A Follow-up Study to Monitor Adult Height Among Spanish Children with Growth Hormone Deficiency Who Received Biosimilar Human Recombinant Growth Hormone (Omnitrope®) During a Phase III Clinical Trial
Introduction An initial Phase III clinical trial has evaluated the efficacy and safety of biosimilar recombinant human growth hormone (rhGH; Omnitrope ® , Sandoz) in Spanish children with growth hormone deficiency (GHD). At the end of the study, those patients still growing were offered to remain on...
Gespeichert in:
| Veröffentlicht in: | Advances in therapy 2015-02, Vol.32 (2), p.148-156 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 156 |
|---|---|
| container_issue | 2 |
| container_start_page | 148 |
| container_title | Advances in therapy |
| container_volume | 32 |
| creator | Borrás Pérez, Victoria López-Siguero, Juan Pedro Martínez, Gabriela Corripio, Raquel Fernández, Juan Manuel Labarta, Jose Ignacio Ferrer, Marta Cabrinety, Nuria Prieto, Pablo Ramón-Krauel, Marta Bosch, Jordi Espino, Rafael Palla Garcia, Margarida Rebollo, Francisco Jose |
| description | Introduction
An initial Phase III clinical trial has evaluated the efficacy and safety of biosimilar recombinant human growth hormone (rhGH; Omnitrope
®
, Sandoz) in Spanish children with growth hormone deficiency (GHD). At the end of the study, those patients still growing were offered to remain on treatment (as in usual clinical practice), and continued to be monitored. The aim of this study was to determine the adult height achieved by the Spanish children who participated in the initial Phase III clinical trial, and to evaluate the long-term safety of rhGH treatment.
Methods
This study was a multicenter, observational, retrospective follow-up study of patients who participated in the Phase III clinical trial (70 patients recruited). Auxological parameters [including height, height velocity, and their associated height standard deviation scores (HSDS)] were obtained from 39 patients. Safety was assessed by recording any adverse events (AEs).
Results
In total, 27 men and 12 women provided auxological data. At the start of the follow-up study, the mean age of the patients was 12.5 ± 2.7 years, mean height was 144.8 ± 13.9 cm and mean HSDS was −1.16 ± 0.63. By the end of the follow-up period, mean height had increased to 163.1 ± 7.6 cm (
n
= 36; men 165.5 ± 7.8 cm, women 157.6 ± 3.2 cm) and mean HSDS also increased to −1.01 ± 0.59 (
n
= 36; men −1.07 ± 0.52, women −0.86 ± 0.72). In terms of safety, no treatment-related AEs were reported during the study.
Conclusion
This cohort of Spanish patients with GHD showed a positive response to rhGH treatment, achieving adult height within the local normal ranges. In addition, rhGH treatment was well tolerated, with no new or additional safety concerns. |
| doi_str_mv | 10.1007/s12325-015-0181-9 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4349959</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1661335328</sourcerecordid><originalsourceid>FETCH-LOGICAL-c442t-f0ab28f03297a85808586e983d17629f4cb35c9c68131c247cf5326f6cd123723</originalsourceid><addsrcrecordid>eNp9UktuFDEUtBCIDIEDsEFvGRZN_OnvBmkyIZmREgWRINhZHrd72pHbbuzujOZSHIIVx4pbEyLCgkXpLV656qlcCL0l-APBuDgOhDKaJZhMKElSPUMzUuZZEkGfoxkuUpJQVn4_QK9CuMWY4iIrX6IDmuV5QRidod9zOHPGuG0y9nA9jPUOBgeXzurBeZjXoxlgqfSmHWDeObuB615YHVpYtNrUXlnY6qGFc--2cSydjyQFp6rRUisrd_CtdfBFSaXvVA0n2gXdaSM8LMdO2GnjurW2wg7_ahxddfEI73r16-d7OB29ju4CPrciKFitVrAw2mopDNx4Lcxr9KIRJqg3D_MQfT37dLNYJhdX56vF_CKRaUqHpMFiTcsGM1oVosxKHJGrqmQ1KXJaNalcs0xWMi8JI5KmhWwyRvMml3UMu6DsEH3c6_bjulO1VHbwwvDe6074HXdC86cbq1u-cXc8ZWlVZVUUOHoQ8O7HqMLAOx2kMkZY5cbASZ4TxqJpGalkT5XeheBV82hDMJ8awPcN4LEBfGoAn-Tf_X3f44s_Xx4JdE8I_RSp8vzWjd7GzP6jeg8DF79f</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1661335328</pqid></control><display><type>article</type><title>A Follow-up Study to Monitor Adult Height Among Spanish Children with Growth Hormone Deficiency Who Received Biosimilar Human Recombinant Growth Hormone (Omnitrope®) During a Phase III Clinical