Cost-Effectiveness Analysis of Different Genetic Testing Strategies for Lynch Syndrome in Taiwan
Patients with Lynch syndrome (LS) have a significantly increased risk of developing colorectal cancer (CRC) and other cancers. Genetic screening for LS among patients with newly diagnosed CRC aims to identify mutations in the disease-causing genes (i.e., the DNA mismatch repair genes) in the patient...
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| description | Patients with Lynch syndrome (LS) have a significantly increased risk of developing colorectal cancer (CRC) and other cancers. Genetic screening for LS among patients with newly diagnosed CRC aims to identify mutations in the disease-causing genes (i.e., the DNA mismatch repair genes) in the patients, to offer genetic testing for relatives of the patients with the mutations, and then to provide early prevention for the relatives with the mutations. Several genetic tests are available for LS, such as DNA sequencing for MMR genes and tumor testing using microsatellite instability and immunohistochemical analyses. Cost-effectiveness analyses of different genetic testing strategies for LS have been performed in several studies from different countries such as the US and Germany. However, a cost-effectiveness analysis for the testing has not yet been performed in Taiwan. In this study, we evaluated the cost-effectiveness of four genetic testing strategies for LS described in previous studies, while population-specific parameters, such as the mutation rates of the DNA mismatch repair genes and treatment costs for CRC in Taiwan, were used. The incremental cost-effectiveness ratios based on discounted life years gained due to genetic screening were calculated for the strategies relative to no screening and to the previous strategy. Using the World Health Organization standard, which was defined based on Taiwan's Gross Domestic Product per capita, the strategy based on immunohistochemistry as a genetic test followed by BRAF mutation testing was considered to be highly cost-effective relative to no screening. Our probabilistic sensitivity analysis results also suggest that the strategy has a probability of 0.939 of being cost-effective relative to no screening based on the commonly used threshold of $50,000 to determine cost-effectiveness. To the best of our knowledge, this is the first cost-effectiveness analysis for evaluating different genetic testing strategies for LS in Taiwan. The results will be informative for the government when considering offering screening for LS in patients newly diagnosed with CRC. |
| doi_str_mv | 10.1371/journal.pone.0160599 |
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Genetic screening for LS among patients with newly diagnosed CRC aims to identify mutations in the disease-causing genes (i.e., the DNA mismatch repair genes) in the patients, to offer genetic testing for relatives of the patients with the mutations, and then to provide early prevention for the relatives with the mutations. Several genetic tests are available for LS, such as DNA sequencing for MMR genes and tumor testing using microsatellite instability and immunohistochemical analyses. Cost-effectiveness analyses of different genetic testing strategies for LS have been performed in several studies from different countries such as the US and Germany. However, a cost-effectiveness analysis for the testing has not yet been performed in Taiwan. In this study, we evaluated the cost-effectiveness of four genetic testing strategies for LS described in previous studies, while population-specific parameters, such as the mutation rates of the DNA mismatch repair genes and treatment costs for CRC in Taiwan, were used. The incremental cost-effectiveness ratios based on discounted life years gained due to genetic screening were calculated for the strategies relative to no screening and to the previous strategy. Using the World Health Organization standard, which was defined based on Taiwan's Gross Domestic Product per capita, the strategy based on immunohistochemistry as a genetic test followed by BRAF mutation testing was considered to be highly cost-effective relative to no screening. Our probabilistic sensitivity analysis results also suggest that the strategy has a probability of 0.939 of being cost-effective relative to no screening based on the commonly used threshold of $50,000 to determine cost-effectiveness. To the best of our knowledge, this is the first cost-effectiveness analysis for evaluating different genetic testing strategies for LS in Taiwan. The results will be informative for the government when considering offering screening for LS in patients newly diagnosed with CRC.