Darunavir Pharmacokinetics With an Increased Dose During Pregnancy
BACKGROUND:This study aims to evaluate the pharmacokinetics of an increased dose of darunavir (800 mg twice daily) with 100 mg ritonavir during pregnancy and postpartum. METHODS:Darunavir (DRV) and ritonavir (RTV; r) intensive pharmacokinetic evaluations were performed at steady state during the sec...
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| Veröffentlicht in: | Journal of acquired immune deficiency syndromes (1999) 2020-04, Vol.83 (4), p.373-380 |
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| creator | Eke, Ahizechukwu C. Stek, Alice M. Wang, Jiajia Kreitchmann, Regis Shapiro, David E. Smith, Elizabeth Chakhtoura, Nahida Capparelli, Edmund V. Mirochnick, Mark Best, Brookie M. |
| description | BACKGROUND:This study aims to evaluate the pharmacokinetics of an increased dose of darunavir (800 mg twice daily) with 100 mg ritonavir during pregnancy and postpartum.
METHODS:Darunavir (DRV) and ritonavir (RTV; r) intensive pharmacokinetic evaluations were performed at steady state during the second and third trimesters of pregnancy (DRV/r 800/100 mg bid) and 2–3 weeks postpartum (DRV/r 600/100 mg twice daily). Plasma concentrations of darunavir and ritonavir were measured using high-performance liquid chromatography. Target darunavir area under the concentration time curve (AUC) was >70% (43.6 μg × h/mL) of median AUC (62.3 μg × h/mL) in nonpregnant adults on twice daily darunavir-ritonavir 600/100 mg.
RESULTS:Twenty-four women were included in the analysis. Darunavir AUC0–12 was lower with the increased dose during the second {[geometric mean ratio (GMR) of 0.62 (IQR 0.44–0.88); P = 0.055]} and third trimesters [GMR 0.64 (IQR 0.55–0.73); P = |
| doi_str_mv | 10.1097/QAI.0000000000002261 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7258985</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2378043964</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5301-95f1d3a8428f4f9f75a404194078a33cc5dcac7571fc4c3c10ba6fd36790615d3</originalsourceid><addsrcrecordid>eNqFUdFqFTEQDaLYWv0DkQWft06SySZ5EWpv1QsFKyg-hmk2e3fbvdma7Lb07025tVQfdF5mYM45czjD2GsOhxysfvf1aH0Ij0qIhj9h-9wi1toYfFpmJVSNXKo99iLnCwDeINrnbE9yKyQYvc8-rCgtka6HVJ31lLbkp8shhnnwufoxzH1FsVpHnwLl0FarKYdqtaQhbqqzFDaRor99yZ51NObw6r4fsO8fT74df65Pv3xaHx-d1l5J4LVVHW8lGRSmw852WhECFrugDUnpvWo9ea007zx66TmcU9O1stEWGq5aecDe73SvlvNtaH2Ic6LRXaVhS-nWTTS4Pzdx6N1munZaKGONKgJv7wXS9HMJeXYX05Ji8eyE1AZQ2gYLCncon6acU-geLnBwd8m7krz7O_lCe_PY3QPpd9QFYHaAm2mcQ8qX43ITkusDjXP_P238B7W8VTRSYi1AACBwqO-YRv4CvwufEA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2378043964</pqid></control><display><type>article</type><title>Darunavir Pharmacokinetics With an Increased Dose During Pregnancy</title><source>Journals@OVID</source><source>MEDLINE</source><source>Free E- Journals</source><creator>Eke, Ahizechukwu C. ; Stek, Alice M. ; Wang, Jiajia ; Kreitchmann, Regis ; Shapiro, David E. ; Smith, Elizabeth ; Chakhtoura, Nahida ; Capparelli, Edmund V. ; Mirochnick, Mark ; Best, Brookie M.</creator><creatorcontrib>Eke, Ahizechukwu C. ; Stek, Alice M. ; Wang, Jiajia ; Kreitchmann, Regis ; Shapiro, David E. ; Smith, Elizabeth ; Chakhtoura, Nahida ; Capparelli, Edmund V. ; Mirochnick, Mark ; Best, Brookie M. ; IMPAACT P1026s Protocol Team</creatorcontrib><description>BACKGROUND:This study aims to evaluate the pharmacokinetics of an increased dose of darunavir (800 mg twice daily) with 100 mg ritonavir during pregnancy and postpartum.
