Loading…

Effect of metformin on all-cause and cardiovascular mortality in patients with coronary artery diseases: a systematic review and an updated meta-analysis

Metformin is the most widely prescribed drug to lower glucose and has a definitive effect on the cardiovascular system. The goal of this systematic review and meta-analysis is to assess the effects of metformin on mortality and cardiac function among patients with coronary artery disease (CAD). Rele...

Full description

Saved in:
Bibliographic Details
Published in:Cardiovascular diabetology 2019-07, Vol.18 (1), p.96-16, Article 96
Main Authors: Han, Yechen, Xie, Hongzhi, Liu, Yongtai, Gao, Peng, Yang, Xufei, Shen, Zhujun
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by cdi_FETCH-LOGICAL-c532t-7cb8354165237db733f8d07bb8e0f410a9a8838d500c6bbd17bc62da54efff893
cites cdi_FETCH-LOGICAL-c532t-7cb8354165237db733f8d07bb8e0f410a9a8838d500c6bbd17bc62da54efff893
container_end_page 16
container_issue 1
container_start_page 96
container_title Cardiovascular diabetology
container_volume 18
creator Han, Yechen
Xie, Hongzhi
Liu, Yongtai
Gao, Peng
Yang, Xufei
Shen, Zhujun
description Metformin is the most widely prescribed drug to lower glucose and has a definitive effect on the cardiovascular system. The goal of this systematic review and meta-analysis is to assess the effects of metformin on mortality and cardiac function among patients with coronary artery disease (CAD). Relevant studies reported before October 2018 was retrieved from databases including PubMed, EMBASE, Cochrane Library and Web of Science. Hazard ratio (HR) was calculated to evaluate the all-cause mortality, cardiovascular mortality and incidence of cardiovascular events (CV events), to figure out the level of left ventricular ejection fraction (LVEF), creatine kinase MB (CK-MB), type B natriuretic peptide (BNP) and to compare the average level of low density lipoprotein (LDL). In this meta-analysis were included 40 studies comprising 1,066,408 patients. The cardiovascular mortality, all-cause mortality and incidence of CV events were lowered to adjusted HR (aHR) = 0.81, aHR = 0.67 and aHR = 0. 83 respectively after the patients with CAD were given metformin. Subgroup analysis showed that metformin reduced all-cause mortality in myocardial infarction (MI) (aHR = 0.79) and heart failure (HF) patients (aHR = 0.84), the incidence of CV events in HF (aHR = 0.83) and type II diabetes mellitus (T2DM) patients (aHR = 0.83), but had no significant effect on MI (aHR = 0.87) and non-T2DM patients (aHR = 0.92). Metformin is superior to sulphonylurea (aHR = 0.81) in effects on lowering the incidence of CV events and in effects on patients who don't use medication. The CK-MB level in the metformin group was lower than that in the control group standard mean difference (SMD) = - 0.11). There was no significant evidence that metformin altered LVEF (MD = 2.91), BNP (MD = - 0.02) and LDL (MD = - 0.08). Metformin reduces cardiovascular mortality, all-cause mortality and CV events in CAD patients. For MI patients and CAD patients without T2DM, metformin has no significant effect of reducing the incidence of CV events. Metformin has a better effect of reducing the incidence of CV events than sulfonylureas.