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0160599</identifier><identifier>PMID: 27482709</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Aged ; Biology and Life Sciences ; Colonoscopy ; Colorectal cancer ; Colorectal carcinoma ; Colorectal Neoplasms, Hereditary Nonpolyposis - diagnosis ; Colorectal Neoplasms, Hereditary Nonpolyposis - economics ; Colorectal Neoplasms, Hereditary Nonpolyposis - genetics ; Colorectal Neoplasms, Hereditary Nonpolyposis - pathology ; Cost analysis ; Cost-Benefit Analysis - statistics & numerical data ; Deoxyribonucleic acid ; Diagnosis ; DNA ; DNA Mismatch Repair ; DNA repair ; DNA sequencing ; DNA-Binding Proteins - genetics ; Female ; Gastroenterology ; Gene mutation ; Gene sequencing ; Genes ; Genetic aspects ; Genetic disorders ; Genetic screening ; Genetic testing ; Genetic Testing - economics ; Genetic Testing - methods ; Genetics ; Health insurance ; Health risks ; Hospitals ; Humans ; Immunohistochemistry ; Immunohistochemistry - economics ; Male ; Medical diagnosis ; Medicine and Health Sciences ; Microsatellite Instability ; Microsatellites ; Middle Aged ; Mismatch repair ; Mismatch Repair Endonuclease PMS2 - genetics ; Mortality ; Mutation ; Mutation Rate ; Mutation rates ; MutL Protein Homolog 1 - genetics ; MutS Homolog 2 Protein - genetics ; Patients ; People and Places ; Population ; Population studies ; Proteins ; Proto-Oncogene Proteins B-raf - genetics ; Repair ; Risk factors ; Screening ; Sensitivity analysis ; Sequence Analysis, DNA - economics ; Social Sciences ; Stability ; Stability analysis ; Statistical analysis ; Strategy ; Studies ; Taiwan ; Working groups</subject><ispartof>PloS one, 2016-08, Vol.11 (8), p.e0160599-e0160599</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Chen 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>2016 Chen et al 2016 Chen et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c725t-98b894b1524f188c6a0428e8a59e88c3f7afa5c9a5aabeb2db7e0fbea4b688273</citedby><cites>FETCH-LOGICAL-c725t-98b894b1524f188c6a0428e8a59e88c3f7afa5c9a5aabeb2db7e0fbea4b688273</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/PMC4970721/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4970721/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27482709$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Ying-Erh</creatorcontrib><creatorcontrib>Kao, Sung-Shuo</creatorcontrib><creatorcontrib>Chung, Ren-Hua</creatorcontrib><title>Cost-Effectiveness Analysis of Different Genetic Testing Strategies for Lynch Syndrome in Taiwan</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Patients with Lynch syndrome (LS) have a significantly increased risk of developing colorectal cancer (CRC) and other cancers. Genetic screening for LS among patients with newly diagnosed CRC aims to identify mutations in the disease-causing genes (i.e., the DNA mismatch repair genes) in the patients, to offer genetic testing for relatives of the patients with the mutations, and then to provide early prevention for the relatives with the mutations. Several genetic tests are available for LS, such as DNA sequencing for MMR genes and tumor testing using microsatellite instability and immunohistochemical analyses. Cost-effectiveness analyses of different genetic testing strategies for LS have been performed in several studies from different countries such as the US and Germany. However, a cost-effectiveness analysis for the testing has not yet been performed in Taiwan. In this study, we evaluated the cost-effectiveness of four genetic testing strategies for LS described in previous studies, while population-specific parameters, such as the mutation rates of the DNA mismatch repair genes and treatment costs for CRC in Taiwan, were used. The incremental cost-effectiveness ratios based on discounted life years gained due to genetic screening were calculated for the strategies relative to no screening and to the previous strategy. Using the World Health Organization standard, which was defined based on Taiwan's Gross Domestic Product per capita, the strategy based on immunohistochemistry as a genetic test followed by BRAF mutation testing was considered to be highly cost-effective relative to no screening. Our probabilistic sensitivity analysis results also suggest that the strategy has a probability of 0.939 of being cost-effective relative to no screening based on the commonly used threshold of $50,000 to determine cost-effectiveness. To the best of our knowledge, this is the first cost-effectiveness analysis for evaluating different genetic testing strategies for LS in Taiwan. The results will be informative for the government when considering offering screening for LS in patients newly diagnosed with CRC.