Loading…
Frailty based on the memorial Sloan Kettering Frailty Index is associated with surgical decision making, clinical trial participation, and overall survival among older women with ovarian cancer
To determine whether the Memorial Sloan Kettering Frailty Index (MSK-FI) is associated with decision-making in older women surgically treated for advanced-stage ovarian cancer. We retrospectively applied the MSK-FI to women ≥70 years with newly diagnosed advanced-stage ovarian cancer surgically trea...
Saved in:
| Published in: | Gynecologic oncology 2021-06, Vol.161 (3), p.687-692 |
|---|---|
| Main Authors: | , , , , , , , , , , |
| Format: | Article |
| Language: | English |
| Subjects: | |
| Citations: | Items that this one cites Items that cite this one |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| cited_by | cdi_FETCH-LOGICAL-c459t-3ada525d912cf259ba4cfe972150d0ba1b8c8cd507424025f58083326bad1adb3 |
|---|---|
| cites | cdi_FETCH-LOGICAL-c459t-3ada525d912cf259ba4cfe972150d0ba1b8c8cd507424025f58083326bad1adb3 |
| container_end_page | 692 |
| container_issue | 3 |
| container_start_page | 687 |
| container_title | Gynecologic oncology |
| container_volume | 161 |
| creator | Filippova, Olga T. Tin, Amy L. Alonso, Joanne Vickers, Andrew J. Tew, William P. Gardner, Ginger J. Sonoda, Yukio Roche, Kara Long Zivanovic, Oliver Chi, Dennis S. Shahrokni, Armin |
| description | To determine whether the Memorial Sloan Kettering Frailty Index (MSK-FI) is associated with decision-making in older women surgically treated for advanced-stage ovarian cancer.
We retrospectively applied the MSK-FI to women ≥70 years with newly diagnosed advanced-stage ovarian cancer surgically treated at our institution from 01/2001–05/2017. MSK-FI components, including 10 comorbidities and functional assessment, were extracted from medical records. The MSK-FI ranges from 0 to 11, with higher scores indicating greater frailty. The primary outcome was the association between frailty and rate of primary debulking surgery (PDS), for which a multivariable logistic regression was used, adjusted for stage and histology.
We identified 430 women treated with PDS (n = 231, 54%) or neoadjuvant chemotherapy/interval debulking (n = 199, 46%) with complete data. MSK-FI score distribution was: “0”, 95 patients (22%); “1”, 172 (40%); “2”, 89 (21%); and “3+”, 74 (17%). More-frail patients were less likely to have undergone PDS (OR for a unit increase of MSK-FI: 0.64; 95%CI, 0.53–0.77; p |
| doi_str_mv | 10.1016/j.ygyno.2021.03.016 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8164977</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0090825821002523</els_id><sourcerecordid>2506504793</sourcerecordid><originalsourceid>FETCH-LOGICAL-c459t-3ada525d912cf259ba4cfe972150d0ba1b8c8cd507424025f58083326bad1adb3</originalsourceid><addsrcrecordid>eNp9kc1uEzEUhS0EomngCZCQlyya4J9xZmYBEqooVFRiAaytO_ZN4jBjB9uZksfjzeokbQUbVpauv3PO1T2EvOJszhlfvN3M96u9D3PBBJ8zOS-zJ2TCWatmi0a1T8mEsZbNGqGaM3Ke0oYxJhkXz8mZlHUtG1ZPyJ-rCK7Pe9pBQkuDp3mNdMAhRAc9_dYH8PQL5ozR-RV9oK-9xd_UJQopBeMgF-2ty2uadnHlTFFaNC654jfAz6K8oKZ3_viTj85biNkZt4VcoAsKvoSPGKHvDx6jGwsDQyiZobcY6W0Y0J8ywgjFwlMD3mB8QZ4toU_48v6dkh9XH79ffp7dfP10ffnhZmYq1eaZBAtKKNtyYZZCtR1UZoltLbhilnXAu8Y0xipWV6JiQi1VwxopxaIDy8F2ckren3y3u25Aa9Dnsq3eRjdA3OsATv_7491ar8KoG76o2nLvKXlzbxDDrx2mrAeXDPY9eAy7pIViC8WqupUFlSfUxJBSxOVjDGf6UL7e6GP5-lC-ZlKXWVG9_nvDR81D2wV4dwKw3Gl0GHUyDssRrYtosrbB_TfgDsn0yEo</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2506504793</pqid></control><display><type>article</type><title>Frailty based on the memorial Sloan Kettering Frailty Index is associated with surgical decision making, clinical trial participation, and overall survival among older women with ovarian cancer</title><source>ScienceDirect Freedom Collection 2022-2024</source><creator>Filippova, Olga T. ; Tin, Amy L. ; Alonso, Joanne ; Vickers, Andrew J. ; Tew, William P. ; Gardner, Ginger J. ; Sonoda, Yukio ; Roche, Kara Long ; Zivanovic, Oliver ; Chi, Dennis S. ; Shahrokni, Armin</creator><creatorcontrib>Filippova, Olga T. ; Tin, Amy L. ; Alonso, Joanne ; Vickers, Andrew J. ; Tew, William P. ; Gardner, Ginger J. ; Sonoda, Yukio ; Roche, Kara Long ; Zivanovic, Oliver ; Chi, Dennis S. ; Shahrokni, Armin</creatorcontrib><description>To determine whether the Memorial Sloan Kettering Frailty Index (MSK-FI) is associated with decision-making in older women surgically treated for advanced-stage ovarian cancer.
