Loading…
Interferon-γ release assay as a sensitive diagnostic tool of latent tuberculosis infection in patients with HIV: a cross-sectional study
In developing countries, tuberculosis (TB) is a major public health problem and the leading cause of death among patients with HIV (Human Immunodeficiency Virus). Until 2001, the tuberculin skin test (TST) was the only available tool for the diagnosis of latent tuberculosis infection (LTBI), but fal...
Saved in:
Published in: | BMC infectious diseases 2018-11, Vol.18 (1), p.585-585, Article 585 |
---|---|
Main Authors: | , , , , |
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-c465t-261bcec7519a5975e45e3d6414f52c28ee3a90fa695656572f6329cd0b2efa233 |
---|---|
cites | cdi_FETCH-LOGICAL-c465t-261bcec7519a5975e45e3d6414f52c28ee3a90fa695656572f6329cd0b2efa233 |
container_end_page | 585 |
container_issue | 1 |
container_start_page | 585 |
container_title | BMC infectious diseases |
container_volume | 18 |
creator | Klautau, Giselle Burlamaqui da Mota, Nadijane Valéria Ferreira Salles, Mauro José Costa Burattini, Marcelo Nascimento Rodrigues, Denise Silva |
description | In developing countries, tuberculosis (TB) is a major public health problem and the leading cause of death among patients with HIV (Human Immunodeficiency Virus). Until 2001, the tuberculin skin test (TST) was the only available tool for the diagnosis of latent tuberculosis infection (LTBI), but false-negative TST results are frequently reported. Recently, the interferon-γ (IFN-γ) release assay (IGRA) has gained ground because it can detect the IFN-γ secreted by circulating lymphocytes T cells when stimulated by specific TB antigens. However, the role of IGRA in the diagnosis of LTBI in HIV-infected patients has not been well established.
This cross-sectional study compared the accuracy of TST (performed by the Mantoux method) and IGRA (QuantiFERON-TB Gold In-Tube, Cellestis, Carnegie, Australia) on the diagnosis of LTBI among patients with HIV. LTBI is defined by LTBI risk and at least one positive test (TST or IGRA), without clinical evidence of active TB. We also assessed the accuracy of TST and IGRA among HIV patients with high and low risk for LTBI.
Among 90 HIV patients, 80 met the study criteria for LTBI, fifty-nine (73.7%) patients were TST positive, 21 (26.2%) were negative, whereas 75 patients (93.7%) were IGRA positive, and five (6.2%) were negative. TST showed poor agreement with the diagnosis of LTBI (Kappa: 0.384), while IGRA demonstrated good agreement (Kappa: 0.769). Among 69 patients with high risk and 21 with low risk for LTBI, TST was positive in 48 (69.5%) and 11 (52.4%), while IGRA was positive in 68 (98.5%) and 7 (33.3%) patients, respectively. There were no association between TST and the level of risk (P = 0,191). Conversely, we observed a strong association between the IGRA and risk for LTBI (p |
doi_str_mv | 10.1186/s12879-018-3508-8 |
format | article |
