Liver-related events and mortality among elderly patients with advanced chronic hepatitis C treated with direct-acting antivirals
Direct-acting antivirals (DAAs) are effective in patients aged ≥65 years. However, little is known about the effects of DAAs on survival, liver decompensation and development of hepatocellular carcinoma (HCC). To compare the incidence of liver-related events and mortality between patients aged ≥65 a...
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| Veröffentlicht in: | PloS one 2019-06, Vol.14 (6), p.e0217052-e0217052 |
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| creator | Rodríguez-Osorio, Iria Mena, Alvaro Meijide, Héctor Morano, Luis Delgado, Manuel Cid, Purificación Margusino, Luis Pedreira, José Domingo Castro, Ángeles |
| description | Direct-acting antivirals (DAAs) are effective in patients aged ≥65 years. However, little is known about the effects of DAAs on survival, liver decompensation and development of hepatocellular carcinoma (HCC).
To compare the incidence of liver-related events and mortality between patients aged ≥65 and |
| doi_str_mv | 10.1371/journal.pone.0217052 |
| format | Article |
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To compare the incidence of liver-related events and mortality between patients aged ≥65 and <65 years.
Prospective study comparing patients aged ≥65 and <65 years treated with DAAs. The incidence of liver-related events and mortality, and HCC was compared between age groups.
Five hundred patients (120 aged ≥65 and 380 aged <65 years) were included. The incidence of liver-related events was 2.62 per 100 patient-years (py) in older and 1.41/100 py in younger patients. All-cause mortality was 3.89 and 1.27/100 py in older and younger patients, respectively. The respective liver-related mortality rates were 1.12 and 0.31/100 py. In patients with cirrhosis (stage F4), all-cause mortality (P = 0.283) and liver-related mortality (P = 0.254) did not differ between groups. All five liver-related deaths were related to multifocal HCC. The incidence of HCC was 1.91 and 1.43 per 100 py in the older and younger groups, respectively (P = 0.747). The diagnosis of HCC was 8 months after the end of treatment.
The incidence of liver-related events and liver-related mortality was low in older people treated with DAAs and was similar to that in younger patients. The extra mortality in people aged ≥65 years treated with DAAs seems to be secondary to non-liver-related causes. These results support the utilization of DAAs in patients aged ≥65 years.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0217052</identifier><identifier>PMID: 31158237</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Aged ; Antiviral agents ; Antiviral Agents - pharmacology ; Antiviral Agents - therapeutic use ; Antiviral drugs ; Biology and Life Sciences ; Cancer ; Carcinogenesis ; Carcinoma ; Carcinoma, Hepatocellular - complications ; Carcinoma, Hepatocellular - pathology ; Cirrhosis ; Complications and side effects ; Cost analysis ; Development and progression ; Drug therapy ; Elderly patients ; Epidemiology ; Female ; Geriatrics ; Health aspects ; Hepatitis ; Hepatitis C ; Hepatitis C, Chronic - complications ; Hepatitis C, Chronic - drug therapy ; Hepatitis C, Chronic - mortality ; Hepatocellular carcinoma ; Hepatology ; Humans ; Incidence ; Infections ; Interferon ; Liver ; Liver - drug effects ; Liver - pathology ; Liver cancer ; Liver cirrhosis ; Liver Neoplasms - complications ; Liver Neoplasms - pathology ; Liver transplants ; Male ; Medical research ; Medicine and Health Sciences ; Middle Aged ; Mortality ; Older people ; Patient outcomes ; Patients ; People and Places ; Studies ; Transplants & implants</subject><ispartof>PloS one, 2019-06, Vol.14 (6), p.e0217052-e0217052</ispartof><rights>COPYRIGHT 2019 Public Library of Science</rights><rights>2019 Rodríguez-Osorio et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2019 Rodríguez-Osorio et al 2019 Rodríguez-Osorio et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-1aa1722ce588ab80d2902169ef22f3022f7eacf13f157abbb569bd620194a24b3</citedby><cites>FETCH-LOGICAL-c692t-1aa1722ce588ab80d2902169ef22f3022f7eacf13f157abbb569bd620194a24b3</cites><orcidid>0000-0002-9165-6798 ; 0000-0002-0560-3260 ; 0000-0003-4309-1662</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/PMC6546209/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6546209/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53770,53772,79347,79348</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31158237$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Bonino, Ferruccio</contributor><creatorcontrib>Rodríguez-Osorio, Iria</creatorcontrib><creatorcontrib>Mena, Alvaro</creatorcontrib><creatorcontrib>Meijide, Héctor</creatorcontrib><creatorcontrib>Morano, Luis</creatorcontrib><creatorcontrib>Delgado, Manuel</creatorcontrib><creatorcontrib>Cid, Purificación</creatorcontrib><creatorcontrib>Margusino, Luis</creatorcontrib><creatorcontrib>Pedreira, José Domingo</creatorcontrib><creatorcontrib>Castro, Ángeles</creatorcontrib><title>Liver-related events and mortality among elderly patients with advanced chronic hepatitis C treated with direct-acting antivirals</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Direct-acting antivirals (DAAs) are effective in patients aged ≥65 years. However, little is known about the effects of DAAs on survival, liver decompensation and development of hepatocellular carcinoma (HCC).
