Loading…

Preliminary study of the impact of elevated circulating plasma levels of catecholamines on opioid requirements for acute surgical pain

The objective of this study is to determine whether elevated circulating plasma catecholamine levels significantly impact opioid requirements during the first 24 hours postoperative period in individuals with acute surgical pain. We retrospectively reviewed 15 electronic medical records (EMRs) from...

Full description

Saved in:
Bibliographic Details
Published in:Journal of clinical and translational science 2021-01, Vol.5 (1), p.e114-e114, Article e114
Main Authors: Uribe-Rivera, Armando, Rasubala, Linda, Machado-Perez, Ana C, Ren, Yan-Fang, Malmström, Hans, Carinci, Adam
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-c478t-9ad293993666cd2647180ae15467acb0c5697041f8dd057cdbe65f6ac1f5b2283
cites cdi_FETCH-LOGICAL-c478t-9ad293993666cd2647180ae15467acb0c5697041f8dd057cdbe65f6ac1f5b2283
container_end_page e114
container_issue 1
container_start_page e114
container_title Journal of clinical and translational science
container_volume 5
creator Uribe-Rivera, Armando
Rasubala, Linda
Machado-Perez, Ana C
Ren, Yan-Fang
Malmström, Hans
Carinci, Adam
description The objective of this study is to determine whether elevated circulating plasma catecholamine levels significantly impact opioid requirements during the first 24 hours postoperative period in individuals with acute surgical pain. We retrospectively reviewed 15 electronic medical records (EMRs) from adults 18 years and older, with confirmed elevated plasma catecholamine levels (experimental) and 15 electronic health records (EHRs) from matched-controls for age, gender, race and type of surgery, with a follow up of 24 hours postoperatively. The total morphine milligram equivalents (MMEs) requirements from the experimental group were not statistically different when compared with controls [44.1 (13 to 163) mg versus 47.5 (13 to 151) mg respectively; p 0.4965]. However, the intraoperative MMEs showed a significant difference, among the two groups; [(experimental) 32.5 (13. to 130) mg, (control) 15 (6.5 to 130) mg; p 0.0734]. The intraoperative dosage of midazolam showed a highly significant positive correlation to the total MMEs (p 0.0005). The subjects with both elevated plasma catecholamines and hypertension used significantly higher intraoperative MMEs compared to controls [34.1 (13 to 130) mg versus 15 (6.5 to 130) mg, respectively; p 0.0292)]. Those 51 years and younger, with elevated circulating levels of catecholamines, required significantly higher levels of both the postoperative MMEs [29.1 (0 to 45) mg versus 12 (0 to 71.5) mg; (p 0.0553)] and total MMEs [544.05 (13 to 81) mg versus 29.42 (13 to 92.5) mg; (p 0.00018), when compared to controls with history of nicotine and alcohol use. This preliminary study evaluated a biologic factor, which have promising clinical usefulness for predicting analgesic requirements that can drive clinical decisions on acute surgical pain.
