Apixaban plasma concentrations before and after catheter ablation for atrial fibrillation
Catheter ablation in patients with atrial fibrillation is associated with a transient increase in thromboembolic risk and adequate anticoagulation is highly important. When patients are anticoagulated with apixaban, monitoring of plasma concentrations of the drug is not routinely performed. This stu...
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| creator | Aakerøy, Rachel Loennechen, Jan Pål Dyrkorn, Roar Lydersen, Stian Helland, Arne Spigset, Olav |
| description | Catheter ablation in patients with atrial fibrillation is associated with a transient increase in thromboembolic risk and adequate anticoagulation is highly important. When patients are anticoagulated with apixaban, monitoring of plasma concentrations of the drug is not routinely performed. This study aimed to assess the influence of clinical patient characteristics, concomitant drug treatment and self-reported adherence on apixaban concentrations, and to describe the intra- and inter-individual variability in apixaban concentrations in this group of patients. Method Apixaban concentrations from 141 patients were measured in plasma one week before ablation and two, six and ten weeks after ablation, employing ultra-high performance liquid chromatography coupled with tandem mass spectrometry. In samples not obtained at trough, apixaban concentrations were adjusted to trough levels. Self-reported adherence was registered by means of the 8-item Morisky Medication Adherence Scale before and after ablation.
There were statistically significant, positive correlations between apixaban concentrations and increased age, female sex, lower glomerular filtration rate, higher CHA2DS2-VASc score, use of cytochrome P450 3A4 and/or p-glycoprotein inhibitors, and use of amiodarone. Self-reported adherence was generally high. The mean intra-individual and inter-individual coefficients of variation were 29% and 49%, respectively.
In patients undergoing catheter ablation for atrial fibrillation, age, sex, renal function, interacting drugs and cerebrovascular risk profile were all associated with altered plasma apixaban concentration. In this group of patients with a generally high self-reported adherence, intra-individual variability was modest, but the inter-individual variability was substantial, and similar to those previously reported in other patient apixaban-treated populations. If a therapeutic concentration range is established, there might be a need for a more flexible approach to apixaban dosing, guided by therapeutic drug monitoring. |
| doi_str_mv | 10.1371/journal.pone.0308022 |
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There were statistically significant, positive correlations between apixaban concentrations and increased age, female sex, lower glomerular filtration rate, higher CHA2DS2-VASc score, use of cytochrome P450 3A4 and/or p-glycoprotein inhibitors, and use of amiodarone. Self-reported adherence was generally high. The mean intra-individual and inter-individual coefficients of variation were 29% and 49%, respectively.
In patients undergoing catheter ablation for atrial fibrillation, age, sex, renal function, interacting drugs and cerebrovascular risk profile were all associated with altered plasma apixaban concentration. In this group of patients with a generally high self-reported adherence, intra-individual variability was modest, but the inter-individual variability was substantial, and similar to those previously reported in other patient apixaban-treated populations. If a therapeutic concentration range is established, there might be a need for a more flexible approach to apixaban dosing, guided by therapeutic drug monitoring.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0308022</identifier><identifier>PMID: 39083480</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Ablation ; Ablation (Surgery) ; Aged ; Amiodarone ; Anticoagulants ; Apixaban ; Atrial fibrillation ; Atrial Fibrillation - blood ; Atrial Fibrillation - drug therapy ; Atrial Fibrillation - surgery ; Biology and Life Sciences ; Cardiac arrhythmia ; Care and treatment ; Catheter Ablation ; Catheters ; Chromatography ; Cytochrome P450 ; Cytochromes P450 ; Drug dosages ; Engineering and Technology ; Factor Xa Inhibitors - administration & dosage ; Factor Xa Inhibitors - blood ; Factor Xa Inhibitors - pharmacokinetics ; Factor Xa Inhibitors - therapeutic use ; Female ; Fibrillation ; Glomerular filtration rate ; Glycoproteins ; High performance liquid chromatography ; Humans ; Ischemia ; Liquid chromatography ; Male ; Mass spectrometry ; Mass spectroscopy ; Medical instruments ; Medical research ; Medication Adherence ; Medicine and Health Sciences ; Medicine, Experimental ; Middle Aged ; Monitoring ; P-Glycoprotein ; Patient compliance ; Patients ; Plasma ; Pyrazoles - administration & dosage ; Pyrazoles - blood ; Pyrazoles - pharmacokinetics ; Pyrazoles - therapeutic use ; Pyridones - administration & dosage ; Pyridones - blood ; Pyridones - therapeutic use ; Radiofrequency ablation ; Renal function ; Risk assessment ; Rivaroxaban ; Sex ; Statistical analysis ; Stroke ; Telemedicine ; Thromboembolism ; Variability ; Variables</subject><ispartof>PloS one, 2024-07, Vol.19 (7), p.e0308022</ispartof><rights>Copyright: © 2024 Aakerøy et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</rights><rights>COPYRIGHT 2024 Public Library of Science</rights><rights>2024 Aakerøy et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2024 Aakerøy et al 2024 Aakerøy et al</rights><rights>2024 Aakerøy et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c572t-293abd7b20b4eddd42e11f26a1f9871916e774b16119b6933450c49a945082483</cites><orcidid>0000-0001-7902-9014 ; 0000-0002-2348-4015</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/PMC11290617/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11290617/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2100,2919,23857,27915,27916,53782,53784,79361,79362</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39083480$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Shantsila, Eduard</contributor><creatorcontrib>Aakerøy, Rachel</creatorcontrib><creatorcontrib>Loennechen, Jan Pål</creatorcontrib><creatorcontrib>Dyrkorn, Roar</creatorcontrib><creatorcontrib>Lydersen, Stian</creatorcontrib><creatorcontrib>Helland, Arne</creatorcontrib><creatorcontrib>Spigset, Olav</creatorcontrib><title>Apixaban plasma concentrations before and after catheter ablation for atrial fibrillation</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Catheter ablation in patients with atrial fibrillation is associated with a transient increase in thromboembolic risk and adequate anticoagulation is highly important. When patients are anticoagulated with apixaban, monitoring of plasma concentrations of the drug is not routinely performed. This study aimed to assess the influence of clinical patient characteristics, concomitant drug treatment and self-reported adherence on apixaban concentrations, and to describe the intra- and inter-individual variability in apixaban concentrations in this group of patients. Method Apixaban concentrations from 141 patients were measured in plasma one week before ablation and two, six and ten weeks after ablation, employing ultra-high performance liquid chromatography coupled with tandem mass spectrometry. In samples not obtained at trough, apixaban concentrations were adjusted to trough levels. Self-reported adherence was registered by means of the 8-item Morisky Medication Adherence Scale before and after ablation.
There were statistically significant, positive correlations between apixaban concentrations and increased age, female sex, lower glomerular filtration rate, higher CHA2DS2-VASc score, use of cytochrome P450 3A4 and/or p-glycoprotein inhibitors, and use of amiodarone. Self-reported adherence was generally high. The mean intra-individual and inter-individual coefficients of variation were 29% and 49%, respectively.
In patients undergoing catheter ablation for atrial fibrillation, age, sex, renal function, interacting drugs and cerebrovascular risk profile were all associated with altered plasma apixaban concentration. In this group of patients with a generally high self-reported adherence, intra-individual variability was modest, but the inter-individual variability was substantial, and similar to those previously reported in other patient apixaban-treated populations. If a therapeutic concentration range is established, there might be a need for a more flexible approach to apixaban dosing, guided by therapeutic drug monitoring.</description><subject>Ablation</subject><subject>Ablation (Surgery)</subject><subject>Aged</subject><subject>Amiodarone</subject><subject>Anticoagulants</subject><subject>Apixaban</subject><subject>Atrial fibrillation</subject><subject>Atrial Fibrillation - blood</subject><subject>Atrial Fibrillation - drug therapy</subject><subject>Atrial Fibrillation - surgery</subject><subject>Biology and Life Sciences</subject><subject>Cardiac arrhythmia</subject><subject>Care and treatment</subject><subject>Catheter Ablation</subject><subject>Catheters</subject><subject>Chromatography</subject><subject>Cytochrome P450</subject><subject>Cytochromes P450</subject><subject>Drug dosages</subject><subject>Engineering and Technology</subject><subject>Factor Xa Inhibitors - administration & dosage</subject><subject>Factor Xa Inhibitors - blood</subject><subject>Factor Xa Inhibitors - pharmacokinetics</subject><subject>Factor Xa Inhibitors - therapeutic use</subject><subject>Female</subject><subject>Fibrillation</subject><subject>Glomerular filtration rate</subject><subject>Glycoproteins</subject><subject>High performance liquid chromatography</subject><subject>Humans</subject><subject>Ischemia</subject><subject>Liquid chromatography</subject><subject>Male</subject><subject>Mass spectrometry</subject><subject>Mass spectroscopy</subject><subject>Medical instruments</subject><subject>Medical research</subject><subject>Medication Adherence</subject><subject>Medicine and Health Sciences</subject><subject>Medicine, Experimental</subject><subject>Middle Aged</subject><subject>Monitoring</subject><subject>P-Glycoprotein</subject><subject>Patient compliance</subject><subject>Patients</subject><subject>Plasma</subject><subject>Pyrazoles - administration & dosage</subject><subject>Pyrazoles - blood</subject><subject>Pyrazoles - pharmacokinetics</subject><subject>Pyrazoles - therapeutic use</subject><subject>Pyridones - administration & dosage</subject><subject>Pyridones - blood</subject><subject>Pyridones - therapeutic use</subject><subject>Radiofrequency ablation</subject><subject>Renal function</subject><subject>Risk assessment</subject><subject>Rivaroxaban</subject><subject>Sex</subject><subject>Statistical analysis</subject><subject>Stroke</subject><subject>Telemedicine</subject><subject>Thromboembolism</subject><subject>Variability</subject><subject>Variables</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk1uLEzEUxwdR3LX6DUQHBNGH1lzmkjxJWbwUFha8gU_hZCZpU9JJTTKy--037cwuHdkHyUPCye_8k_NPTpa9xGiBaY0_bF3vO7CLvevUAlHEECGPsnPMKZlXBNHHJ-uz7FkIW4RKyqrqaXZGOWK0YOg8-73cm2uQ0OV7C2EHeeO6RnXRQzSuC7lU2nmVQ9fmoKPyeQNxow4LkPbI5AnIIXoDNtdGemOH-PPsiQYb1ItxnmU_P3_6cfF1fnn1ZXWxvJw3ZU3inHAKsq0lQbJQbdsWRGGsSQVYc1ZjjitV14XEFcZcVpzSokRNwYGnmZGC0Vn2etDdWxfE6EoQyZCK4bJONc-y1UC0DrZi780O_I1wYMQx4PxagI-msUqohmLKoG45g6TNpFYl4VoWpdRIl23S-jie1sudager7ER0utOZjVi7vwJjwlGF66TwblTw7k-vQhQ7ExqVXOuU64eL87Ko0aG0N_-gD5c3UmtIFZhOu3RwcxAVS4aSYVVdVolaPECl0aqdSY-utEnxScL7SUJiorqOa-hDEKvv3_6fvfo1Zd-esBsFNm6Cs_3xv03BYgAb70LwSt-7jJE4tMCdG-LQAmJsgZT26vSF7pPu_jy9BWnqAGw</recordid><startdate>20240731</startdate><enddate>20240731</enddate><creator>Aakerøy, Rachel</creator><creator>Loennechen, Jan Pål</creator><creator>Dyrkorn, Roar</creator><creator>Lydersen, Stian</creator><creator>Helland, Arne</creator><creator>Spigset, Olav</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0001-7902-9014</orcidid><orcidid>https://orcid.org/0000-0002-2348-4015</orcidid></search><sort><creationdate>20240731</creationdate><title>Apixaban plasma concentrations before and after catheter ablation for atrial fibrillation</title><author>Aakerøy, Rachel ; Loennechen, Jan Pål ; Dyrkorn, Roar ; Lydersen, Stian ; Helland, Arne ; Spigset, Olav</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c572t-293abd7b20b4eddd42e11f26a1f9871916e774b16119b6933450c49a945082483</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Ablation</topic><topic>Ablation (Surgery)</topic><topic>Aged</topic><topic>Amiodarone</topic><topic>Anticoagulants</topic><topic>Apixaban</topic><topic>Atrial fibrillation</topic><topic>Atrial Fibrillation - blood</topic><topic>Atrial Fibrillation - drug therapy</topic><topic>Atrial Fibrillation - surgery</topic><topic>Biology and Life Sciences</topic><topic>Cardiac arrhythmia</topic><topic>Care and treatment</topic><topic>Catheter Ablation</topic><topic>Catheters</topic><topic>Chromatography</topic><topic>Cytochrome P450</topic><topic>Cytochromes P450</topic><topic>Drug dosages</topic><topic>Engineering and Technology</topic><topic>Factor Xa Inhibitors - administration & dosage</topic><topic>Factor Xa Inhibitors - blood</topic><topic>Factor Xa Inhibitors - pharmacokinetics</topic><topic>Factor Xa Inhibitors - therapeutic use</topic><topic>Female</topic><topic>Fibrillation</topic><topic>Glomerular filtration rate</topic><topic>Glycoproteins</topic><topic>High performance liquid chromatography</topic><topic>Humans</topic><topic>Ischemia</topic><topic>Liquid chromatography</topic><topic>Male</topic><topic>Mass spectrometry</topic><topic>Mass spectroscopy</topic><topic>Medical instruments</topic><topic>Medical research</topic><topic>Medication Adherence</topic><topic>Medicine and Health Sciences</topic><topic>Medicine, Experimental</topic><topic>Middle Aged</topic><topic>Monitoring</topic><topic>P-Glycoprotein</topic><topic>Patient compliance</topic><topic>Patients</topic><topic>Plasma</topic><topic>Pyrazoles - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Aakerøy, Rachel</au><au>Loennechen, Jan Pål</au><au>Dyrkorn, Roar</au><au>Lydersen, Stian</au><au>Helland, Arne</au><au>Spigset, Olav</au><au>Shantsila, Eduard</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Apixaban