To compare the incidence of liver-related events and mortality between patients aged ≥65 and <65 years.
Prospective study comparing patients aged ≥65 and <65 years treated with DAAs. The incidence of liver-related events and mortality, and HCC was compared between age groups.
Five hundred patients (120 aged ≥65 and 380 aged <65 years) were included. The incidence of liver-related events was 2.62 per 100 patient-years (py) in older and 1.41/100 py in younger patients. All-cause mortality was 3.89 and 1.27/100 py in older and younger patients, respectively. The respective liver-related mortality rates were 1.12 and 0.31/100 py. In patients with cirrhosis (stage F4), all-cause mortality (P = 0.283) and liver-related mortality (P = 0.254) did not differ between groups. All five liver-related deaths were related to multifocal HCC. The incidence of HCC was 1.91 and 1.43 per 100 py in the older and younger groups, respectively (P = 0.747). The diagnosis of HCC was 8 months after the end of treatment.
The incidence of liver-related events and liver-related mortality was low in older people treated with DAAs and was similar to that in younger patients. The extra mortality in people aged ≥65 years treated with DAAs seems to be secondary to non-liver-related causes. These results support the utilization of DAAs in patients aged ≥65 years.</description><subject>Aged</subject><subject>Antiviral agents</subject><subject>Antiviral Agents - pharmacology</subject><subject>Antiviral Agents - therapeutic use</subject><subject>Antiviral drugs</subject><subject>Biology and Life Sciences</subject><subject>Cancer</subject><subject>Carcinogenesis</subject><subject>Carcinoma</subject><subject>Carcinoma, Hepatocellular - complications</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>Cirrhosis</subject><subject>Complications and side effects</subject><subject>Cost analysis</subject><subject>Development and progression</subject><subject>Drug therapy</subject><subject>Elderly patients</subject><subject>Epidemiology</subject><subject>Female</subject><subject>Geriatrics</subject><subject>Health aspects</subject><subject>Hepatitis</subject><subject>Hepatitis C</subject><subject>Hepatitis C, Chronic - complications</subject><subject>Hepatitis C, Chronic - drug therapy</subject><subject>Hepatitis C, Chronic - mortality</subject><subject>Hepatocellular carcinoma</subject><subject>Hepatology</subject><subject>Humans</subject><subject>Incidence</subject><subject>Infections</subject><subject>Interferon</subject><subject>Liver</subject><subject>Liver - drug effects</subject><subject>Liver - pathology</subject><subject>Liver cancer</subject><subject>Liver cirrhosis</subject><subject>Liver Neoplasms - complications</subject><subject>Liver Neoplasms - pathology</subject><subject>Liver transplants</subject><subject>Male</subject><subject>Medical research</subject><subject>Medicine and Health Sciences</subject><subject>Middle Aged</subject><subject>Mortality</subject><subject>Older people</subject><subject>Patient outcomes</subject><subject>Patients</subject><subject>People and Places</subject><subject>Studies</subject><subject>Transplants & implants</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk1uL1DAYhoso7jr6D0QLguhFxyZpergRlsHDwMCCp9vwJU2nWTLJmKSjc-k_NzPTXaayFxJoQvq873dovyR5jvI5IhV6d2MHZ0DPt9bIeY5RlVP8ILlEDcFZiXPy8Ox8kTzx_ibPKanL8nFyQRCiNSbVZfJnpXbSZU5qCLJN5U6a4FMwbbqxLoBWYZ_Cxpp1KnUrnd6nWwjqCP1SoU-h3YERUSl6Z40SaS8PQFA-XaTByaPrkWyVkyJkIIKKbmCC2ikH2j9NHnVxk8_GfZZ8__jh2-Jztrr-tFxcrTJRNjhkCABVGAtJ6xp4nbe4iUWXjeww7kgeH5UE0SHSIVoB55yWDW9j8agpABeczJKXJ9-ttp6N3fMMY1IUtCkoisTyRLQWbtjWqQ24PbOg2PHCujUDF5TQkqGiqQjHiNcNFDkRNeZc1LziTU0FjwnNkvdjtIFvZCtix2KxE9PpG6N6trY7VtIiJt1EgzejgbM_B-kD2ygvpNZgpB2OedO8JCWqIvrqH_T-6kZqDbEAZTob44qDKbuidRWDxhWp-T1UXK3cKBF_tU7F-4ng7UQQmSB_hzUM3rPl1y__z17_mLKvz9hegg69t3oIyho_BYsTKJz13snurskoZ4dJue0GO0wKGyclyl6cf6A70e1okL9UsA-6</recordid><startdate>20190603</startdate><enddate>20190603</enddate><creator>Rodríguez-Osorio, Iria</creator><creator>Mena, Alvaro</creator><creator>Meijide, Héctor</creator><creator>Morano, Luis</creator><creator>Delgado, Manuel</creator><creator>Cid, Purificación</creator><creator>Margusino, Luis</creator><creator>Pedreira, José