Off-label use of anticancer drugs in eastern Switzerland: a population-based prospective cohort study
Purpose Prevalence data on the off-label use (OLU) of anticancer drugs are limited despite OLU being controversial for medical, pharmaco-economic, and ethical reasons. We therefore quantified and characterized the OLU of anticancer drugs and compared OLU based on the national drug label with interna...
Gespeichert in:
| Veröffentlicht in: | European journal of clinical pharmacology 2014-06, Vol.70 (6), p.719-725 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 725 |
|---|---|
| container_issue | 6 |
| container_start_page | 719 |
| container_title | European journal of clinical pharmacology |
| container_volume | 70 |
| creator | Joerger, M. Schaer-Thuer, C. Koeberle, D. Matter-Walstra, K. Gibbons-Marsico, J. Diem, S. Thuerlimann, B. Cerny, T. |
| description | Purpose
Prevalence data on the off-label use (OLU) of anticancer drugs are limited despite OLU being controversial for medical, pharmaco-economic, and ethical reasons. We therefore quantified and characterized the OLU of anticancer drugs and compared OLU based on the national drug label with international treatment recommendations.
Methods
We prospectively collected data on patients receiving systemic anticancer therapy between October and December 2012 at hospitals affiliated with the Eastern Switzerland Oncology Network. Individual data on patient characteristics, tumor disease, and systemic treatment were collected, and each individual treatment was compared with the national drug label and international treatment guidelines.
Results
A total of 985 consecutive patients receiving 1,737 anticancer drug treatments were included in the study. Overall, 32.4 % of all patients received at least one off-label drug, corresponding to 27.2 % of all anticancer drugs administered. Major reasons for OLU were the lack of approval for the specific disease entity (15.7 %) and modified application of the anticancer drug (10 %). OLU that was unsupported by the current European Society for Medical Oncology (ESMO) treatment recommendations was rare (6.6 %) but higher for bevacizumab (29.6 %) due to its use in treating advanced ovarian cancer beyond the second-line setting and advanced breast cancer beyond the first-line setting and for lenalidomide (22.6 %) due to its use in treating Non-Hodgkin lymphoma.
Conclusions
Based on data collected on our patient cohort, OLU of anticancer drugs in a European clinical setting applies to one-third of all cancer patients. ESMO-unsupported use of chemotherapies or molecularly-targeted drugs is rare, opposing concerns that the off-label use of newer anticancer drugs is a substantial clinical problem. |
| doi_str_mv | 10.1007/s00228-014-1662-5 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1526131831</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3307079741</sourcerecordid><originalsourceid>FETCH-LOGICAL-c402t-94edca82a38b3643c987475d02a94b818f619d3f269fdaaed16c20a4f5d830e53</originalsourceid><addsrcrecordid>eNp1kUtv1TAQRi1ERS-FH8AGWUJIbFzGjzg2O1Txkip1Aawtxx6XVLlJsBNQ-fV1dC8PIXU1izmeOZ6PkGcczjlA-7oACGEYcMW41oI1D8iOKykYB8Ufkh2A5EzbFk7J41JuAHhjQT4ip0JpsEqbHcGrlNjgOxzoWpBOifpx6YMfA2Ya83pdaD9S9GXBPNLPP_vlF-bBj_EN9XSe5nXwSz-NrPMFI53zVGYMS_8DaZi-TXmhZVnj7RNykvxQ8OmxnpGv7999ufjILq8-fLp4e8mCArEwqzAGb4SXppNayWBNq9omgvBWdYabpLmNMgltU_QeI9dBgFepiUYCNvKMvDrMrSLfVyyL2_cl4FCFcVqL443QXHIjeUVf_IfeTGseq91GNW1rjGgrxQ9UqD8rGZObc7_3-dZxcFsG7pCBqxm4LQO3STw_Tl67PcY_L34fvQIvj4AvwQ8p12v35S9nGmsatS0XB67U1niN-R_Fe7ffAYxXnm4</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1525778827</pqid></control><display><type>article</type><title>Off-label use of anticancer drugs in eastern Switzerland: a population-based prospective cohort study</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Joerger, M. ; Schaer-Thuer, C. ; Koeberle, D. ; Matter-Walstra, K. ; Gibbons-Marsico, J. ; Diem, S. ; Thuerlimann, B. ; Cerny, T.</creator><creatorcontrib>Joerger, M. ; Schaer-Thuer, C. ; Koeberle, D. ; Matter-Walstra, K. ; Gibbons-Marsico, J. ; Diem, S. ; Thuerlimann, B. ; Cerny, T.</creatorcontrib><description>Purpose
Prevalence data on the off-label use (OLU) of anticancer drugs are limited despite OLU being controversial for medical, pharmaco-economic, and ethical reasons. We therefore quantified and characterized the OLU of anticancer drugs and compared OLU based on the national drug label with international treatment recommendations.
