What do we know about micronutrients in critically ill patients? A narrative review

Micronutrient (MN) status alterations (both depletion and deficiency) are associated with several complications and worse outcomes in critically ill patients. On the other side of the spectrum, improving MN status has been shown to be a potential co‐adjuvant therapy. This review aims to collect exis...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:JPEN. Journal of parenteral and enteral nutrition 2024-11
Hauptverfasser: de Man, Angelique M. E., Stoppe, C., Koekkoek, W. A. C., Briassoulis, G., Subasinghe, S. D. L. P., Cobilinschi, C., Deane, A. M., Manzanares, W., Grințescu, I., Mirea, L., Roshdy, A., Cotoia, A., Bear, D. E., Boraso, S., Fraipont, V., Christopher, K. B., Casaer, M., Gunst, J., Pantet, O., Elhadi, M., Bolondi, G., Forceville, X., Angstwurm, M. W. A., Gurjar, M., Biondi, R., van Zanten, A. R. H., Berger, M. M.
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page
container_issue
container_start_page
container_title JPEN. Journal of parenteral and enteral nutrition
container_volume
creator de Man, Angelique M. E.
Stoppe, C.
Koekkoek, W. A. C.
Briassoulis, G.
Subasinghe, S. D. L. P.
Cobilinschi, C.
Deane, A. M.
Manzanares, W.
Grințescu, I.
Mirea, L.
Roshdy, A.
Cotoia, A.
Bear, D. E.
Boraso, S.
Fraipont, V.
Christopher, K. B.
Casaer, M.
Gunst, J.
Pantet, O.
Elhadi, M.
Bolondi, G.
Forceville, X.
Angstwurm, M. W. A.
Gurjar, M.
Biondi, R.
van Zanten, A. R. H.
Berger, M. M.
description Micronutrient (MN) status alterations (both depletion and deficiency) are associated with several complications and worse outcomes in critically ill patients. On the other side of the spectrum, improving MN status has been shown to be a potential co‐adjuvant therapy. This review aims to collect existing data to better guide research in the critical care setting. This narrative review was conducted by the European Society of Intensive Care Medicine Feeding, Rehabilitation, Endocrinology, and Metabolism MN group. The primary objective was to identify studies focusing on individual MNs in critically ill patients, selecting the MNs that appear to be most relevant and most frequently investigated in the last decade: A, B 1 , B 2 , B 3 , B 6 , folate, C, D, E, copper, iron, selenium, zinc, and carnitine. Given the limited number of interventional studies for most MNs, observational studies were included. For each selected MN, the review summarizes the main form and functions, special needs and risk factors, optimal treatment strategies, pharmacological dosing, and clinical implications all specific to critically ill patients. A rigorous rebalancing of research strategies and priorities is needed to improve clinical practice. An important finding is that high‐dose monotherapy of MNs is not recommended. Basal daily needs must be provided, with higher doses in diseases with known higher needs, and identified deficiencies treated. Finally, the review provides a list of ongoing trials on MNs in critically ill patients and identifies a priority list of future research topics.
doi_str_mv 10.1002/jpen.2700
format Article
fullrecord <record><control><sourceid>proquest_hal_p</sourceid><recordid>TN_cdi_hal_primary_oai_HAL_hal_04797338v1</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3129689655</sourcerecordid><originalsourceid>FETCH-LOGICAL-c1015-2b70bb8dc7fb6d310e0f8c836d8117370656545d65809214982599555af933c23</originalsourceid><addsrcrecordid>eNpFkE1Lw0AQhhdRbK0e_Ad71EPqbPb7JKWoFQoeVDwum2RDt6ZJ3E1a-u9trOhpmHlfHoYHoWsCUwKQ3q1bV09TCXCCxkQzkqSMsVM0BsJUIkCSEbqIcQ0AVACcoxHVnHMl-Bi9fqxsh4sG7xz-rJsdtlnTd3jj89DUfRe8q7uIfY3z4Duf26raY19VuLXdT3SPZ7i2IRzWrcPBbb3bXaKz0lbRXf3OCXp_fHibL5Lly9PzfLZMcgKEJ2kmIctUkcsyEwUl4KBUuaKiUIRIKkFwwRkvBFegU8K0SrkeHrelpjRP6QTdHrkrW5k2-I0Ne9NYbxazpRluwKSWlKotOXRvjt02NF-9i53Z-Ji7qrK1a_poKEm1UFpw_o89KIgxuPKPTcAMvs3g2wy-6TejPW8u</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3129689655</pqid></control><display><type>article</type><title>What do we know about micronutrients in critically ill patients? A narrative review</title><source>Access via Wiley Online Library</source><creator>de Man, Angelique M. E. ; Stoppe, C. ; Koekkoek, W. A. C. ; Briassoulis, G. ; Subasinghe, S. D. L. P. ; Cobilinschi, C. ; Deane, A. M. ; Manzanares, W. ; Grințescu, I. ; Mirea, L. ; Roshdy, A. ; Cotoia, A. ; Bear, D. E. ; Boraso, S. ; Fraipont, V. ; Christopher, K. B. ; Casaer, M. ; Gunst, J. ; Pantet, O. ; Elhadi, M. ; Bolondi, G. ; Forceville, X. ; Angstwurm, M. W. A. ; Gurjar, M. ; Biondi, R. ; van Zanten, A. R. H. ; Berger, M. M.