Genotyping-guided approach versus the conventional approach in selection of oral P2Y12 receptor blockers in Chinese patients suffering from acute coronary syndrome
Objective The CYP2C19 loss-of-function (LoF) allele is present in half of the East Asian population and is associated with high on-treatment platelet reactivity (HTPR). This study aimed to investigate whether a rapid genotyping-guided approach is feasible and efficacious for selecting P2Y12 receptor...
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| Veröffentlicht in: | Journal of international medical research 2017-02, Vol.45 (1), p.134-146 |
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| creator | Tam, Chor Cheung Kwok, Janette Wong, Anthony Yung, Arthur Shea, Catherine Kong, Shun Ling Tang, Wing Hong Siu, David Chan, Raymond Lee, Stephen |
| description | Objective
The CYP2C19 loss-of-function (LoF) allele is present in half of the East Asian population and is associated with high on-treatment platelet reactivity (HTPR). This study aimed to investigate whether a rapid genotyping-guided approach is feasible and efficacious for selecting P2Y12 receptor blockers in Chinese patients suffering from acute coronary syndrome (ACS).
Methods
This was a single-centre, prospective, randomized, open-label study. A total of 132 patients with ACS were randomized to the rapid genotyping-guided treatment group (GG, N = 65) or the standard treatment group (SG, N = 67). Patients in the GG group were genotyped by the Verigene system. Patients with the CYP2C19 LoF allele were switched to ticagrelor and all remaining patients continued on clopidogrel. The endpoints were HTPR at 24 hours after the first loading dose of clopidogrel and 1 month afterwards.
Results
Forty patients in the GG group switched to ticagrelor, while others continued on clopidogrel. The incidence of HTPR in the GG vs SG groups was 9.2% vs 40.3% at 24 hours and 6.5% vs 32.3% at 1 month, respectively. Rapid point-of-care genotyping showed 100% concordance with conventional genotyping by real-time polymerase chain reaction.
Conclusions
In Chinese patients suffering from ACS, the rapid genotyping-guided approach for selecting P2Y12 receptor blockers is feasible and reduces the incidence of HTPR.
Clinical Trial Registration
URL: http://clinicaltrials.gov. Unique identifier: NCT01994941. |
| doi_str_mv | 10.1177/0300060516677190 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5536604</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sage_id>10.1177_0300060516677190</sage_id><sourcerecordid>1870988777</sourcerecordid><originalsourceid>FETCH-LOGICAL-c434t-ef8e265309b9aec815b417149db9cdae98531a72f90ee230c1e9dab6104794f83</originalsourceid><addsrcrecordid>eNp1UT2P1DAUtBCIWw56KuSSJmA7Thw3SGh1HEgnQQEFleU4z7s-snbwS1ba38MfxdEex4dEZenNvJl5HkKec_aKc6Ves5ox1rKGt61SXLMHZMOlqitR5g_JZoWrFb8gTxBvGZOibcRjciE6IUQr-Yb8uIaY5tMU4q7aLWGAgdppysm6PT1CxgXpvAfqUjxCnEOKdvxNCJEijODWOU2eplzQT-IrFzSDg2lOmfZjct-K0Ere7kMEBDrZORQ1pLh4D7l4U5_TgVq3zKtXLjb5RPEUhzKGp-SRtyPCs7v3knx5d_V5-766-Xj9Yfv2pnKylnMFvoNyX810ry24jje95IpLPfTaDRZ019TcKuE1Ayg_5DjowfYtZ1Jp6bv6krw5605Lf4DBlYjlIDPlcChxTLLB_I3EsDe7dDRNU7ctk0Xg5Z1ATt8XwNkcAjoYRxshLWh4p5juOqVUobIz1eWEmMHf23Bm1m7Nv92WlRd_xrtf-FVmIVRnAtodmNu05NIW_l_wJ7AasMs</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1870988777</pqid></control><display><type>article</type><title>Genotyping-guided approach versus the conventional approach in selection of oral P2Y12 receptor blockers in Chinese patients suffering from acute coronary syndrome</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Sage Journals GOLD Open Access 2024</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><creator>Tam, Chor Cheung ; Kwok, Janette ; Wong, Anthony ; Yung, Arthur ; Shea, Catherine ; Kong, Shun Ling ; Tang, Wing Hong ; Siu, David ; Chan, Raymond ; Lee, Stephen</creator><creatorcontrib>Tam, Chor Cheung ; Kwok, Janette ; Wong, Anthony ; Yung, Arthur ; Shea, Catherine ; Kong, Shun Ling ; Tang, Wing Hong ; Siu, David ; Chan, Raymond ; Lee, Stephen</creatorcontrib><description>Objective
The CYP2C19 loss-of-function (LoF) allele is present in half of the East Asian population and is associated with high on-treatment platelet reactivity (HTPR). This study aimed to investigate whether a rapid genotyping-guided approach is feasible and efficacious for selecting P2Y12 receptor blockers in Chinese patients suffering from acute coronary syndrome (ACS).
