Add‐on therapy with dapagliflozin under full closed loop control improves time in range in adolescents and young adults with type 1 diabetes: The DAPADream study
Aim To investigate the effect of the sodium‐glucose co‐transporter‐2 inhibitor dapagliflozin on glucose levels overnight and during the following day after two unannounced meals under full closed loop (FCL) conditions. Materials and Methods For this single‐centre, double‐blind, randomized, placebo‐c...
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| Veröffentlicht in: | Diabetes, obesity & metabolism obesity & metabolism, 2021-02, Vol.23 (2), p.599-608 |
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| creator | Biester, Torben Muller, Ido von dem Berge, Thekla Atlas, Eran Nimri, Revital Phillip, Moshe Battelino, Tadej Bratina, Natasa Dovc, Klemen Scheerer, Markus F. Kordonouri, Olga Danne, Thomas |
| description | Aim
To investigate the effect of the sodium‐glucose co‐transporter‐2 inhibitor dapagliflozin on glucose levels overnight and during the following day after two unannounced meals under full closed loop (FCL) conditions.
Materials and Methods
For this single‐centre, double‐blind, randomized, placebo‐controlled, cross‐over trial, non‐obese persons with type 1 diabetes (T1D) were studied twice (10 mg dapagliflozin bid vs. placebo) for 24 hours with two unannounced mixed meal tests 6 hours apart under FCL conditions. Primary outcome was sensor glucose time in range (TIR; 3.9‐10 mmol/L). For safety evaluation, ß‐hydroxybutyrate (BHB), glucagon, insulin and gastric inhibitory polypeptide were measured.
Results
Fifteen adolescents (aged 15.4 ± 1.6 years, diabetes duration 10.0 ± 3.4 years, HbA1c 8.4% ± 0.9% [67.7 ± 10.1 mmol/mol]) and 15 young adults (aged 18.7 ± 0.8 years; diabetes duration 12.5 ± 3.6 years; HbA1c 8.3% ± 0.9% [68.5 ± 11.2 mmol/mol]) completed the trial. TIR was significantly higher in the intervention group compared with placebo (68% ± 6% vs. 50% ± 13%; P |
| doi_str_mv | 10.1111/dom.14258 |
| format | Article |
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To investigate the effect of the sodium‐glucose co‐transporter‐2 inhibitor dapagliflozin on glucose levels overnight and during the following day after two unannounced meals under full closed loop (FCL) conditions.
Materials and Methods
For this single‐centre, double‐blind, randomized, placebo‐controlled, cross‐over trial, non‐obese persons with type 1 diabetes (T1D) were studied twice (10 mg dapagliflozin bid vs. placebo) for 24 hours with two unannounced mixed meal tests 6 hours apart under FCL conditions. Primary outcome was sensor glucose time in range (TIR; 3.9‐10 mmol/L). For safety evaluation, ß‐hydroxybutyrate (BHB), glucagon, insulin and gastric inhibitory polypeptide were measured.
Results
Fifteen adolescents (aged 15.4 ± 1.6 years, diabetes duration 10.0 ± 3.4 years, HbA1c 8.4% ± 0.9% [67.7 ± 10.1 mmol/mol]) and 15 young adults (aged 18.7 ± 0.8 years; diabetes duration 12.5 ± 3.6 years; HbA1c 8.3% ± 0.9% [68.5 ± 11.2 mmol/mol]) completed the trial. TIR was significantly higher in the intervention group compared with placebo (68% ± 6% vs. 50% ± 13%; P < .001); nocturnal glucose was significantly lower with dapagliflozin (6.2 ± 0.7 vs. 7.3 ± 1.7 mmol/L; P = .003) without an increase in time at less than 3.9 mmol/L (3.3% ± 6.0% vs 3.1% ± 5.2%; P = .75). Urinary glucose excretion was increased 3‐fold using dapagliflozin (149 ± 42 vs. 49 ± 23 g/24 hours) with a total insulin reduction of 22% (39.7 ± 12.7 vs. 30.6 ± 10.4 U; P = .004). No abnormal elevated BHB values were observed.
