Clopidogrel and ischemic stroke outcomes by smoking status: Smoker's paradox?
Active smokers with myocardial infarction were shown to have enhanced benefit with clopidogrel compared with aspirin. Whether this “paradox” exists in ischemic stroke patients is unknown. We aimed to investigate whether smoking status has a differential impact on the efficacy of clopidogrel vs. aspi...
Gespeichert in:
Veröffentlicht in: | Journal of the neurological sciences 2017-02, Vol.373, p.41-44 |
---|---|
Hauptverfasser: | , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 44 |
---|---|
container_issue | |
container_start_page | 41 |
container_title | Journal of the neurological sciences |
container_volume | 373 |
creator | Zhang, Qian Wang, Yuan Song, Haiqing Hou, Chengbei Cao, Qingyu Dong, Kai Huang, Xiaoqin Feng, Wuwei Ovbiagele, Bruce Wang, Moli Ji, Xunming |
description | Active smokers with myocardial infarction were shown to have enhanced benefit with clopidogrel compared with aspirin. Whether this “paradox” exists in ischemic stroke patients is unknown. We aimed to investigate whether smoking status has a differential impact on the efficacy of clopidogrel vs. aspirin in patients with non-cardioembolic strokes.
This single-center study retrospectively assessed 1792 non-cardioembolic ischemic stroke patients discharged from January 2013 to October 2014, and followed for 12months. Patients were categorized as current-smokers and never-smokers. Primary outcome was a composite of secondary ischemic stroke, myocardial infarction and all-cause death. Secondary outcome was secondary ischemic stroke.
1066 patients were current-smokers and 726 were never-smokers. Compared with never-smokers, current-smokers had significantly higher rates of ischemic stroke (4.3% vs. 1.2%; adjusted OR: 3.60, 95%CI: 1.50–8.64, p=0.004). Regarding the primary outcome, among smokers, rates showed a lower trend in clopidogrel vs. aspirin groups (3.7% vs. 6.4%; adjusted OR 0.57, 95%CI: 0.31–1.07, p=0.08), but no difference among never-smokers (2.1% vs. 1.0%; adjusted OR: 1.67, 95%CI: 0.47–5.89, p=0.42). Similarly, among smokers, trending lower rates for recurrent ischemic stroke were observed in clopidogrel vs. aspirin group (3.1% vs. 5.0%; adjusted OR: 0.60, 95%CI: 0.31–1.18, p=0.14); but no difference between the two groups among never-smokers (1.7% vs. 1.0%; adjusted OR 1.36, 95%CI: 0.36–5.52, p=0.65).
Smoking is a major risk factor for recurrent stroke in our retrospective non-cardioembolic ischemic stroke cohort. Active-smokers trend toward better cardiovascular outcomes when on clopidogrel. This finding needs to be confirmed in a prospective cohort.
•Smoking is a high risk for cardiovascular events in stroke patients.•Stroke patients who are smokers may have better cardiovascular outcomes if they take clopidogrel versus aspirin.•Clopidogrel may be recommended to stroke survivors as a prefer antiplatelet agent if they have difficulty in quitting. |
doi_str_mv | 10.1016/j.jns.2016.12.025 |
format | Article |
fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5800495</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0022510X16308188</els_id><sourcerecordid>1862943879</sourcerecordid><originalsourceid>FETCH-LOGICAL-c451t-7b261ae2b6d039dbbfd30180d08df68e9582dfc6efd3aab36b0ce75c11dac2d03</originalsourceid><addsrcrecordid>eNp9UU1P3DAQtaqisgV-ABeUW7kkzDibrAMSCK1aQAJxoJW4WY49Wbwk8WInqPx7jBYQXDh5PPPem4_H2C5ChoDlwTJb9iHjMcyQZ8CLb2yCYibSQoj8O5sAcJ4WCLeb7GcISwAohah-sE0uMEfO-YRdzVu3ssYtPLWJ6k1ig76jzuokDN7dU-LGQbuOQlI_JaFz97ZfxJIaxnCY3MQ_-V8hWSmvjPt_ss02GtUG2nl9t9i_P7__zs_Ty-uzi_npZaqnBQ7prOYlKuJ1aSCvTF03JgcUYECYphRUFYKbRpcU80rVeVmDplmhEY3SPHK22PFadzXWHRlN_eBVK1fedso_Saes_Fzp7Z1cuEdZCIBpVUSB_VcB7x5GCoPs4uLUtqonNwaJouTVNBezKkJxDdXeheCpeW-DIF9skEsZbZAvNkjkMtoQOXsf53tnvN09Ao7WAIpXerTkZdCWek3GetKDNM5-If8MGVmbNQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1862943879</pqid></control><display><type>article</type><title>Clopidogrel and ischemic stroke outcomes by smoking status: Smoker's paradox?</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><creator>Zhang, Qian ; Wang, Yuan ; Song, Haiqing ; Hou, Chengbei ; Cao, Qingyu ; Dong, Kai ; Huang, Xiaoqin ; Feng, Wuwei ; Ovbiagele, Bruce ; Wang, Moli ; Ji, Xunming</creator><creatorcontrib>Zhang, Qian ; Wang, Yuan ; Song, Haiqing ; Hou, Chengbei ; Cao, Qingyu ; Dong, Kai ; Huang, Xiaoqin ; Feng, Wuwei ; Ovbiagele, Bruce ; Wang, Moli ; Ji, Xunming</creatorcontrib><description>Active smokers with myocardial infarction were shown to have enhanced benefit with clopidogrel compared with aspirin. Whether this “paradox” exists in ischemic stroke patients is unknown. We aimed to investigate whether smoking status has a differential impact on the efficacy of clopidogrel vs. aspirin in patients with non-cardioembolic strokes.
This single-center study retrospectively assessed 1792 non-cardioembolic ischemic stroke patients discharged from January 2013 to October 2014, and followed for 12months. Patients were categorized as current-smokers and never-smokers. Primary outcome was a composite of secondary ischemic stroke, myocardial infarction and all-cause death. Secondary outcome was secondary ischemic stroke.
1066 patients were current-smokers and 726 were never-smokers. Compared with never-smokers, current-smokers had significantly higher rates of ischemic stroke (4.3% vs. 1.2%; adjusted OR: 3.60, 95%CI: 1.50–8.64, p=0.004). Regarding the primary outcome, among smokers, rates showed a lower trend in clopidogrel vs. aspirin groups (3.7% vs. 6.4%; adjusted OR 0.57, 95%CI: 0.31–1.07, p=0.08), but no difference among never-smokers (2.1% vs. 1.0%; adjusted OR: 1.67, 95%CI: 0.47–5.89, p=0.42). Similarly, among smokers, trending lower rates for recurrent ischemic stroke were observed in clopidogrel vs. aspirin group (3.1% vs. 5.0%; adjusted OR: 0.60, 95%CI: 0.31–1.18, p=0.14); but no difference between the two groups among never-smokers (1.7% vs. 1.0%; adjusted OR 1.36, 95%CI: 0.36–5.52, p=0.65).
Smoking is a major risk factor for recurrent stroke in our retrospective non-cardioembolic ischemic stroke cohort. Active-smokers trend toward better cardiovascular outcomes when on clopidogrel. This finding needs to be confirmed in a prospective cohort.
•Smoking is a high risk for cardiovascular events in stroke patients.•Stroke patients who are smokers may have better cardiovascular outcomes if they take clopidogrel versus aspirin.•Clopidogrel may be recommended to stroke survivors as a prefer antiplatelet agent if they have difficulty in quitting.