Methods
We prospectively collected data on patients receiving systemic anticancer therapy between October and December 2012 at hospitals affiliated with the Eastern Switzerland Oncology Network. Individual data on patient characteristics, tumor disease, and systemic treatment were collected, and each individual treatment was compared with the national drug label and international treatment guidelines.
Results
A total of 985 consecutive patients receiving 1,737 anticancer drug treatments were included in the study. Overall, 32.4 % of all patients received at least one off-label drug, corresponding to 27.2 % of all anticancer drugs administered. Major reasons for OLU were the lack of approval for the specific disease entity (15.7 %) and modified application of the anticancer drug (10 %). OLU that was unsupported by the current European Society for Medical Oncology (ESMO) treatment recommendations was rare (6.6 %) but higher for bevacizumab (29.6 %) due to its use in treating advanced ovarian cancer beyond the second-line setting and advanced breast cancer beyond the first-line setting and for lenalidomide (22.6 %) due to its use in treating Non-Hodgkin lymphoma.
Conclusions
Based on data collected on our patient cohort, OLU of anticancer drugs in a European clinical setting applies to one-third of all cancer patients. ESMO-unsupported use of chemotherapies or molecularly-targeted drugs is rare, opposing concerns that the off-label use of newer anticancer drugs is a substantial clinical problem.</description><identifier>ISSN: 0031-6970</identifier><identifier>EISSN: 1432-1041</identifier><identifier>DOI: 10.1007/s00228-014-1662-5</identifier><identifier>PMID: 24609468</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Antineoplastic Agents - administration & dosage ; Antineoplastic Agents - supply & distribution ; Antineoplastic Agents - therapeutic use ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Cancer ; Cohort Studies ; Descriptive labeling ; Drug Utilization Review - statistics & numerical data ; Female ; Health economics ; Humans ; Male ; Medical ethics ; Medical sciences ; Middle Aged ; Neoplasms - drug therapy ; Neoplasms - epidemiology ; Off-Label Use - economics ; Off-Label Use - statistics & numerical data ; Pharmacoepidemiology and Prescription ; Pharmacology ; Pharmacology. Drug treatments ; Pharmacology/Toxicology ; Practice Guidelines as Topic ; Prescription drugs ; Prospective Studies ; Switzerland</subject><ispartof>European journal of clinical pharmacology, 2014-06, Vol.70 (6), p.719-725</ispartof><rights>Springer-Verlag Berlin Heidelberg 2014</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c402t-94edca82a38b3643c987475d02a94b818f619d3f269fdaaed16c20a4f5d830e53</citedby><cites>FETCH-LOGICAL-c402t-94edca82a38b3643c987475d02a94b818f619d3f269fdaaed16c20a4f5d830e53</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/s00228-014-1662-5$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00228-014-1662-5$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=28598547$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24609468$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Joerger, M.</creatorcontrib><creatorcontrib>Schaer-Thuer, C.</creatorcontrib><creatorcontrib>Koeberle, D.</creatorcontrib><creatorcontrib>Matter-Walstra, K.</creatorcontrib><creatorcontrib>Gibbons-Marsico, J.</creatorcontrib><creatorcontrib>Diem, S.</creatorcontrib><creatorcontrib>Thuerlimann, B.</creatorcontrib><creatorcontrib>Cerny, T.</creatorcontrib><title>Off-label use of anticancer drugs in eastern Switzerland: a population-based prospective cohort study</title><title>European journal of clinical pharmacology</title><addtitle>Eur J Clin Pharmacol</addtitle><addtitle>Eur J Clin Pharmacol</addtitle><description>Purpose
Prevalence data on the off-label use (OLU) of anticancer drugs are limited despite OLU being controversial for medical, pharmaco-economic, and ethical reasons. We therefore quantified and characterized the OLU of anticancer drugs and compared OLU based on the national drug label with international treatment recommendations.
Methods
We prospectively collected data on patients receiving systemic anticancer therapy between October and December 2012 at hospitals affiliated with the Eastern Switzerland Oncology Network. Individual data on patient characteristics, tumor disease, and systemic treatment were collected, and each individual treatment was compared with the national drug label and international treatment guidelines.