We retrospectively applied the MSK-FI to women ≥70 years with newly diagnosed advanced-stage ovarian cancer surgically treated at our institution from 01/2001–05/2017. MSK-FI components, including 10 comorbidities and functional assessment, were extracted from medical records. The MSK-FI ranges from 0 to 11, with higher scores indicating greater frailty. The primary outcome was the association between frailty and rate of primary debulking surgery (PDS), for which a multivariable logistic regression was used, adjusted for stage and histology.
We identified 430 women treated with PDS (n = 231, 54%) or neoadjuvant chemotherapy/interval debulking (n = 199, 46%) with complete data. MSK-FI score distribution was: “0”, 95 patients (22%); “1”, 172 (40%); “2”, 89 (21%); and “3+”, 74 (17%). More-frail patients were less likely to have undergone PDS (OR for a unit increase of MSK-FI: 0.64; 95%CI, 0.53–0.77; p < 0.0001). Grade 3+ complications and unintended intensive care admission occurred in 40 (9%) and 38 (9%) women, respectively, but were not associated with frailty (OR 1.21; 95%CI, 0.96–1.52; p = 0.11). More-frail patients were more likely to delay postoperative chemotherapy (non-linear association p = 0.009) and less likely to enroll in research (OR 0.84; 95%CI, 0.70–1.00; p = 0.049). Greater frailty was associated with poorer overall survival (HR 1.16; 95%CI, 1.05–1.30; p = 0.005).
Frailty, as calculated by the MSK-FI, is strongly associated with treatment approach in older women with advanced ovarian cancer, suggesting objective or subjective correlates of the MSK-FI influence decision-making.
•Higher MSK-FI score was associated with forgoing primary debulking surgery.•Higher MSK-FI score was associated with delays in chemotherapy and worse overall survival.•Major complications or unintended intensive care unit admission were not associated with frailty.</description><identifier>ISSN: 0090-8258</identifier><identifier>EISSN: 1095-6859</identifier><identifier>DOI: 10.1016/j.ygyno.2021.03.016</identifier><identifier>PMID: 33773807</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Aged ; Aged, 80 and over ; Carcinoma, Ovarian Epithelial - mortality ; Carcinoma, Ovarian Epithelial - pathology ; Carcinoma, Ovarian Epithelial - surgery ; Clinical Decision-Making ; Cytoreduction Surgical Procedures ; Female ; Frail Elderly ; Frailty ; Frailty index ; Humans ; MSK-FI ; Neoadjuvant chemotherapy ; Neoplasm Metastasis ; New York ; Ovarian cancer ; Ovarian Neoplasms - mortality ; Ovarian Neoplasms - pathology ; Ovarian Neoplasms - surgery ; Retrospective Studies ; Surgery ; Survival Analysis</subject><ispartof>Gynecologic oncology, 2021-06, Vol.161 (3), p.687-692</ispartof><rights>2021 Elsevier Inc.</rights><rights>Copyright © 2021 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c459t-3ada525d912cf259ba4cfe972150d0ba1b8c8cd507424025f58083326bad1adb3</citedby><cites>FETCH-LOGICAL-c459t-3ada525d912cf259ba4cfe972150d0ba1b8c8cd507424025f58083326bad1adb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33773807$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Filippova, Olga T.</creatorcontrib><creatorcontrib>Tin, Amy L.</creatorcontrib><creatorcontrib>Alonso, Joanne</creatorcontrib><creatorcontrib>Vickers, Andrew J.</creatorcontrib><creatorcontrib>Tew, William P.</creatorcontrib><creatorcontrib>Gardner, Ginger J.</creatorcontrib><creatorcontrib>Sonoda, Yukio</creatorcontrib><creatorcontrib>Roche, Kara Long</creatorcontrib><creatorcontrib>Zivanovic, Oliver</creatorcontrib><creatorcontrib>Chi, Dennis S.</creatorcontrib><creatorcontrib>Shahrokni, Armin</creatorcontrib><title>Frailty based on the memorial Sloan Kettering Frailty Index is associated with surgical decision making, clinical trial participation, and overall survival among older women with ovarian cancer</title><title>Gynecologic oncology</title><addtitle>Gynecol Oncol</addtitle><description>To determine whether the Memorial Sloan Kettering Frailty Index (MSK-FI) is associated with decision-making in older women surgically treated for advanced-stage ovarian cancer.