Methods
This was a single-centre, prospective, randomized, open-label study. A total of 132 patients with ACS were randomized to the rapid genotyping-guided treatment group (GG, N = 65) or the standard treatment group (SG, N = 67). Patients in the GG group were genotyped by the Verigene system. Patients with the CYP2C19 LoF allele were switched to ticagrelor and all remaining patients continued on clopidogrel. The endpoints were HTPR at 24 hours after the first loading dose of clopidogrel and 1 month afterwards.
Results
Forty patients in the GG group switched to ticagrelor, while others continued on clopidogrel. The incidence of HTPR in the GG vs SG groups was 9.2% vs 40.3% at 24 hours and 6.5% vs 32.3% at 1 month, respectively. Rapid point-of-care genotyping showed 100% concordance with conventional genotyping by real-time polymerase chain reaction.
Conclusions
In Chinese patients suffering from ACS, the rapid genotyping-guided approach for selecting P2Y12 receptor blockers is feasible and reduces the incidence of HTPR.
Clinical Trial Registration
URL: http://clinicaltrials.gov. Unique identifier: NCT01994941.</description><identifier>ISSN: 0300-0605</identifier><identifier>EISSN: 1473-2300</identifier><identifier>DOI: 10.1177/0300060516677190</identifier><identifier>PMID: 28222641</identifier><language>eng</language><publisher>London, England: SAGE Publications</publisher><subject>Acute Coronary Syndrome - blood ; Acute Coronary Syndrome - diagnosis ; Acute Coronary Syndrome - drug therapy ; Acute Coronary Syndrome - genetics ; Adenosine - analogs & derivatives ; Adenosine - therapeutic use ; Aged ; Alleles ; Asian Continental Ancestry Group ; Blood Platelets - drug effects ; Blood Platelets - metabolism ; Blood Platelets - pathology ; Cytochrome P-450 CYP2C19 - deficiency ; Cytochrome P-450 CYP2C19 - genetics ; Female ; Gene Expression ; Gene Frequency ; Genotype ; Genotyping Techniques ; Humans ; Male ; Middle Aged ; Mutation ; Platelet Aggregation - drug effects ; Platelet Aggregation Inhibitors - therapeutic use ; Prospective Studies ; Purinergic P2Y Receptor Antagonists - therapeutic use ; Receptors, Purinergic P2Y12 - genetics ; Receptors, Purinergic P2Y12 - metabolism ; Research Reports ; Thrombosis - diagnosis ; Thrombosis - genetics ; Thrombosis - metabolism ; Thrombosis - prevention & control ; Ticlopidine - analogs & derivatives ; Ticlopidine - therapeutic use</subject><ispartof>Journal of international medical research, 2017-02, Vol.45 (1), p.134-146</ispartof><rights>The Author(s) 2016</rights><rights>The Author(s) 2016 2016 SAGE Publications</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c434t-ef8e265309b9aec815b417149db9cdae98531a72f90ee230c1e9dab6104794f83</citedby><cites>FETCH-LOGICAL-c434t-ef8e265309b9aec815b417149db9cdae98531a72f90ee230c1e9dab6104794f83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5536604/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5536604/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,21945,27830,27901,27902,44921,45309,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28222641$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tam, Chor Cheung</creatorcontrib><creatorcontrib>Kwok, Janette</creatorcontrib><creatorcontrib>Wong, Anthony</creatorcontrib><creatorcontrib>Yung, Arthur</creatorcontrib><creatorcontrib>Shea, Catherine</creatorcontrib><creatorcontrib>Kong, Shun Ling</creatorcontrib><creatorcontrib>Tang, Wing Hong</creatorcontrib><creatorcontrib>Siu, David</creatorcontrib><creatorcontrib>Chan, Raymond</creatorcontrib><creatorcontrib>Lee, Stephen</creatorcontrib><title>Genotyping-guided approach versus the conventional approach in selection of oral P2Y12 receptor blockers in Chinese patients suffering from acute coronary syndrome</title><title>Journal of international medical research</title><addtitle>J Int Med Res</addtitle><description>Objective
The CYP2C19 loss-of-function (LoF) allele is present in half of the East Asian population and is associated with high on-treatment platelet reactivity (HTPR). This study aimed to investigate whether a rapid genotyping-guided approach is feasible and efficacious for selecting P2Y12 receptor blockers in Chinese patients suffering from acute coronary syndrome (ACS).