</description><subject>Adult</subject><subject>Aged</subject><subject>Biology and Life Sciences</subject><subject>Colonoscopy</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Colorectal Neoplasms, Hereditary Nonpolyposis - diagnosis</subject><subject>Colorectal Neoplasms, Hereditary Nonpolyposis - economics</subject><subject>Colorectal Neoplasms, Hereditary Nonpolyposis - genetics</subject><subject>Colorectal Neoplasms, Hereditary Nonpolyposis - pathology</subject><subject>Cost analysis</subject><subject>Cost-Benefit Analysis - statistics & numerical data</subject><subject>Deoxyribonucleic acid</subject><subject>Diagnosis</subject><subject>DNA</subject><subject>DNA Mismatch Repair</subject><subject>DNA repair</subject><subject>DNA sequencing</subject><subject>DNA-Binding Proteins - genetics</subject><subject>Female</subject><subject>Gastroenterology</subject><subject>Gene mutation</subject><subject>Gene sequencing</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetic disorders</subject><subject>Genetic screening</subject><subject>Genetic testing</subject><subject>Genetic Testing - economics</subject><subject>Genetic Testing - methods</subject><subject>Genetics</subject><subject>Health insurance</subject><subject>Health risks</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Immunohistochemistry - economics</subject><subject>Male</subject><subject>Medical diagnosis</subject><subject>Medicine and Health Sciences</subject><subject>Microsatellite Instability</subject><subject>Microsatellites</subject><subject>Middle Aged</subject><subject>Mismatch repair</subject><subject>Mismatch Repair Endonuclease PMS2 - genetics</subject><subject>Mortality</subject><subject>Mutation</subject><subject>Mutation Rate</subject><subject>Mutation rates</subject><subject>MutL Protein Homolog 1 - genetics</subject><subject>MutS Homolog 2 Protein - genetics</subject><subject>Patients</subject><subject>People and Places</subject><subject>Population</subject><subject>Population studies</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins B-raf - genetics</subject><subject>Repair</subject><subject>Risk factors</subject><subject>Screening</subject><subject>Sensitivity analysis</subject><subject>Sequence Analysis, DNA - economics</subject><subject>Social Sciences</subject><subject>Stability</subject><subject>Stability analysis</subject><subject>Statistical analysis</subject><subject>Strategy</subject><subject>Studies</subject><subject>Taiwan</subject><subject>Working groups</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk1Fv0zAQxyMEYmPwDRBEQkLw0GLHdmK_IFVljEqVJtHCq3EcO3WV2p2dDPrtcWg2NWgSKA9JfL_75-5_uSR5CcEUogJ-2LrOW9FM986qKYA5IIw9Ss4hQ9kkzwB6fPJ8ljwLYQsAQTTPnyZnWYFpVgB2nvyYu9BOLrVWsjW3yqoQ0lmUPQQTUqfTTyaGvLJtehWDrZHpWoXW2DpdtV60qjYqpNr5dHmwcpOuDrbybqdSY9O1MD-FfZ480aIJ6sVwv0i-fb5cz79MltdXi_lsOZFFRtoJoyVluIQkwxpSKnMBcEYVFYSp-Ip0IbQgkgkiRKnKrCoLBXSpBC5zGntBF8nro-6-cYEP5gQOKaAIY4hhJBZHonJiy_fe7IQ_cCcM_3PgfM2Fjx02iue4AhmqIEVI4xwRAQkoqMJE5FKTkkatj8PXunKnKhkN8qIZiY4j1mx47W45ZgUosr6Yd4OAdzddtJTvTJCqaYRVruvrhpAyROPw_o0CBjCFpDfhzV_ow0YMVC1ir8ZqF0uUvSifYcKKArKcRWr6ABWvSu2MjD-dNvF8lPB-lBCZVv1qa9GFwBerr__PXn8fs29P2I0STbsJrula42wYg_gISu9C8ErfzwMC3u_MnRu83xk-7ExMe3U6y_ukuyVBvwF4CxET</recordid><startdate>20160802</startdate><enddate>20160802</enddate><creator>Chen, Ying-Erh</creator><creator>Kao, Sung-Shuo</creator><creator>Chung, Ren-Hua</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>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20160802</creationdate><title>Cost-Effectiveness Analysis of Different Genetic Testing Strategies for Lynch Syndrome in Taiwan</title><author>Chen, Ying-Erh ; Kao, Sung-Shuo ; Chung, Ren-Hua</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c725t-98b894b1524f188c6a0428e8a59e88c3f7afa5c9a5aabeb2db7e0fbea4b688273</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Biology and Life Sciences</topic><topic>Colonoscopy</topic><topic>Colorectal cancer</topic><topic>Colorectal carcinoma</topic><topic>Colorectal Neoplasms, Hereditary Nonpolyposis - diagnosis</topic><topic>Colorectal Neoplasms, Hereditary Nonpolyposis - economics</topic><topic>Colorectal Neoplasms, Hereditary Nonpolyposis - genetics</topic><topic>Colorectal Neoplasms, Hereditary Nonpolyposis - pathology</topic><topic>Cost analysis</topic><topic>Cost-Benefit Analysis - statistics & numerical data</topic><topic>Deoxyribonucleic acid</topic><topic>Diagnosis</topic><topic>DNA</topic><topic>DNA Mismatch Repair</topic><topic>DNA repair</topic><topic>DNA sequencing</topic><topic>DNA-Binding Proteins - genetics</topic><topic>Female</topic><topic>Gastroenterology</topic><topic>Gene mutation</topic><topic>Gene sequencing</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genetic disorders</topic><topic>Genetic screening</topic><topic>Genetic testing</topic><topic>Genetic Testing - economics</topic><topic>Genetic Testing - methods</topic><topic>Genetics</topic><topic>Health insurance</topic><topic>Health risks</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Immunohistochemistry - 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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>Chen, Ying-Erh</au><au>Kao, Sung-Shuo</au><au>Chung, Ren-Hua</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cost-Effectiveness