We retrospectively applied the MSK-FI to women ≥70 years with newly diagnosed advanced-stage ovarian cancer surgically treated at our institution from 01/2001–05/2017. MSK-FI components, including 10 comorbidities and functional assessment, were extracted from medical records. The MSK-FI ranges from 0 to 11, with higher scores indicating greater frailty. The primary outcome was the association between frailty and rate of primary debulking surgery (PDS), for which a multivariable logistic regression was used, adjusted for stage and histology.
We identified 430 women treated with PDS (n = 231, 54%) or neoadjuvant chemotherapy/interval debulking (n = 199, 46%) with complete data. MSK-FI score distribution was: “0”, 95 patients (22%); “1”, 172 (40%); “2”, 89 (21%); and “3+”, 74 (17%). More-frail patients were less likely to have undergone PDS (OR for a unit increase of MSK-FI: 0.64; 95%CI, 0.53–0.77; p < 0.0001). Grade 3+ complications and unintended intensive care admission occurred in 40 (9%) and 38 (9%) women, respectively, but were not associated with frailty (OR 1.21; 95%CI, 0.96–1.52; p = 0.11). More-frail patients were more likely to delay postoperative chemotherapy (non-linear association p = 0.009) and less likely to enroll in research (OR 0.84; 95%CI, 0.70–1.00; p = 0.049). Greater frailty was associated with poorer overall survival (HR 1.16; 95%CI, 1.05–1.30; p = 0.005).
Frailty, as calculated by the MSK-FI, is strongly associated with treatment approach in older women with advanced ovarian cancer, suggesting objective or subjective correlates of the MSK-FI influence decision-making.
•Higher MSK-FI score was associated with forgoing primary debulking surgery.•Higher MSK-FI score was associated with delays in chemotherapy and worse overall survival.•Major complications or unintended intensive care unit admission were not associated with frailty.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Carcinoma, Ovarian Epithelial - mortality</subject><subject>Carcinoma, Ovarian Epithelial - pathology</subject><subject>Carcinoma, Ovarian Epithelial - surgery</subject><subject>Clinical Decision-Making</subject><subject>Cytoreduction Surgical Procedures</subject><subject>Female</subject><subject>Frail Elderly</subject><subject>Frailty</subject><subject>Frailty index</subject><subject>Humans</subject><subject>MSK-FI</subject><subject>Neoadjuvant chemotherapy</subject><subject>Neoplasm Metastasis</subject><subject>New York</subject><subject>Ovarian cancer</subject><subject>Ovarian Neoplasms - mortality</subject><subject>Ovarian Neoplasms - pathology</subject><subject>Ovarian Neoplasms - surgery</subject><subject>Retrospective Studies</subject><subject>Surgery</subject><subject>Survival Analysis</subject><issn>0090-8258</issn><issn>1095-6859</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNp9kc1uEzEUhS0EomngCZCQlyya4J9xZmYBEqooVFRiAaytO_ZN4jBjB9uZksfjzeokbQUbVpauv3PO1T2EvOJszhlfvN3M96u9D3PBBJ8zOS-zJ2TCWatmi0a1T8mEsZbNGqGaM3Ke0oYxJhkXz8mZlHUtG1ZPyJ-rCK7Pe9pBQkuDp3mNdMAhRAc9_dYH8PQL5ozR-RV9oK-9xd_UJQopBeMgF-2ty2uadnHlTFFaNC654jfAz6K8oKZ3_viTj85biNkZt4VcoAsKvoSPGKHvDx6jGwsDQyiZobcY6W0Y0J8ywgjFwlMD3mB8QZ4toU_48v6dkh9XH79ffp7dfP10ffnhZmYq1eaZBAtKKNtyYZZCtR1UZoltLbhilnXAu8Y0xipWV6JiQi1VwxopxaIDy8F2ckren3y3u25Aa9Dnsq3eRjdA3OsATv_7491ar8KoG76o2nLvKXlzbxDDrx2mrAeXDPY9eAy7pIViC8WqupUFlSfUxJBSxOVjDGf6UL7e6GP5-lC-ZlKXWVG9_nvDR81D2wV4dwKw3Gl0GHUyDssRrYtosrbB_TfgDsn0yEo</recordid><startdate>20210601</startdate><enddate>20210601</enddate><creator>Filippova, Olga T.