Results
A total of 985 consecutive patients receiving 1,737 anticancer drug treatments were included in the study. Overall, 32.4 % of all patients received at least one off-label drug, corresponding to 27.2 % of all anticancer drugs administered. Major reasons for OLU were the lack of approval for the specific disease entity (15.7 %) and modified application of the anticancer drug (10 %). OLU that was unsupported by the current European Society for Medical Oncology (ESMO) treatment recommendations was rare (6.6 %) but higher for bevacizumab (29.6 %) due to its use in treating advanced ovarian cancer beyond the second-line setting and advanced breast cancer beyond the first-line setting and for lenalidomide (22.6 %) due to its use in treating Non-Hodgkin lymphoma.
Conclusions
Based on data collected on our patient cohort, OLU of anticancer drugs in a European clinical setting applies to one-third of all cancer patients. ESMO-unsupported use of chemotherapies or molecularly-targeted drugs is rare, opposing concerns that the off-label use of newer anticancer drugs is a substantial clinical problem.</description><subject>Antineoplastic Agents - administration & dosage</subject><subject>Antineoplastic Agents - supply & distribution</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer</subject><subject>Cohort Studies</subject><subject>Descriptive labeling</subject><subject>Drug Utilization Review - statistics & numerical data</subject><subject>Female</subject><subject>Health economics</subject><subject>Humans</subject><subject>Male</subject><subject>Medical ethics</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Neoplasms - drug therapy</subject><subject>Neoplasms - epidemiology</subject><subject>Off-Label Use - economics</subject><subject>Off-Label Use - statistics & numerical data</subject><subject>Pharmacoepidemiology and Prescription</subject><subject>Pharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Pharmacology/Toxicology</subject><subject>Practice Guidelines as Topic</subject><subject>Prescription drugs</subject><subject>Prospective Studies</subject><subject>Switzerland</subject><issn>0031-6970</issn><issn>1432-1041</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kUtv1TAQRi1ERS-FH8AGWUJIbFzGjzg2O1Txkip1Aawtxx6XVLlJsBNQ-fV1dC8PIXU1izmeOZ6PkGcczjlA-7oACGEYcMW41oI1D8iOKykYB8Ufkh2A5EzbFk7J41JuAHhjQT4ip0JpsEqbHcGrlNjgOxzoWpBOifpx6YMfA2Ya83pdaD9S9GXBPNLPP_vlF-bBj_EN9XSe5nXwSz-NrPMFI53zVGYMS_8DaZi-TXmhZVnj7RNykvxQ8OmxnpGv7999ufjILq8-fLp4e8mCArEwqzAGb4SXppNayWBNq9omgvBWdYabpLmNMgltU_QeI9dBgFepiUYCNvKMvDrMrSLfVyyL2_cl4FCFcVqL443QXHIjeUVf_IfeTGseq91GNW1rjGgrxQ9UqD8rGZObc7_3-dZxcFsG7pCBqxm4LQO3STw_Tl67PcY_L34fvQIvj4AvwQ8p12v35S9nGmsatS0XB67U1niN-R_Fe7ffAYxXnm4</recordid><startdate>20140601</startdate><enddate>20140601</enddate><creator>Joerger, M.</creator><creator>Schaer-Thuer, C.</creator><creator>Koeberle, D.</creator><creator>Matter-Walstra, K.</creator><creator>Gibbons-Marsico, J.</creator><creator>Diem, S.</creator><creator>Thuerlimann, B.</creator><creator>Cerny, T.</creator><general>Springer Berlin Heidelberg</general><general>Springer</general><general>Springer Nature B.V</general><scope>IQODW</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>3V.</scope><scope>7RV</scope><scope>7TK</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20140601</creationdate><title>Off-label use of anticancer drugs in eastern Switzerland: a population-based prospective cohort study</title><author>Joerger, M. ; Schaer-Thuer, C. ; Koeberle, D. ; Matter-Walstra, K. ; Gibbons-Marsico, J. ; Diem, S. ; Thuerlimann, B. ; Cerny, T.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c402t-94edca82a38b3643c987475d02a94b818f619d3f269fdaaed16c20a4f5d830e53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Antineoplastic Agents - administration & dosage</topic><topic>Antineoplastic Agents - supply & distribution</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer</topic><topic>Cohort Studies</topic><topic>Descriptive labeling</topic><topic>Drug Utilization Review - statistics & numerical data</topic><topic>Female</topic><topic>Health economics</topic><topic>Humans</topic><topic>Male</topic><topic>Medical ethics</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Neoplasms - drug therapy</topic><topic>Neoplasms - epidemiology</topic><topic>Off-Label Use - economics</topic><topic>Off-Label Use - statistics & numerical data</topic><topic>Pharmacoepidemiology and Prescription</topic><topic>Pharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>Pharmacology/Toxicology</topic><topic>Practice Guidelines as Topic</topic><topic>Prescription drugs</topic><topic>Prospective Studies</topic><topic>Switzerland</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Joerger, M.</creatorcontrib><creatorcontrib>Schaer-Thuer, C.