Domingo</creator><creator>Castro, Ángeles</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-9165-6798</orcidid><orcidid>https://orcid.org/0000-0002-0560-3260</orcidid><orcidid>https://orcid.org/0000-0003-4309-1662</orcidid></search><sort><creationdate>20190603</creationdate><title>Liver-related events and mortality among elderly patients with advanced chronic hepatitis C treated with direct-acting antivirals</title><author>Rodríguez-Osorio, Iria ; Mena, Alvaro ; Meijide, Héctor ; Morano, Luis ; Delgado, Manuel ; Cid, Purificación ; Margusino, Luis ; Pedreira, José Domingo ; Castro, Ángeles</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-1aa1722ce588ab80d2902169ef22f3022f7eacf13f157abbb569bd620194a24b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Aged</topic><topic>Antiviral agents</topic><topic>Antiviral Agents - pharmacology</topic><topic>Antiviral Agents - therapeutic use</topic><topic>Antiviral drugs</topic><topic>Biology and Life Sciences</topic><topic>Cancer</topic><topic>Carcinogenesis</topic><topic>Carcinoma</topic><topic>Carcinoma, Hepatocellular - complications</topic><topic>Carcinoma, Hepatocellular - pathology</topic><topic>Cirrhosis</topic><topic>Complications and side effects</topic><topic>Cost analysis</topic><topic>Development and progression</topic><topic>Drug therapy</topic><topic>Elderly patients</topic><topic>Epidemiology</topic><topic>Female</topic><topic>Geriatrics</topic><topic>Health aspects</topic><topic>Hepatitis</topic><topic>Hepatitis C</topic><topic>Hepatitis C, Chronic - complications</topic><topic>Hepatitis C, Chronic - drug therapy</topic><topic>Hepatitis C, Chronic - mortality</topic><topic>Hepatocellular carcinoma</topic><topic>Hepatology</topic><topic>Humans</topic><topic>Incidence</topic><topic>Infections</topic><topic>Interferon</topic><topic>Liver</topic><topic>Liver - drug effects</topic><topic>Liver - pathology</topic><topic>Liver cancer</topic><topic>Liver cirrhosis</topic><topic>Liver Neoplasms - complications</topic><topic>Liver Neoplasms - pathology</topic><topic>Liver transplants</topic><topic>Male</topic><topic>Medical research</topic><topic>Medicine and Health Sciences</topic><topic>Middle Aged</topic><topic>Mortality</topic><topic>Older people</topic><topic>Patient outcomes</topic><topic>Patients</topic><topic>People and Places</topic><topic>Studies</topic><topic>Transplants & implants</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rodríguez-Osorio, Iria</creatorcontrib><creatorcontrib>Mena, Alvaro</creatorcontrib><creatorcontrib>Meijide, Héctor</creatorcontrib><creatorcontrib>Morano, Luis</creatorcontrib><creatorcontrib>Delgado, Manuel</creatorcontrib><creatorcontrib>Cid, Purificación</creatorcontrib><creatorcontrib>Margusino, Luis</creatorcontrib><creatorcontrib>Pedreira, José Domingo</creatorcontrib><creatorcontrib>Castro, Ángeles</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Opposing Viewpoints Resource Center</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>ProQuest Nursing and Allied Health Journals</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</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>ProQuest Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Database (1962 - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rodríguez-Osorio, Iria</au><au>Mena, Alvaro</au><au>Meijide, Héctor</au><au>Morano, Luis</au><au>Delgado, Manuel</au><au>Cid, Purificación</au><au>Margusino, Luis</au><au>Pedreira, José Domingo</au><au>Castro, Ángeles</au><au>Bonino, Ferruccio</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Liver-related events and mortality among elderly patients with advanced chronic hepatitis C treated with direct-acting antivirals</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2019-06-03</date><risdate>2019</risdate><volume>14</volume><issue>6</issue><spage>e0217052</spage><epage>e0217052</epage><pages>e0217052-e0217052</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Direct-acting antivirals (DAAs) are effective in patients aged ≥65 years. However, little is known about the effects of DAAs on survival, liver decompensation and development of hepatocellular carcinoma (HCC).