doi_str_mv 10.1017/cts.2020.573
format article
fullrecord <record><control><sourceid>proquest_doaj_</sourceid><recordid>TN_cdi_doaj_primary_oai_doaj_org_article_9e520eb49ef6471db47eb19306b24212</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_9e520eb49ef6471db47eb19306b24212</doaj_id><sourcerecordid>2548627605</sourcerecordid><originalsourceid>FETCH-LOGICAL-c478t-9ad293993666cd2647180ae15467acb0c5697041f8dd057cdbe65f6ac1f5b2283</originalsourceid><addsrcrecordid>eNpdkk1rFTEUhgdRbKnduZaAGxfea75nshGkaC0UdKHrkEnO3JtLZjJNMoX-AX-3GW9bWldJznl4khPepnlL8JZg0n6yJW8ppngrWvaiOaVYqE0nJXn5ZH_SnOd8wBiTjkrJ2OvmhHFKCRfytPnzM0Hwo59MukO5LO4OxQGVPSA_zsaW9QQBbk0Bh6xPdgmm-GmH5mDyaFBtQcgrZSti9zGYKoNamVCcffQOJbhZfIIRppLREBMydimA8pJ23pqAZuOnN82rwYQM5_frWfP729dfF9831z8ury6-XG8sb7uyUcZRxZRiUkrrqOQt6bABIrhsje2xFVK1mJOhcw6L1roepBiksWQQPaUdO2uujl4XzUHPyY91bh2N1_8KMe20ScXbAFqBoBh6rmBY73E9b6EnimHZU04Jra7PR9e89CM4W-dLJjyTPu9Mfq938VZ3lDIiVRV8uBekeLNALnr02UIIZoK4ZE0F7yRtJRYVff8feohLmupXrRRjUuBuFX48UjbFnBMMj48hWK950TUves2Lrnmp-LunAzzCD-lgfwFeXr2S</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2543365089</pqid></control><display><type>article</type><title>Preliminary study of the impact of elevated circulating plasma levels of catecholamines on opioid requirements for acute surgical pain</title><source>Cambridge University Press</source><source>PubMed Central</source><creator>Uribe-Rivera, Armando ; Rasubala, Linda ; Machado-Perez, Ana C ; Ren, Yan-Fang ; Malmström, Hans ; Carinci, Adam</creator><creatorcontrib>Uribe-Rivera, Armando ; Rasubala, Linda ; Machado-Perez, Ana C ; Ren, Yan-Fang ; Malmström, Hans ; Carinci, Adam</creatorcontrib><description>The objective of this study is to determine whether elevated circulating plasma catecholamine levels significantly impact opioid requirements during the first 24 hours postoperative period in individuals with acute surgical pain. We retrospectively reviewed 15 electronic medical records (EMRs) from adults 18 years and older, with confirmed elevated plasma catecholamine levels (experimental) and 15 electronic health records (EHRs) from matched-controls for age, gender, race and type of surgery, with a follow up of 24 hours postoperatively. The total morphine milligram equivalents (MMEs) requirements from the experimental group were not statistically different when compared with controls [44.1 (13 to 163) mg versus 47.5 (13 to 151) mg respectively; p 0.4965]. However, the intraoperative MMEs showed a significant difference, among the two groups; [(experimental) 32.5 (13. to 130) mg, (control) 15 (6.5 to 130) mg; p 0.0734]. The intraoperative dosage of midazolam showed a highly significant positive correlation to the total MMEs (p 0.0005). The subjects with both elevated plasma catecholamines and hypertension used significantly higher intraoperative MMEs compared to controls [34.1 (13 to 130) mg versus 15 (6.5 to 130) mg, respectively; p 0.0292)]. Those 51 years and younger, with elevated circulating levels of catecholamines, required significantly higher levels of both the postoperative MMEs [29.1 (0 to 45) mg versus 12 (0 to 71.5) mg; (p 0.0553)] and total MMEs [544.05 (13 to 81) mg versus 29.42 (13 to 92.5) mg; (p 0.00018), when compared to controls with history of nicotine and alcohol use. This preliminary study evaluated a biologic factor, which have promising clinical usefulness for predicting analgesic requirements that can drive clinical decisions on acute surgical pain.</description><identifier>ISSN: 2059-8661</identifier><identifier>EISSN: 2059-8661</identifier><identifier>DOI: 10.1017/cts.2020.573</identifier><identifier>PMID: 34221456</identifier><language>eng</language><publisher>England: Cambridge University Press</publisher><subject>acute pain ; Age ; Alcohol use ; Analgesics ; Anxiety ; Asthma ; Body mass index ; Catecholamines ; Clinical Research ; Codes ; Demographics ; Diabetes ; Dosage ; Drug abuse ; Electronic health records ; Electronic medical records ; Fibromyalgia ; Hypertension ; Informatics ; Medical records ; Midazolam ; Morphine ; morphine milligram equivalents ; Narcotics ; Nicotine ; Opioids ; Pain ; Pain management ; Plasma levels ; postoperative pain ; Postoperative period ; Re-engineering the Clinical Research Enterprise in Response to COVID-19: The CTSA Experience ; Surgery ; Variables</subject><ispartof>Journal of clinical and translational science, 2021-01, Vol.5 (1), p.e114-e114, Article e114</ispartof><rights>The Association for Clinical and Translational Science 2021.