Assessing the role of innovative therapeutic paradigm on multiple sclerosis treatment response
Objective Within the last decade, many changes have been made to the management of patients with multiple sclerosis (MS). The aim of our study was to investigate the global impact of all these changes on the disease's course. Materials and methods This single‐centre study was carried out on pat...
Gespeichert in:
| Veröffentlicht in: | Acta neurologica Scandinavica 2018-11, Vol.138 (5), p.447-453 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 453 |
|---|---|
| container_issue | 5 |
| container_start_page | 447 |
| container_title | Acta neurologica Scandinavica |
| container_volume | 138 |
| creator | Romeo, Marzia A. L. Martinelli, Vittorio Dalla Costa, Gloria Colombo, Bruno De Feo, Donatella Esposito, Federica Ferrè, Laura Guaschino, Clara Guerrieri, Simone Liberatore, Giuseppe Martinelli Boneschi, Filippo Merlini, Arianna Messina, Mariajosè Messina, Roberta Nuara, Arturo Preziosa, Paolo Radaelli, Marta Rocca, Maria A. Rodegher, Mariaemma Sangalli, Francesca Strambo, Davide Moiola, Lucia Comi, Giancarlo |
| description | Objective
Within the last decade, many changes have been made to the management of patients with multiple sclerosis (MS). The aim of our study was to investigate the global impact of all these changes on the disease's course.
Materials and methods
This single‐centre study was carried out on patients with multiple sclerosis (pwMS) who started treatment with first‐line disease‐modifying therapies. We have compared three large cohorts of patients with MS diagnosis, for three consecutive periods within July 2001, August 2001‐December 2005, and January 2006‐September 2011.
Results
A total of 1068 relapsing‐remitting pwMS cases were included. Patients in the last cohort began treatment earlier (P |
| doi_str_mv | 10.1111/ane.12999 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2074134275</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2116808463</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3889-a414f4d1c43a9d56bcf0a697db0a595dcb929e3ea0ddf51a08ecec83da2d32ce3</originalsourceid><addsrcrecordid>eNp1kE1P3DAQhi3UChbKoX-gstRLOYQdfyQbH1dogUqrcoFrLa89oV4lcWonW-2_x7DAoRJzGc3o0aOZl5CvDC5Zrrnp8ZJxpdQRmbEKoAAJ8hOZAQArKsHkCTlNaZsnvpDymJwIACEqzmbk9zIlTMn3j3T8gzSGFmloqO_7sDOj3-HzOpoBp9FbOphonH_saOhpN7WjHzKebIsxJJ_oGNGMHfYjjZiG0Cf8Qj43pk14_trPyMP16v7qtljf3fy8Wq4LK-paFUYy2UjHrBRGubLa2AZMpRZuA6ZUpbMbxRUKNOBcUzIDNVq0tXCGO8EtijPy4-AdYvg7YRp155PFts3RhClpDgvJhOSLMqPf_0O3YYp9vk5zxqoaalmJTF0cKJtfSxEbPUTfmbjXDPRz6Dqb9Uvomf32apw2Hbp38i3lDMwPwD_f4v5jk17-Wh2UT_aYjTI</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2116808463</pqid></control><display><type>article</type><title>Assessing the role of innovative therapeutic paradigm on multiple sclerosis treatment response</title><source>MEDLINE</source><source>Wiley Online Library All Journals</source><creator>Romeo, Marzia A. L. ; Martinelli, Vittorio ; Dalla Costa, Gloria ; Colombo, Bruno ; De Feo, Donatella ; Esposito, Federica ; Ferrè, Laura ; Guaschino, Clara ; Guerrieri, Simone ; Liberatore, Giuseppe ; Martinelli Boneschi, Filippo ; Merlini, Arianna ; Messina, Mariajosè ; Messina, Roberta ; Nuara, Arturo ; Preziosa, Paolo ; Radaelli, Marta ; Rocca, Maria A. ; Rodegher, Mariaemma ; Sangalli, Francesca ; Strambo, Davide ; Moiola, Lucia ; Comi, Giancarlo</creator><creatorcontrib>Romeo, Marzia A. L. ; Martinelli, Vittorio ; Dalla Costa, Gloria ; Colombo, Bruno ; De Feo, Donatella ; Esposito, Federica ; Ferrè, Laura ; Guaschino, Clara ; Guerrieri, Simone ; Liberatore, Giuseppe ; Martinelli Boneschi, Filippo ; Merlini, Arianna ; Messina, Mariajosè ; Messina, Roberta ; Nuara, Arturo ; Preziosa, Paolo ; Radaelli, Marta ; Rocca, Maria A. ; Rodegher, Mariaemma ; Sangalli, Francesca ; Strambo, Davide ; Moiola, Lucia ; Comi, Giancarlo</creatorcontrib><description>Objective
Within the last decade, many changes have been made to the management of patients with multiple sclerosis (MS). The aim of our study was to investigate the global impact of all these changes on the disease's course.