</creator><creator>Tin, Amy L.</creator><creator>Alonso, Joanne</creator><creator>Vickers, Andrew J.</creator><creator>Tew, William P.</creator><creator>Gardner, Ginger J.</creator><creator>Sonoda, Yukio</creator><creator>Roche, Kara Long</creator><creator>Zivanovic, Oliver</creator><creator>Chi, Dennis S.</creator><creator>Shahrokni, Armin</creator><general>Elsevier Inc</general><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>5PM</scope></search><sort><creationdate>20210601</creationdate><title>Frailty based on the memorial Sloan Kettering Frailty Index is associated with surgical decision making, clinical trial participation, and overall survival among older women with ovarian cancer</title><author>Filippova, Olga T. ; Tin, Amy L. ; Alonso, Joanne ; Vickers, Andrew J. ; Tew, William P. ; Gardner, Ginger J. ; Sonoda, Yukio ; Roche, Kara Long ; Zivanovic, Oliver ; Chi, Dennis S. ; Shahrokni, Armin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c459t-3ada525d912cf259ba4cfe972150d0ba1b8c8cd507424025f58083326bad1adb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Carcinoma, Ovarian Epithelial - mortality</topic><topic>Carcinoma, Ovarian Epithelial - pathology</topic><topic>Carcinoma, Ovarian Epithelial - surgery</topic><topic>Clinical Decision-Making</topic><topic>Cytoreduction Surgical Procedures</topic><topic>Female</topic><topic>Frail Elderly</topic><topic>Frailty</topic><topic>Frailty index</topic><topic>Humans</topic><topic>MSK-FI</topic><topic>Neoadjuvant chemotherapy</topic><topic>Neoplasm Metastasis</topic><topic>New York</topic><topic>Ovarian cancer</topic><topic>Ovarian Neoplasms - mortality</topic><topic>Ovarian Neoplasms - pathology</topic><topic>Ovarian Neoplasms - surgery</topic><topic>Retrospective Studies</topic><topic>Surgery</topic><topic>Survival Analysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Filippova, Olga T.</creatorcontrib><creatorcontrib>Tin, Amy L.</creatorcontrib><creatorcontrib>Alonso, Joanne</creatorcontrib><creatorcontrib>Vickers, Andrew J.</creatorcontrib><creatorcontrib>Tew, William P.</creatorcontrib><creatorcontrib>Gardner, Ginger J.</creatorcontrib><creatorcontrib>Sonoda, Yukio</creatorcontrib><creatorcontrib>Roche, Kara Long</creatorcontrib><creatorcontrib>Zivanovic, Oliver</creatorcontrib><creatorcontrib>Chi, Dennis S.</creatorcontrib><creatorcontrib>Shahrokni, Armin</creatorcontrib><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>PubMed Central (Full Participant titles)</collection><jtitle>Gynecologic oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Filippova, Olga T.</au><au>Tin, Amy L.</au><au>Alonso, Joanne</au><au>Vickers, Andrew J.</au><au>Tew, William P.</au><au>Gardner, Ginger J.</au><au>Sonoda, Yukio</au><au>Roche, Kara Long</au><au>Zivanovic, Oliver</au><au>Chi, Dennis S.</au><au>Shahrokni, Armin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Frailty based on the memorial Sloan Kettering Frailty Index is associated with surgical decision making, clinical trial participation, and overall survival among older women with ovarian cancer</atitle><jtitle>Gynecologic oncology</jtitle><addtitle>Gynecol Oncol</addtitle><date>2021-06-01</date><risdate>2021</risdate><volume>161</volume><issue>3</issue><spage>687</spage><epage>692</epage><pages>687-692</pages><issn>0090-8258</issn><eissn>1095-6859</eissn><abstract>To determine whether the Memorial Sloan Kettering Frailty Index (MSK-FI) is associated with decision-making in older women surgically treated for advanced-stage ovarian cancer.
