Statin Use in Relation to Intraocular Pressure, Glaucoma, and Ocular Coherence Tomography Parameters in the UK Biobank
The purpose of this study was to evaluate the relationship between statin use and glaucoma-related traits. In a cross-sectional study, we included 118,153 UK Biobank participants with data on statin use and corneal-compensated IOP. In addition, we included 192,283 participants (8982 cases) with data...
Gespeichert in:
Veröffentlicht in: | Investigative ophthalmology & visual science 2022-05, Vol.63 (5), p.31 |
---|---|
Hauptverfasser: | , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | |
---|---|
container_issue | 5 |
container_start_page | 31 |
container_title | Investigative ophthalmology & visual science |
container_volume | 63 |
creator | Kim, Jihye Kennedy Neary, Marianne T Aschard, Hugues Palakkamanil, Mathew M Do, Ron Wiggs, Janey L Khawaja, Anthony P Pasquale, Louis R Kang, Jae H |
description | The purpose of this study was to evaluate the relationship between statin use and glaucoma-related traits.
In a cross-sectional study, we included 118,153 UK Biobank participants with data on statin use and corneal-compensated IOP. In addition, we included 192,283 participants (8982 cases) with data on glaucoma status. After excluding participants with neurodegenerative diseases, 41,638 participants with macular retinal nerve fiber layer thickness (mRNFL) and 41,547 participants with macular ganglion cell inner plexiform layer thickness (mGCIPL) were available for analysis. We examined associations of statin use with IOP, mRNFL, mGCIPL, and glaucoma status utilizing multivariable-adjusted regression models. We assessed whether a glaucoma polygenic risk score (PRS) modified associations. We performed Mendelian randomization (MR) experiments to investigate associations with various glaucoma-related outcomes.
Statin users had higher unadjusted mean IOP ± SD than nonusers, but in a multivariable-adjusted model, IOP did not differ by statin use (difference = 0.05 mm Hg, 95% confidence interval [CI] = -0.02 to 0.13, P = 0.17). Similarly, statin use was not associated with prevalent glaucoma (odds ratio [OR] = 1.05, 95% CI = 0.98 to 1.13). Statin use was weakly associated with thinner mRNFL (difference = -0.15 microns, 95% CI = -0.28 to -0.01, P = 0.03) but not with mGCIPL thickness (difference = -0.12 microns, 95% CI = -0.29 to 0.05, P = 0.17). No association was modified by the glaucoma PRS (Pinteraction≥ 0.16). MR experiments showed no evidence for a causal association between the cholesterol-altering effect of statins and several glaucoma traits (inverse weighted variance P ≥ 0.14).
We found no evidence of a protective association between statin use and glaucoma or related traits after adjusting for key confounders. |
doi_str_mv | 10.1167/iovs.63.5.31 |
format | Article |
fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9150836</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2669502435</sourcerecordid><originalsourceid>FETCH-LOGICAL-c418t-aa656a1db0c46859ac557b81fcb3ce47db713acf478878c0b0a11865671c5b973</originalsourceid><addsrcrecordid>eNpdkU1v1DAQhi1E1ZbSG2fkI0i7iyeOP3JBKitoq67UCrpna-KdbQJJvNjJSv33JNpSFU4z43nnGY1fxt6BWABo86kO-7TQcqEWEl6xU1Aqmytj5esX-Ql7k9JPITKATByzE6k0ZFbqU7b_0WNfd3ydiI_hOzVjGTreB37d9RGDHxqM_C5SSkOkGb9scPChxRnHbsNvD-1lqChS54nfhzY8RNxVj_wOI7bUU0wTua-Ir2_4lzqU2P16y4622CQ6f4pnbP3t6_3yar66vbxeXqzmPgfbzxG10gibUvhcW1WgV8qUFra-lJ5ysykNSPTb3FhrrBelQAA7zhjwqiyMPGOfD9zdULa08TTd1LhdrFuMjy5g7f7tdHXlHsLeFaDE-EEj4OMBUP03dnWxctObyCHPbWH3MGo_PC2L4fdAqXdtnTw1DXYUhuQyrQslslyqUTo7SH0MKUXaPrNBuMlWN9nqtHTKyYn8_uUZz-K_Pso_YGKfhg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2669502435</pqid></control><display><type>article</type><title>Statin Use in Relation to Intraocular Pressure, Glaucoma, and Ocular Coherence Tomography Parameters in the UK Biobank</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>Kim, Jihye ; Kennedy Neary, Marianne T ; Aschard, Hugues ; Palakkamanil, Mathew M ; Do, Ron ; Wiggs, Janey L ; Khawaja, Anthony P ; Pasquale, Louis R ; Kang, Jae H</creator><creatorcontrib>Kim, Jihye ; Kennedy Neary, Marianne T ; Aschard, Hugues ; Palakkamanil, Mathew M ; Do, Ron ; Wiggs, Janey L ; Khawaja, Anthony P ; Pasquale, Louis R ; Kang, Jae H ; International Glaucoma Genetics Consortium (IGGC), UK Biobank Eye and Vision Consortium, and Modifiable Risk Factors for Glaucoma Collaboration ; for the International Glaucoma Genetics Consortium (IGGC), UK Biobank Eye and Vision Consortium, and Modifiable Risk Factors for Glaucoma Collaboration</creatorcontrib><description>The purpose of this study was to evaluate the relationship between statin use and glaucoma-related traits.