fullrecord | <record><control><sourceid>proquest_doaj_</sourceid><recordid>TN_cdi_doaj_primary_oai_doaj_org_article_eae8a9c7bc7845c1bf5efd30ac222f51</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_eae8a9c7bc7845c1bf5efd30ac222f51</doaj_id><sourcerecordid>2136068841</sourcerecordid><originalsourceid>FETCH-LOGICAL-c465t-261bcec7519a5975e45e3d6414f52c28ee3a90fa695656572f6329cd0b2efa233</originalsourceid><addsrcrecordid>eNpVkktuFDEQhlsIRELgAGyQl2wa_Gi7bRZIKAIyUiQ2wNaqdpcnjnrag-1ONEfgPLlHzoQnE6JEluySXfXVw3_TvGX0A2NafcyM6960lOlWSKpb_aw5Zl3PWi5E9_yRfdS8yvmSUtZrbl42R4J2Uhgqjpu_q7lg8pji3N7ekIQTQkYCOcOu7gRIxjmHEq6QjAHWc8wlOFJinEj0ZIKCcyFlGTC5ZYo5ZBJmj66EOFeLbKGE6pHJdSgX5Gz1-1NFuhRzbvPBCyaSyzLuXjcvPEwZ39yfJ82vb19_np615z--r06_nLeuU7K0XLHBoeslMyBNL7GTKEbVsc5L7rhGFGCoB2WkqqvnXglu3EgHjh7qME6a1YE7Rri02xQ2kHY2QrB3FzGtLaTa44QWATUY1w-u1510bPAS_SgoOM65l6yyPh9Y22XY4OhqpwmmJ9CnL3O4sOt4ZRXvpDJ9Bby_B6T4Z8Fc7CZkh9MEM8YlW86Eokrrbp-LHVzvppfQP6Rh1O7lYA9ysFUOdi8Hq2vMu8f1PUT8_3_xDzi5tRk</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2136068841</pqid></control><display><type>article</type><title>Interferon-γ release assay as a sensitive diagnostic tool of latent tuberculosis infection in patients with HIV: a cross-sectional study</title><source>Open Access: PubMed Central</source><source>Publicly Available Content Database (Proquest) (PQ_SDU_P3)</source><creator>Klautau, Giselle Burlamaqui ; da Mota, Nadijane Valéria Ferreira ; Salles, Mauro José Costa ; Burattini, Marcelo Nascimento ; Rodrigues, Denise Silva</creator><creatorcontrib>Klautau, Giselle Burlamaqui ; da Mota, Nadijane Valéria Ferreira ; Salles, Mauro José Costa ; Burattini, Marcelo Nascimento ; Rodrigues, Denise Silva</creatorcontrib><description>In developing countries, tuberculosis (TB) is a major public health problem and the leading cause of death among patients with HIV (Human Immunodeficiency Virus). Until 2001, the tuberculin skin test (TST) was the only available tool for the diagnosis of latent tuberculosis infection (LTBI), but false-negative TST results are frequently reported. Recently, the interferon-γ (IFN-γ) release assay (IGRA) has gained ground because it can detect the IFN-γ secreted by circulating lymphocytes T cells when stimulated by specific TB antigens. However, the role of IGRA in the diagnosis of LTBI in HIV-infected patients has not been well established.
This cross-sectional study compared the accuracy of TST (performed by the Mantoux method) and IGRA (QuantiFERON-TB Gold In-Tube, Cellestis, Carnegie, Australia) on the diagnosis of LTBI among patients with HIV. LTBI is defined by LTBI risk and at least one positive test (TST or IGRA), without clinical evidence of active TB. We also assessed the accuracy of TST and IGRA among HIV patients with high and low risk for LTBI.
Among 90 HIV patients, 80 met the study criteria for LTBI, fifty-nine (73.7%) patients were TST positive, 21 (26.2%) were negative, whereas 75 patients (93.7%) were IGRA positive, and five (6.2%) were negative. TST showed poor agreement with the diagnosis of LTBI (Kappa: 0.384), while IGRA demonstrated good agreement (Kappa: 0.769). Among 69 patients with high risk and 21 with low risk for LTBI, TST was positive in 48 (69.5%) and 11 (52.4%), while IGRA was positive in 68 (98.5%) and 7 (33.3%) patients, respectively. There were no association between TST and the level of risk (P = 0,191). Conversely, we observed a strong association between the IGRA and risk for LTBI (p < 0.001).