METHODS:Darunavir (DRV) and ritonavir (RTV; r) intensive pharmacokinetic evaluations were performed at steady state during the second and third trimesters of pregnancy (DRV/r 800/100 mg bid) and 2–3 weeks postpartum (DRV/r 600/100 mg twice daily). Plasma concentrations of darunavir and ritonavir were measured using high-performance liquid chromatography. Target darunavir area under the concentration time curve (AUC) was >70% (43.6 μg × h/mL) of median AUC (62.3 μg × h/mL) in nonpregnant adults on twice daily darunavir-ritonavir 600/100 mg.
RESULTS:Twenty-four women were included in the analysis. Darunavir AUC0–12 was lower with the increased dose during the second {[geometric mean ratio (GMR) of 0.62 (IQR 0.44–0.88); P = 0.055]} and third trimesters [GMR 0.64 (IQR 0.55–0.73); P = <0.001] compared with postpartum. Darunavir apparent clearance was higher during the second [GMR 1.77 (IQR 1.24–2.51); P = 0.039] and third trimesters [GMR 2.01 (IQR 1.17–2.35); P = <0.001] compared with postpartum. Similarly, ritonavir AUC0–12 was lower during the third trimester [GMR 0.65 (IQR 0.52–0.82); P = 0.007] compared with postpartum, whereas its apparent clearance was higher during the third trimester [GMR 1.53 (IQR 1.22–1.92); P = 0.008] compared with postpartum. No major drug-related safety concerns were noted.
CONCLUSIONS:Increasing darunavir dose to 800 mg BID failed to significantly increase darunavir exposure compared with 600 mg BID. Other strategies, such as increasing the ritonavir dose should be investigated.</description><identifier>ISSN: 1525-4135</identifier><identifier>EISSN: 1944-7884</identifier><identifier>DOI: 10.1097/QAI.0000000000002261</identifier><identifier>PMID: 31923087</identifier><language>eng</language><publisher>United States: JAIDS Journal of Acquired Immune Deficiency Syndromes</publisher><subject>Adult ; Antiretroviral drugs ; Concentration time ; Darunavir - administration & dosage ; Darunavir - pharmacokinetics ; Darunavir - therapeutic use ; Dose-Response Relationship, Drug ; Drug Combinations ; Female ; High performance liquid chromatography ; HIV - drug effects ; HIV Infections - blood ; HIV Infections - drug therapy ; Humans ; Liquid chromatography ; Pharmacokinetics ; Pharmacology ; Postpartum ; Pregnancy ; Pregnancy Complications, Infectious - blood ; Pregnancy Complications, Infectious - drug therapy ; Ritonavir ; Ritonavir - administration & dosage ; Ritonavir - pharmacokinetics ; Ritonavir - therapeutic use ; Statistics as Topic ; Young Adult</subject><ispartof>Journal of acquired immune deficiency syndromes (1999), 2020-04, Vol.83 (4), p.373-380</ispartof><rights>JAIDS Journal of Acquired Immune Deficiency Syndromes</rights><rights>Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.</rights><rights>Copyright Lippincott Williams & Wilkins Ovid Technologies Apr 1, 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5301-95f1d3a8428f4f9f75a404194078a33cc5dcac7571fc4c3c10ba6fd36790615d3</citedby><cites>FETCH-LOGICAL-c5301-95f1d3a8428f4f9f75a404194078a33cc5dcac7571fc4c3c10ba6fd36790615d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttp://ovidsp.ovid.com/ovidweb.cgi?T=JS&NEWS=n&CSC=Y&PAGE=fulltext&D=ovft&AN=00126334-202004010-00008$$EHTML$$P50$$Gwolterskluwer$$H</linktohtml><link.rule.ids>230,314,777,781,882,4595,27905,27906,65212</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31923087$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Eke, Ahizechukwu C.</creatorcontrib><creatorcontrib>Stek, Alice M.