</description><identifier>ISSN: 0022-510X</identifier><identifier>EISSN: 1878-5883</identifier><identifier>DOI: 10.1016/j.jns.2016.12.025</identifier><identifier>PMID: 28131222</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Aspirin ; Aspirin - therapeutic use ; Brain Ischemia - complications ; Brain Ischemia - drug therapy ; Brain Ischemia - mortality ; Clopidogrel ; Female ; Humans ; Ischemic stroke ; Male ; Middle Aged ; Myocardial Infarction - complications ; Myocardial Infarction - mortality ; Outcome ; Platelet Aggregation Inhibitors - therapeutic use ; Recurrence ; Retrospective Studies ; Smoking ; Smoking - mortality ; Stroke - complications ; Stroke - drug therapy ; Stroke - mortality ; Ticlopidine - analogs & derivatives ; Ticlopidine - therapeutic use ; Treatment Outcome</subject><ispartof>Journal of the neurological sciences, 2017-02, Vol.373, p.41-44</ispartof><rights>2016</rights><rights>Copyright © 2016. Published by Elsevier B.V.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c451t-7b261ae2b6d039dbbfd30180d08df68e9582dfc6efd3aab36b0ce75c11dac2d03</citedby><cites>FETCH-LOGICAL-c451t-7b261ae2b6d039dbbfd30180d08df68e9582dfc6efd3aab36b0ce75c11dac2d03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jns.2016.12.025$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3536,27903,27904,45974</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28131222$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Qian</creatorcontrib><creatorcontrib>Wang, Yuan</creatorcontrib><creatorcontrib>Song, Haiqing</creatorcontrib><creatorcontrib>Hou, Chengbei</creatorcontrib><creatorcontrib>Cao, Qingyu</creatorcontrib><creatorcontrib>Dong, Kai</creatorcontrib><creatorcontrib>Huang, Xiaoqin</creatorcontrib><creatorcontrib>Feng, Wuwei</creatorcontrib><creatorcontrib>Ovbiagele, Bruce</creatorcontrib><creatorcontrib>Wang, Moli</creatorcontrib><creatorcontrib>Ji, Xunming</creatorcontrib><title>Clopidogrel and ischemic stroke outcomes by smoking status: Smoker's paradox?</title><title>Journal of the neurological sciences</title><addtitle>J Neurol Sci</addtitle><description>Active smokers with myocardial infarction were shown to have enhanced benefit with clopidogrel compared with aspirin. Whether this “paradox” exists in ischemic stroke patients is unknown. We aimed to investigate whether smoking status has a differential impact on the efficacy of clopidogrel vs. aspirin in patients with non-cardioembolic strokes.
This single-center study retrospectively assessed 1792 non-cardioembolic ischemic stroke patients discharged from January 2013 to October 2014, and followed for 12months. Patients were categorized as current-smokers and never-smokers. Primary outcome was a composite of secondary ischemic stroke, myocardial infarction and all-cause death. Secondary outcome was secondary ischemic stroke.
1066 patients were current-smokers and 726 were never-smokers. Compared with never-smokers, current-smokers had significantly higher rates of ischemic stroke (4.3% vs. 1.2%; adjusted OR: 3.60, 95%CI: 1.50–8.64, p=0.004). Regarding the primary outcome, among smokers, rates showed a lower trend in clopidogrel vs. aspirin groups (3.7% vs. 6.4%; adjusted OR 0.57, 95%CI: 0.31–1.07, p=0.08), but no difference among never-smokers (2.1% vs. 1.0%; adjusted OR: 1.67, 95%CI: 0.47–5.89, p=0.42). Similarly, among smokers, trending lower rates for recurrent ischemic stroke were observed in clopidogrel vs. aspirin group (3.1% vs. 5.0%; adjusted OR: 0.60, 95%CI: 0.31–1.18, p=0.14); but no difference between the two groups among never-smokers (1.7% vs. 1.0%; adjusted OR 1.36, 95%CI: 0.36–5.52, p=0.65).
Smoking is a major risk factor for recurrent stroke in our retrospective non-cardioembolic ischemic stroke cohort. Active-smokers trend toward better cardiovascular outcomes when on clopidogrel. This finding needs to be confirmed in a prospective cohort.