Materials and methods
This single‐centre study was carried out on patients with multiple sclerosis (pwMS) who started treatment with first‐line disease‐modifying therapies. We have compared three large cohorts of patients with MS diagnosis, for three consecutive periods within July 2001, August 2001‐December 2005, and January 2006‐September 2011.
Results
A total of 1068 relapsing‐remitting pwMS cases were included. Patients in the last cohort began treatment earlier (P < 0.0001), started more frequent treatment with high‐dose interferon beta or glatiramer acetate (P < 0.0001), and had experienced a more frequent treatment escalation strategy (P = 0.004) than patients in other cohorts. The multivariate analysis adjusted for baseline characteristics showed that pwMS of the last cohort had a high probability of showing no evidence of disease activity (NEDA3) at 4 years (OR 3.22, 95% CIs 1.89‐5.47; P < 0.0001). These results were confirmed in a propensity score analysis.
Conclusions
Our study showed an improvement over the last 15 years in the treatment response; this observation can be associated to a paradigm shift in MS treatment strategies.</description><identifier>ISSN: 0001-6314</identifier><identifier>EISSN: 1600-0404</identifier><identifier>DOI: 10.1111/ane.12999</identifier><identifier>PMID: 30033621</identifier><language>eng</language><publisher>Denmark: Hindawi Limited</publisher><subject>Adult ; Cohort Studies ; Copolymer 1 ; Disease Progression ; Female ; Glatiramer Acetate - therapeutic use ; Humans ; Immunosuppressive Agents - therapeutic use ; Interferon ; Interferon beta-1a - therapeutic use ; Interferon-beta - therapeutic use ; Male ; Medical innovations ; Middle Aged ; Multiple sclerosis ; Multiple Sclerosis, Relapsing-Remitting - drug therapy ; Multivariate analysis ; Neurology - trends ; no evidence of disease activity ; paradigm shift treatment response ; Patients ; Peptides - therapeutic use</subject><ispartof>Acta neurologica Scandinavica, 2018-11, Vol.138 (5), p.447-453</ispartof><rights>2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd</rights><rights>2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.</rights><rights>Copyright © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3889-a414f4d1c43a9d56bcf0a697db0a595dcb929e3ea0ddf51a08ecec83da2d32ce3</citedby><cites>FETCH-LOGICAL-c3889-a414f4d1c43a9d56bcf0a697db0a595dcb929e3ea0ddf51a08ecec83da2d32ce3</cites><orcidid>0000-0002-2210-7314 ; 0000-0002-5987-5739 ; 0000-0002-7826-0019</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%2Fane.12999$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fane.12999$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30033621$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Romeo, Marzia A. L.</creatorcontrib><creatorcontrib>Martinelli, Vittorio</creatorcontrib><creatorcontrib>Dalla Costa, Gloria</creatorcontrib><creatorcontrib>Colombo, Bruno</creatorcontrib><creatorcontrib>De Feo, Donatella</creatorcontrib><creatorcontrib>Esposito, Federica</creatorcontrib><creatorcontrib>Ferrè, Laura</creatorcontrib><creatorcontrib>Guaschino, Clara</creatorcontrib><creatorcontrib>Guerrieri, Simone</creatorcontrib><creatorcontrib>Liberatore, Giuseppe</creatorcontrib><creatorcontrib>Martinelli Boneschi, Filippo</creatorcontrib><creatorcontrib>Merlini, Arianna</creatorcontrib><creatorcontrib>Messina, Mariajosè</creatorcontrib><creatorcontrib>Messina, Roberta</creatorcontrib><creatorcontrib>Nuara, Arturo</creatorcontrib><creatorcontrib>Preziosa, Paolo</creatorcontrib><creatorcontrib>Radaelli, Marta</creatorcontrib><creatorcontrib>Rocca, Maria A.</creatorcontrib><creatorcontrib>Rodegher, Mariaemma</creatorcontrib><creatorcontrib>Sangalli, Francesca</creatorcontrib><creatorcontrib>Strambo, Davide</creatorcontrib><creatorcontrib>Moiola, Lucia</creatorcontrib><creatorcontrib>Comi, Giancarlo</creatorcontrib><title>Assessing the role of innovative therapeutic paradigm on multiple sclerosis treatment response</title><title>Acta neurologica Scandinavica</title><addtitle>Acta Neurol Scand</addtitle><description>Objective
Within the last decade, many changes have been made to the management of patients with multiple sclerosis (MS). The aim of our study was to investigate the global impact of all these changes on the disease's course.