plasma concentrations before and after catheter ablation for atrial fibrillation</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2024-07-31</date><risdate>2024</risdate><volume>19</volume><issue>7</issue><spage>e0308022</spage><pages>e0308022-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Catheter ablation in patients with atrial fibrillation is associated with a transient increase in thromboembolic risk and adequate anticoagulation is highly important. When patients are anticoagulated with apixaban, monitoring of plasma concentrations of the drug is not routinely performed. This study aimed to assess the influence of clinical patient characteristics, concomitant drug treatment and self-reported adherence on apixaban concentrations, and to describe the intra- and inter-individual variability in apixaban concentrations in this group of patients. Method Apixaban concentrations from 141 patients were measured in plasma one week before ablation and two, six and ten weeks after ablation, employing ultra-high performance liquid chromatography coupled with tandem mass spectrometry. In samples not obtained at trough, apixaban concentrations were adjusted to trough levels. Self-reported adherence was registered by means of the 8-item Morisky Medication Adherence Scale before and after ablation.
There were statistically significant, positive correlations between apixaban concentrations and increased age, female sex, lower glomerular filtration rate, higher CHA2DS2-VASc score, use of cytochrome P450 3A4 and/or p-glycoprotein inhibitors, and use of amiodarone. Self-reported adherence was generally high. The mean intra-individual and inter-individual coefficients of variation were 29% and 49%, respectively.
In patients undergoing catheter ablation for atrial fibrillation, age, sex, renal function, interacting drugs and cerebrovascular risk profile were all associated with altered plasma apixaban concentration. In this group of patients with a generally high self-reported adherence, intra-individual variability was modest, but the inter-individual variability was substantial, and similar to those previously reported in other patient apixaban-treated populations. If a therapeutic concentration range is established, there might be a need for a more flexible approach to apixaban dosing, guided by therapeutic drug monitoring.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>39083480</pmid><doi>10.1371/journal.pone.0308022</doi><tpages>e0308022</tpages><orcidid>https://orcid.org/0000-0001-7902-9014</orcidid><orcidid>https://orcid.org/0000-0002-2348-4015</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2024-07, Vol.19 (7), p.e0308022 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_3086815705 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Ablation Ablation (Surgery) Aged Amiodarone Anticoagulants Apixaban Atrial fibrillation Atrial Fibrillation - blood Atrial Fibrillation - drug therapy Atrial Fibrillation - surgery Biology and Life Sciences Cardiac arrhythmia Care and treatment Catheter Ablation Catheters Chromatography Cytochrome P450 Cytochromes P450 Drug dosages Engineering and Technology Factor Xa Inhibitors - administration & dosage Factor Xa Inhibitors - blood Factor Xa Inhibitors - pharmacokinetics Factor Xa Inhibitors - therapeutic use Female Fibrillation Glomerular filtration rate Glycoproteins High performance liquid chromatography Humans Ischemia Liquid chromatography Male Mass spectrometry Mass spectroscopy Medical instruments Medical research Medication Adherence Medicine and Health Sciences Medicine, Experimental Middle Aged Monitoring P-Glycoprotein Patient compliance Patients Plasma Pyrazoles - administration & dosage Pyrazoles - blood Pyrazoles - pharmacokinetics Pyrazoles - therapeutic use Pyridones - administration & dosage Pyridones - blood Pyridones - therapeutic use Radiofrequency ablation Renal function Risk assessment Rivaroxaban Sex Statistical analysis Stroke Telemedicine Thromboembolism Variability Variables |
| title | Apixaban plasma concentrations before and after catheter ablation for atrial fibrillation |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-15T07%3A12%3A31IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Apixaban%20plasma%20concentrations%20before%20and%20after%20catheter%20ablation%20for%20atrial%20fibrillation&rft.jtitle=PloS%20one&rft.au=Aaker%C3%B8y,%20Rachel&rft.date=2024-07-31&rft.volume=19&rft.issue=7&rft.spage=e0308022&rft.pages=e0308022-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0308022&rft_dat=%3Cgale_plos_%3EA803346756%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3086815705&rft_id=info:pmid/39083480&rft_galeid=A803346756&rft_doaj_id=oai_doaj_org_article_ec3138a7d98a4838bfe529fb45bf0f5d&rfr_iscdi=true |