Trial</title><source>MEDLINE</source><source>SpringerLink Journals</source><creator>Borrás Pérez, Victoria ; López-Siguero, Juan Pedro ; Martínez, Gabriela ; Corripio, Raquel ; Fernández, Juan Manuel ; Labarta, Jose Ignacio ; Ferrer, Marta ; Cabrinety, Nuria ; Prieto, Pablo ; Ramón-Krauel, Marta ; Bosch, Jordi ; Espino, Rafael ; Palla Garcia, Margarida ; Rebollo, Francisco Jose</creator><creatorcontrib>Borrás Pérez, Victoria ; López-Siguero, Juan Pedro ; Martínez, Gabriela ; Corripio, Raquel ; Fernández, Juan Manuel ; Labarta, Jose Ignacio ; Ferrer, Marta ; Cabrinety, Nuria ; Prieto, Pablo ; Ramón-Krauel, Marta ; Bosch, Jordi ; Espino, Rafael ; Palla Garcia, Margarida ; Rebollo, Francisco Jose</creatorcontrib><description>Introduction
An initial Phase III clinical trial has evaluated the efficacy and safety of biosimilar recombinant human growth hormone (rhGH; Omnitrope
®
, Sandoz) in Spanish children with growth hormone deficiency (GHD). At the end of the study, those patients still growing were offered to remain on treatment (as in usual clinical practice), and continued to be monitored. The aim of this study was to determine the adult height achieved by the Spanish children who participated in the initial Phase III clinical trial, and to evaluate the long-term safety of rhGH treatment.
Methods
This study was a multicenter, observational, retrospective follow-up study of patients who participated in the Phase III clinical trial (70 patients recruited). Auxological parameters [including height, height velocity, and their associated height standard deviation scores (HSDS)] were obtained from 39 patients. Safety was assessed by recording any adverse events (AEs).
Results
In total, 27 men and 12 women provided auxological data. At the start of the follow-up study, the mean age of the patients was 12.5 ± 2.7 years, mean height was 144.8 ± 13.9 cm and mean HSDS was −1.16 ± 0.63. By the end of the follow-up period, mean height had increased to 163.1 ± 7.6 cm (
n
= 36; men 165.5 ± 7.8 cm, women 157.6 ± 3.2 cm) and mean HSDS also increased to −1.01 ± 0.59 (
n
= 36; men −1.07 ± 0.52, women −0.86 ± 0.72). In terms of safety, no treatment-related AEs were reported during the study.
Conclusion
This cohort of Spanish patients with GHD showed a positive response to rhGH treatment, achieving adult height within the local normal ranges. In addition, rhGH treatment was well tolerated, with no new or additional safety concerns.</description><identifier>ISSN: 0741-238X</identifier><identifier>EISSN: 1865-8652</identifier><identifier>DOI: 10.1007/s12325-015-0181-9</identifier><identifier>PMID: 25667132</identifier><language>eng</language><publisher>Heidelberg: Springer Healthcare</publisher><subject>Adolescent ; Biosimilar Pharmaceuticals - therapeutic use ; Body Height ; Cardiology ; Child ; Endocrinology ; Female ; Follow-Up Studies ; Growth Disorders - drug therapy ; Health technology assessment ; Human Growth Hormone - therapeutic use ; Humans ; Internal Medicine ; Male ; Medicine ; Medicine & Public Health ; Oncology ; Original Research ; Pharmacology/Toxicology ; Retrospective Studies ; Rheumatology</subject><ispartof>Advances in therapy, 2015-02, Vol.32 (2), p.148-156</ispartof><rights>The Author(s) 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c442t-f0ab28f03297a85808586e983d17629f4cb35c9c68131c247cf5326f6cd123723</citedby><cites>FETCH-LOGICAL-c442t-f0ab28f03297a85808586e983d17629f4cb35c9c68131c247cf5326f6cd123723</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/s12325-015-0181-9$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12325-015-0181-9$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25667132$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Borrás Pérez, Victoria</creatorcontrib><creatorcontrib>López-Siguero, Juan Pedro</creatorcontrib><creatorcontrib>Martínez, Gabriela</creatorcontrib><creatorcontrib>Corripio, Raquel</creatorcontrib><creatorcontrib>Fernández, Juan Manuel</creatorcontrib><creatorcontrib>Labarta, Jose