</creator><creatorcontrib>de Man, Angelique M. E. ; Stoppe, C. ; Koekkoek, W. A. C. ; Briassoulis, G. ; Subasinghe, S. D. L. P. ; Cobilinschi, C. ; Deane, A. M. ; Manzanares, W. ; Grințescu, I. ; Mirea, L. ; Roshdy, A. ; Cotoia, A. ; Bear, D. E. ; Boraso, S. ; Fraipont, V. ; Christopher, K. B. ; Casaer, M. ; Gunst, J. ; Pantet, O. ; Elhadi, M. ; Bolondi, G. ; Forceville, X. ; Angstwurm, M. W. A. ; Gurjar, M. ; Biondi, R. ; van Zanten, A. R. H. ; Berger, M. M. ; ESICM/FREM MN group</creatorcontrib><description>Micronutrient (MN) status alterations (both depletion and deficiency) are associated with several complications and worse outcomes in critically ill patients. On the other side of the spectrum, improving MN status has been shown to be a potential co‐adjuvant therapy. This review aims to collect existing data to better guide research in the critical care setting. This narrative review was conducted by the European Society of Intensive Care Medicine Feeding, Rehabilitation, Endocrinology, and Metabolism MN group. The primary objective was to identify studies focusing on individual MNs in critically ill patients, selecting the MNs that appear to be most relevant and most frequently investigated in the last decade: A, B 1 , B 2 , B 3 , B 6 , folate, C, D, E, copper, iron, selenium, zinc, and carnitine. Given the limited number of interventional studies for most MNs, observational studies were included. For each selected MN, the review summarizes the main form and functions, special needs and risk factors, optimal treatment strategies, pharmacological dosing, and clinical implications all specific to critically ill patients. A rigorous rebalancing of research strategies and priorities is needed to improve clinical practice. An important finding is that high‐dose monotherapy of MNs is not recommended. Basal daily needs must be provided, with higher doses in diseases with known higher needs, and identified deficiencies treated. Finally, the review provides a list of ongoing trials on MNs in critically ill patients and identifies a priority list of future research topics.</description><identifier>ISSN: 0148-6071</identifier><identifier>ISSN: 1941-2444</identifier><identifier>EISSN: 1941-2444</identifier><identifier>DOI: 10.1002/jpen.2700</identifier><identifier>PMID: 39555865</identifier><language>eng</language><publisher>SAGE Publications (UK and US)</publisher><subject>Food and Nutrition ; Life Sciences</subject><ispartof>JPEN. Journal of parenteral and enteral nutrition, 2024-11</ispartof><rights>2024 The Author(s). Journal of Parenteral and Enteral Nutrition published by Wiley Periodicals LLC on behalf of American Society for Parenteral and Enteral Nutrition.</rights><rights>Attribution - NonCommercial</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c1015-2b70bb8dc7fb6d310e0f8c836d8117370656545d65809214982599555af933c23</cites><orcidid>0000-0002-8489-0324 ; 0000-0001-8738-8295 ; 0000-0002-2028-2039 ; 0000-0003-2470-6393 ; 0000-0001-6276-7192 ; 0000-0002-7620-5577 ; 0000-0001-6679-2504 ; 0000-0002-5627-8445 ; 0000-0002-0812-3617 ; 0000-0001-5211-5553 ; 0000-0001-5427-1648 ; 0000-0002-8656-9606 ; 0000-0001-6067-972X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,782,786,887,27933,27934</link.rule.ids><backlink>$$Uhttps://univ-rennes.hal.science/hal-04797338$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>de Man, Angelique M. E.</creatorcontrib><creatorcontrib>Stoppe, C.