Methods
This was a single-centre, prospective, randomized, open-label study. A total of 132 patients with ACS were randomized to the rapid genotyping-guided treatment group (GG, N = 65) or the standard treatment group (SG, N = 67). Patients in the GG group were genotyped by the Verigene system. Patients with the CYP2C19 LoF allele were switched to ticagrelor and all remaining patients continued on clopidogrel. The endpoints were HTPR at 24 hours after the first loading dose of clopidogrel and 1 month afterwards.
Results
Forty patients in the GG group switched to ticagrelor, while others continued on clopidogrel. The incidence of HTPR in the GG vs SG groups was 9.2% vs 40.3% at 24 hours and 6.5% vs 32.3% at 1 month, respectively. Rapid point-of-care genotyping showed 100% concordance with conventional genotyping by real-time polymerase chain reaction.
Conclusions
In Chinese patients suffering from ACS, the rapid genotyping-guided approach for selecting P2Y12 receptor blockers is feasible and reduces the incidence of HTPR.
Clinical Trial Registration
URL: http://clinicaltrials.gov. Unique identifier: NCT01994941.</description><subject>Acute Coronary Syndrome - blood</subject><subject>Acute Coronary Syndrome - diagnosis</subject><subject>Acute Coronary Syndrome - drug therapy</subject><subject>Acute Coronary Syndrome - genetics</subject><subject>Adenosine - analogs & derivatives</subject><subject>Adenosine - therapeutic use</subject><subject>Aged</subject><subject>Alleles</subject><subject>Asian Continental Ancestry Group</subject><subject>Blood Platelets - drug effects</subject><subject>Blood Platelets - metabolism</subject><subject>Blood Platelets - pathology</subject><subject>Cytochrome P-450 CYP2C19 - deficiency</subject><subject>Cytochrome P-450 CYP2C19 - genetics</subject><subject>Female</subject><subject>Gene Expression</subject><subject>Gene Frequency</subject><subject>Genotype</subject><subject>Genotyping Techniques</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Platelet Aggregation - drug effects</subject><subject>Platelet Aggregation Inhibitors - therapeutic use</subject><subject>Prospective Studies</subject><subject>Purinergic P2Y Receptor Antagonists - therapeutic use</subject><subject>Receptors, Purinergic P2Y12 - genetics</subject><subject>Receptors, Purinergic P2Y12 - metabolism</subject><subject>Research Reports</subject><subject>Thrombosis - diagnosis</subject><subject>Thrombosis - genetics</subject><subject>Thrombosis - metabolism</subject><subject>Thrombosis - prevention & control</subject><subject>Ticlopidine - analogs & derivatives</subject><subject>Ticlopidine - therapeutic use</subject><issn>0300-0605</issn><issn>1473-2300</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>AFRWT</sourceid><sourceid>EIF</sourceid><recordid>eNp1UT2P1DAUtBCIWw56KuSSJmA7Thw3SGh1HEgnQQEFleU4z7s-snbwS1ba38MfxdEex4dEZenNvJl5HkKec_aKc6Ves5ox1rKGt61SXLMHZMOlqitR5g_JZoWrFb8gTxBvGZOibcRjciE6IUQr-Yb8uIaY5tMU4q7aLWGAgdppysm6PT1CxgXpvAfqUjxCnEOKdvxNCJEijODWOU2eplzQT-IrFzSDg2lOmfZjct-K0Ere7kMEBDrZORQ1pLh4D7l4U5_TgVq3zKtXLjb5RPEUhzKGp-SRtyPCs7v3knx5d_V5-766-Xj9Yfv2pnKylnMFvoNyX810ry24jje95IpLPfTaDRZ019TcKuE1Ayg_5DjowfYtZ1Jp6bv6krw5605Lf4DBlYjlIDPlcChxTLLB_I3EsDe7dDRNU7ctk0Xg5Z1ATt8XwNkcAjoYRxshLWh4p5juOqVUobIz1eWEmMHf23Bm1m7Nv92WlRd_xrtf-FVmIVRnAtodmNu05NIW_l_wJ7AasMs</recordid><startdate>20170201</startdate><enddate>20170201</enddate><creator>Tam, Chor