Conclusions
In adolescents and adults with T1D, dapagliflozin significantly increased TIR on average by 259 minutes/day while reducing glycaemic variability during FCL control without any signs of hypoglycaemia or ketosis.</description><identifier>ISSN: 1462-8902</identifier><identifier>EISSN: 1463-1326</identifier><identifier>DOI: 10.1111/dom.14258</identifier><identifier>PMID: 33217117</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Adolescents ; Antidiabetics ; Diabetes ; Diabetes mellitus (insulin dependent) ; Glucagon ; Glucose ; Glucose transporter ; Hypoglycemia ; Insulin ; Ketosis ; Placebos ; Teenagers ; Young adults ; ß‐hydroxybutyrate, DKA, insulin, ketone, SGLT2 inhibitor, type 1 diabetes</subject><ispartof>Diabetes, obesity & metabolism, 2021-02, Vol.23 (2), p.599-608</ispartof><rights>2020 John Wiley & Sons Ltd</rights><rights>2020 John Wiley & Sons Ltd.</rights><rights>2021 John Wiley & Sons Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3538-c3f380ae9da102908ef6a6f650473ec984f5efdf5e6f0d78effc130211a3e02d3</citedby><cites>FETCH-LOGICAL-c3538-c3f380ae9da102908ef6a6f650473ec984f5efdf5e6f0d78effc130211a3e02d3</cites><orcidid>0000-0002-0273-4732 ; 0000-0002-6616-5612 ; 0000-0003-2653-6359 ; 0000-0001-8185-5366 ; 0000-0001-8051-5562 ; 0000-0002-8424-3944 ; 0000-0001-9201-2145 ; 0000-0003-3571-4938 ; 0000-0001-9563-3537</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fdom.14258$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fdom.14258$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,778,782,1414,27907,27908,45557,45558</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33217117$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Biester, Torben</creatorcontrib><creatorcontrib>Muller, Ido</creatorcontrib><creatorcontrib>von dem Berge, Thekla</creatorcontrib><creatorcontrib>Atlas, Eran</creatorcontrib><creatorcontrib>Nimri, Revital</creatorcontrib><creatorcontrib>Phillip, Moshe</creatorcontrib><creatorcontrib>Battelino, Tadej</creatorcontrib><creatorcontrib>Bratina, Natasa</creatorcontrib><creatorcontrib>Dovc, Klemen</creatorcontrib><creatorcontrib>Scheerer, Markus F.</creatorcontrib><creatorcontrib>Kordonouri, Olga</creatorcontrib><creatorcontrib>Danne, Thomas</creatorcontrib><title>Add‐on therapy with dapagliflozin under full closed loop control improves time in range in adolescents and young adults with type 1 diabetes: The DAPADream study</title><title>Diabetes, obesity & metabolism</title><addtitle>Diabetes Obes Metab</addtitle><description>Aim
To investigate the effect of the sodium‐glucose co‐transporter‐2 inhibitor dapagliflozin on glucose levels overnight and during the following day after two unannounced meals under full closed loop (FCL) conditions.
Materials and Methods
For this single‐centre, double‐blind, randomized, placebo‐controlled, cross‐over trial, non‐obese persons with type 1 diabetes (T1D) were studied twice (10 mg dapagliflozin bid vs. placebo) for 24 hours with two unannounced mixed meal tests 6 hours apart under FCL conditions. Primary outcome was sensor glucose time in range (TIR; 3.9‐10 mmol/L). For safety evaluation, ß‐hydroxybutyrate (BHB), glucagon, insulin and gastric inhibitory polypeptide were measured.
Results
Fifteen adolescents (aged 15.4 ± 1.6 years, diabetes duration 10.0 ± 3.4 years, HbA1c 8.4% ± 0.9% [67.7 ± 10.1 mmol/mol]) and 15 young adults (aged 18.7 ± 0.8 years; diabetes duration 12.5 ± 3.6 years; HbA1c 8.3% ± 0.9% [68.5 ± 11.2 mmol/mol]) completed the trial. TIR was significantly higher in the intervention group compared with placebo (68% ± 6% vs. 50% ± 13%; P < .001); nocturnal glucose was significantly lower with dapagliflozin (6.2 ± 0.7 vs. 7.3 ± 1.7 mmol/L; P = .003) without an increase in time at less than 3.9 mmol/L (3.3% ± 6.0% vs 3.1% ± 5.2%; P = .75). Urinary glucose excretion was increased 3‐fold using dapagliflozin (149 ± 42 vs. 49 ± 23 g/24 hours) with a total insulin reduction of 22% (39.7 ± 12.7 vs. 30.6 ± 10.4 U; P = .004). No abnormal elevated BHB values were observed.