Materials and methods
This single‐centre study was carried out on patients with multiple sclerosis (pwMS) who started treatment with first‐line disease‐modifying therapies. We have compared three large cohorts of patients with MS diagnosis, for three consecutive periods within July 2001, August 2001‐December 2005, and January 2006‐September 2011.
Results
A total of 1068 relapsing‐remitting pwMS cases were included. Patients in the last cohort began treatment earlier (P < 0.0001), started more frequent treatment with high‐dose interferon beta or glatiramer acetate (P < 0.0001), and had experienced a more frequent treatment escalation strategy (P = 0.004) than patients in other cohorts. The multivariate analysis adjusted for baseline characteristics showed that pwMS of the last cohort had a high probability of showing no evidence of disease activity (NEDA3) at 4 years (OR 3.22, 95% CIs 1.89‐5.47; P < 0.0001). These results were confirmed in a propensity score analysis.
Conclusions
Our study showed an improvement over the last 15 years in the treatment response; this observation can be associated to a paradigm shift in MS treatment strategies.</description><subject>Adult</subject><subject>Cohort Studies</subject><subject>Copolymer 1</subject><subject>Disease Progression</subject><subject>Female</subject><subject>Glatiramer Acetate - therapeutic use</subject><subject>Humans</subject><subject>Immunosuppressive Agents - therapeutic use</subject><subject>Interferon</subject><subject>Interferon beta-1a - therapeutic use</subject><subject>Interferon-beta - therapeutic use</subject><subject>Male</subject><subject>Medical innovations</subject><subject>Middle Aged</subject><subject>Multiple sclerosis</subject><subject>Multiple Sclerosis, Relapsing-Remitting - drug therapy</subject><subject>Multivariate analysis</subject><subject>Neurology - trends</subject><subject>no evidence of disease activity</subject><subject>paradigm shift treatment response</subject><subject>Patients</subject><subject>Peptides - therapeutic use</subject><issn>0001-6314</issn><issn>1600-0404</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kE1P3DAQhi3UChbKoX-gstRLOYQdfyQbH1dogUqrcoFrLa89oV4lcWonW-2_x7DAoRJzGc3o0aOZl5CvDC5Zrrnp8ZJxpdQRmbEKoAAJ8hOZAQArKsHkCTlNaZsnvpDymJwIACEqzmbk9zIlTMn3j3T8gzSGFmloqO_7sDOj3-HzOpoBp9FbOphonH_saOhpN7WjHzKebIsxJJ_oGNGMHfYjjZiG0Cf8Qj43pk14_trPyMP16v7qtljf3fy8Wq4LK-paFUYy2UjHrBRGubLa2AZMpRZuA6ZUpbMbxRUKNOBcUzIDNVq0tXCGO8EtijPy4-AdYvg7YRp155PFts3RhClpDgvJhOSLMqPf_0O3YYp9vk5zxqoaalmJTF0cKJtfSxEbPUTfmbjXDPRz6Dqb9Uvomf32apw2Hbp38i3lDMwPwD_f4v5jk17-Wh2UT_aYjTI</recordid><startdate>201811</startdate><enddate>201811</enddate><creator>Romeo, Marzia A. L.</creator><creator>Martinelli, Vittorio</creator><creator>Dalla Costa, Gloria</creator><creator>Colombo, Bruno</creator><creator>De Feo, Donatella</creator><creator>Esposito, Federica</creator><creator>Ferrè, Laura</creator><creator>Guaschino, Clara</creator><creator>Guerrieri, Simone</creator><creator>Liberatore, Giuseppe</creator><creator>Martinelli Boneschi, Filippo</creator><creator>Merlini, Arianna</creator><creator>Messina, Mariajosè</creator><creator>Messina, Roberta</creator><creator>Nuara, Arturo</creator><creator>Preziosa, Paolo</creator><creator>Radaelli, Marta</creator><creator>Rocca, Maria A.