doi_str_mv 10.1186/s12933-019-0900-7
format article
fullrecord <record><control><sourceid>proquest_doaj_</sourceid><recordid>TN_cdi_doaj_primary_oai_doaj_org_article_28ea73657834463ca28e260723304a35</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_28ea73657834463ca28e260723304a35</doaj_id><sourcerecordid>2267408144</sourcerecordid><originalsourceid>FETCH-LOGICAL-c532t-7cb8354165237db733f8d07bb8e0f410a9a8838d500c6bbd17bc62da54efff893</originalsourceid><addsrcrecordid>eNpVkstuFDEQRVsIRELgA9ggL9k0-NW2mwUSigJEisQG1la1H4kjd3uw3RPNp-Rv8cyEKFmVVb516tq6Xfee4E-EKPG5EDoy1mMy9njEuJcvulPC5dBTxfHLJ-eT7k0ptxgTqQR53Z0wwgSVnJ129xfeO1NR8mh21ac8hwWlBUGMvYG1OASLRQayDWkLxawRMppTrhBD3aEm3kANbqkF3YV6g0zKaYG8Q5Cra8WG4qC48gUBKrtS3dzkBmW3De7uwIYFrRsL1dm9A-hhgbgrobztXnmIxb17qGfdn-8Xv89_9le_flyef7vqzcBo7aWZFBs4EQNl0k6SMa8sltOkHPacYBhBKabsgLER02SJnIygFgbuvPdqZGfd5ZFrE9zqTQ5zs68TBH1opHyt21uCiU5T5UAyMUjFOBfMQGtQgSVlDHNgQ2N9PbI26zQ7a9q_ZIjPoM9vlnCjr9NWCyEUOZj5-ADI6e_qStVzKMbFCItLa9GUCsmxIpw3KTlKTU6lZOcf1xCs9_HQx3joFg-9j4eWbebDU3-PE__zwP4BQs65SQ</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2267408144</pqid></control><display><type>article</type><title>Effect of metformin on all-cause and cardiovascular mortality in patients with coronary artery diseases: a systematic review and an updated meta-analysis</title><source>Publicly Available Content Database (Proquest) (PQ_SDU_P3)</source><source>NCBI_PubMed Central(免费)</source><creator>Han, Yechen ; Xie, Hongzhi ; Liu, Yongtai ; Gao, Peng ; Yang, Xufei ; Shen, Zhujun</creator><creatorcontrib>Han, Yechen ; Xie, Hongzhi ; Liu, Yongtai ; Gao, Peng ; Yang, Xufei ; Shen, Zhujun</creatorcontrib><description>Metformin is the most widely prescribed drug to lower glucose and has a definitive effect on the cardiovascular system. The goal of this systematic review and meta-analysis is to assess the effects of metformin on mortality and cardiac function among patients with coronary artery disease (CAD). Relevant studies reported before October 2018 was retrieved from databases including PubMed, EMBASE, Cochrane Library and Web of Science. Hazard ratio (HR) was calculated to evaluate the all-cause mortality, cardiovascular mortality and incidence of cardiovascular events (CV events), to figure out the level of left ventricular ejection fraction (LVEF), creatine kinase MB (CK-MB), type B natriuretic peptide (BNP) and to compare the average level of low density lipoprotein (LDL). In this meta-analysis were included 40 studies comprising 1,066,408 patients. The cardiovascular mortality, all-cause mortality and incidence of CV events were lowered to adjusted HR (aHR) = 0.81, aHR = 0.67 and aHR = 0. 83 respectively after the patients with CAD were given metformin. Subgroup analysis showed that metformin reduced all-cause mortality in myocardial infarction (MI) (aHR = 0.79) and heart failure (HF) patients (aHR = 0.84), the incidence of CV events in HF (aHR = 0.83) and type II diabetes mellitus (T2DM) patients (aHR = 0.83), but had no significant effect on MI (aHR = 0.87) and non-T2DM patients (aHR = 0.92). Metformin is superior to sulphonylurea (aHR = 0.81) in effects on lowering the incidence of CV events and in effects on patients who don't use medication. The CK-MB level in the metformin group was lower than that in the control group standard mean difference (SMD) = - 0.11). There was no significant evidence that metformin altered LVEF (MD = 2.91), BNP (MD = - 0.02) and LDL (MD = - 0.08). Metformin reduces cardiovascular mortality, all-cause mortality and CV events in CAD patients. For MI patients and CAD patients without T2DM, metformin has no significant effect of reducing the incidence of CV events. Metformin has a better effect of reducing the incidence of CV events than sulfonylureas.