•Smoking is a high risk for cardiovascular events in stroke patients.•Stroke patients who are smokers may have better cardiovascular outcomes if they take clopidogrel versus aspirin.•Clopidogrel may be recommended to stroke survivors as a prefer antiplatelet agent if they have difficulty in quitting.</description><subject>Aspirin</subject><subject>Aspirin - therapeutic use</subject><subject>Brain Ischemia - complications</subject><subject>Brain Ischemia - drug therapy</subject><subject>Brain Ischemia - mortality</subject><subject>Clopidogrel</subject><subject>Female</subject><subject>Humans</subject><subject>Ischemic stroke</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Myocardial Infarction - complications</subject><subject>Myocardial Infarction - mortality</subject><subject>Outcome</subject><subject>Platelet Aggregation Inhibitors - therapeutic use</subject><subject>Recurrence</subject><subject>Retrospective Studies</subject><subject>Smoking</subject><subject>Smoking - mortality</subject><subject>Stroke - complications</subject><subject>Stroke - drug therapy</subject><subject>Stroke - mortality</subject><subject>Ticlopidine - analogs & derivatives</subject><subject>Ticlopidine - therapeutic use</subject><subject>Treatment Outcome</subject><issn>0022-510X</issn><issn>1878-5883</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UU1P3DAQtaqisgV-ABeUW7kkzDibrAMSCK1aQAJxoJW4WY49Wbwk8WInqPx7jBYQXDh5PPPem4_H2C5ChoDlwTJb9iHjMcyQZ8CLb2yCYibSQoj8O5sAcJ4WCLeb7GcISwAohah-sE0uMEfO-YRdzVu3ssYtPLWJ6k1ig76jzuokDN7dU-LGQbuOQlI_JaFz97ZfxJIaxnCY3MQ_-V8hWSmvjPt_ss02GtUG2nl9t9i_P7__zs_Ty-uzi_npZaqnBQ7prOYlKuJ1aSCvTF03JgcUYECYphRUFYKbRpcU80rVeVmDplmhEY3SPHK22PFadzXWHRlN_eBVK1fedso_Saes_Fzp7Z1cuEdZCIBpVUSB_VcB7x5GCoPs4uLUtqonNwaJouTVNBezKkJxDdXeheCpeW-DIF9skEsZbZAvNkjkMtoQOXsf53tnvN09Ao7WAIpXerTkZdCWek3GetKDNM5-If8MGVmbNQ</recordid><startdate>20170215</startdate><enddate>20170215</enddate><creator>Zhang, Qian</creator><creator>Wang, Yuan</creator><creator>Song, Haiqing</creator><creator>Hou, Chengbei</creator><creator>Cao, Qingyu</creator><creator>Dong, Kai</creator><creator>Huang, Xiaoqin</creator><creator>Feng, Wuwei</creator><creator>Ovbiagele, Bruce</creator><creator>Wang, Moli</creator><creator>Ji, Xunming</creator><general>Elsevier B.V</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20170215</creationdate><title>Clopidogrel and ischemic stroke outcomes by smoking status: Smoker's paradox?</title><author>Zhang, Qian ; Wang, Yuan ; Song, Haiqing ; Hou, Chengbei ; Cao, Qingyu ; Dong, Kai ; Huang, Xiaoqin ; Feng, Wuwei ; Ovbiagele, Bruce ; Wang, Moli ; Ji, Xunming</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c451t-7b261ae2b6d039dbbfd30180d08df68e9582dfc6efd3aab36b0ce75c11dac2d03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Aspirin</topic><topic>Aspirin - therapeutic use</topic><topic>Brain Ischemia - complications</topic><topic>Brain Ischemia - drug therapy</topic><topic>Brain Ischemia - mortality</topic><topic>Clopidogrel</topic><topic>Female</topic><topic>Humans</topic><topic>Ischemic stroke</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Myocardial Infarction - complications</topic><topic>Myocardial Infarction - mortality</topic><topic>Outcome</topic><topic>Platelet Aggregation Inhibitors - therapeutic use</topic><topic>Recurrence</topic><topic>Retrospective Studies</topic><topic>Smoking</topic><topic>Smoking - mortality</topic><topic>Stroke - complications</topic><topic>Stroke - drug therapy</topic><topic>Stroke - mortality</topic><topic>Ticlopidine - analogs & derivatives</topic><topic>Ticlopidine - therapeutic use</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Qian</creatorcontrib><creatorcontrib>Wang, Yuan</creatorcontrib><creatorcontrib>Song, Haiqing</creatorcontrib><creatorcontrib>Hou, Chengbei</creatorcontrib><creatorcontrib>Cao, Qingyu</creatorcontrib><creatorcontrib>Dong, Kai</creatorcontrib><creatorcontrib>Huang, Xiaoqin</creatorcontrib><creatorcontrib>Feng, Wuwei</creatorcontrib><creatorcontrib>Ovbiagele, Bruce</creatorcontrib><creatorcontrib>Wang, Moli</creatorcontrib><creatorcontrib>Ji, Xunming</creatorcontrib><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 the neurological sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Qian</au><au>Wang, Yuan</au><au>Song, Haiqing</au><au>Hou, Chengbei</au><au>Cao, Qingyu</au><au>Dong, Kai</au><au>Huang, Xiaoqin</au><au>Feng, Wuwei</au><au>Ovbiagele, Bruce</au><au>Wang, Moli</au><au>Ji, Xunming</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Clopidogrel and ischemic stroke outcomes by smoking status: Smoker's paradox?</atitle><jtitle>Journal of the neurological sciences</jtitle><addtitle>J Neurol Sci</addtitle><date>2017-02-15</date><risdate>2017</risdate><volume>373</volume><spage>41</spage><epage>44</epage><pages>41-44</pages><issn>0022-510X</issn><eissn>1878-5883</eissn><abstract>Active smokers with myocardial infarction were shown to have enhanced benefit with clopidogrel compared with aspirin. Whether this “paradox” exists in ischemic stroke patients is unknown. We aimed to investigate whether smoking status has a differential impact on the efficacy of clopidogrel vs. aspirin in patients with non-cardioembolic strokes.