In a cross-sectional study, we included 118,153 UK Biobank participants with data on statin use and corneal-compensated IOP. In addition, we included 192,283 participants (8982 cases) with data on glaucoma status. After excluding participants with neurodegenerative diseases, 41,638 participants with macular retinal nerve fiber layer thickness (mRNFL) and 41,547 participants with macular ganglion cell inner plexiform layer thickness (mGCIPL) were available for analysis. We examined associations of statin use with IOP, mRNFL, mGCIPL, and glaucoma status utilizing multivariable-adjusted regression models. We assessed whether a glaucoma polygenic risk score (PRS) modified associations. We performed Mendelian randomization (MR) experiments to investigate associations with various glaucoma-related outcomes.
Statin users had higher unadjusted mean IOP ± SD than nonusers, but in a multivariable-adjusted model, IOP did not differ by statin use (difference = 0.05 mm Hg, 95% confidence interval [CI] = -0.02 to 0.13, P = 0.17). Similarly, statin use was not associated with prevalent glaucoma (odds ratio [OR] = 1.05, 95% CI = 0.98 to 1.13). Statin use was weakly associated with thinner mRNFL (difference = -0.15 microns, 95% CI = -0.28 to -0.01, P = 0.03) but not with mGCIPL thickness (difference = -0.12 microns, 95% CI = -0.29 to 0.05, P = 0.17). No association was modified by the glaucoma PRS (Pinteraction≥ 0.16). MR experiments showed no evidence for a causal association between the cholesterol-altering effect of statins and several glaucoma traits (inverse weighted variance P ≥ 0.14).
We found no evidence of a protective association between statin use and glaucoma or related traits after adjusting for key confounders.</description><identifier>ISSN: 1552-5783</identifier><identifier>ISSN: 0146-0404</identifier><identifier>EISSN: 1552-5783</identifier><identifier>DOI: 10.1167/iovs.63.5.31</identifier><identifier>PMID: 35612836</identifier><language>eng</language><publisher>United States: Association for Research in Vision and Ophthalmology</publisher><subject>Biological Specimen Banks ; Clinical and Epidemiologic Research ; Cross-Sectional Studies ; Glaucoma ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use ; Intraocular Pressure ; Life Sciences ; Nerve Fibers ; Retinal Ganglion Cells ; Santé publique et épidémiologie ; Tomography, Optical Coherence - methods ; United Kingdom - epidemiology</subject><ispartof>Investigative ophthalmology & visual science, 2022-05, Vol.63 (5), p.31</ispartof><rights>Attribution - NonCommercial - NoDerivatives</rights><rights>Copyright 2022 The Authors 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c418t-aa656a1db0c46859ac557b81fcb3ce47db713acf478878c0b0a11865671c5b973</citedby><cites>FETCH-LOGICAL-c418t-aa656a1db0c46859ac557b81fcb3ce47db713acf478878c0b0a11865671c5b973</cites><orcidid>0000-0002-7554-6783</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/PMC9150836/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9150836/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,861,882,27905,27906,53772,53774</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35612836$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-04144898$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Kim, Jihye</creatorcontrib><creatorcontrib>Kennedy