</rights><rights>The Association for Clinical and Translational Science 2021. This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the associated terms available at: https://uk.sagepub.com/en-gb/eur/reusing-open-access-and-sage-choice-content</rights><rights>The Association for Clinical and Translational Science 2021 2021 The Association for Clinical and Translational Science</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c478t-9ad293993666cd2647180ae15467acb0c5697041f8dd057cdbe65f6ac1f5b2283</citedby><cites>FETCH-LOGICAL-c478t-9ad293993666cd2647180ae15467acb0c5697041f8dd057cdbe65f6ac1f5b2283</cites><orcidid>0000-0003-3969-0216</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223169/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223169/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34221456$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Uribe-Rivera, Armando</creatorcontrib><creatorcontrib>Rasubala, Linda</creatorcontrib><creatorcontrib>Machado-Perez, Ana C</creatorcontrib><creatorcontrib>Ren, Yan-Fang</creatorcontrib><creatorcontrib>Malmström, Hans</creatorcontrib><creatorcontrib>Carinci, Adam</creatorcontrib><title>Preliminary study of the impact of elevated circulating plasma levels of catecholamines on opioid requirements for acute surgical pain</title><title>Journal of clinical and translational science</title><addtitle>J Clin Transl Sci</addtitle><description>The objective of this study is to determine whether elevated circulating plasma catecholamine levels significantly impact opioid requirements during the first 24 hours postoperative period in individuals with acute surgical pain. We retrospectively reviewed 15 electronic medical records (EMRs) from adults 18 years and older, with confirmed elevated plasma catecholamine levels (experimental) and 15 electronic health records (EHRs) from matched-controls for age, gender, race and type of surgery, with a follow up of 24 hours postoperatively. The total morphine milligram equivalents (MMEs) requirements from the experimental group were not statistically different when compared with controls [44.1 (13 to 163) mg versus 47.5 (13 to 151) mg respectively; p 0.4965]. However, the intraoperative MMEs showed a significant difference, among the two groups; [(experimental) 32.5 (13. to 130) mg, (control) 15 (6.5 to 130) mg; p 0.0734]. The intraoperative dosage of midazolam showed a highly significant positive correlation to the total MMEs (p 0.0005). The subjects with both elevated plasma catecholamines and hypertension used significantly higher intraoperative MMEs compared to controls [34.1 (13 to 130) mg versus 15 (6.5 to 130) mg, respectively; p 0.0292)]. Those 51 years and younger, with elevated circulating levels of catecholamines, required significantly higher levels of both the postoperative MMEs [29.1 (0 to 45) mg versus 12 (0 to 71.5) mg; (p 0.0553)] and total MMEs [544.05 (13 to 81) mg versus 29.42 (13 to 92.5) mg; (p 0.00018), when compared to controls with history of nicotine and alcohol use. This preliminary study evaluated a biologic factor, which have promising clinical usefulness for predicting analgesic requirements that can drive clinical decisions on acute surgical pain.