</creator><creator>Rodegher, Mariaemma</creator><creator>Sangalli, Francesca</creator><creator>Strambo, Davide</creator><creator>Moiola, Lucia</creator><creator>Comi, Giancarlo</creator><general>Hindawi Limited</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>7TK</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-2210-7314</orcidid><orcidid>https://orcid.org/0000-0002-5987-5739</orcidid><orcidid>https://orcid.org/0000-0002-7826-0019</orcidid></search><sort><creationdate>201811</creationdate><title>Assessing the role of innovative therapeutic paradigm on multiple sclerosis treatment response</title><author>Romeo, Marzia A. L. ; Martinelli, Vittorio ; Dalla Costa, Gloria ; Colombo, Bruno ; De Feo, Donatella ; Esposito, Federica ; Ferrè, Laura ; Guaschino, Clara ; Guerrieri, Simone ; Liberatore, Giuseppe ; Martinelli Boneschi, Filippo ; Merlini, Arianna ; Messina, Mariajosè ; Messina, Roberta ; Nuara, Arturo ; Preziosa, Paolo ; Radaelli, Marta ; Rocca, Maria A. ; Rodegher, Mariaemma ; Sangalli, Francesca ; Strambo, Davide ; Moiola, Lucia ; Comi, Giancarlo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3889-a414f4d1c43a9d56bcf0a697db0a595dcb929e3ea0ddf51a08ecec83da2d32ce3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adult</topic><topic>Cohort Studies</topic><topic>Copolymer 1</topic><topic>Disease Progression</topic><topic>Female</topic><topic>Glatiramer Acetate - therapeutic use</topic><topic>Humans</topic><topic>Immunosuppressive Agents - therapeutic use</topic><topic>Interferon</topic><topic>Interferon beta-1a - therapeutic use</topic><topic>Interferon-beta - therapeutic use</topic><topic>Male</topic><topic>Medical innovations</topic><topic>Middle Aged</topic><topic>Multiple sclerosis</topic><topic>Multiple Sclerosis, Relapsing-Remitting - drug therapy</topic><topic>Multivariate analysis</topic><topic>Neurology - trends</topic><topic>no evidence of disease activity</topic><topic>paradigm shift treatment response</topic><topic>Patients</topic><topic>Peptides - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Romeo, Marzia A. L.</creatorcontrib><creatorcontrib>Martinelli, Vittorio</creatorcontrib><creatorcontrib>Dalla Costa, Gloria</creatorcontrib><creatorcontrib>Colombo, Bruno</creatorcontrib><creatorcontrib>De Feo, Donatella</creatorcontrib><creatorcontrib>Esposito, Federica</creatorcontrib><creatorcontrib>Ferrè, Laura</creatorcontrib><creatorcontrib>Guaschino, Clara</creatorcontrib><creatorcontrib>Guerrieri, Simone</creatorcontrib><creatorcontrib>Liberatore, Giuseppe</creatorcontrib><creatorcontrib>Martinelli Boneschi, Filippo</creatorcontrib><creatorcontrib>Merlini, Arianna</creatorcontrib><creatorcontrib>Messina, Mariajosè</creatorcontrib><creatorcontrib>Messina, Roberta</creatorcontrib><creatorcontrib>Nuara, Arturo</creatorcontrib><creatorcontrib>Preziosa, Paolo</creatorcontrib><creatorcontrib>Radaelli, Marta</creatorcontrib><creatorcontrib>Rocca, Maria A.</creatorcontrib><creatorcontrib>Rodegher, Mariaemma</creatorcontrib><creatorcontrib>Sangalli, Francesca</creatorcontrib><creatorcontrib>Strambo, Davide</creatorcontrib><creatorcontrib>Moiola, Lucia</creatorcontrib><creatorcontrib>Comi, Giancarlo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Acta neurologica Scandinavica</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Romeo, Marzia A. L.</au><au>Martinelli, Vittorio</au><au>Dalla Costa, Gloria</au><au>Colombo, Bruno</au><au>De Feo, Donatella</au><au>Esposito, Federica</au><au>Ferrè, Laura</au><au>Guaschino, Clara</au><au>Guerrieri, Simone</au><au>Liberatore, Giuseppe</au><au>Martinelli Boneschi, Filippo</au><au>Merlini, Arianna</au><au>Messina, Mariajosè</au><au>Messina, Roberta</au><au>Nuara, Arturo</au><au>Preziosa, Paolo</au><au>Radaelli, Marta</au><au>Rocca, Maria A.</au><au>Rodegher, Mariaemma</au><au>Sangalli, Francesca</au><au>Strambo, Davide</au><au>Moiola, Lucia</au><au>Comi, Giancarlo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Assessing the role of innovative therapeutic paradigm on multiple sclerosis treatment response</atitle><jtitle>Acta neurologica Scandinavica</jtitle><addtitle>Acta Neurol Scand</addtitle><date>2018-11</date><risdate>2018</risdate><volume>138</volume><issue>5</issue><spage>447</spage><epage>453</epage><pages>447-453</pages><issn>0001-6314</issn><eissn>1600-0404</eissn><abstract>Objective