</creatorcontrib><creatorcontrib>Wang, Jiajia</creatorcontrib><creatorcontrib>Kreitchmann, Regis</creatorcontrib><creatorcontrib>Shapiro, David E.</creatorcontrib><creatorcontrib>Smith, Elizabeth</creatorcontrib><creatorcontrib>Chakhtoura, Nahida</creatorcontrib><creatorcontrib>Capparelli, Edmund V.</creatorcontrib><creatorcontrib>Mirochnick, Mark</creatorcontrib><creatorcontrib>Best, Brookie M.</creatorcontrib><creatorcontrib>IMPAACT P1026s Protocol Team</creatorcontrib><title>Darunavir Pharmacokinetics With an Increased Dose During Pregnancy</title><title>Journal of acquired immune deficiency syndromes (1999)</title><addtitle>J Acquir Immune Defic Syndr</addtitle><description>BACKGROUND:This study aims to evaluate the pharmacokinetics of an increased dose of darunavir (800 mg twice daily) with 100 mg ritonavir during pregnancy and postpartum.
METHODS:Darunavir (DRV) and ritonavir (RTV; r) intensive pharmacokinetic evaluations were performed at steady state during the second and third trimesters of pregnancy (DRV/r 800/100 mg bid) and 2–3 weeks postpartum (DRV/r 600/100 mg twice daily). Plasma concentrations of darunavir and ritonavir were measured using high-performance liquid chromatography. Target darunavir area under the concentration time curve (AUC) was >70% (43.6 μg × h/mL) of median AUC (62.3 μg × h/mL) in nonpregnant adults on twice daily darunavir-ritonavir 600/100 mg.
RESULTS:Twenty-four women were included in the analysis. Darunavir AUC0–12 was lower with the increased dose during the second {[geometric mean ratio (GMR) of 0.62 (IQR 0.44–0.88); P = 0.055]} and third trimesters [GMR 0.64 (IQR 0.55–0.73); P = <0.001] compared with postpartum. Darunavir apparent clearance was higher during the second [GMR 1.77 (IQR 1.24–2.51); P = 0.039] and third trimesters [GMR 2.01 (IQR 1.17–2.35); P = <0.001] compared with postpartum. Similarly, ritonavir AUC0–12 was lower during the third trimester [GMR 0.65 (IQR 0.52–0.82); P = 0.007] compared with postpartum, whereas its apparent clearance was higher during the third trimester [GMR 1.53 (IQR 1.22–1.92); P = 0.008] compared with postpartum. No major drug-related safety concerns were noted.
CONCLUSIONS:Increasing darunavir dose to 800 mg BID failed to significantly increase darunavir exposure compared with 600 mg BID. Other strategies, such as increasing the ritonavir dose should be investigated.</description><subject>Adult</subject><subject>Antiretroviral drugs</subject><subject>Concentration time</subject><subject>Darunavir - administration & dosage</subject><subject>Darunavir - pharmacokinetics</subject><subject>Darunavir - therapeutic use</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Combinations</subject><subject>Female</subject><subject>High performance liquid chromatography</subject><subject>HIV - drug effects</subject><subject>HIV Infections - blood</subject><subject>HIV Infections - drug therapy</subject><subject>Humans</subject><subject>Liquid chromatography</subject><subject>Pharmacokinetics</subject><subject>Pharmacology</subject><subject>Postpartum</subject><subject>Pregnancy</subject><subject>Pregnancy Complications, Infectious - blood</subject><subject>Pregnancy Complications, Infectious - drug therapy</subject><subject>Ritonavir</subject><subject>Ritonavir - administration & dosage</subject><subject>Ritonavir - pharmacokinetics</subject><subject>Ritonavir - therapeutic use</subject><subject>Statistics as Topic</subject><subject>Young