Cheung</creator><creator>Kwok, Janette</creator><creator>Wong, Anthony</creator><creator>Yung, Arthur</creator><creator>Shea, Catherine</creator><creator>Kong, Shun Ling</creator><creator>Tang, Wing Hong</creator><creator>Siu, David</creator><creator>Chan, Raymond</creator><creator>Lee, Stephen</creator><general>SAGE Publications</general><scope>AFRWT</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>20170201</creationdate><title>Genotyping-guided approach versus the conventional approach in selection of oral P2Y12 receptor blockers in Chinese patients suffering from acute coronary syndrome</title><author>Tam, Chor Cheung ; Kwok, Janette ; Wong, Anthony ; Yung, Arthur ; Shea, Catherine ; Kong, Shun Ling ; Tang, Wing Hong ; Siu, David ; Chan, Raymond ; Lee, Stephen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c434t-ef8e265309b9aec815b417149db9cdae98531a72f90ee230c1e9dab6104794f83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Acute Coronary Syndrome - blood</topic><topic>Acute Coronary Syndrome - diagnosis</topic><topic>Acute Coronary Syndrome - drug therapy</topic><topic>Acute Coronary Syndrome - genetics</topic><topic>Adenosine - analogs & derivatives</topic><topic>Adenosine - therapeutic use</topic><topic>Aged</topic><topic>Alleles</topic><topic>Asian Continental Ancestry Group</topic><topic>Blood Platelets - drug effects</topic><topic>Blood Platelets - metabolism</topic><topic>Blood Platelets - pathology</topic><topic>Cytochrome P-450 CYP2C19 - deficiency</topic><topic>Cytochrome P-450 CYP2C19 - genetics</topic><topic>Female</topic><topic>Gene Expression</topic><topic>Gene Frequency</topic><topic>Genotype</topic><topic>Genotyping Techniques</topic><topic>Humans</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Mutation</topic><topic>Platelet Aggregation - drug effects</topic><topic>Platelet Aggregation Inhibitors - therapeutic use</topic><topic>Prospective Studies</topic><topic>Purinergic P2Y Receptor Antagonists - therapeutic use</topic><topic>Receptors, Purinergic P2Y12 - genetics</topic><topic>Receptors, Purinergic P2Y12 - metabolism</topic><topic>Research Reports</topic><topic>Thrombosis - diagnosis</topic><topic>Thrombosis - genetics</topic><topic>Thrombosis - metabolism</topic><topic>Thrombosis - prevention & control</topic><topic>Ticlopidine - analogs & derivatives</topic><topic>Ticlopidine - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tam, Chor Cheung</creatorcontrib><creatorcontrib>Kwok, Janette</creatorcontrib><creatorcontrib>Wong, Anthony</creatorcontrib><creatorcontrib>Yung, Arthur</creatorcontrib><creatorcontrib>Shea, Catherine</creatorcontrib><creatorcontrib>Kong, Shun Ling</creatorcontrib><creatorcontrib>Tang, Wing Hong</creatorcontrib><creatorcontrib>Siu, David</creatorcontrib><creatorcontrib>Chan, Raymond</creatorcontrib><creatorcontrib>Lee, Stephen</creatorcontrib><collection>Sage Journals GOLD Open Access 2024</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>Journal of international medical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tam, Chor Cheung</au><au>Kwok, Janette</au><au>Wong, Anthony</au><au>Yung, Arthur</au><au>Shea, Catherine</au><au>Kong, Shun Ling</au><au>Tang, Wing Hong</au><au>Siu, David</au><au>Chan, Raymond</au><au>Lee, Stephen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genotyping-guided approach versus the conventional approach in selection of oral P2Y12 receptor blockers in Chinese patients suffering from acute coronary syndrome</atitle><jtitle>Journal of international medical research</jtitle><addtitle>J Int Med Res</addtitle><date>2017-02-01</date><risdate>2017</risdate><volume>45</volume><issue>1</issue><spage>134</spage><epage>146</epage><pages>134-146</pages><issn>0300-0605</issn><eissn>1473-2300</eissn><abstract>Objective