Analysis of Different Genetic Testing Strategies for Lynch Syndrome in Taiwan</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2016-08-02</date><risdate>2016</risdate><volume>11</volume><issue>8</issue><spage>e0160599</spage><epage>e0160599</epage><pages>e0160599-e0160599</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Patients with Lynch syndrome (LS) have a significantly increased risk of developing colorectal cancer (CRC) and other cancers. Genetic screening for LS among patients with newly diagnosed CRC aims to identify mutations in the disease-causing genes (i.e., the DNA mismatch repair genes) in the patients, to offer genetic testing for relatives of the patients with the mutations, and then to provide early prevention for the relatives with the mutations. Several genetic tests are available for LS, such as DNA sequencing for MMR genes and tumor testing using microsatellite instability and immunohistochemical analyses. Cost-effectiveness analyses of different genetic testing strategies for LS have been performed in several studies from different countries such as the US and Germany. However, a cost-effectiveness analysis for the testing has not yet been performed in Taiwan. In this study, we evaluated the cost-effectiveness of four genetic testing strategies for LS described in previous studies, while population-specific parameters, such as the mutation rates of the DNA mismatch repair genes and treatment costs for CRC in Taiwan, were used. The incremental cost-effectiveness ratios based on discounted life years gained due to genetic screening were calculated for the strategies relative to no screening and to the previous strategy. Using the World Health Organization standard, which was defined based on Taiwan's Gross Domestic Product per capita, the strategy based on immunohistochemistry as a genetic test followed by BRAF mutation testing was considered to be highly cost-effective relative to no screening. Our probabilistic sensitivity analysis results also suggest that the strategy has a probability of 0.939 of being cost-effective relative to no screening based on the commonly used threshold of $50,000 to determine cost-effectiveness. To the best of our knowledge, this is the first cost-effectiveness analysis for evaluating different genetic testing strategies for LS in Taiwan. The results will be informative for the government when considering offering screening for LS in patients newly diagnosed with CRC.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>27482709</pmid><doi>10.1371/journal.pone.0160599</doi><tpages>e0160599</tpages><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_1808344141 |
| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adult Aged Biology and Life Sciences Colonoscopy Colorectal cancer Colorectal carcinoma Colorectal Neoplasms, Hereditary Nonpolyposis - diagnosis Colorectal Neoplasms, Hereditary Nonpolyposis - economics Colorectal Neoplasms, Hereditary Nonpolyposis - genetics Colorectal Neoplasms, Hereditary Nonpolyposis - pathology Cost analysis Cost-Benefit Analysis - statistics & numerical data Deoxyribonucleic acid Diagnosis DNA DNA Mismatch Repair DNA repair DNA sequencing DNA-Binding Proteins - genetics Female Gastroenterology Gene mutation Gene sequencing Genes Genetic aspects Genetic disorders Genetic screening Genetic testing Genetic Testing - economics Genetic Testing - methods Genetics Health insurance Health risks Hospitals Humans Immunohistochemistry Immunohistochemistry - economics Male Medical diagnosis Medicine and Health Sciences Microsatellite Instability Microsatellites Middle Aged Mismatch repair Mismatch Repair Endonuclease PMS2 - genetics Mortality Mutation Mutation Rate Mutation rates MutL Protein Homolog 1 - genetics MutS Homolog 2 Protein - genetics Patients People and Places Population Population studies Proteins Proto-Oncogene Proteins B-raf - genetics Repair Risk factors Screening Sensitivity analysis Sequence Analysis, DNA - economics Social Sciences Stability Stability analysis Statistical analysis Strategy Studies Taiwan Working groups |
| title | Cost-Effectiveness Analysis of Different Genetic Testing Strategies for Lynch Syndrome in Taiwan |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-11T10%3A24%3A19IST&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=Cost-Effectiveness%20Analysis%20of%20Different%20Genetic%20Testing%20Strategies%20for%20Lynch%20Syndrome%20in%20Taiwan&rft.jtitle=PloS%20one&rft.au=Chen,%20Ying-Erh&rft.date=2016-08-02&rft.volume=11&rft.issue=8&rft.spage=e0160599&rft.epage=e0160599&rft.pages=e0160599-e0160599&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0160599&rft_dat=%3Cgale_plos_%3EA459771969%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=1808344141&rft_id=info:pmid/27482709&rft_galeid=A459771969&rft_doaj_id=oai_doaj_org_article_64d023d1833f4635a15078e45a6cf5b8&rfr_iscdi=true |