To compare the incidence of liver-related events and mortality between patients aged ≥65 and <65 years.
Prospective study comparing patients aged ≥65 and <65 years treated with DAAs. The incidence of liver-related events and mortality, and HCC was compared between age groups.
Five hundred patients (120 aged ≥65 and 380 aged <65 years) were included. The incidence of liver-related events was 2.62 per 100 patient-years (py) in older and 1.41/100 py in younger patients. All-cause mortality was 3.89 and 1.27/100 py in older and younger patients, respectively. The respective liver-related mortality rates were 1.12 and 0.31/100 py. In patients with cirrhosis (stage F4), all-cause mortality (P = 0.283) and liver-related mortality (P = 0.254) did not differ between groups. All five liver-related deaths were related to multifocal HCC. The incidence of HCC was 1.91 and 1.43 per 100 py in the older and younger groups, respectively (P = 0.747). The diagnosis of HCC was 8 months after the end of treatment.
The incidence of liver-related events and liver-related mortality was low in older people treated with DAAs and was similar to that in younger patients. The extra mortality in people aged ≥65 years treated with DAAs seems to be secondary to non-liver-related causes. These results support the utilization of DAAs in patients aged ≥65 years.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>31158237</pmid><doi>10.1371/journal.pone.0217052</doi><tpages>e0217052</tpages><orcidid>https://orcid.org/0000-0002-9165-6798</orcidid><orcidid>https://orcid.org/0000-0002-0560-3260</orcidid><orcidid>https://orcid.org/0000-0003-4309-1662</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | PloS one, 2019-06, Vol.14 (6), p.e0217052-e0217052 |
| issn | 1932-6203 1932-6203 |
| language | eng |
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| source | PubMed (Medline); MEDLINE; Public Library of Science; DOAJ Directory of Open Access Journals; Free Full-Text Journals in Chemistry; EZB Electronic Journals Library |
| subjects | Aged Antiviral agents Antiviral Agents - pharmacology Antiviral Agents - therapeutic use Antiviral drugs Biology and Life Sciences Cancer Carcinogenesis Carcinoma Carcinoma, Hepatocellular - complications Carcinoma, Hepatocellular - pathology Cirrhosis Complications and side effects Cost analysis Development and progression Drug therapy Elderly patients Epidemiology Female Geriatrics Health aspects Hepatitis Hepatitis C Hepatitis C, Chronic - complications Hepatitis C, Chronic - drug therapy Hepatitis C, Chronic - mortality Hepatocellular carcinoma Hepatology Humans Incidence Infections Interferon Liver Liver - drug effects Liver - pathology Liver cancer Liver cirrhosis Liver Neoplasms - complications Liver Neoplasms - pathology Liver transplants Male Medical research Medicine and Health Sciences Middle Aged Mortality Older people Patient outcomes Patients People and Places Studies Transplants & implants |
| title | Liver-related events and mortality among elderly patients with advanced chronic hepatitis C treated with direct-acting antivirals |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-22T19%3A53%3A16IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Liver-related%20events%20and%20mortality%20among%20elderly%20patients%20with%20advanced%20chronic%20hepatitis%20C%20treated%20with%20direct-acting%20antivirals&rft.jtitle=PloS%20one&rft.au=Rodr%C3%ADguez-Osorio,%20Iria&rft.date=2019-06-03&rft.volume=14&rft.issue=6&rft.spage=e0217052&rft.epage=e0217052&rft.pages=e0217052-e0217052&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0217052&rft_dat=%3Cgale_plos_%3EA587620202%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2234459451&rft_id=info:pmid/31158237&rft_galeid=A587620202&rft_doaj_id=oai_doaj_org_article_14973b21b89a403c82bbc8b7b985cb2f&rfr_iscdi=true |