Compared to TST, IGRA positivity is consistent with the risk of TB infection and seems to be a better diagnostic tool for LTBI in HIV-infected patients.</description><identifier>ISSN: 1471-2334</identifier><identifier>EISSN: 1471-2334</identifier><identifier>DOI: 10.1186/s12879-018-3508-8</identifier><identifier>PMID: 30453903</identifier><language>eng</language><publisher>England: BioMed Central</publisher><subject>Adult ; AIDS ; AIDS-Related Opportunistic Infections - blood ; AIDS-Related Opportunistic Infections - diagnosis ; AIDS-Related Opportunistic Infections - epidemiology ; Brazil - epidemiology ; Cross-Sectional Studies ; Female ; HIV ; HIV Infections - blood ; HIV Infections - complications ; HIV Infections - epidemiology ; Humans ; Interferon-gamma - blood ; Interferon-gamma Release Tests - methods ; Interferon-γ release assay ; Latent Tuberculosis - blood ; Latent Tuberculosis - complications ; Latent Tuberculosis - diagnosis ; Latent Tuberculosis - epidemiology ; Latent tuberculosis infection ; Male ; Middle Aged ; Predictive Value of Tests ; Sensitivity and Specificity ; Tuberculin skin testing ; Tuberculin Test - methods</subject><ispartof>BMC infectious diseases, 2018-11, Vol.18 (1), p.585-585, Article 585</ispartof><rights>The Author(s). 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c465t-261bcec7519a5975e45e3d6414f52c28ee3a90fa695656572f6329cd0b2efa233</citedby><cites>FETCH-LOGICAL-c465t-261bcec7519a5975e45e3d6414f52c28ee3a90fa695656572f6329cd0b2efa233</cites><orcidid>0000-0002-5443-6024</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/PMC6245697/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6245697/$$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/30453903$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Klautau, Giselle Burlamaqui</creatorcontrib><creatorcontrib>da Mota, Nadijane Valéria Ferreira</creatorcontrib><creatorcontrib>Salles, Mauro José Costa</creatorcontrib><creatorcontrib>Burattini, Marcelo Nascimento</creatorcontrib><creatorcontrib>Rodrigues, Denise Silva</creatorcontrib><title>Interferon-γ release assay as a sensitive diagnostic tool of latent tuberculosis infection in patients with HIV: a cross-sectional study</title><title>BMC infectious diseases</title><addtitle>BMC Infect Dis</addtitle><description>In developing countries, tuberculosis (TB) is a major public health problem and the leading cause of death among patients with HIV (Human Immunodeficiency Virus). Until 2001, the tuberculin skin test (TST) was the only available tool for the diagnosis of latent tuberculosis infection (LTBI), but false-negative TST results are frequently reported. Recently, the interferon-γ (IFN-γ) release assay (IGRA) has gained ground because it can detect the IFN-γ secreted by circulating lymphocytes T cells when stimulated by specific TB antigens. However, the role of IGRA in the diagnosis of LTBI in HIV-infected patients has not been well established.
This cross-sectional study compared the accuracy of TST (performed by the Mantoux method) and IGRA (QuantiFERON-TB Gold In-Tube, Cellestis, Carnegie, Australia) on the diagnosis of LTBI among patients with HIV. LTBI is defined by LTBI risk and at least one positive test (TST or IGRA), without clinical evidence of active TB. We also assessed the accuracy of TST and IGRA among HIV patients with high and low risk for LTBI.
Among 90 HIV patients, 80 met the study criteria for LTBI, fifty-nine (73.7%) patients were TST positive, 21 (26.2%) were negative, whereas 75 patients (93.7%) were IGRA positive, and five (6.2%) were negative. TST showed poor agreement with the diagnosis of LTBI (Kappa: 0.384), while IGRA demonstrated good agreement (Kappa: 0.769). Among 69 patients with high risk and 21 with low risk for LTBI, TST was positive in 48 (69.5%) and 11 (52.4%), while IGRA was positive in 68 (98.5%) and 7 (33.3%) patients, respectively. There were no association between TST and the level of risk (P = 0,191). Conversely, we observed a strong association between the IGRA and risk for LTBI (p < 0.001).
Compared to TST, IGRA positivity is consistent with the risk of TB infection and seems to be a better diagnostic tool for LTBI in HIV-infected patients.