Ignacio</creatorcontrib><creatorcontrib>Ferrer, Marta</creatorcontrib><creatorcontrib>Cabrinety, Nuria</creatorcontrib><creatorcontrib>Prieto, Pablo</creatorcontrib><creatorcontrib>Ramón-Krauel, Marta</creatorcontrib><creatorcontrib>Bosch, Jordi</creatorcontrib><creatorcontrib>Espino, Rafael</creatorcontrib><creatorcontrib>Palla Garcia, Margarida</creatorcontrib><creatorcontrib>Rebollo, Francisco Jose</creatorcontrib><title>A Follow-up Study to Monitor Adult Height Among Spanish Children with Growth Hormone Deficiency Who Received Biosimilar Human Recombinant Growth Hormone (Omnitrope®) During a Phase III Clinical Trial</title><title>Advances in therapy</title><addtitle>Adv Ther</addtitle><addtitle>Adv Ther</addtitle><description>Introduction
An initial Phase III clinical trial has evaluated the efficacy and safety of biosimilar recombinant human growth hormone (rhGH; Omnitrope
®
, Sandoz) in Spanish children with growth hormone deficiency (GHD). At the end of the study, those patients still growing were offered to remain on treatment (as in usual clinical practice), and continued to be monitored. The aim of this study was to determine the adult height achieved by the Spanish children who participated in the initial Phase III clinical trial, and to evaluate the long-term safety of rhGH treatment.
Methods
This study was a multicenter, observational, retrospective follow-up study of patients who participated in the Phase III clinical trial (70 patients recruited). Auxological parameters [including height, height velocity, and their associated height standard deviation scores (HSDS)] were obtained from 39 patients. Safety was assessed by recording any adverse events (AEs).
Results
In total, 27 men and 12 women provided auxological data. At the start of the follow-up study, the mean age of the patients was 12.5 ± 2.7 years, mean height was 144.8 ± 13.9 cm and mean HSDS was −1.16 ± 0.63. By the end of the follow-up period, mean height had increased to 163.1 ± 7.6 cm (
n
= 36; men 165.5 ± 7.8 cm, women 157.6 ± 3.2 cm) and mean HSDS also increased to −1.01 ± 0.59 (
n
= 36; men −1.07 ± 0.52, women −0.86 ± 0.72). In terms of safety, no treatment-related AEs were reported during the study.
Conclusion
This cohort of Spanish patients with GHD showed a positive response to rhGH treatment, achieving adult height within the local normal ranges. In addition, rhGH treatment was well tolerated, with no new or additional safety concerns.</description><subject>Adolescent</subject><subject>Biosimilar Pharmaceuticals - therapeutic use</subject><subject>Body Height</subject><subject>Cardiology</subject><subject>Child</subject><subject>Endocrinology</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Growth Disorders - drug therapy</subject><subject>Health technology assessment</subject><subject>Human Growth Hormone - therapeutic use</subject><subject>Humans</subject><subject>Internal Medicine</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Oncology</subject><subject>Original Research</subject><subject>Pharmacology/Toxicology</subject><subject>Retrospective Studies</subject><subject>Rheumatology</subject><issn>0741-238X</issn><issn>1865-8652</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><recordid>eNp9UktuFDEUtBCIDIEDsEFvGRZN_OnvBmkyIZmREgWRINhZHrd72pHbbuzujOZSHIIVx4pbEyLCgkXpLV656qlcCL0l-APBuDgOhDKaJZhMKElSPUMzUuZZEkGfoxkuUpJQVn4_QK9CuMWY4iIrX6IDmuV5QRidod9zOHPGuG0y9nA9jPUOBgeXzurBeZjXoxlgqfSmHWDeObuB615YHVpYtNrUXlnY6qGFc--2cSydjyQFp6rRUisrd_CtdfBFSaXvVA0n2gXdaSM8LMdO2GnjurW2wg7_ahxddfEI73r16-d7OB29ju4CPrciKFitVrAw2mopDNx4Lcxr9KIRJqg3D_MQfT37dLNYJhdX56vF_CKRaUqHpMFiTcsGM1oVosxKHJGrqmQ1KXJaNalcs0xWMi8JI5KmhWwyRvMml3UMu6DsEH3c6_bjulO1VHbwwvDe6074HXdC86cbq1u-cXc8ZWlVZVUUOHoQ8O7HqMLAOx2kMkZY5cbASZ4TxqJpGalkT5XeheBV82hDMJ8awPcN4LEBfGoAn-Tf_X3f44s_Xx4JdE8I_RSp8vzWjd7GzP6jeg8DF79f</recordid><startdate>20150201</startdate><enddate>20150201</enddate><creator>Borrás Pérez, Victoria</creator><creator>López-Siguero, Juan Pedro</creator><creator>Martínez, Gabriela</creator><creator>Corripio, Raquel</creator><creator>Fernández, Juan