The CYP2C19 loss-of-function (LoF) allele is present in half of the East Asian population and is associated with high on-treatment platelet reactivity (HTPR). This study aimed to investigate whether a rapid genotyping-guided approach is feasible and efficacious for selecting P2Y12 receptor blockers in Chinese patients suffering from acute coronary syndrome (ACS).
Methods
This was a single-centre, prospective, randomized, open-label study. A total of 132 patients with ACS were randomized to the rapid genotyping-guided treatment group (GG, N = 65) or the standard treatment group (SG, N = 67). Patients in the GG group were genotyped by the Verigene system. Patients with the CYP2C19 LoF allele were switched to ticagrelor and all remaining patients continued on clopidogrel. The endpoints were HTPR at 24 hours after the first loading dose of clopidogrel and 1 month afterwards.
Results
Forty patients in the GG group switched to ticagrelor, while others continued on clopidogrel. The incidence of HTPR in the GG vs SG groups was 9.2% vs 40.3% at 24 hours and 6.5% vs 32.3% at 1 month, respectively. Rapid point-of-care genotyping showed 100% concordance with conventional genotyping by real-time polymerase chain reaction.
Conclusions
In Chinese patients suffering from ACS, the rapid genotyping-guided approach for selecting P2Y12 receptor blockers is feasible and reduces the incidence of HTPR.
Clinical Trial Registration
URL: http://clinicaltrials.gov. Unique identifier: NCT01994941.</abstract><cop>London, England</cop><pub>SAGE Publications</pub><pmid>28222641</pmid><doi>10.1177/0300060516677190</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Sage Journals GOLD Open Access 2024; PubMed Central; Alma/SFX Local Collection |
| subjects | Acute Coronary Syndrome - blood Acute Coronary Syndrome - diagnosis Acute Coronary Syndrome - drug therapy Acute Coronary Syndrome - genetics Adenosine - analogs & derivatives Adenosine - therapeutic use Aged Alleles Asian Continental Ancestry Group Blood Platelets - drug effects Blood Platelets - metabolism Blood Platelets - pathology Cytochrome P-450 CYP2C19 - deficiency Cytochrome P-450 CYP2C19 - genetics Female Gene Expression Gene Frequency Genotype Genotyping Techniques Humans Male Middle Aged Mutation Platelet Aggregation - drug effects Platelet Aggregation Inhibitors - therapeutic use Prospective Studies Purinergic P2Y Receptor Antagonists - therapeutic use Receptors, Purinergic P2Y12 - genetics Receptors, Purinergic P2Y12 - metabolism Research Reports Thrombosis - diagnosis Thrombosis - genetics Thrombosis - metabolism Thrombosis - prevention & control Ticlopidine - analogs & derivatives Ticlopidine - therapeutic use |
| title | Genotyping-guided approach versus the conventional approach in selection of oral P2Y12 receptor blockers in Chinese patients suffering from acute coronary syndrome |
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