</description><subject>Adult</subject><subject>AIDS</subject><subject>AIDS-Related Opportunistic Infections - blood</subject><subject>AIDS-Related Opportunistic Infections - diagnosis</subject><subject>AIDS-Related Opportunistic Infections - epidemiology</subject><subject>Brazil - epidemiology</subject><subject>Cross-Sectional Studies</subject><subject>Female</subject><subject>HIV</subject><subject>HIV Infections - blood</subject><subject>HIV Infections - complications</subject><subject>HIV Infections - epidemiology</subject><subject>Humans</subject><subject>Interferon-gamma - blood</subject><subject>Interferon-gamma Release Tests - methods</subject><subject>Interferon-γ release assay</subject><subject>Latent Tuberculosis - blood</subject><subject>Latent Tuberculosis - complications</subject><subject>Latent Tuberculosis - diagnosis</subject><subject>Latent Tuberculosis - epidemiology</subject><subject>Latent tuberculosis infection</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Predictive Value of Tests</subject><subject>Sensitivity and Specificity</subject><subject>Tuberculin skin testing</subject><subject>Tuberculin Test - methods</subject><issn>1471-2334</issn><issn>1471-2334</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>DOA</sourceid><recordid>eNpVkktuFDEQhlsIRELgAGyQl2wa_Gi7bRZIKAIyUiQ2wNaqdpcnjnrag-1ONEfgPLlHzoQnE6JEluySXfXVw3_TvGX0A2NafcyM6960lOlWSKpb_aw5Zl3PWi5E9_yRfdS8yvmSUtZrbl42R4J2Uhgqjpu_q7lg8pji3N7ekIQTQkYCOcOu7gRIxjmHEq6QjAHWc8wlOFJinEj0ZIKCcyFlGTC5ZYo5ZBJmj66EOFeLbKGE6pHJdSgX5Gz1-1NFuhRzbvPBCyaSyzLuXjcvPEwZ39yfJ82vb19_np615z--r06_nLeuU7K0XLHBoeslMyBNL7GTKEbVsc5L7rhGFGCoB2WkqqvnXglu3EgHjh7qME6a1YE7Rri02xQ2kHY2QrB3FzGtLaTa44QWATUY1w-u1510bPAS_SgoOM65l6yyPh9Y22XY4OhqpwmmJ9CnL3O4sOt4ZRXvpDJ9Bby_B6T4Z8Fc7CZkh9MEM8YlW86Eokrrbp-LHVzvppfQP6Rh1O7lYA9ysFUOdi8Hq2vMu8f1PUT8_3_xDzi5tRk</recordid><startdate>20181119</startdate><enddate>20181119</enddate><creator>Klautau, Giselle Burlamaqui</creator><creator>da Mota, Nadijane Valéria Ferreira</creator><creator>Salles, Mauro José Costa</creator><creator>Burattini, Marcelo Nascimento</creator><creator>Rodrigues, Denise Silva</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/0000-0002-5443-6024</orcidid></search><sort><creationdate>20181119</creationdate><title>Interferon-γ release assay as a sensitive diagnostic tool of latent tuberculosis infection in patients with HIV: a cross-sectional study</title><author>Klautau, Giselle Burlamaqui ; da Mota, Nadijane Valéria Ferreira ; Salles, Mauro José Costa ; Burattini, Marcelo Nascimento ; Rodrigues, Denise Silva</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c465t-261bcec7519a5975e45e3d6414f52c28ee3a90fa695656572f6329cd0b2efa233</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adult</topic><topic>AIDS</topic><topic>AIDS-Related Opportunistic Infections - blood</topic><topic>AIDS-Related Opportunistic Infections - diagnosis</topic><topic>AIDS-Related Opportunistic Infections - epidemiology</topic><topic>Brazil - epidemiology</topic><topic>Cross-Sectional Studies</topic><topic>Female</topic><topic>HIV</topic><topic>HIV Infections - blood</topic><topic>HIV Infections - complications</topic><topic>HIV Infections - epidemiology</topic><topic>Humans</topic><topic>Interferon-gamma - blood</topic><topic>Interferon-gamma Release Tests - methods</topic><topic>Interferon-γ release assay</topic><topic>Latent Tuberculosis - blood</topic><topic>Latent Tuberculosis - complications</topic><topic>Latent Tuberculosis - diagnosis</topic><topic>Latent Tuberculosis - epidemiology</topic><topic>Latent tuberculosis infection</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Predictive Value of Tests</topic><topic>Sensitivity and Specificity</topic><topic>Tuberculin skin testing</topic><topic>Tuberculin Test - methods</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Klautau, Giselle Burlamaqui</creatorcontrib><creatorcontrib>da Mota, Nadijane Valéria Ferreira</creatorcontrib><creatorcontrib>Salles, Mauro José Costa</creatorcontrib><creatorcontrib>Burattini, Marcelo Nascimento</creatorcontrib><creatorcontrib>Rodrigues, Denise Silva</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>DOAJ Directory of Open Access Journals</collection><jtitle>BMC infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Klautau, Giselle Burlamaqui</au><au>da Mota, Nadijane Valéria Ferreira</au><au>Salles, Mauro José Costa</au><au>Burattini, Marcelo Nascimento</au><au>Rodrigues, Denise Silva</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Interferon-γ release assay as a sensitive diagnostic tool of latent tuberculosis infection in patients with HIV: a cross-sectional study</atitle><jtitle>BMC infectious diseases</jtitle><addtitle>BMC Infect Dis</addtitle><date>2018-11-19</date><risdate>2018</risdate><volume>18</volume><issue>1</issue><spage>585</spage><epage>585</epage><pages>585-585</pages><artnum>585</artnum><issn>1471-2334</issn><eissn>1471-2334</eissn><abstract>In developing countries, tuberculosis (TB) is a major public health problem and the leading cause of death among patients with HIV (Human Immunodeficiency Virus). Until 2001, the tuberculin skin test (TST) was the only available tool for the diagnosis of latent tuberculosis infection (LTBI), but false-negative TST results are frequently reported. Recently, the interferon-γ (IFN-γ) release assay (IGRA) has gained ground because it can detect the IFN-γ secreted by circulating lymphocytes T cells when stimulated by specific TB antigens. However, the role of IGRA in the diagnosis of LTBI in HIV-infected patients has not been well established.