Adult</subject><issn>1525-4135</issn><issn>1944-7884</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUdFqFTEQDaLYWv0DkQWft06SySZ5EWpv1QsFKyg-hmk2e3fbvdma7Lb07025tVQfdF5mYM45czjD2GsOhxysfvf1aH0Ij0qIhj9h-9wi1toYfFpmJVSNXKo99iLnCwDeINrnbE9yKyQYvc8-rCgtka6HVJ31lLbkp8shhnnwufoxzH1FsVpHnwLl0FarKYdqtaQhbqqzFDaRor99yZ51NObw6r4fsO8fT74df65Pv3xaHx-d1l5J4LVVHW8lGRSmw852WhECFrugDUnpvWo9ea007zx66TmcU9O1stEWGq5aecDe73SvlvNtaH2Ic6LRXaVhS-nWTTS4Pzdx6N1munZaKGONKgJv7wXS9HMJeXYX05Ji8eyE1AZQ2gYLCncon6acU-geLnBwd8m7krz7O_lCe_PY3QPpd9QFYHaAm2mcQ8qX43ITkusDjXP_P238B7W8VTRSYi1AACBwqO-YRv4CvwufEA</recordid><startdate>20200401</startdate><enddate>20200401</enddate><creator>Eke, Ahizechukwu C.</creator><creator>Stek, Alice M.</creator><creator>Wang, Jiajia</creator><creator>Kreitchmann, Regis</creator><creator>Shapiro, David E.</creator><creator>Smith, Elizabeth</creator><creator>Chakhtoura, Nahida</creator><creator>Capparelli, Edmund V.</creator><creator>Mirochnick, Mark</creator><creator>Best, Brookie M.</creator><general>JAIDS Journal of Acquired Immune Deficiency Syndromes</general><general>Copyright Wolters Kluwer Health, Inc. All rights reserved</general><general>Lippincott Williams & Wilkins Ovid Technologies</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>7T2</scope><scope>7T5</scope><scope>7TK</scope><scope>7U7</scope><scope>7U9</scope><scope>C1K</scope><scope>H94</scope><scope>K9.</scope><scope>5PM</scope></search><sort><creationdate>20200401</creationdate><title>Darunavir Pharmacokinetics With an Increased Dose During Pregnancy</title><author>Eke, Ahizechukwu C. ; Stek, Alice M. ; Wang, Jiajia ; Kreitchmann, Regis ; Shapiro, David E. ; Smith, Elizabeth ; Chakhtoura, Nahida ; Capparelli, Edmund V. ; Mirochnick, Mark ; Best, Brookie M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5301-95f1d3a8428f4f9f75a404194078a33cc5dcac7571fc4c3c10ba6fd36790615d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adult</topic><topic>Antiretroviral drugs</topic><topic>Concentration time</topic><topic>Darunavir - administration & dosage</topic><topic>Darunavir - pharmacokinetics</topic><topic>Darunavir - therapeutic use</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Combinations</topic><topic>Female</topic><topic>High performance liquid chromatography</topic><topic>HIV - drug effects</topic><topic>HIV Infections - blood</topic><topic>HIV Infections - drug therapy</topic><topic>Humans</topic><topic>Liquid chromatography</topic><topic>Pharmacokinetics</topic><topic>Pharmacology</topic><topic>Postpartum</topic><topic>Pregnancy</topic><topic>Pregnancy Complications, Infectious - blood</topic><topic>Pregnancy Complications, Infectious - drug therapy</topic><topic>Ritonavir</topic><topic>Ritonavir - administration & dosage</topic><topic>Ritonavir - pharmacokinetics</topic><topic>Ritonavir - therapeutic use</topic><topic>Statistics as Topic</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Eke, Ahizechukwu C.</creatorcontrib><creatorcontrib>Stek, Alice M.</creatorcontrib><creatorcontrib>Wang, Jiajia</creatorcontrib><creatorcontrib>Kreitchmann, Regis</creatorcontrib><creatorcontrib>Shapiro, David E.</creatorcontrib><creatorcontrib>Smith, Elizabeth</creatorcontrib><creatorcontrib>Chakhtoura, Nahida</creatorcontrib><creatorcontrib>Capparelli, Edmund V.</creatorcontrib><creatorcontrib>Mirochnick, Mark</creatorcontrib><creatorcontrib>Best, Brookie M.