Conclusions
In adolescents and adults with T1D, dapagliflozin significantly increased TIR on average by 259 minutes/day while reducing glycaemic variability during FCL control without any signs of hypoglycaemia or ketosis.</description><subject>Adolescents</subject><subject>Antidiabetics</subject><subject>Diabetes</subject><subject>Diabetes mellitus (insulin dependent)</subject><subject>Glucagon</subject><subject>Glucose</subject><subject>Glucose transporter</subject><subject>Hypoglycemia</subject><subject>Insulin</subject><subject>Ketosis</subject><subject>Placebos</subject><subject>Teenagers</subject><subject>Young adults</subject><subject>ß‐hydroxybutyrate, DKA, insulin, ketone, SGLT2 inhibitor, type 1 diabetes</subject><issn>1462-8902</issn><issn>1463-1326</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNp1kUtuFDEQhi0EIiGw4AKoJDawmMSPfrIbZXhJQWER1i2nXZ5x5LYbP4iaFUfgDtyMk2BmAgskvCiXqj79LtdPyFNGT1k5Z8pPp6zidXePHLOqESsmeHN_n_NV11N-RB7FeEMprUTXPiRHQnDWMtYekx9rpX5---4dpB0GOS9wa9IOlJzl1hpt_VfjIDuFAXS2FkbrIyqw3s8wepeCt2CmOfgvGCGZCaHwQbrtPpHKW4wjuhRBOgWLz25bqtmWwv6htMwIDJSR15gwvoKrHcJm_XG9CSgniCmr5TF5oKWN-OTuPiGf3ry-On-3urh8-_58fbEaRS26ErXoqMReSUZ5TzvUjWx0U9OqFTj2XaVr1KqERlPVlrYemaCcMSmQciVOyIuDbvnO54wxDZMpw1srHfocB15Wy2jb93VBn_-D3vgcXJmuUG1TV7yrm0K9PFBj8DEG1MMczCTDMjA6_HZuKM4Ne-cK--xOMV9PqP6Sf6wqwNkBuDUWl_8rDZvLDwfJX60hpWA</recordid><startdate>202102</startdate><enddate>202102</enddate><creator>Biester, Torben</creator><creator>Muller, Ido</creator><creator>von dem Berge, Thekla</creator><creator>Atlas, Eran</creator><creator>Nimri, Revital</creator><creator>Phillip, Moshe</creator><creator>Battelino, Tadej</creator><creator>Bratina, Natasa</creator><creator>Dovc, Klemen</creator><creator>Scheerer, Markus F.</creator><creator>Kordonouri, Olga</creator><creator>Danne, Thomas</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TK</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-0273-4732</orcidid><orcidid>https://orcid.org/0000-0002-6616-5612</orcidid><orcidid>https://orcid.org/0000-0003-2653-6359</orcidid><orcidid>https://orcid.org/0000-0001-8185-5366</orcidid><orcidid>https://orcid.org/0000-0001-8051-5562</orcidid><orcidid>https://orcid.org/0000-0002-8424-3944</orcidid><orcidid>https://orcid.org/0000-0001-9201-2145</orcidid><orcidid>https://orcid.org/0000-0003-3571-4938</orcidid><orcidid>https://orcid.org/0000-0001-9563-3537</orcidid></search><sort><creationdate>202102</creationdate><title>Add‐on therapy with dapagliflozin under full closed loop control improves time in range in adolescents and young adults with type 1 diabetes: The DAPADream study</title><author>Biester, Torben ; Muller, Ido ; von dem Berge, Thekla ; Atlas, Eran ; Nimri, Revital ; Phillip, Moshe ; Battelino, Tadej ; Bratina, Natasa ; Dovc, Klemen ; Scheerer, Markus F. ; Kordonouri, Olga ; Danne, Thomas</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3538-c3f380ae9da102908ef6a6f650473ec984f5efdf5e6f0d78effc130211a3e02d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adolescents</topic><topic>Antidiabetics</topic><topic>Diabetes</topic><topic>Diabetes mellitus (insulin dependent)</topic><topic>Glucagon</topic><topic>Glucose</topic><topic>Glucose transporter</topic><topic>Hypoglycemia</topic><topic>Insulin</topic><topic>Ketosis</topic><topic>Placebos</topic><topic>Teenagers</topic><topic>Young adults</topic><topic>ß‐hydroxybutyrate, DKA, insulin, ketone, SGLT2 inhibitor, type 1 diabetes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Biester, Torben</creatorcontrib><creatorcontrib>Muller, Ido</creatorcontrib><creatorcontrib>von dem Berge, Thekla</creatorcontrib><creatorcontrib>Atlas, Eran</creatorcontrib><creatorcontrib>Nimri, Revital</creatorcontrib><creatorcontrib>Phillip, Moshe</creatorcontrib><creatorcontrib>Battelino, Tadej</creatorcontrib><creatorcontrib>Bratina, Natasa</creatorcontrib><creatorcontrib>Dovc, Klemen</creatorcontrib><creatorcontrib>Scheerer, Markus F.</creatorcontrib><creatorcontrib>Kordonouri, Olga</creatorcontrib><creatorcontrib>Danne, Thomas</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Diabetes, obesity & metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Biester, Torben</au><au>Muller, Ido</au><au>von dem Berge, Thekla</au><au>Atlas, Eran</au><au>Nimri, Revital</au><au>Phillip, Moshe</au><au>Battelino, Tadej</au><au>Bratina, Natasa</au><au>Dovc, Klemen</au><au>Scheerer, Markus F.</au><au>Kordonouri, Olga</au><au>Danne, Thomas</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Add‐on therapy with dapagliflozin under full closed loop control improves time in range in adolescents and young adults with type 1 diabetes: The DAPADream study</atitle><jtitle>Diabetes, obesity & metabolism</jtitle><addtitle>Diabetes Obes Metab</addtitle><date>2021-02</date><risdate>2021</risdate><volume>23</volume><issue>2</issue><spage>599</spage><epage>608</epage><pages>599-608</pages><issn>1462-8902</issn><eissn>1463-1326</eissn><abstract>Aim
To investigate the effect of the sodium‐glucose co‐transporter‐2 inhibitor dapagliflozin on glucose levels overnight and during the following day after two unannounced meals under full closed loop (FCL) conditions.