This cross-sectional study compared the accuracy of TST (performed by the Mantoux method) and IGRA (QuantiFERON-TB Gold In-Tube, Cellestis, Carnegie, Australia) on the diagnosis of LTBI among patients with HIV. LTBI is defined by LTBI risk and at least one positive test (TST or IGRA), without clinical evidence of active TB. We also assessed the accuracy of TST and IGRA among HIV patients with high and low risk for LTBI.
Among 90 HIV patients, 80 met the study criteria for LTBI, fifty-nine (73.7%) patients were TST positive, 21 (26.2%) were negative, whereas 75 patients (93.7%) were IGRA positive, and five (6.2%) were negative. TST showed poor agreement with the diagnosis of LTBI (Kappa: 0.384), while IGRA demonstrated good agreement (Kappa: 0.769). Among 69 patients with high risk and 21 with low risk for LTBI, TST was positive in 48 (69.5%) and 11 (52.4%), while IGRA was positive in 68 (98.5%) and 7 (33.3%) patients, respectively. There were no association between TST and the level of risk (P = 0,191). Conversely, we observed a strong association between the IGRA and risk for LTBI (p < 0.001).
Compared to TST, IGRA positivity is consistent with the risk of TB infection and seems to be a better diagnostic tool for LTBI in HIV-infected patients.</abstract><cop>England</cop><pub>BioMed Central</pub><pmid>30453903</pmid><doi>10.1186/s12879-018-3508-8</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-5443-6024</orcidid><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1471-2334 |
ispartof | BMC infectious diseases, 2018-11, Vol.18 (1), p.585-585, Article 585 |
issn | 1471-2334 1471-2334 |
language | eng |
recordid | cdi_doaj_primary_oai_doaj_org_article_eae8a9c7bc7845c1bf5efd30ac222f51 |
source | Open Access: PubMed Central; Publicly Available Content Database (Proquest) (PQ_SDU_P3) |
subjects | Adult AIDS AIDS-Related Opportunistic Infections - blood AIDS-Related Opportunistic Infections - diagnosis AIDS-Related Opportunistic Infections - epidemiology Brazil - epidemiology Cross-Sectional Studies Female HIV HIV Infections - blood HIV Infections - complications HIV Infections - epidemiology Humans Interferon-gamma - blood Interferon-gamma Release Tests - methods Interferon-γ release assay Latent Tuberculosis - blood Latent Tuberculosis - complications Latent Tuberculosis - diagnosis Latent Tuberculosis - epidemiology Latent tuberculosis infection Male Middle Aged Predictive Value of Tests Sensitivity and Specificity Tuberculin skin testing Tuberculin Test - methods |
title | Interferon-γ release assay as a sensitive diagnostic tool of latent tuberculosis infection in patients with HIV: a cross-sectional study |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-27T09%3A01%3A17IST&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=Interferon-%CE%B3%20release%20assay%20as%20a%20sensitive%20diagnostic%20tool%20of%20latent%20tuberculosis%20infection%20in%20patients%20with%20HIV:%20a%20cross-sectional%20study&rft.jtitle=BMC%20infectious%20diseases&rft.au=Klautau,%20Giselle%20Burlamaqui&rft.date=2018-11-19&rft.volume=18&rft.issue=1&rft.spage=585&rft.epage=585&rft.pages=585-585&rft.artnum=585&rft.issn=1471-2334&rft.eissn=1471-2334&rft_id=info:doi/10.1186/s12879-018-3508-8&rft_dat=%3Cproquest_doaj_%3E2136068841%3C/proquest_doaj_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c465t-261bcec7519a5975e45e3d6414f52c28ee3a90fa695656572f6329cd0b2efa233%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2136068841&rft_id=info:pmid/30453903&rfr_iscdi=true |