This single-center study retrospectively assessed 1792 non-cardioembolic ischemic stroke patients discharged from January 2013 to October 2014, and followed for 12months. Patients were categorized as current-smokers and never-smokers. Primary outcome was a composite of secondary ischemic stroke, myocardial infarction and all-cause death. Secondary outcome was secondary ischemic stroke.
1066 patients were current-smokers and 726 were never-smokers. Compared with never-smokers, current-smokers had significantly higher rates of ischemic stroke (4.3% vs. 1.2%; adjusted OR: 3.60, 95%CI: 1.50–8.64, p=0.004). Regarding the primary outcome, among smokers, rates showed a lower trend in clopidogrel vs. aspirin groups (3.7% vs. 6.4%; adjusted OR 0.57, 95%CI: 0.31–1.07, p=0.08), but no difference among never-smokers (2.1% vs. 1.0%; adjusted OR: 1.67, 95%CI: 0.47–5.89, p=0.42). Similarly, among smokers, trending lower rates for recurrent ischemic stroke were observed in clopidogrel vs. aspirin group (3.1% vs. 5.0%; adjusted OR: 0.60, 95%CI: 0.31–1.18, p=0.14); but no difference between the two groups among never-smokers (1.7% vs. 1.0%; adjusted OR 1.36, 95%CI: 0.36–5.52, p=0.65).
Smoking is a major risk factor for recurrent stroke in our retrospective non-cardioembolic ischemic stroke cohort. Active-smokers trend toward better cardiovascular outcomes when on clopidogrel. This finding needs to be confirmed in a prospective cohort.
•Smoking is a high risk for cardiovascular events in stroke patients.•Stroke patients who are smokers may have better cardiovascular outcomes if they take clopidogrel versus aspirin.•Clopidogrel may be recommended to stroke survivors as a prefer antiplatelet agent if they have difficulty in quitting.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>28131222</pmid><doi>10.1016/j.jns.2016.12.025</doi><tpages>4</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0022-510X |
ispartof | Journal of the neurological sciences, 2017-02, Vol.373, p.41-44 |
issn | 0022-510X 1878-5883 |
language | eng |
recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5800495 |
source | MEDLINE; Elsevier ScienceDirect Journals |
subjects | Aspirin Aspirin - therapeutic use Brain Ischemia - complications Brain Ischemia - drug therapy Brain Ischemia - mortality Clopidogrel Female Humans Ischemic stroke Male Middle Aged Myocardial Infarction - complications Myocardial Infarction - mortality Outcome Platelet Aggregation Inhibitors - therapeutic use Recurrence Retrospective Studies Smoking Smoking - mortality Stroke - complications Stroke - drug therapy Stroke - mortality Ticlopidine - analogs & derivatives Ticlopidine - therapeutic use Treatment Outcome |
title | Clopidogrel and ischemic stroke outcomes by smoking status: Smoker's paradox? |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-23T03%3A33%3A17IST&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=Clopidogrel%20and%20ischemic%20stroke%20outcomes%20by%20smoking%20status:%20Smoker's%20paradox?&rft.jtitle=Journal%20of%20the%20neurological%20sciences&rft.au=Zhang,%20Qian&rft.date=2017-02-15&rft.volume=373&rft.spage=41&rft.epage=44&rft.pages=41-44&rft.issn=0022-510X&rft.eissn=1878-5883&rft_id=info:doi/10.1016/j.jns.2016.12.025&rft_dat=%3Cproquest_pubme%3E1862943879%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=1862943879&rft_id=info:pmid/28131222&rft_els_id=S0022510X16308188&rfr_iscdi=true |