Neary, Marianne T</creatorcontrib><creatorcontrib>Aschard, Hugues</creatorcontrib><creatorcontrib>Palakkamanil, Mathew M</creatorcontrib><creatorcontrib>Do, Ron</creatorcontrib><creatorcontrib>Wiggs, Janey L</creatorcontrib><creatorcontrib>Khawaja, Anthony P</creatorcontrib><creatorcontrib>Pasquale, Louis R</creatorcontrib><creatorcontrib>Kang, Jae H</creatorcontrib><creatorcontrib>International Glaucoma Genetics Consortium (IGGC), UK Biobank Eye and Vision Consortium, and Modifiable Risk Factors for Glaucoma Collaboration</creatorcontrib><creatorcontrib>for the International Glaucoma Genetics Consortium (IGGC), UK Biobank Eye and Vision Consortium, and Modifiable Risk Factors for Glaucoma Collaboration</creatorcontrib><title>Statin Use in Relation to Intraocular Pressure, Glaucoma, and Ocular Coherence Tomography Parameters in the UK Biobank</title><title>Investigative ophthalmology & visual science</title><addtitle>Invest Ophthalmol Vis Sci</addtitle><description>The purpose of this study was to evaluate the relationship between statin use and glaucoma-related traits.
In a cross-sectional study, we included 118,153 UK Biobank participants with data on statin use and corneal-compensated IOP. In addition, we included 192,283 participants (8982 cases) with data on glaucoma status. After excluding participants with neurodegenerative diseases, 41,638 participants with macular retinal nerve fiber layer thickness (mRNFL) and 41,547 participants with macular ganglion cell inner plexiform layer thickness (mGCIPL) were available for analysis. We examined associations of statin use with IOP, mRNFL, mGCIPL, and glaucoma status utilizing multivariable-adjusted regression models. We assessed whether a glaucoma polygenic risk score (PRS) modified associations. We performed Mendelian randomization (MR) experiments to investigate associations with various glaucoma-related outcomes.
Statin users had higher unadjusted mean IOP ± SD than nonusers, but in a multivariable-adjusted model, IOP did not differ by statin use (difference = 0.05 mm Hg, 95% confidence interval [CI] = -0.02 to 0.13, P = 0.17). Similarly, statin use was not associated with prevalent glaucoma (odds ratio [OR] = 1.05, 95% CI = 0.98 to 1.13). Statin use was weakly associated with thinner mRNFL (difference = -0.15 microns, 95% CI = -0.28 to -0.01, P = 0.03) but not with mGCIPL thickness (difference = -0.12 microns, 95% CI = -0.29 to 0.05, P = 0.17). No association was modified by the glaucoma PRS (Pinteraction≥ 0.16). MR experiments showed no evidence for a causal association between the cholesterol-altering effect of statins and several glaucoma traits (inverse weighted variance P ≥ 0.14).