Materials and Methods
For this single‐centre, double‐blind, randomized, placebo‐controlled, cross‐over trial, non‐obese persons with type 1 diabetes (T1D) were studied twice (10 mg dapagliflozin bid vs. placebo) for 24 hours with two unannounced mixed meal tests 6 hours apart under FCL conditions. Primary outcome was sensor glucose time in range (TIR; 3.9‐10 mmol/L). For safety evaluation, ß‐hydroxybutyrate (BHB), glucagon, insulin and gastric inhibitory polypeptide were measured.
Results
Fifteen adolescents (aged 15.4 ± 1.6 years, diabetes duration 10.0 ± 3.4 years, HbA1c 8.4% ± 0.9% [67.7 ± 10.1 mmol/mol]) and 15 young adults (aged 18.7 ± 0.8 years; diabetes duration 12.5 ± 3.6 years; HbA1c 8.3% ± 0.9% [68.5 ± 11.2 mmol/mol]) completed the trial. TIR was significantly higher in the intervention group compared with placebo (68% ± 6% vs. 50% ± 13%; P < .001); nocturnal glucose was significantly lower with dapagliflozin (6.2 ± 0.7 vs. 7.3 ± 1.7 mmol/L; P = .003) without an increase in time at less than 3.9 mmol/L (3.3% ± 6.0% vs 3.1% ± 5.2%; P = .75). Urinary glucose excretion was increased 3‐fold using dapagliflozin (149 ± 42 vs. 49 ± 23 g/24 hours) with a total insulin reduction of 22% (39.7 ± 12.7 vs. 30.6 ± 10.4 U; P = .004). No abnormal elevated BHB values were observed.
Conclusions
In adolescents and adults with T1D, dapagliflozin significantly increased TIR on average by 259 minutes/day while reducing glycaemic variability during FCL control without any signs of hypoglycaemia or ketosis.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>33217117</pmid><doi>10.1111/dom.14258</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-0273-4732</orcidid><orcidid>https://orcid.org/0000-0002-6616-5612</orcidid><orcidid>https://orcid.org/0000-0003-2653-6359</orcidid><orcidid>https://orcid.org/0000-0001-8185-5366</orcidid><orcidid>https://orcid.org/0000-0001-8051-5562</orcidid><orcidid>https://orcid.org/0000-0002-8424-3944</orcidid><orcidid>https://orcid.org/0000-0001-9201-2145</orcidid><orcidid>https://orcid.org/0000-0003-3571-4938</orcidid><orcidid>https://orcid.org/0000-0001-9563-3537</orcidid></addata></record> |
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| ispartof | Diabetes, obesity & metabolism, 2021-02, Vol.23 (2), p.599-608 |
| issn | 1462-8902 1463-1326 |
| language | eng |
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| source | Wiley Online Library Journals Frontfile Complete |
| subjects | Adolescents Antidiabetics Diabetes Diabetes mellitus (insulin dependent) Glucagon Glucose Glucose transporter Hypoglycemia Insulin Ketosis Placebos Teenagers Young adults ß‐hydroxybutyrate, DKA, insulin, ketone, SGLT2 inhibitor, type 1 diabetes |
| title | Add‐on therapy with dapagliflozin under full closed loop control improves time in range in adolescents and young adults with type 1 diabetes: The DAPADream study |
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