</description><identifier>ISSN: 1475-2840</identifier><identifier>EISSN: 1475-2840</identifier><identifier>DOI: 10.1186/s12933-019-0900-7</identifier><identifier>PMID: 31362743</identifier><language>eng</language><publisher>England: BioMed Central</publisher><subject>Adult ; Aged ; Biomarkers - blood ; Blood Glucose - drug effects ; Blood Glucose - metabolism ; Cause of Death ; Coronary artery disease ; Coronary Artery Disease - diagnosis ; Coronary Artery Disease - epidemiology ; Coronary Artery Disease - mortality ; Diabetes ; Diabetes Mellitus, Type 2 - blood ; Diabetes Mellitus, Type 2 - diagnosis ; Diabetes Mellitus, Type 2 - drug therapy ; Diabetes Mellitus, Type 2 - mortality ; Female ; Humans ; Hypoglycemic Agents - therapeutic use ; Incidence ; Male ; Meta-analysis ; Metformin - therapeutic use ; Middle Aged ; Original Investigation ; Risk Assessment ; Risk Factors ; Systemic review ; Time Factors ; Treatment Outcome</subject><ispartof>Cardiovascular diabetology, 2019-07, Vol.18 (1), p.96-16, Article 96</ispartof><rights>The Author(s) 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c532t-7cb8354165237db733f8d07bb8e0f410a9a8838d500c6bbd17bc62da54efff893</citedby><cites>FETCH-LOGICAL-c532t-7cb8354165237db733f8d07bb8e0f410a9a8838d500c6bbd17bc62da54efff893</cites><orcidid>0000-0003-0787-1303</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6668189/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6668189/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,37013,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31362743$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Han, Yechen</creatorcontrib><creatorcontrib>Xie, Hongzhi</creatorcontrib><creatorcontrib>Liu, Yongtai</creatorcontrib><creatorcontrib>Gao, Peng</creatorcontrib><creatorcontrib>Yang, Xufei</creatorcontrib><creatorcontrib>Shen, Zhujun</creatorcontrib><title>Effect of metformin on all-cause and cardiovascular mortality in patients with coronary artery diseases: a systematic review and an updated meta-analysis</title><title>Cardiovascular diabetology</title><addtitle>Cardiovasc Diabetol</addtitle><description>Metformin is the most widely prescribed drug to lower glucose and has a definitive effect on the cardiovascular system. The goal of this systematic review and meta-analysis is to assess the effects of metformin on mortality and cardiac function among patients with coronary artery disease (CAD). Relevant studies reported before October 2018 was retrieved from databases including PubMed, EMBASE, Cochrane Library and Web of Science. Hazard ratio (HR) was calculated to evaluate the all-cause mortality, cardiovascular mortality and incidence of cardiovascular events (CV events), to figure out the level of left ventricular ejection fraction (LVEF), creatine kinase MB (CK-MB), type B natriuretic peptide (BNP) and to compare the average level of low density lipoprotein (LDL). In this meta-analysis were included 40 studies comprising 1,066,408 patients. The cardiovascular mortality, all-cause mortality and incidence of CV events were lowered to adjusted HR (aHR) = 0.81, aHR = 0.67 and aHR = 0. 83 respectively after the patients with CAD were given metformin. Subgroup analysis showed that metformin reduced all-cause mortality in myocardial infarction (MI) (aHR = 0.79) and heart failure (HF) patients (aHR = 0.84), the incidence of CV events in HF (aHR = 0.83) and type II diabetes mellitus (T2DM) patients (aHR = 0.83), but had no significant effect on MI (aHR = 0.87) and non-T2DM patients (aHR = 0.92). Metformin is superior to sulphonylurea (aHR = 0.81) in effects on lowering the incidence of CV events and in effects on patients who don't use medication. The CK-MB level in the metformin group was lower than that in the control group standard mean difference (SMD) = - 0.11). There was no significant evidence that metformin altered LVEF (MD = 2.91), BNP (MD = - 0.02) and LDL (MD = - 0.08). Metformin reduces cardiovascular mortality, all-cause mortality and CV events in CAD patients. For MI patients and CAD patients without T2DM, metformin has no significant effect of reducing the incidence of CV events. Metformin has a better effect of reducing the incidence of CV events than sulfonylureas.