</creatorcontrib><creatorcontrib>Koekkoek, W. A. C.</creatorcontrib><creatorcontrib>Briassoulis, G.</creatorcontrib><creatorcontrib>Subasinghe, S. D. L. P.</creatorcontrib><creatorcontrib>Cobilinschi, C.</creatorcontrib><creatorcontrib>Deane, A. M.</creatorcontrib><creatorcontrib>Manzanares, W.</creatorcontrib><creatorcontrib>Grințescu, I.</creatorcontrib><creatorcontrib>Mirea, L.</creatorcontrib><creatorcontrib>Roshdy, A.</creatorcontrib><creatorcontrib>Cotoia, A.</creatorcontrib><creatorcontrib>Bear, D. E.</creatorcontrib><creatorcontrib>Boraso, S.</creatorcontrib><creatorcontrib>Fraipont, V.</creatorcontrib><creatorcontrib>Christopher, K. B.</creatorcontrib><creatorcontrib>Casaer, M.</creatorcontrib><creatorcontrib>Gunst, J.</creatorcontrib><creatorcontrib>Pantet, O.</creatorcontrib><creatorcontrib>Elhadi, M.</creatorcontrib><creatorcontrib>Bolondi, G.</creatorcontrib><creatorcontrib>Forceville, X.</creatorcontrib><creatorcontrib>Angstwurm, M. W. A.</creatorcontrib><creatorcontrib>Gurjar, M.</creatorcontrib><creatorcontrib>Biondi, R.</creatorcontrib><creatorcontrib>van Zanten, A. R. H.</creatorcontrib><creatorcontrib>Berger, M. M.</creatorcontrib><creatorcontrib>ESICM/FREM MN group</creatorcontrib><title>What do we know about micronutrients in critically ill patients? A narrative review</title><title>JPEN. Journal of parenteral and enteral nutrition</title><description>Micronutrient (MN) status alterations (both depletion and deficiency) are associated with several complications and worse outcomes in critically ill patients. On the other side of the spectrum, improving MN status has been shown to be a potential co‐adjuvant therapy. This review aims to collect existing data to better guide research in the critical care setting. This narrative review was conducted by the European Society of Intensive Care Medicine Feeding, Rehabilitation, Endocrinology, and Metabolism MN group. The primary objective was to identify studies focusing on individual MNs in critically ill patients, selecting the MNs that appear to be most relevant and most frequently investigated in the last decade: A, B 1 , B 2 , B 3 , B 6 , folate, C, D, E, copper, iron, selenium, zinc, and carnitine. Given the limited number of interventional studies for most MNs, observational studies were included. For each selected MN, the review summarizes the main form and functions, special needs and risk factors, optimal treatment strategies, pharmacological dosing, and clinical implications all specific to critically ill patients. A rigorous rebalancing of research strategies and priorities is needed to improve clinical practice. An important finding is that high‐dose monotherapy of MNs is not recommended. Basal daily needs must be provided, with higher doses in diseases with known higher needs, and identified deficiencies treated. Finally, the review provides a list of ongoing trials on MNs in critically ill patients and identifies a priority list of future research topics.</description><subject>Food and Nutrition</subject><subject>Life Sciences</subject><issn>0148-6071</issn><issn>1941-2444</issn><issn>1941-2444</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNpFkE1Lw0AQhhdRbK0e_Ad71EPqbPb7JKWoFQoeVDwum2RDt6ZJ3E1a-u9trOhpmHlfHoYHoWsCUwKQ3q1bV09TCXCCxkQzkqSMsVM0BsJUIkCSEbqIcQ0AVACcoxHVnHMl-Bi9fqxsh4sG7xz-rJsdtlnTd3jj89DUfRe8q7uIfY3z4Duf26raY19VuLXdT3SPZ7i2IRzWrcPBbb3bXaKz0lbRXf3OCXp_fHibL5Lly9PzfLZMcgKEJ2kmIctUkcsyEwUl4KBUuaKiUIRIKkFwwRkvBFegU8K0SrkeHrelpjRP6QTdHrkrW5k2-I0Ne9NYbxazpRluwKSWlKotOXRvjt02NF-9i53Z-Ji7qrK1a_poKEm1UFpw_o89KIgxuPKPTcAMvs3g2wy-6TejPW8u</recordid><startdate>20241118</startdate><enddate>20241118</enddate><creator>de Man, Angelique M. E.</creator><creator>Stoppe, C.</creator><creator>Koekkoek, W. A. C.</creator><creator>Briassoulis, G.</creator><creator>Subasinghe, S. D. L. P.</creator><creator>Cobilinschi, C.</creator><creator>Deane, A. M.</creator><creator>Manzanares, W.</creator><creator>Grințescu, I.</creator><creator>Mirea, L.</creator><creator>Roshdy, A.</creator><creator>Cotoia, A.