Predictors and outcome of first line treatment failure among under-five children with community acquired severe pneumonia at Bugando Medical Centre, Mwanza, Tanzania: A prospective cohort study
Despite recent advances in management and preventive strategies, high rates of first line antibiotics treatment failure and case fatality for Severe Community Acquired Pneumonia (SCAP) continue to occur in children in low and middle-income countries. This study aimed to identify the predictors and o...
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| Veröffentlicht in: | PloS one 2020-12, Vol.15 (12), p.e0243636-e0243636 |
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| creator | Muro, Restituta Phabian Masoza, Tulla Sylvester Kasanga, Godfrey Kayange, Neema Kidenya, Benson R |
| description | Despite recent advances in management and preventive strategies, high rates of first line antibiotics treatment failure and case fatality for Severe Community Acquired Pneumonia (SCAP) continue to occur in children in low and middle-income countries. This study aimed to identify the predictors and outcome of first line antibiotics treatment failure among children under-five years of age with SCAP admitted at Bugando Medical Centre (BMC) in Mwanza, Tanzania.
The study involved under-five children admitted with SCAP, treated with first line antibiotics as recommended by WHO. Patients with treatment failure at 48 hours were shifted to second line of antibiotics treatment and followed up for 7 days. Generalized linear model was used to determine predictors of first line antibiotics treatment failure for SCAP.
A total of 250 children with SCAP with a median age of 18 [IQR 9-36] months were enrolled, 8.4% had HIV infection and 28% had acute malnutrition. The percentage of first line antibiotics treatment failure for the children with SCAP was 50.4%. Predictors of first line treatment failure were; presentation with convulsion (RR 1.55; 95% CI [1.11-2.16]; p-value 0.009), central cyanosis (RR 1.55; 95% CI [1.16-2.07]; p-value 0.003), low oxygen saturation (RR 1.28; 95% CI [1.01-1.62]; p-value 0.04), abnormal chest X-ray (RR 1.71; 95% CI [1.28-2.29]; p-value |
| doi_str_mv | 10.1371/journal.pone.0243636 |
| format | Article |
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The study involved under-five children admitted with SCAP, treated with first line antibiotics as recommended by WHO. Patients with treatment failure at 48 hours were shifted to second line of antibiotics treatment and followed up for 7 days. Generalized linear model was used to determine predictors of first line antibiotics treatment failure for SCAP.
A total of 250 children with SCAP with a median age of 18 [IQR 9-36] months were enrolled, 8.4% had HIV infection and 28% had acute malnutrition. The percentage of first line antibiotics treatment failure for the children with SCAP was 50.4%. Predictors of first line treatment failure were; presentation with convulsion (RR 1.55; 95% CI [1.11-2.16]; p-value 0.009), central cyanosis (RR 1.55; 95% CI [1.16-2.07]; p-value 0.003), low oxygen saturation (RR 1.28; 95% CI [1.01-1.62]; p-value 0.04), abnormal chest X-ray (RR 1.71; 95% CI [1.28-2.29]; p-value <0.001), HIV infection (RR 1.80; 95% CI [1.42-2.27]; p-value 0.001), moderate acute malnutrition (RR 1.48; 95% CI [1.04-2.12]; p-value = 0.030) and severe acute malnutrition (RR 2.02; 95% CI [1.56-2.61]; p-value<0.001). Mortality in children who failed first line treatment was 4.8%.
