Phase 2 Randomized Clinical Study of Netarsudil Ophthalmic Solution in Japanese Patients with Primary Open-Angle Glaucoma or Ocular Hypertension
Introduction Netarsudil reduces intraocular pressure (IOP) by increasing aqueous outflow through the trabecular meshwork (TM) pathway and decreasing episcleral venous pressure. The primary objective of this phase 2 study was to evaluate ocular hypotensive efficacy and safety of three netarsudil conc...
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| creator | Araie, Makoto Sugiyama, Kazuhisa Aso, Kenji Kanemoto, Koji Kothapalli, Kalyani Kopczynski, Casey Senchyna, Michelle Hollander, David A. |
| description | Introduction
Netarsudil reduces intraocular pressure (IOP) by increasing aqueous outflow through the trabecular meshwork (TM) pathway and decreasing episcleral venous pressure. The primary objective of this phase 2 study was to evaluate ocular hypotensive efficacy and safety of three netarsudil concentrations (0.01%, 0.02%, and 0.04%) relative to its placebo over 4 weeks in Japanese patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT).
Methods
Patients were randomized to one of four treatment arms, netarsudil ophthalmic solution 0.01%, 0.02%, 0.04%, or placebo, and treated once-daily (QD) in the evening (
p.m.
) for 4 weeks. The primary efficacy variable was mean diurnal IOP (average of diurnal time points at 9
a.m.
, 11
a.m.
, and 4
p.m.
) at week 4.
Results
A total of 215 patients were randomized and 207 (96.3%) completed the study. The mean of mean diurnal IOP at baseline ranged from 20.28 to 21.14 mmHg across groups. At week 4, least squares (LS) mean of mean diurnal IOP adjusted for baseline was 16.53, 15.82, 16.06, and 18.94 mmHg in the netarsudil 0.01%, 0.02%, 0.04%, and placebo groups, respectively, demonstrating the superiority of netarsudil (all concentrations) over placebo. At week 4, mean reduction (mean percentage reduction) from baseline in mean diurnal IOP was 4.10 (19.8%), 4.80 (23.5%), 4.81 (23.8%), and 1.73 mmHg (8.2%), respectively, demonstrating statistically significant reductions (
p
|
| doi_str_mv | 10.1007/s12325-021-01634-9 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8004483</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2493449741</sourcerecordid><originalsourceid>FETCH-LOGICAL-c446t-94f426d6e98d7941ce0e0e1ea23a4c3eb2448c4f6114db418aacfbc176c067463</originalsourceid><addsrcrecordid>eNp9kc1u1DAUhS0EokPhBVggL9kE_DdOskGqRtCCKmZEQWJneZybiSvHDrYDGt6CN-BZeDIMKRVskGV5cc85ProfQo8peUYJqZ8nyjhbV4TRilDJRdXeQSvayHVVLruLVqQWtGK8-XiCHqR0TQgj9bq5j044l6xlrF6hb7tBJ_jxneF32ndhtF-hwxtnvTXa4as8d0ccevwWso5p7qzD22nIg3ajNfgquDnb4LH1-I2etIcEeKezBZ8T_mLzgHfRjjoeiwt8deYPDvC507MJo8Yh4q2ZnY744jhBzOBTCXuI7vXaJXh0856iD69evt9cVJfb89ebs8vKCCFz1YpeMNlJaJuubgU1QMqhoBnXwnDYMyEaI3pJqej2gjZam35vaC0NkbWQ_BS9WHKneT9CZ0rnqJ2alsIqaKv-nXg7qEP4rBpCSjQvAU9vAmL4NEPKarTJgHNlD2FOiomWC9EWBkXKFqmJIaUI_e03lKhfLNXCUhWW6jdL1RbTk78L3lr-wCsCvghSGfkDRHUd5ujL0v4X-xOZYa6b</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2493449741</pqid></control><display><type>article</type><title>Phase 2 Randomized Clinical Study of Netarsudil Ophthalmic Solution in Japanese Patients with Primary Open-Angle Glaucoma or Ocular Hypertension</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Araie, Makoto ; Sugiyama, Kazuhisa ; Aso, Kenji ; Kanemoto, Koji ; Kothapalli, Kalyani ; Kopczynski, Casey ; Senchyna, Michelle ; Hollander, David A.</creator><creatorcontrib>Araie, Makoto ; Sugiyama, Kazuhisa ; Aso, Kenji ; Kanemoto, Koji ; Kothapalli, Kalyani ; Kopczynski, Casey ; Senchyna, Michelle ; Hollander, David A.</creatorcontrib><description>Introduction
Netarsudil reduces intraocular pressure (IOP) by increasing aqueous outflow through the trabecular meshwork (TM) pathway and decreasing episcleral venous pressure. The primary objective of this phase 2 study was to evaluate ocular hypotensive efficacy and safety of three netarsudil concentrations (0.01%, 0.02%, and 0.04%) relative to its placebo over 4 weeks in Japanese patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT).