Within the last decade, many changes have been made to the management of patients with multiple sclerosis (MS). The aim of our study was to investigate the global impact of all these changes on the disease's course.
Materials and methods
This single‐centre study was carried out on patients with multiple sclerosis (pwMS) who started treatment with first‐line disease‐modifying therapies. We have compared three large cohorts of patients with MS diagnosis, for three consecutive periods within July 2001, August 2001‐December 2005, and January 2006‐September 2011.
Results
A total of 1068 relapsing‐remitting pwMS cases were included. Patients in the last cohort began treatment earlier (P < 0.0001), started more frequent treatment with high‐dose interferon beta or glatiramer acetate (P < 0.0001), and had experienced a more frequent treatment escalation strategy (P = 0.004) than patients in other cohorts. The multivariate analysis adjusted for baseline characteristics showed that pwMS of the last cohort had a high probability of showing no evidence of disease activity (NEDA3) at 4 years (OR 3.22, 95% CIs 1.89‐5.47; P < 0.0001). These results were confirmed in a propensity score analysis.
Conclusions
Our study showed an improvement over the last 15 years in the treatment response; this observation can be associated to a paradigm shift in MS treatment strategies.</abstract><cop>Denmark</cop><pub>Hindawi Limited</pub><pmid>30033621</pmid><doi>10.1111/ane.12999</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0002-2210-7314</orcidid><orcidid>https://orcid.org/0000-0002-5987-5739</orcidid><orcidid>https://orcid.org/0000-0002-7826-0019</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0001-6314 |
| ispartof | Acta neurologica Scandinavica, 2018-11, Vol.138 (5), p.447-453 |
| issn | 0001-6314 1600-0404 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2074134275 |
| source | MEDLINE; Wiley Online Library All Journals |
| subjects | Adult Cohort Studies Copolymer 1 Disease Progression Female Glatiramer Acetate - therapeutic use Humans Immunosuppressive Agents - therapeutic use Interferon Interferon beta-1a - therapeutic use Interferon-beta - therapeutic use Male Medical innovations Middle Aged Multiple sclerosis Multiple Sclerosis, Relapsing-Remitting - drug therapy Multivariate analysis Neurology - trends no evidence of disease activity paradigm shift treatment response Patients Peptides - therapeutic use |
| title | Assessing the role of innovative therapeutic paradigm on multiple sclerosis treatment response |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-06T12%3A44%3A18IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Assessing%20the%20role%20of%20innovative%20therapeutic%20paradigm%20on%20multiple%20sclerosis%20treatment%20response&rft.jtitle=Acta%20neurologica%20Scandinavica&rft.au=Romeo,%20Marzia%20A.%20L.&rft.date=2018-11&rft.volume=138&rft.issue=5&rft.spage=447&rft.epage=453&rft.pages=447-453&rft.issn=0001-6314&rft.eissn=1600-0404&rft_id=info:doi/10.1111/ane.12999&rft_dat=%3Cproquest_cross%3E2116808463%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2116808463&rft_id=info:pmid/30033621&rfr_iscdi=true |