</creator><creator>Bear, D. E.</creator><creator>Boraso, S.</creator><creator>Fraipont, V.</creator><creator>Christopher, K. B.</creator><creator>Casaer, M.</creator><creator>Gunst, J.</creator><creator>Pantet, O.</creator><creator>Elhadi, M.</creator><creator>Bolondi, G.</creator><creator>Forceville, X.</creator><creator>Angstwurm, M. W. A.</creator><creator>Gurjar, M.</creator><creator>Biondi, R.</creator><creator>van Zanten, A. R. H.</creator><creator>Berger, M. M.</creator><general>SAGE Publications (UK and US)</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>1XC</scope><scope>VOOES</scope><orcidid>https://orcid.org/0000-0002-8489-0324</orcidid><orcidid>https://orcid.org/0000-0001-8738-8295</orcidid><orcidid>https://orcid.org/0000-0002-2028-2039</orcidid><orcidid>https://orcid.org/0000-0003-2470-6393</orcidid><orcidid>https://orcid.org/0000-0001-6276-7192</orcidid><orcidid>https://orcid.org/0000-0002-7620-5577</orcidid><orcidid>https://orcid.org/0000-0001-6679-2504</orcidid><orcidid>https://orcid.org/0000-0002-5627-8445</orcidid><orcidid>https://orcid.org/0000-0002-0812-3617</orcidid><orcidid>https://orcid.org/0000-0001-5211-5553</orcidid><orcidid>https://orcid.org/0000-0001-5427-1648</orcidid><orcidid>https://orcid.org/0000-0002-8656-9606</orcidid><orcidid>https://orcid.org/0000-0001-6067-972X</orcidid></search><sort><creationdate>20241118</creationdate><title>What do we know about micronutrients in critically ill patients? A narrative review</title><author>de Man, Angelique M. E. ; Stoppe, C. ; Koekkoek, W. A. C. ; Briassoulis, G. ; Subasinghe, S. D. L. P. ; Cobilinschi, C. ; Deane, A. M. ; Manzanares, W. ; Grințescu, I. ; Mirea, L. ; Roshdy, A. ; Cotoia, A. ; Bear, D. E. ; Boraso, S. ; Fraipont, V. ; Christopher, K. B. ; Casaer, M. ; Gunst, J. ; Pantet, O. ; Elhadi, M. ; Bolondi, G. ; Forceville, X. ; Angstwurm, M. W. A. ; Gurjar, M. ; Biondi, R. ; van Zanten, A. R. H. ; Berger, M. M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1015-2b70bb8dc7fb6d310e0f8c836d8117370656545d65809214982599555af933c23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Food and Nutrition</topic><topic>Life Sciences</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>de Man, Angelique M. E.</creatorcontrib><creatorcontrib>Stoppe, C.</creatorcontrib><creatorcontrib>Koekkoek, W. A. C.</creatorcontrib><creatorcontrib>Briassoulis, G.</creatorcontrib><creatorcontrib>Subasinghe, S. D. L. P.</creatorcontrib><creatorcontrib>Cobilinschi, C.</creatorcontrib><creatorcontrib>Deane, A. M.</creatorcontrib><creatorcontrib>Manzanares, W.</creatorcontrib><creatorcontrib>Grințescu, I.</creatorcontrib><creatorcontrib>Mirea, L.</creatorcontrib><creatorcontrib>Roshdy, A.</creatorcontrib><creatorcontrib>Cotoia, A.</creatorcontrib><creatorcontrib>Bear, D. E.</creatorcontrib><creatorcontrib>Boraso, S.</creatorcontrib><creatorcontrib>Fraipont, V.</creatorcontrib><creatorcontrib>Christopher, K. B.</creatorcontrib><creatorcontrib>Casaer, M.</creatorcontrib><creatorcontrib>Gunst, J.</creatorcontrib><creatorcontrib>Pantet, O.</creatorcontrib><creatorcontrib>Elhadi, M.</creatorcontrib><creatorcontrib>Bolondi, G.</creatorcontrib><creatorcontrib>Forceville, X.</creatorcontrib><creatorcontrib>Angstwurm, M. W. A.</creatorcontrib><creatorcontrib>Gurjar, M.</creatorcontrib><creatorcontrib>Biondi, R.</creatorcontrib><creatorcontrib>van Zanten, A. R. H.</creatorcontrib><creatorcontrib>Berger, M. M.</creatorcontrib><creatorcontrib>ESICM/FREM MN group</creatorcontrib><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><jtitle>JPEN. Journal of parenteral and enteral nutrition</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>de Man, Angelique M. E.</au><au>Stoppe, C.</au><au>Koekkoek, W. A. C.</au><au>Briassoulis, G.</au><au>Subasinghe, S. D. L. P.</au><au>Cobilinschi, C.</au><au>Deane, A. M.</au><au>Manzanares, W.</au><au>Grințescu, I.</au><au>Mirea, L.</au><au>Roshdy, A.</au><au>Cotoia, A.</au><au>Bear, D. E.</au><au>Boraso, S.</au><au>Fraipont, V.</au><au>Christopher, K. B.