</creatorcontrib><creatorcontrib>IMPAACT P1026s Protocol Team</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of acquired immune deficiency syndromes (1999)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Eke, Ahizechukwu C.</au><au>Stek, Alice M.</au><au>Wang, Jiajia</au><au>Kreitchmann, Regis</au><au>Shapiro, David E.</au><au>Smith, Elizabeth</au><au>Chakhtoura, Nahida</au><au>Capparelli, Edmund V.</au><au>Mirochnick, Mark</au><au>Best, Brookie M.</au><aucorp>IMPAACT P1026s Protocol Team</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Darunavir Pharmacokinetics With an Increased Dose During Pregnancy</atitle><jtitle>Journal of acquired immune deficiency syndromes (1999)</jtitle><addtitle>J Acquir Immune Defic Syndr</addtitle><date>2020-04-01</date><risdate>2020</risdate><volume>83</volume><issue>4</issue><spage>373</spage><epage>380</epage><pages>373-380</pages><issn>1525-4135</issn><eissn>1944-7884</eissn><abstract>BACKGROUND:This study aims to evaluate the pharmacokinetics of an increased dose of darunavir (800 mg twice daily) with 100 mg ritonavir during pregnancy and postpartum.
METHODS:Darunavir (DRV) and ritonavir (RTV; r) intensive pharmacokinetic evaluations were performed at steady state during the second and third trimesters of pregnancy (DRV/r 800/100 mg bid) and 2–3 weeks postpartum (DRV/r 600/100 mg twice daily). Plasma concentrations of darunavir and ritonavir were measured using high-performance liquid chromatography. Target darunavir area under the concentration time curve (AUC) was >70% (43.6 μg × h/mL) of median AUC (62.3 μg × h/mL) in nonpregnant adults on twice daily darunavir-ritonavir 600/100 mg.
RESULTS:Twenty-four women were included in the analysis. Darunavir AUC0–12 was lower with the increased dose during the second {[geometric mean ratio (GMR) of 0.62 (IQR 0.44–0.88); P = 0.055]} and third trimesters [GMR 0.64 (IQR 0.55–0.73); P = <0.001] compared with postpartum. Darunavir apparent clearance was higher during the second [GMR 1.77 (IQR 1.24–2.51); P = 0.039] and third trimesters [GMR 2.01 (IQR 1.17–2.35); P = <0.001] compared with postpartum. Similarly, ritonavir AUC0–12 was lower during the third trimester [GMR 0.65 (IQR 0.52–0.82); P = 0.007] compared with postpartum, whereas its apparent clearance was higher during the third trimester [GMR 1.53 (IQR 1.22–1.92); P = 0.008] compared with postpartum. No major drug-related safety concerns were noted.
CONCLUSIONS:Increasing darunavir dose to 800 mg BID failed to significantly increase darunavir exposure compared with 600 mg BID. Other strategies, such as increasing the ritonavir dose should be investigated.</abstract><cop>United States</cop><pub>JAIDS Journal of Acquired Immune Deficiency Syndromes</pub><pmid>31923087</pmid><doi>10.1097/QAI.0000000000002261</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Antiretroviral drugs Concentration time Darunavir - administration & dosage Darunavir - pharmacokinetics Darunavir - therapeutic use Dose-Response Relationship, Drug Drug Combinations Female High performance liquid chromatography HIV - drug effects HIV Infections - blood HIV Infections - drug therapy Humans Liquid chromatography Pharmacokinetics Pharmacology Postpartum Pregnancy Pregnancy Complications, Infectious - blood Pregnancy Complications, Infectious - drug therapy Ritonavir Ritonavir - administration & dosage Ritonavir - pharmacokinetics Ritonavir - therapeutic use Statistics as Topic Young Adult |
| title | Darunavir Pharmacokinetics With an Increased Dose During Pregnancy |
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