We retrospectively applied the MSK-FI to women ≥70 years with newly diagnosed advanced-stage ovarian cancer surgically treated at our institution from 01/2001–05/2017. MSK-FI components, including 10 comorbidities and functional assessment, were extracted from medical records. The MSK-FI ranges from 0 to 11, with higher scores indicating greater frailty. The primary outcome was the association between frailty and rate of primary debulking surgery (PDS), for which a multivariable logistic regression was used, adjusted for stage and histology.
We identified 430 women treated with PDS (n = 231, 54%) or neoadjuvant chemotherapy/interval debulking (n = 199, 46%) with complete data. MSK-FI score distribution was: “0”, 95 patients (22%); “1”, 172 (40%); “2”, 89 (21%); and “3+”, 74 (17%). More-frail patients were less likely to have undergone PDS (OR for a unit increase of MSK-FI: 0.64; 95%CI, 0.53–0.77; p < 0.0001). Grade 3+ complications and unintended intensive care admission occurred in 40 (9%) and 38 (9%) women, respectively, but were not associated with frailty (OR 1.21; 95%CI, 0.96–1.52; p = 0.11). More-frail patients were more likely to delay postoperative chemotherapy (non-linear association p = 0.009) and less likely to enroll in research (OR 0.84; 95%CI, 0.70–1.00; p = 0.049). Greater frailty was associated with poorer overall survival (HR 1.16; 95%CI, 1.05–1.30; p = 0.005).
Frailty, as calculated by the MSK-FI, is strongly associated with treatment approach in older women with advanced ovarian cancer, suggesting objective or subjective correlates of the MSK-FI influence decision-making.
•Higher MSK-FI score was associated with forgoing primary debulking surgery.•Higher MSK-FI score was associated with delays in chemotherapy and worse overall survival.•Major complications or unintended intensive care unit admission were not associated with frailty.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>33773807</pmid><doi>10.1016/j.ygyno.2021.03.016</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0090-8258 |
| ispartof | Gynecologic oncology, 2021-06, Vol.161 (3), p.687-692 |
| issn | 0090-8258 1095-6859 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8164977 |
| source | ScienceDirect Freedom Collection 2022-2024 |
| subjects | Aged Aged, 80 and over Carcinoma, Ovarian Epithelial - mortality Carcinoma, Ovarian Epithelial - pathology Carcinoma, Ovarian Epithelial - surgery Clinical Decision-Making Cytoreduction Surgical Procedures Female Frail Elderly Frailty Frailty index Humans MSK-FI Neoadjuvant chemotherapy Neoplasm Metastasis New York Ovarian cancer Ovarian Neoplasms - mortality Ovarian Neoplasms - pathology Ovarian Neoplasms - surgery Retrospective Studies Surgery Survival Analysis |
| title | Frailty based on the memorial Sloan Kettering Frailty Index is associated with surgical decision making, clinical trial participation, and overall survival among older women with ovarian cancer |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-12T02%3A43%3A35IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Frailty%20based%20on%20the%20memorial%20Sloan%20Kettering%20Frailty%20Index%20is%20associated%20with%20surgical%20decision%20making,%20clinical%20trial%20participation,%20and%20overall%20survival%20among%20older%20women%20with%20ovarian%20cancer&rft.jtitle=Gynecologic%20oncology&rft.au=Filippova,%20Olga%20T.&rft.date=2021-06-01&rft.volume=161&rft.issue=3&rft.spage=687&rft.epage=692&rft.pages=687-692&rft.issn=0090-8258&rft.eissn=1095-6859&rft_id=info:doi/10.1016/j.ygyno.2021.03.016&rft_dat=%3Cproquest_pubme%3E2506504793%3C/proquest_pubme%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c459t-3ada525d912cf259ba4cfe972150d0ba1b8c8cd507424025f58083326bad1adb3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2506504793&rft_id=info:pmid/33773807&rfr_iscdi=true |