</description><subject>Adult</subject><subject>Aged</subject><subject>Biomarkers - blood</subject><subject>Blood Glucose - drug effects</subject><subject>Blood Glucose - metabolism</subject><subject>Cause of Death</subject><subject>Coronary artery disease</subject><subject>Coronary Artery Disease - diagnosis</subject><subject>Coronary Artery Disease - epidemiology</subject><subject>Coronary Artery Disease - mortality</subject><subject>Diabetes</subject><subject>Diabetes Mellitus, Type 2 - blood</subject><subject>Diabetes Mellitus, Type 2 - diagnosis</subject><subject>Diabetes Mellitus, Type 2 - drug therapy</subject><subject>Diabetes Mellitus, Type 2 - mortality</subject><subject>Female</subject><subject>Humans</subject><subject>Hypoglycemic Agents - therapeutic use</subject><subject>Incidence</subject><subject>Male</subject><subject>Meta-analysis</subject><subject>Metformin - therapeutic use</subject><subject>Middle Aged</subject><subject>Original Investigation</subject><subject>Risk Assessment</subject><subject>Risk Factors</subject><subject>Systemic review</subject><subject>Time Factors</subject><subject>Treatment Outcome</subject><issn>1475-2840</issn><issn>1475-2840</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>DOA</sourceid><recordid>eNpVkstuFDEQRVsIRELgA9ggL9k0-NW2mwUSigJEisQG1la1H4kjd3uw3RPNp-Rv8cyEKFmVVb516tq6Xfee4E-EKPG5EDoy1mMy9njEuJcvulPC5dBTxfHLJ-eT7k0ptxgTqQR53Z0wwgSVnJ129xfeO1NR8mh21ac8hwWlBUGMvYG1OASLRQayDWkLxawRMppTrhBD3aEm3kANbqkF3YV6g0zKaYG8Q5Cra8WG4qC48gUBKrtS3dzkBmW3De7uwIYFrRsL1dm9A-hhgbgrobztXnmIxb17qGfdn-8Xv89_9le_flyef7vqzcBo7aWZFBs4EQNl0k6SMa8sltOkHPacYBhBKabsgLER02SJnIygFgbuvPdqZGfd5ZFrE9zqTQ5zs68TBH1opHyt21uCiU5T5UAyMUjFOBfMQGtQgSVlDHNgQ2N9PbI26zQ7a9q_ZIjPoM9vlnCjr9NWCyEUOZj5-ADI6e_qStVzKMbFCItLa9GUCsmxIpw3KTlKTU6lZOcf1xCs9_HQx3joFg-9j4eWbebDU3-PE__zwP4BQs65SQ</recordid><startdate>20190730</startdate><enddate>20190730</enddate><creator>Han, Yechen</creator><creator>Xie, Hongzhi</creator><creator>Liu, Yongtai</creator><creator>Gao, Peng</creator><creator>Yang, Xufei</creator><creator>Shen, Zhujun</creator><general>BioMed Central</general><general>BMC</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><scope>DOA</scope><orcidid>https://orcid.org/0000-0003-0787-1303</orcidid></search><sort><creationdate>20190730</creationdate><title>Effect of metformin on all-cause and cardiovascular mortality in patients with coronary artery diseases: a systematic review and an updated meta-analysis</title><author>Han, Yechen ; Xie, Hongzhi ; Liu, Yongtai ; Gao, Peng ; Yang, Xufei ; Shen, Zhujun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c532t-7cb8354165237db733f8d07bb8e0f410a9a8838d500c6bbd17bc62da54efff893</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Biomarkers - blood</topic><topic>Blood Glucose - drug effects</topic><topic>Blood Glucose - metabolism</topic><topic>Cause of Death</topic><topic>Coronary artery disease</topic><topic>Coronary Artery Disease - diagnosis</topic><topic>Coronary Artery Disease - epidemiology</topic><topic>Coronary Artery Disease - mortality</topic><topic>Diabetes</topic><topic>Diabetes Mellitus, Type 2 - blood</topic><topic>Diabetes Mellitus, Type 2 - diagnosis</topic><topic>Diabetes Mellitus, Type 2 - drug therapy</topic><topic>Diabetes Mellitus, Type 2 - mortality</topic><topic>Female</topic><topic>Humans</topic><topic>Hypoglycemic Agents - therapeutic use</topic><topic>Incidence</topic><topic>Male</topic><topic>Meta-analysis</topic><topic>Metformin - therapeutic use</topic><topic>Middle Aged</topic><topic>Original Investigation</topic><topic>Risk Assessment</topic><topic>Risk Factors</topic><topic>Systemic review</topic><topic>Time Factors</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Han, Yechen</creatorcontrib><creatorcontrib>Xie, Hongzhi</creatorcontrib><creatorcontrib>Liu, Yongtai</creatorcontrib><creatorcontrib>Gao, Peng</creatorcontrib><creatorcontrib>Yang, Xufei</creatorcontrib><creatorcontrib>Shen, Zhujun</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><collection>Open Access: DOAJ - Directory of Open Access Journals</collection><jtitle>Cardiovascular diabetology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Han, Yechen</au><au>Xie, Hongzhi</au><au>Liu, Yongtai</au><au>Gao, Peng</au><au>Yang, Xufei</au><au>Shen, Zhujun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of metformin on all-cause and cardiovascular mortality in patients with coronary artery diseases: a systematic review and an updated meta-analysis</atitle><jtitle>Cardiovascular diabetology</jtitle><addtitle>Cardiovasc Diabetol</addtitle><date>2019-07-30</date><risdate>2019</risdate><volume>18</volume><issue>1</issue><spage>96</spage><epage>16</epage><pages>96-16</pages><artnum>96</artnum><issn>1475-2840</issn><eissn>1475-2840</eissn><abstract>Metformin is the most widely prescribed drug