</description><subject>acute pain</subject><subject>Age</subject><subject>Alcohol use</subject><subject>Analgesics</subject><subject>Anxiety</subject><subject>Asthma</subject><subject>Body mass index</subject><subject>Catecholamines</subject><subject>Clinical Research</subject><subject>Codes</subject><subject>Demographics</subject><subject>Diabetes</subject><subject>Dosage</subject><subject>Drug abuse</subject><subject>Electronic health records</subject><subject>Electronic medical records</subject><subject>Fibromyalgia</subject><subject>Hypertension</subject><subject>Informatics</subject><subject>Medical records</subject><subject>Midazolam</subject><subject>Morphine</subject><subject>morphine milligram equivalents</subject><subject>Narcotics</subject><subject>Nicotine</subject><subject>Opioids</subject><subject>Pain</subject><subject>Pain management</subject><subject>Plasma levels</subject><subject>postoperative pain</subject><subject>Postoperative period</subject><subject>Re-engineering the Clinical Research Enterprise in Response to COVID-19: The CTSA Experience</subject><subject>Surgery</subject><subject>Variables</subject><issn>2059-8661</issn><issn>2059-8661</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>DOA</sourceid><recordid>eNpdkk1rFTEUhgdRbKnduZaAGxfea75nshGkaC0UdKHrkEnO3JtLZjJNMoX-AX-3GW9bWldJznl4khPepnlL8JZg0n6yJW8ppngrWvaiOaVYqE0nJXn5ZH_SnOd8wBiTjkrJ2OvmhHFKCRfytPnzM0Hwo59MukO5LO4OxQGVPSA_zsaW9QQBbk0Bh6xPdgmm-GmH5mDyaFBtQcgrZSti9zGYKoNamVCcffQOJbhZfIIRppLREBMydimA8pJ23pqAZuOnN82rwYQM5_frWfP729dfF9831z8ury6-XG8sb7uyUcZRxZRiUkrrqOQt6bABIrhsje2xFVK1mJOhcw6L1roepBiksWQQPaUdO2uujl4XzUHPyY91bh2N1_8KMe20ScXbAFqBoBh6rmBY73E9b6EnimHZU04Jra7PR9e89CM4W-dLJjyTPu9Mfq938VZ3lDIiVRV8uBekeLNALnr02UIIZoK4ZE0F7yRtJRYVff8feohLmupXrRRjUuBuFX48UjbFnBMMj48hWK950TUves2Lrnmp-LunAzzCD-lgfwFeXr2S</recordid><startdate>20210105</startdate><enddate>20210105</enddate><creator>Uribe-Rivera, Armando</creator><creator>Rasubala, Linda</creator><creator>Machado-Perez, Ana C</creator><creator>Ren, Yan-Fang</creator><creator>Malmström, Hans</creator><creator>Carinci, Adam</creator><general>Cambridge University Press</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8FE</scope><scope>8FH</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0003-3969-0216</orcidid></search><sort><creationdate>20210105</creationdate><title>Preliminary study of the impact of elevated circulating plasma levels of catecholamines on opioid requirements for acute surgical pain</title><author>Uribe-Rivera, Armando ; Rasubala, Linda ; Machado-Perez, Ana C ; Ren, Yan-Fang ; Malmström, Hans ; Carinci, Adam</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c478t-9ad293993666cd2647180ae15467acb0c5697041f8dd057cdbe65f6ac1f5b2283</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>acute pain</topic><topic>Age</topic><topic>Alcohol use</topic><topic>Analgesics</topic><topic>Anxiety</topic><topic>Asthma</topic><topic>Body mass index</topic><topic>Catecholamines</topic><topic>Clinical Research</topic><topic>Codes</topic><topic>Demographics</topic><topic>Diabetes</topic><topic>Dosage</topic><topic>Drug abuse</topic><topic>Electronic health records</topic><topic>Electronic medical records</topic><topic>Fibromyalgia</topic><topic>Hypertension</topic><topic>Informatics</topic><topic>Medical records</topic><topic>Midazolam</topic><topic>Morphine</topic><topic>morphine milligram equivalents</topic><topic>Narcotics</topic><topic>Nicotine</topic><topic>Opioids</topic><topic>Pain</topic><topic>Pain management</topic><topic>Plasma levels</topic><topic>postoperative pain</topic><topic>Postoperative period</topic><topic>Re-engineering the Clinical Research Enterprise in Response to COVID-19: The CTSA Experience</topic><topic>Surgery</topic><topic>Variables</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Uribe-Rivera, Armando</creatorcontrib><creatorcontrib>Rasubala, Linda</creatorcontrib><creatorcontrib>Machado-Perez, Ana C</creatorcontrib><creatorcontrib>Ren, Yan-Fang</creatorcontrib><creatorcontrib>Malmström, Hans</creatorcontrib><creatorcontrib>Carinci, Adam</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>Biological Sciences</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ: Directory of Open Access Journals</collection><jtitle>Journal of clinical and translational science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Uribe-Rivera, Armando</au><au>Rasubala, Linda</au><au>Machado-Perez, Ana C</au><au>Ren, Yan-Fang</au><au>Malmström, Hans</au><au>Carinci, Adam</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Preliminary study of the impact of elevated circulating plasma levels of catecholamines on opioid requirements for acute surgical pain</atitle><jtitle>Journal of clinical and translational