45·6] months; HR 2·8 [95% CI 2·2–3·7]; p<0·0001); V2 (11·9 [95% CI 8·8–18·1] vs 40·8 [32·0–45·6] months, HR 3·5 [2·5–4·9]; p<0·0001); and V3 (18·1 [95% CI 15·8–31·8] vs 43·0 [40·6–49·7] months, HR 2·6 [1·9 to 3·7]; p<0·0001).
The GVS has high prognostic performance for overall survival in patients with advanced ovarian cancer, independently of geographic and historic effect (V1), as well as treatment patterns (V3), validated in an international population. Even though the GVS is time consuming it will allow the stratification of populations for clinical research and might permit the orientation of the geriatric intervention to specific domains.
French National Cancer Institute.
For the French translation of the abstract see Supplementary Materials section.]]></abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>36098291</pmid><doi>10.1016/S2666-7568(22)00002-2</doi><orcidid>https://orcid.org/0000-0001-5881-9383</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2666-7568 |
| ispartof | The Lancet. Healthy longevity, 2022-03, Vol.3 (3), p.e176-e185 |
| issn | 2666-7568 2666-7568 |
| language | eng |
| recordid | cdi_hal_primary_oai_HAL_hal_04768782v1 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Aged Antineoplastic Combined Chemotherapy Protocols - therapeutic use Cancer Carboplatin - therapeutic use Carcinoma, Ovarian Epithelial - drug therapy Female Humans Life Sciences Ovarian Neoplasms - drug therapy Paclitaxel - therapeutic use |
| title | Validation of the geriatric vulnerability score in older patients with ovarian cancer: an analysis from the GCIG-ENGOT-GINECO EWOC-1 study |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-15T19%3A51%3A24IST&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=Validation%20of%20the%20geriatric%20vulnerability%20score%20in%20older%20patients%20with%20ovarian%20cancer:%20an%20analysis%20from%20the%20GCIG-ENGOT-GINECO%20EWOC-1%20study&rft.jtitle=The%20Lancet.%20Healthy%20longevity&rft.au=Falandry,%20Claire&rft.date=2022-03&rft.volume=3&rft.issue=3&rft.spage=e176&rft.epage=e185&rft.pages=e176-e185&rft.issn=2666-7568&rft.eissn=2666-7568&rft_id=info:doi/10.1016/S2666-7568(22)00002-2&rft_dat=%3Cproquest_hal_p%3E2714064472%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=2714064472&rft_id=info:pmid/36098291&rft_els_id=S2666756822000022&rfr_iscdi=true |