to lower glucose and has a definitive effect on the cardiovascular system. The goal of this systematic review and meta-analysis is to assess the effects of metformin on mortality and cardiac function among patients with coronary artery disease (CAD). Relevant studies reported before October 2018 was retrieved from databases including PubMed, EMBASE, Cochrane Library and Web of Science. Hazard ratio (HR) was calculated to evaluate the all-cause mortality, cardiovascular mortality and incidence of cardiovascular events (CV events), to figure out the level of left ventricular ejection fraction (LVEF), creatine kinase MB (CK-MB), type B natriuretic peptide (BNP) and to compare the average level of low density lipoprotein (LDL). In this meta-analysis were included 40 studies comprising 1,066,408 patients. The cardiovascular mortality, all-cause mortality and incidence of CV events were lowered to adjusted HR (aHR) = 0.81, aHR = 0.67 and aHR = 0. 83 respectively after the patients with CAD were given metformin. Subgroup analysis showed that metformin reduced all-cause mortality in myocardial infarction (MI) (aHR = 0.79) and heart failure (HF) patients (aHR = 0.84), the incidence of CV events in HF (aHR = 0.83) and type II diabetes mellitus (T2DM) patients (aHR = 0.83), but had no significant effect on MI (aHR = 0.87) and non-T2DM patients (aHR = 0.92). Metformin is superior to sulphonylurea (aHR = 0.81) in effects on lowering the incidence of CV events and in effects on patients who don't use medication. The CK-MB level in the metformin group was lower than that in the control group standard mean difference (SMD) = - 0.11). There was no significant evidence that metformin altered LVEF (MD = 2.91), BNP (MD = - 0.02) and LDL (MD = - 0.08). Metformin reduces cardiovascular mortality, all-cause mortality and CV events in CAD patients. For MI patients and CAD patients without T2DM, metformin has no significant effect of reducing the incidence of CV events. Metformin has a better effect of reducing the incidence of CV events than sulfonylureas.</abstract><cop>England</cop><pub>BioMed Central</pub><pmid>31362743</pmid><doi>10.1186/s12933-019-0900-7</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0003-0787-1303</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1475-2840
ispartof Cardiovascular diabetology, 2019-07, Vol.18 (1), p.96-16, Article 96
issn 1475-2840
1475-2840
language eng
recordid cdi_doaj_primary_oai_doaj_org_article_28ea73657834463ca28e260723304a35
source Publicly Available Content Database (Proquest) (PQ_SDU_P3); NCBI_PubMed Central(免费)
subjects Adult
Aged
Biomarkers - blood
Blood Glucose - drug effects
Blood Glucose - metabolism
Cause of Death
Coronary artery disease
Coronary Artery Disease - diagnosis
Coronary Artery Disease - epidemiology
Coronary Artery Disease - mortality
Diabetes
Diabetes Mellitus, Type 2 - blood
Diabetes Mellitus, Type 2 - diagnosis
Diabetes Mellitus, Type 2 - drug therapy
Diabetes Mellitus, Type 2 - mortality
Female
Humans
Hypoglycemic Agents - therapeutic use
Incidence
Male
Meta-analysis
Metformin - therapeutic use
Middle Aged
Original Investigation
Risk Assessment
Risk Factors
Systemic review
Time Factors
Treatment Outcome
title Effect of metformin on all-cause and cardiovascular mortality in patients with coronary artery diseases: a systematic review and an updated meta-analysis
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-29T09%3A57%3A25IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_doaj_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Effect%20of%20metformin%20on%20all-cause%20and%20cardiovascular%20mortality%20in%20patients%20with%20coronary%20artery%20diseases:%20a%20systematic%20review%20and%20an%20updated%20meta-analysis&rft.jtitle=Cardiovascular%20diabetology&rft.au=Han,%20Yechen&rft.date=2019-07-30&rft.volume=18&rft.issue=1&rft.spage=96&rft.epage=16&rft.pages=96-16&rft.artnum=96&rft.issn=1475-2840&rft.eissn=1475-2840&rft_id=info:doi/10.1186/s12933-019-0900-7&rft_dat=%3Cproquest_doaj_%3E2267408144%3C/proquest_doaj_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c532t-7cb8354165237db733f8d07bb8e0f410a9a8838d500c6bbd17bc62da54efff893%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2267408144&rft_id=info:pmid/31362743&rfr_iscdi=true