Manuel</creator><creator>Labarta, Jose Ignacio</creator><creator>Ferrer, Marta</creator><creator>Cabrinety, Nuria</creator><creator>Prieto, Pablo</creator><creator>Ramón-Krauel, Marta</creator><creator>Bosch, Jordi</creator><creator>Espino, Rafael</creator><creator>Palla Garcia, Margarida</creator><creator>Rebollo, Francisco Jose</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>20150201</creationdate><title>A Follow-up Study to Monitor Adult Height Among Spanish Children with Growth Hormone Deficiency Who Received Biosimilar Human Recombinant Growth Hormone (Omnitrope®) During a Phase III Clinical Trial</title><author>Borrás Pérez, Victoria ; López-Siguero, Juan Pedro ; Martínez, Gabriela ; Corripio, Raquel ; Fernández, Juan Manuel ; Labarta, Jose Ignacio ; Ferrer, Marta ; Cabrinety, Nuria ; Prieto, Pablo ; Ramón-Krauel, Marta ; Bosch, Jordi ; Espino, Rafael ; Palla Garcia, Margarida ; Rebollo, Francisco Jose</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c442t-f0ab28f03297a85808586e983d17629f4cb35c9c68131c247cf5326f6cd123723</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adolescent</topic><topic>Biosimilar Pharmaceuticals - therapeutic use</topic><topic>Body Height</topic><topic>Cardiology</topic><topic>Child</topic><topic>Endocrinology</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Growth Disorders - drug therapy</topic><topic>Health technology assessment</topic><topic>Human Growth Hormone - therapeutic use</topic><topic>Humans</topic><topic>Internal Medicine</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Oncology</topic><topic>Original Research</topic><topic>Pharmacology/Toxicology</topic><topic>Retrospective Studies</topic><topic>Rheumatology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Borrás Pérez, Victoria</creatorcontrib><creatorcontrib>López-Siguero, Juan Pedro</creatorcontrib><creatorcontrib>Martínez, Gabriela</creatorcontrib><creatorcontrib>Corripio, Raquel</creatorcontrib><creatorcontrib>Fernández, Juan Manuel</creatorcontrib><creatorcontrib>Labarta, Jose Ignacio</creatorcontrib><creatorcontrib>Ferrer, Marta</creatorcontrib><creatorcontrib>Cabrinety, Nuria</creatorcontrib><creatorcontrib>Prieto, Pablo</creatorcontrib><creatorcontrib>Ramón-Krauel, Marta</creatorcontrib><creatorcontrib>Bosch, Jordi</creatorcontrib><creatorcontrib>Espino, Rafael</creatorcontrib><creatorcontrib>Palla Garcia, Margarida</creatorcontrib><creatorcontrib>Rebollo, Francisco Jose</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>Borrás Pérez, Victoria</au><au>López-Siguero, Juan Pedro</au><au>Martínez, Gabriela</au><au>Corripio, Raquel</au><au>Fernández, Juan Manuel</au><au>Labarta, Jose Ignacio</au><au>Ferrer, Marta</au><au>Cabrinety, Nuria</au><au>Prieto, Pablo</au><au>Ramón-Krauel, Marta</au><au>Bosch, Jordi</au><au>Espino, Rafael</au><au>Palla Garcia, Margarida</au><au>Rebollo, Francisco Jose</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Follow-up Study to Monitor Adult Height Among Spanish Children with Growth Hormone Deficiency Who Received Biosimilar Human Recombinant Growth Hormone (Omnitrope®) During a Phase III Clinical Trial</atitle><jtitle>Advances in therapy</jtitle><stitle>Adv Ther</stitle><addtitle>Adv Ther</addtitle><date>2015-02-01</date><risdate>2015</risdate><volume>32</volume><issue>2</issue><spage>148</spage><epage>156</epage><pages>148-156</pages><issn>0741-238X</issn><eissn>1865-8652</eissn><abstract>Introduction
An initial Phase III clinical trial has evaluated the efficacy and safety of biosimilar recombinant human growth hormone (rhGH; Omnitrope
®
, Sandoz) in Spanish children with growth hormone deficiency (GHD). At the end of the study, those patients still growing were offered to remain on treatment (as in usual clinical practice), and continued to be monitored. The aim of this study was to determine the adult height achieved by the Spanish children who participated in the initial Phase III clinical trial, and to evaluate the long-term safety of rhGH treatment.