Methods
Patients were randomized to one of four treatment arms, netarsudil ophthalmic solution 0.01%, 0.02%, 0.04%, or placebo, and treated once-daily (QD) in the evening (
p.m.
) for 4 weeks. The primary efficacy variable was mean diurnal IOP (average of diurnal time points at 9
a.m.
, 11
a.m.
, and 4
p.m.
) at week 4.
Results
A total of 215 patients were randomized and 207 (96.3%) completed the study. The mean of mean diurnal IOP at baseline ranged from 20.28 to 21.14 mmHg across groups. At week 4, least squares (LS) mean of mean diurnal IOP adjusted for baseline was 16.53, 15.82, 16.06, and 18.94 mmHg in the netarsudil 0.01%, 0.02%, 0.04%, and placebo groups, respectively, demonstrating the superiority of netarsudil (all concentrations) over placebo. At week 4, mean reduction (mean percentage reduction) from baseline in mean diurnal IOP was 4.10 (19.8%), 4.80 (23.5%), 4.81 (23.8%), and 1.73 mmHg (8.2%), respectively, demonstrating statistically significant reductions (
p
< 0.0001) in all netarsudil concentrations over placebo. Adverse events (AEs) occurred in a concentration-dependent manner, and the incidence of ocular AEs was 34.5%, 42.6%, 68.6%, and 9.1% in the netarsudil 0.01%, 0.02%, 0.04%, and placebo groups, respectively. The most frequently reported AE was conjunctival hyperemia, with an incidence of 23.6%, 37.0%, 56.9%, and 1.8%, respectively. No serious AEs were reported.
Conclusion
Netarsudil ophthalmic solutions 0.01%, 0.02%, and 0.04% dosed QD (
p.m.
) demonstrated superiority to placebo in terms of hypotensive effectiveness at week 4 and were found to be safe and generally well tolerated. Netarsudil 0.02% QD provided an optimal efficacy and safety profile for the treatment of Japanese patients with POAG or OHT.