</au><au>Casaer, M.</au><au>Gunst, J.</au><au>Pantet, O.</au><au>Elhadi, M.</au><au>Bolondi, G.</au><au>Forceville, X.</au><au>Angstwurm, M. W. A.</au><au>Gurjar, M.</au><au>Biondi, R.</au><au>van Zanten, A. R. H.</au><au>Berger, M. M.</au><aucorp>ESICM/FREM MN group</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>What do we know about micronutrients in critically ill patients? A narrative review</atitle><jtitle>JPEN. Journal of parenteral and enteral nutrition</jtitle><date>2024-11-18</date><risdate>2024</risdate><issn>0148-6071</issn><issn>1941-2444</issn><eissn>1941-2444</eissn><abstract>Micronutrient (MN) status alterations (both depletion and deficiency) are associated with several complications and worse outcomes in critically ill patients. On the other side of the spectrum, improving MN status has been shown to be a potential co‐adjuvant therapy. This review aims to collect existing data to better guide research in the critical care setting. This narrative review was conducted by the European Society of Intensive Care Medicine Feeding, Rehabilitation, Endocrinology, and Metabolism MN group. The primary objective was to identify studies focusing on individual MNs in critically ill patients, selecting the MNs that appear to be most relevant and most frequently investigated in the last decade: A, B 1 , B 2 , B 3 , B 6 , folate, C, D, E, copper, iron, selenium, zinc, and carnitine. Given the limited number of interventional studies for most MNs, observational studies were included. For each selected MN, the review summarizes the main form and functions, special needs and risk factors, optimal treatment strategies, pharmacological dosing, and clinical implications all specific to critically ill patients. A rigorous rebalancing of research strategies and priorities is needed to improve clinical practice. An important finding is that high‐dose monotherapy of MNs is not recommended. Basal daily needs must be provided, with higher doses in diseases with known higher needs, and identified deficiencies treated. Finally, the review provides a list of ongoing trials on MNs in critically ill patients and identifies a priority list of future research topics.</abstract><pub>SAGE Publications (UK and US)</pub><pmid>39555865</pmid><doi>10.1002/jpen.2700</doi><orcidid>https://orcid.org/0000-0002-8489-0324</orcidid><orcidid>https://orcid.org/0000-0001-8738-8295</orcidid><orcidid>https://orcid.org/0000-0002-2028-2039</orcidid><orcidid>https://orcid.org/0000-0003-2470-6393</orcidid><orcidid>https://orcid.org/0000-0001-6276-7192</orcidid><orcidid>https://orcid.org/0000-0002-7620-5577</orcidid><orcidid>https://orcid.org/0000-0001-6679-2504</orcidid><orcidid>https://orcid.org/0000-0002-5627-8445</orcidid><orcidid>https://orcid.org/0000-0002-0812-3617</orcidid><orcidid>https://orcid.org/0000-0001-5211-5553</orcidid><orcidid>https://orcid.org/0000-0001-5427-1648</orcidid><orcidid>https://orcid.org/0000-0002-8656-9606</orcidid><orcidid>https://orcid.org/0000-0001-6067-972X</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0148-6071
ispartof JPEN. Journal of parenteral and enteral nutrition, 2024-11
issn 0148-6071
1941-2444
1941-2444
language eng
recordid cdi_hal_primary_oai_HAL_hal_04797338v1
source Access via Wiley Online Library
subjects Food and Nutrition
Life Sciences
title What do we know about micronutrients in critically ill patients? A narrative review
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-03T03%3A20%3A31IST&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=What%20do%20we%20know%20about%20micronutrients%20in%20critically%20ill%20patients?%20A%20narrative%20review&rft.jtitle=JPEN.%20Journal%20of%20parenteral%20and%20enteral%20nutrition&rft.au=de%20Man,%20Angelique%20M.%20E.&rft.aucorp=ESICM/FREM%20MN%20group&rft.date=2024-11-18&rft.issn=0148-6071&rft.eissn=1941-2444&rft_id=info:doi/10.1002/jpen.2700&rft_dat=%3Cproquest_hal_p%3E3129689655%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=3129689655&rft_id=info:pmid/39555865&rfr_iscdi=true