</creatorcontrib><creatorcontrib>Koeberle, D.</creatorcontrib><creatorcontrib>Matter-Walstra, K.</creatorcontrib><creatorcontrib>Gibbons-Marsico, J.</creatorcontrib><creatorcontrib>Diem, S.</creatorcontrib><creatorcontrib>Thuerlimann, B.</creatorcontrib><creatorcontrib>Cerny, T.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of clinical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Joerger, M.</au><au>Schaer-Thuer, C.</au><au>Koeberle, D.</au><au>Matter-Walstra, K.</au><au>Gibbons-Marsico, J.</au><au>Diem, S.</au><au>Thuerlimann, B.</au><au>Cerny, T.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Off-label use of anticancer drugs in eastern Switzerland: a population-based prospective cohort study</atitle><jtitle>European journal of clinical pharmacology</jtitle><stitle>Eur J Clin Pharmacol</stitle><addtitle>Eur J Clin Pharmacol</addtitle><date>2014-06-01</date><risdate>2014</risdate><volume>70</volume><issue>6</issue><spage>719</spage><epage>725</epage><pages>719-725</pages><issn>0031-6970</issn><eissn>1432-1041</eissn><abstract>Purpose
Prevalence data on the off-label use (OLU) of anticancer drugs are limited despite OLU being controversial for medical, pharmaco-economic, and ethical reasons. We therefore quantified and characterized the OLU of anticancer drugs and compared OLU based on the national drug label with international treatment recommendations.
Methods
We prospectively collected data on patients receiving systemic anticancer therapy between October and December 2012 at hospitals affiliated with the Eastern Switzerland Oncology Network. Individual data on patient characteristics, tumor disease, and systemic treatment were collected, and each individual treatment was compared with the national drug label and international treatment guidelines.
Results
A total of 985 consecutive patients receiving 1,737 anticancer drug treatments were included in the study. Overall, 32.4 % of all patients received at least one off-label drug, corresponding to 27.2 % of all anticancer drugs administered. Major reasons for OLU were the lack of approval for the specific disease entity (15.7 %) and modified application of the anticancer drug (10 %). OLU that was unsupported by the current European Society for Medical Oncology (ESMO) treatment recommendations was rare (6.6 %) but higher for bevacizumab (29.6 %) due to its use in treating advanced ovarian cancer beyond the second-line setting and advanced breast cancer beyond the first-line setting and for lenalidomide (22.6 %) due to its use in treating Non-Hodgkin lymphoma.
Conclusions
Based on data collected on our patient cohort, OLU of anticancer drugs in a European clinical setting applies to one-third of all cancer patients. ESMO-unsupported use of chemotherapies or molecularly-targeted drugs is rare, opposing concerns that the off-label use of newer anticancer drugs is a substantial clinical problem.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>24609468</pmid><doi>10.1007/s00228-014-1662-5</doi><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0031-6970 |
| ispartof | European journal of clinical pharmacology, 2014-06, Vol.70 (6), p.719-725 |
| issn | 0031-6970 1432-1041 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1526131831 |
| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Antineoplastic Agents - administration & dosage Antineoplastic Agents - supply & distribution Antineoplastic Agents - therapeutic use Biological and medical sciences Biomedical and Life Sciences Biomedicine Cancer Cohort Studies Descriptive labeling Drug Utilization Review - statistics & numerical data Female Health economics Humans Male Medical ethics Medical sciences Middle Aged Neoplasms - drug therapy Neoplasms - epidemiology Off-Label Use - economics Off-Label Use - statistics & numerical data Pharmacoepidemiology and Prescription Pharmacology Pharmacology. Drug treatments Pharmacology/Toxicology Practice Guidelines as Topic Prescription drugs Prospective Studies Switzerland |
| title | Off-label use of anticancer drugs in eastern Switzerland: a population-based prospective cohort study |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T19%3A46%3A39IST&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=Off-label%20use%20of%20anticancer%20drugs%20in%20eastern%20Switzerland:%20a%20population-based%20prospective%20cohort%20study&rft.jtitle=European%20journal%20of%20clinical%20pharmacology&rft.au=Joerger,%20M.&rft.date=2014-06-01&rft.volume=70&rft.issue=6&rft.spage=719&rft.epage=725&rft.pages=719-725&rft.issn=0031-6970&rft.eissn=1432-1041&rft_id=info:doi/10.1007/s00228-014-1662-5&rft_dat=%3Cproquest_cross%3E3307079741%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=1525778827&rft_id=info:pmid/24609468&rfr_iscdi=true |