Trial Registration
NCT03844945.</description><identifier>ISSN: 0741-238X</identifier><identifier>EISSN: 1865-8652</identifier><identifier>DOI: 10.1007/s12325-021-01634-9</identifier><identifier>PMID: 33629227</identifier><language>eng</language><publisher>Cheshire: Springer Healthcare</publisher><subject>Antihypertensive Agents - therapeutic use ; Benzoates ; beta-Alanine - analogs & derivatives ; Cardiology ; Double-Blind Method ; Endocrinology ; Glaucoma, Open-Angle - drug therapy ; Health technology assessment ; Humans ; Internal Medicine ; Intraocular Pressure ; Japan ; Medicine ; Medicine & Public Health ; Ocular Hypertension - drug therapy ; Oncology ; Ophthalmic Solutions ; Original Research ; Pharmacology/Toxicology ; Rheumatology ; Tonometry, Ocular</subject><ispartof>Advances in therapy, 2021-04, Vol.38 (4), p.1757-1775</ispartof><rights>The Author(s) 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c446t-94f426d6e98d7941ce0e0e1ea23a4c3eb2448c4f6114db418aacfbc176c067463</citedby><cites>FETCH-LOGICAL-c446t-94f426d6e98d7941ce0e0e1ea23a4c3eb2448c4f6114db418aacfbc176c067463</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12325-021-01634-9$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12325-021-01634-9$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33629227$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Araie, Makoto</creatorcontrib><creatorcontrib>Sugiyama, Kazuhisa</creatorcontrib><creatorcontrib>Aso, Kenji</creatorcontrib><creatorcontrib>Kanemoto, Koji</creatorcontrib><creatorcontrib>Kothapalli, Kalyani</creatorcontrib><creatorcontrib>Kopczynski, Casey</creatorcontrib><creatorcontrib>Senchyna, Michelle</creatorcontrib><creatorcontrib>Hollander, David A.</creatorcontrib><title>Phase 2 Randomized Clinical Study of Netarsudil Ophthalmic Solution in Japanese Patients with Primary Open-Angle Glaucoma or Ocular Hypertension</title><title>Advances in therapy</title><addtitle>Adv Ther</addtitle><addtitle>Adv Ther</addtitle><description>Introduction
Netarsudil reduces intraocular pressure (IOP) by increasing aqueous outflow through the trabecular meshwork (TM) pathway and decreasing episcleral venous pressure. The primary objective of this phase 2 study was to evaluate ocular hypotensive efficacy and safety of three netarsudil concentrations (0.01%, 0.02%, and 0.04%) relative to its placebo over 4 weeks in Japanese patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT).
Methods
Patients were randomized to one of four treatment arms, netarsudil ophthalmic solution 0.01%, 0.02%, 0.04%, or placebo, and treated once-daily (QD) in the evening (
p.m.
) for 4 weeks. The primary efficacy variable was mean diurnal IOP (average of diurnal time points at 9
a.m.
, 11
a.m.
, and 4
p.m.
) at week 4.
Results
A total of 215 patients were randomized and 207 (96.3%) completed the study. The mean of mean diurnal IOP at baseline ranged from 20.28 to 21.14 mmHg across groups. At week 4, least squares (LS) mean of mean diurnal IOP adjusted for baseline was 16.53, 15.82, 16.06, and 18.94 mmHg in the netarsudil 0.01%, 0.02%, 0.04%, and placebo groups, respectively, demonstrating the superiority of netarsudil (all concentrations) over placebo. At week 4, mean reduction (mean percentage reduction) from baseline in mean diurnal IOP was 4.10 (19.8%), 4.80 (23.5%), 4.81 (23.8%), and 1.73 mmHg (8.2%), respectively, demonstrating statistically significant reductions (
p
< 0.0001) in all netarsudil concentrations over placebo. Adverse events (AEs) occurred in a concentration-dependent manner, and the incidence of ocular AEs was 34.5%, 42.6%, 68.6%, and 9.1% in the netarsudil 0.01%, 0.02%, 0.04%, and placebo groups, respectively. The most frequently reported AE was conjunctival hyperemia, with an incidence of 23.6%, 37.0%, 56.9%, and 1.8%, respectively. No serious AEs were reported.
Conclusion
Netarsudil ophthalmic solutions 0.01%, 0.02%, and 0.04% dosed QD (
p.m.
) demonstrated superiority to placebo in terms of hypotensive effectiveness at week 4 and were found to be safe and generally well tolerated. Netarsudil 0.02% QD provided an optimal efficacy and safety profile for the treatment of Japanese patients with POAG or OHT.