science</jtitle><addtitle>J Clin Transl Sci</addtitle><date>2021-01-05</date><risdate>2021</risdate><volume>5</volume><issue>1</issue><spage>e114</spage><epage>e114</epage><pages>e114-e114</pages><artnum>e114</artnum><issn>2059-8661</issn><eissn>2059-8661</eissn><abstract>The objective of this study is to determine whether elevated circulating plasma catecholamine levels significantly impact opioid requirements during the first 24 hours postoperative period in individuals with acute surgical pain. We retrospectively reviewed 15 electronic medical records (EMRs) from adults 18 years and older, with confirmed elevated plasma catecholamine levels (experimental) and 15 electronic health records (EHRs) from matched-controls for age, gender, race and type of surgery, with a follow up of 24 hours postoperatively. The total morphine milligram equivalents (MMEs) requirements from the experimental group were not statistically different when compared with controls [44.1 (13 to 163) mg versus 47.5 (13 to 151) mg respectively; p 0.4965]. However, the intraoperative MMEs showed a significant difference, among the two groups; [(experimental) 32.5 (13. to 130) mg, (control) 15 (6.5 to 130) mg; p 0.0734]. The intraoperative dosage of midazolam showed a highly significant positive correlation to the total MMEs (p 0.0005). The subjects with both elevated plasma catecholamines and hypertension used significantly higher intraoperative MMEs compared to controls [34.1 (13 to 130) mg versus 15 (6.5 to 130) mg, respectively; p 0.0292)]. Those 51 years and younger, with elevated circulating levels of catecholamines, required significantly higher levels of both the postoperative MMEs [29.1 (0 to 45) mg versus 12 (0 to 71.5) mg; (p 0.0553)] and total MMEs [544.05 (13 to 81) mg versus 29.42 (13 to 92.5) mg; (p 0.00018), when compared to controls with history of nicotine and alcohol use. This preliminary study evaluated a biologic factor, which have promising clinical usefulness for predicting analgesic requirements that can drive clinical decisions on acute surgical pain.</abstract><cop>England</cop><pub>Cambridge University Press</pub><pmid>34221456</pmid><doi>10.1017/cts.2020.573</doi><orcidid>https://orcid.org/0000-0003-3969-0216</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 2059-8661
ispartof Journal of clinical and translational science, 2021-01, Vol.5 (1), p.e114-e114, Article e114
issn 2059-8661
2059-8661
language eng
recordid cdi_doaj_primary_oai_doaj_org_article_9e520eb49ef6471db47eb19306b24212
source Cambridge University Press; PubMed Central
subjects acute pain
Age
Alcohol use
Analgesics
Anxiety
Asthma
Body mass index
Catecholamines
Clinical Research
Codes
Demographics
Diabetes
Dosage
Drug abuse
Electronic health records
Electronic medical records
Fibromyalgia
Hypertension
Informatics
Medical records
Midazolam
Morphine
morphine milligram equivalents
Narcotics
Nicotine
Opioids
Pain
Pain management
Plasma levels
postoperative pain
Postoperative period
Re-engineering the Clinical Research Enterprise in Response to COVID-19: The CTSA Experience
Surgery
Variables
title Preliminary study of the impact of elevated circulating plasma levels of catecholamines on opioid requirements for acute surgical pain
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-04T15%3A07%3A04IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_doaj_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Preliminary%20study%20of%20the%20impact%20of%20elevated%20circulating%20plasma%20levels%20of%20catecholamines%20on%20opioid%20requirements%20for%20acute%20surgical%20pain&rft.jtitle=Journal%20of%20clinical%20and%20translational%20science&rft.au=Uribe-Rivera,%20Armando&rft.date=2021-01-05&rft.volume=5&rft.issue=1&rft.spage=e114&rft.epage=e114&rft.pages=e114-e114&rft.artnum=e114&rft.issn=2059-8661&rft.eissn=2059-8661&rft_id=info:doi/10.1017/cts.2020.573&rft_dat=%3Cproquest_doaj_%3E2548627605%3C/proquest_doaj_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c478t-9ad293993666cd2647180ae15467acb0c5697041f8dd057cdbe65f6ac1f5b2283%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2543365089&rft_id=info:pmid/34221456&rfr_iscdi=true