We found no evidence of a protective association between statin use and glaucoma or related traits after adjusting for key confounders.</description><subject>Biological Specimen Banks</subject><subject>Clinical and Epidemiologic Research</subject><subject>Cross-Sectional Studies</subject><subject>Glaucoma</subject><subject>Humans</subject><subject>Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use</subject><subject>Intraocular Pressure</subject><subject>Life Sciences</subject><subject>Nerve Fibers</subject><subject>Retinal Ganglion Cells</subject><subject>Santé publique et épidémiologie</subject><subject>Tomography, Optical Coherence - methods</subject><subject>United Kingdom - epidemiology</subject><issn>1552-5783</issn><issn>0146-0404</issn><issn>1552-5783</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkU1v1DAQhi1E1ZbSG2fkI0i7iyeOP3JBKitoq67UCrpna-KdbQJJvNjJSv33JNpSFU4z43nnGY1fxt6BWABo86kO-7TQcqEWEl6xU1Aqmytj5esX-Ql7k9JPITKATByzE6k0ZFbqU7b_0WNfd3ydiI_hOzVjGTreB37d9RGDHxqM_C5SSkOkGb9scPChxRnHbsNvD-1lqChS54nfhzY8RNxVj_wOI7bUU0wTua-Ir2_4lzqU2P16y4622CQ6f4pnbP3t6_3yar66vbxeXqzmPgfbzxG10gibUvhcW1WgV8qUFra-lJ5ysykNSPTb3FhrrBelQAA7zhjwqiyMPGOfD9zdULa08TTd1LhdrFuMjy5g7f7tdHXlHsLeFaDE-EEj4OMBUP03dnWxctObyCHPbWH3MGo_PC2L4fdAqXdtnTw1DXYUhuQyrQslslyqUTo7SH0MKUXaPrNBuMlWN9nqtHTKyYn8_uUZz-K_Pso_YGKfhg</recordid><startdate>20220502</startdate><enddate>20220502</enddate><creator>Kim, Jihye</creator><creator>Kennedy Neary, Marianne T</creator><creator>Aschard, Hugues</creator><creator>Palakkamanil, Mathew M</creator><creator>Do, Ron</creator><creator>Wiggs, Janey L</creator><creator>Khawaja, Anthony P</creator><creator>Pasquale, Louis R</creator><creator>Kang, Jae H</creator><general>Association for Research in Vision and Ophthalmology</general><general>The Association for Research in Vision and Ophthalmology</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>1XC</scope><scope>VOOES</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-7554-6783</orcidid></search><sort><creationdate>20220502</creationdate><title>Statin Use in Relation to Intraocular Pressure, Glaucoma, and Ocular Coherence Tomography Parameters in the UK Biobank</title><author>Kim, Jihye ; Kennedy Neary, Marianne T ; Aschard, Hugues ; Palakkamanil, Mathew M ; Do, Ron ; Wiggs, Janey L ; Khawaja, Anthony P ; Pasquale, Louis R ; Kang, Jae H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c418t-aa656a1db0c46859ac557b81fcb3ce47db713acf478878c0b0a11865671c5b973</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Biological Specimen Banks</topic><topic>Clinical and Epidemiologic Research</topic><topic>Cross-Sectional Studies</topic><topic>Glaucoma</topic><topic>Humans</topic><topic>Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use</topic><topic>Intraocular Pressure</topic><topic>Life Sciences</topic><topic>Nerve Fibers</topic><topic>Retinal Ganglion Cells</topic><topic>Santé publique et épidémiologie</topic><topic>Tomography, Optical Coherence - methods</topic><topic>United Kingdom - epidemiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kim, Jihye</creatorcontrib><creatorcontrib>Kennedy Neary, Marianne T</creatorcontrib><creatorcontrib>Aschard, Hugues</creatorcontrib><creatorcontrib>Palakkamanil, Mathew M</creatorcontrib><creatorcontrib>Do, Ron</creatorcontrib><creatorcontrib>Wiggs, Janey L</creatorcontrib><creatorcontrib>Khawaja, Anthony P</creatorcontrib><creatorcontrib>Pasquale, Louis R</creatorcontrib><creatorcontrib>Kang, Jae H</creatorcontrib><creatorcontrib>International Glaucoma Genetics Consortium (IGGC), UK Biobank Eye and Vision Consortium, and Modifiable Risk Factors for Glaucoma Collaboration</creatorcontrib><creatorcontrib>for the International Glaucoma Genetics Consortium (IGGC), UK Biobank Eye and Vision Consortium, and Modifiable Risk Factors for Glaucoma Collaboration</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>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Investigative ophthalmology & visual science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kim, Jihye</au><au>Kennedy Neary, Marianne T</au><au>Aschard, Hugues</au><au>Palakkamanil, Mathew M</au><au>Do, Ron</au><au>Wiggs, Janey L</au><au>Khawaja, Anthony P</au><au>Pasquale, Louis R</au><au>Kang, Jae H</au><aucorp>International Glaucoma Genetics Consortium (IGGC), UK Biobank Eye and Vision Consortium, and Modifiable Risk Factors for Glaucoma Collaboration</aucorp><aucorp>for the International Glaucoma Genetics Consortium (IGGC), UK Biobank Eye and Vision Consortium, and Modifiable Risk Factors for Glaucoma Collaboration</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Statin Use in Relation to Intraocular Pressure, Glaucoma, and Ocular Coherence Tomography Parameters in the UK Biobank</atitle><jtitle>Investigative ophthalmology & visual science</jtitle><addtitle>Invest Ophthalmol Vis Sci</addtitle><date>2022-05-02</date><risdate>2022</risdate><volume>63</volume><issue>5</issue><spage>31</spage><pages>31-</pages><issn>1552-5783</issn><issn>0146-0404</issn><eissn>1552-5783</eissn><abstract>The purpose of this study was to evaluate the relationship between statin use and glaucoma-related traits.