Trial Registration
NCT03844945.</description><subject>Antihypertensive Agents - therapeutic use</subject><subject>Benzoates</subject><subject>beta-Alanine - analogs & derivatives</subject><subject>Cardiology</subject><subject>Double-Blind Method</subject><subject>Endocrinology</subject><subject>Glaucoma, Open-Angle - drug therapy</subject><subject>Health technology assessment</subject><subject>Humans</subject><subject>Internal Medicine</subject><subject>Intraocular Pressure</subject><subject>Japan</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Ocular Hypertension - drug therapy</subject><subject>Oncology</subject><subject>Ophthalmic Solutions</subject><subject>Original Research</subject><subject>Pharmacology/Toxicology</subject><subject>Rheumatology</subject><subject>Tonometry, Ocular</subject><issn>0741-238X</issn><issn>1865-8652</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><recordid>eNp9kc1u1DAUhS0EokPhBVggL9kE_DdOskGqRtCCKmZEQWJneZybiSvHDrYDGt6CN-BZeDIMKRVskGV5cc85ProfQo8peUYJqZ8nyjhbV4TRilDJRdXeQSvayHVVLruLVqQWtGK8-XiCHqR0TQgj9bq5j044l6xlrF6hb7tBJ_jxneF32ndhtF-hwxtnvTXa4as8d0ccevwWso5p7qzD22nIg3ajNfgquDnb4LH1-I2etIcEeKezBZ8T_mLzgHfRjjoeiwt8deYPDvC507MJo8Yh4q2ZnY744jhBzOBTCXuI7vXaJXh0856iD69evt9cVJfb89ebs8vKCCFz1YpeMNlJaJuubgU1QMqhoBnXwnDYMyEaI3pJqej2gjZam35vaC0NkbWQ_BS9WHKneT9CZ0rnqJ2alsIqaKv-nXg7qEP4rBpCSjQvAU9vAmL4NEPKarTJgHNlD2FOiomWC9EWBkXKFqmJIaUI_e03lKhfLNXCUhWW6jdL1RbTk78L3lr-wCsCvghSGfkDRHUd5ujL0v4X-xOZYa6b</recordid><startdate>20210401</startdate><enddate>20210401</enddate><creator>Araie, Makoto</creator><creator>Sugiyama, Kazuhisa</creator><creator>Aso, Kenji</creator><creator>Kanemoto, Koji</creator><creator>Kothapalli, Kalyani</creator><creator>Kopczynski, Casey</creator><creator>Senchyna, Michelle</creator><creator>Hollander, David A.</creator><general>Springer Healthcare</general><scope>C6C</scope><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>20210401</creationdate><title>Phase 2 Randomized Clinical Study of Netarsudil Ophthalmic Solution in Japanese Patients with Primary Open-Angle Glaucoma or Ocular Hypertension</title><author>Araie, Makoto ; Sugiyama, Kazuhisa ; Aso, Kenji ; Kanemoto, Koji ; Kothapalli, Kalyani ; Kopczynski, Casey ; Senchyna, Michelle ; Hollander, David A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c446t-94f426d6e98d7941ce0e0e1ea23a4c3eb2448c4f6114db418aacfbc176c067463</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Antihypertensive Agents - therapeutic use</topic><topic>Benzoates</topic><topic>beta-Alanine - analogs & derivatives</topic><topic>Cardiology</topic><topic>Double-Blind Method</topic><topic>Endocrinology</topic><topic>Glaucoma, Open-Angle - drug therapy</topic><topic>Health technology assessment</topic><topic>Humans</topic><topic>Internal Medicine</topic><topic>Intraocular Pressure</topic><topic>Japan</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Ocular Hypertension - drug therapy</topic><topic>Oncology</topic><topic>Ophthalmic Solutions</topic><topic>Original Research</topic><topic>Pharmacology/Toxicology</topic><topic>Rheumatology</topic><topic>Tonometry, Ocular</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Araie, Makoto</creatorcontrib><creatorcontrib>Sugiyama, Kazuhisa</creatorcontrib><creatorcontrib>Aso, Kenji</creatorcontrib><creatorcontrib>Kanemoto, Koji</creatorcontrib><creatorcontrib>Kothapalli, Kalyani</creatorcontrib><creatorcontrib>Kopczynski, Casey</creatorcontrib><creatorcontrib>Senchyna, Michelle</creatorcontrib><creatorcontrib>Hollander, David A.</creatorcontrib><collection>Springer Nature OA/Free Journals</collection><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>Advances in therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Araie, Makoto</au><au>Sugiyama, Kazuhisa</au><au>Aso, Kenji</au><au>Kanemoto, Koji</au><au>Kothapalli, Kalyani</au><au>Kopczynski, Casey</au><au>Senchyna, Michelle</au><au>Hollander, David A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Phase 2 Randomized Clinical Study of Netarsudil Ophthalmic Solution in Japanese Patients with Primary Open-Angle Glaucoma or Ocular Hypertension</atitle><jtitle>Advances in therapy</jtitle><stitle>Adv Ther</stitle><addtitle>Adv Ther</addtitle><date>2021-04-01</date><risdate>2021</risdate><volume>38</volume><issue>4</issue><spage>1757</spage><epage>1775</epage><pages>1757-1775</pages><issn>0741-238X</issn><eissn>1865-8652</eissn><abstract>Introduction
Netarsudil reduces intraocular pressure (IOP) by increasing aqueous outflow through the trabecular meshwork (TM) pathway and decreasing episcleral venous pressure. The primary objective of this phase 2 study was to evaluate ocular hypotensive efficacy and safety of three netarsudil concentrations (0.01%, 0.02%, and 0.04%) relative to its placebo over 4 weeks in Japanese patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT).