Methods
This study was a multicenter, observational, retrospective follow-up study of patients who participated in the Phase III clinical trial (70 patients recruited). Auxological parameters [including height, height velocity, and their associated height standard deviation scores (HSDS)] were obtained from 39 patients. Safety was assessed by recording any adverse events (AEs).
Results
In total, 27 men and 12 women provided auxological data. At the start of the follow-up study, the mean age of the patients was 12.5 ± 2.7 years, mean height was 144.8 ± 13.9 cm and mean HSDS was −1.16 ± 0.63. By the end of the follow-up period, mean height had increased to 163.1 ± 7.6 cm (
n
= 36; men 165.5 ± 7.8 cm, women 157.6 ± 3.2 cm) and mean HSDS also increased to −1.01 ± 0.59 (
n
= 36; men −1.07 ± 0.52, women −0.86 ± 0.72). In terms of safety, no treatment-related AEs were reported during the study.
Conclusion
This cohort of Spanish patients with GHD showed a positive response to rhGH treatment, achieving adult height within the local normal ranges. In addition, rhGH treatment was well tolerated, with no new or additional safety concerns.</abstract><cop>Heidelberg</cop><pub>Springer Healthcare</pub><pmid>25667132</pmid><doi>10.1007/s12325-015-0181-9</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0741-238X |
| ispartof | Advances in therapy, 2015-02, Vol.32 (2), p.148-156 |
| issn | 0741-238X 1865-8652 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4349959 |
| source | MEDLINE; SpringerLink Journals |
| subjects | Adolescent Biosimilar Pharmaceuticals - therapeutic use Body Height Cardiology Child Endocrinology Female Follow-Up Studies Growth Disorders - drug therapy Health technology assessment Human Growth Hormone - therapeutic use Humans Internal Medicine Male Medicine Medicine & Public Health Oncology Original Research Pharmacology/Toxicology Retrospective Studies Rheumatology |
| title | A Follow-up Study to Monitor Adult Height Among Spanish Children with Growth Hormone Deficiency Who Received Biosimilar Human Recombinant Growth Hormone (Omnitrope®) During a Phase III Clinical Trial |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-09T02%3A58%3A06IST&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=A%20Follow-up%20Study%20to%20Monitor%20Adult%20Height%20Among%20Spanish%20Children%20with%20Growth%20Hormone%20Deficiency%20Who%20Received%20Biosimilar%20Human%20Recombinant%20Growth%20Hormone%20(Omnitrope%C2%AE)%20During%20a%20Phase%20III%20Clinical%20Trial&rft.jtitle=Advances%20in%20therapy&rft.au=Borr%C3%A1s%20P%C3%A9rez,%20Victoria&rft.date=2015-02-01&rft.volume=32&rft.issue=2&rft.spage=148&rft.epage=156&rft.pages=148-156&rft.issn=0741-238X&rft.eissn=1865-8652&rft_id=info:doi/10.1007/s12325-015-0181-9&rft_dat=%3Cproquest_pubme%3E1661335328%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=1661335328&rft_id=info:pmid/25667132&rfr_iscdi=true |