In a cross-sectional study, we included 118,153 UK Biobank participants with data on statin use and corneal-compensated IOP. In addition, we included 192,283 participants (8982 cases) with data on glaucoma status. After excluding participants with neurodegenerative diseases, 41,638 participants with macular retinal nerve fiber layer thickness (mRNFL) and 41,547 participants with macular ganglion cell inner plexiform layer thickness (mGCIPL) were available for analysis. We examined associations of statin use with IOP, mRNFL, mGCIPL, and glaucoma status utilizing multivariable-adjusted regression models. We assessed whether a glaucoma polygenic risk score (PRS) modified associations. We performed Mendelian randomization (MR) experiments to investigate associations with various glaucoma-related outcomes.
Statin users had higher unadjusted mean IOP ± SD than nonusers, but in a multivariable-adjusted model, IOP did not differ by statin use (difference = 0.05 mm Hg, 95% confidence interval [CI] = -0.02 to 0.13, P = 0.17). Similarly, statin use was not associated with prevalent glaucoma (odds ratio [OR] = 1.05, 95% CI = 0.98 to 1.13). Statin use was weakly associated with thinner mRNFL (difference = -0.15 microns, 95% CI = -0.28 to -0.01, P = 0.03) but not with mGCIPL thickness (difference = -0.12 microns, 95% CI = -0.29 to 0.05, P = 0.17). No association was modified by the glaucoma PRS (Pinteraction≥ 0.16). MR experiments showed no evidence for a causal association between the cholesterol-altering effect of statins and several glaucoma traits (inverse weighted variance P ≥ 0.14).
We found no evidence of a protective association between statin use and glaucoma or related traits after adjusting for key confounders.</abstract><cop>United States</cop><pub>Association for Research in Vision and Ophthalmology</pub><pmid>35612836</pmid><doi>10.1167/iovs.63.5.31</doi><orcidid>https://orcid.org/0000-0002-7554-6783</orcidid><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1552-5783 |
ispartof | Investigative ophthalmology & visual science, 2022-05, Vol.63 (5), p.31 |
issn | 1552-5783 0146-0404 1552-5783 |
language | eng |
recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9150836 |
source | MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central |
subjects | Biological Specimen Banks Clinical and Epidemiologic Research Cross-Sectional Studies Glaucoma Humans Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use Intraocular Pressure Life Sciences Nerve Fibers Retinal Ganglion Cells Santé publique et épidémiologie Tomography, Optical Coherence - methods United Kingdom - epidemiology |
title | Statin Use in Relation to Intraocular Pressure, Glaucoma, and Ocular Coherence Tomography Parameters in the UK Biobank |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-17T13%3A03%3A34IST&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=Statin%20Use%20in%20Relation%20to%20Intraocular%20Pressure,%20Glaucoma,%20and%20Ocular%20Coherence%20Tomography%20Parameters%20in%20the%20UK%20Biobank&rft.jtitle=Investigative%20ophthalmology%20&%20visual%20science&rft.au=Kim,%20Jihye&rft.aucorp=International%20Glaucoma%20Genetics%20Consortium%20(IGGC),%20UK%20Biobank%20Eye%20and%20Vision%20Consortium,%20and%20Modifiable%20Risk%20Factors%20for%20Glaucoma%20Collaboration&rft.date=2022-05-02&rft.volume=63&rft.issue=5&rft.spage=31&rft.pages=31-&rft.issn=1552-5783&rft.eissn=1552-5783&rft_id=info:doi/10.1167/iovs.63.5.31&rft_dat=%3Cproquest_pubme%3E2669502435%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2669502435&rft_id=info:pmid/35612836&rfr_iscdi=true |