Methods
Patients were randomized to one of four treatment arms, netarsudil ophthalmic solution 0.01%, 0.02%, 0.04%, or placebo, and treated once-daily (QD) in the evening (
p.m.
) for 4 weeks. The primary efficacy variable was mean diurnal IOP (average of diurnal time points at 9
a.m.
, 11
a.m.
, and 4
p.m.
) at week 4.
Results
A total of 215 patients were randomized and 207 (96.3%) completed the study. The mean of mean diurnal IOP at baseline ranged from 20.28 to 21.14 mmHg across groups. At week 4, least squares (LS) mean of mean diurnal IOP adjusted for baseline was 16.53, 15.82, 16.06, and 18.94 mmHg in the netarsudil 0.01%, 0.02%, 0.04%, and placebo groups, respectively, demonstrating the superiority of netarsudil (all concentrations) over placebo. At week 4, mean reduction (mean percentage reduction) from baseline in mean diurnal IOP was 4.10 (19.8%), 4.80 (23.5%), 4.81 (23.8%), and 1.73 mmHg (8.2%), respectively, demonstrating statistically significant reductions (
p
< 0.0001) in all netarsudil concentrations over placebo. Adverse events (AEs) occurred in a concentration-dependent manner, and the incidence of ocular AEs was 34.5%, 42.6%, 68.6%, and 9.1% in the netarsudil 0.01%, 0.02%, 0.04%, and placebo groups, respectively. The most frequently reported AE was conjunctival hyperemia, with an incidence of 23.6%, 37.0%, 56.9%, and 1.8%, respectively. No serious AEs were reported.
Conclusion
Netarsudil ophthalmic solutions 0.01%, 0.02%, and 0.04% dosed QD (
p.m.
) demonstrated superiority to placebo in terms of hypotensive effectiveness at week 4 and were found to be safe and generally well tolerated. Netarsudil 0.02% QD provided an optimal efficacy and safety profile for the treatment of Japanese patients with POAG or OHT.
Trial Registration
NCT03844945.</abstract><cop>Cheshire</cop><pub>Springer Healthcare</pub><pmid>33629227</pmid><doi>10.1007/s12325-021-01634-9</doi><tpages>19</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Advances in therapy, 2021-04, Vol.38 (4), p.1757-1775 |
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| language | eng |
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| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Antihypertensive Agents - therapeutic use Benzoates beta-Alanine - analogs & derivatives Cardiology Double-Blind Method Endocrinology Glaucoma, Open-Angle - drug therapy Health technology assessment Humans Internal Medicine Intraocular Pressure Japan Medicine Medicine & Public Health Ocular Hypertension - drug therapy Oncology Ophthalmic Solutions Original Research Pharmacology/Toxicology Rheumatology Tonometry, Ocular |
| title | Phase 2 Randomized Clinical Study of Netarsudil Ophthalmic Solution in Japanese Patients with Primary Open-Angle Glaucoma or Ocular Hypertension |
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