Half of the children with SCAP at this tertiary center had first line antibiotics treatment failure. HIV infection, acute malnutrition, low oxygen saturation, convulsions, central cyanosis, and abnormal chest X-ray were independently predictive of first line treatment failure. We recommend consideration of second line treatment and clinical trials for patients with SCAP to reduce associated morbidity and mortality.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0243636</identifier><identifier>PMID: 33306722</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Age ; Anti-Bacterial Agents - therapeutic use ; Antibiotics ; Antibodies ; Biology and Life Sciences ; Breastfeeding & lactation ; Care and treatment ; Chest ; Child, Preschool ; Childhood pneumonia ; Children ; Children & youth ; Childrens health ; Clinical trials ; Cohort analysis ; Community-acquired infections ; Community-Acquired Infections - complications ; Community-Acquired Infections - diagnosis ; Community-Acquired Infections - drug therapy ; Community-Acquired Infections - epidemiology ; Consent ; Convulsions ; Cyanosis ; Ethics ; Failure ; Female ; Generalized linear models ; Health care facilities ; Health services ; HIV ; HIV Infections - complications ; Hospitals ; Human immunodeficiency virus ; Humans ; Infant ; Infections ; Laboratories ; Male ; Malnutrition ; Malnutrition - complications ; Medicine and Health Sciences ; Morbidity ; Mortality ; Oxygen ; Oxygen content ; Oxygen saturation ; Patient outcomes ; Patients ; Pediatrics ; Physical Sciences ; Pneumonia ; Pneumonia - complications ; Pneumonia - diagnosis ; Pneumonia - drug therapy ; Pneumonia - epidemiology ; Prognosis ; Prospective Studies ; Statistical models ; Tanzania ; Treatment Failure ; Vital signs</subject><ispartof>PloS one, 2020-12, Vol.15 (12), p.e0243636-e0243636</ispartof><rights>COPYRIGHT 2020 Public Library of Science</rights><rights>2020 Muro 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>2020 Muro et al 2020 Muro et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c743t-4a1de5b67974c5d5d7f2564755bba3134338f004d1c0495d7c5becf17061af813</citedby><cites>FETCH-LOGICAL-c743t-4a1de5b67974c5d5d7f2564755bba3134338f004d1c0495d7c5becf17061af813</cites><orcidid>0000-0002-3856-8908</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/PMC7732094/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732094/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33306722$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Berkley, James A.</contributor><creatorcontrib>Muro, Restituta Phabian</creatorcontrib><creatorcontrib>Masoza, Tulla Sylvester</creatorcontrib><creatorcontrib>Kasanga, Godfrey</creatorcontrib><creatorcontrib>Kayange, Neema</creatorcontrib><creatorcontrib>Kidenya, Benson R</creatorcontrib><title>Predictors and outcome of first line treatment failure among under-five children with community acquired severe pneumonia at Bugando Medical Centre, Mwanza, Tanzania: A prospective cohort study</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Despite recent advances in management and preventive strategies, high rates of first line antibiotics treatment failure and case fatality for Severe Community Acquired Pneumonia (SCAP) continue to occur in children in low and middle-income countries. This study aimed to identify the predictors and outcome of first line antibiotics treatment failure among children under-five years of age with SCAP admitted at Bugando Medical Centre (BMC) in Mwanza, Tanzania.
The study involved under-five children admitted with SCAP, treated with first line antibiotics as recommended by WHO. Patients with treatment failure at 48 hours were shifted to second line of antibiotics treatment and followed up for 7 days. Generalized linear model was used to determine predictors of first line antibiotics treatment failure for SCAP.
A total of 250 children with SCAP with a median age of 18 [IQR 9-36] months were enrolled, 8.4% had HIV infection and 28% had acute malnutrition. The percentage of first line antibiotics treatment failure for the children with SCAP was 50.4%. Predictors of first line treatment failure were; presentation with convulsion (RR 1.55; 95% CI [1.11-2.16]; p-value 0.009), central cyanosis (RR 1.55; 95% CI [1.16-2.07]; p-value 0.003), low oxygen saturation (RR 1.28; 95% CI [1.01-1.62]; p-value 0.04), abnormal chest X-ray (RR 1.71; 95% CI [1.28-2.29]; p-value <0.001), HIV infection (RR 1.80; 95% CI [1.42-2.27]; p-value 0.001), moderate acute malnutrition (RR 1.48; 95% CI [1.04-2.12]; p-value = 0.030) and severe acute malnutrition (RR 2.02; 95% CI [1.56-2.61]; p-value<0.001). Mortality in children who failed first line treatment was 4.8%.
Half of the children with SCAP at this tertiary center had first line antibiotics treatment failure. HIV infection, acute malnutrition, low oxygen saturation, convulsions, central cyanosis, and abnormal chest X-ray were independently predictive of first line treatment failure. We recommend consideration of second line treatment and clinical trials for patients with SCAP to reduce associated morbidity and mortality.</description><subject>Age</subject><subject>Anti-Bacterial Agents - therapeutic use</subject><subject>Antibiotics</subject><subject>Antibodies</subject><subject>Biology and Life Sciences</subject><subject>Breastfeeding & lactation</subject><subject>Care and treatment</subject><subject>Chest</subject><subject>Child, Preschool</subject><subject>Childhood pneumonia</subject><subject>Children</subject><subject>Children & youth</subject><subject>Childrens health</subject><subject>Clinical trials</subject><subject>Cohort analysis</subject><subject>Community-acquired infections</subject><subject>Community-Acquired Infections - complications</subject><subject>Community-Acquired Infections - diagnosis</subject><subject>Community-Acquired Infections - drug therapy</subject><subject>Community-Acquired Infections - epidemiology</subject><subject>Consent</subject><subject>Convulsions</subject><subject>Cyanosis</subject><subject>Ethics</subject><subject>Failure</subject><subject>Female</subject><subject>Generalized linear models</subject><subject>Health care facilities</subject><subject>Health services</subject><subject>HIV</subject><subject>HIV Infections - complications</subject><subject>Hospitals</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Infant</subject><subject>Infections</subject><subject>Laboratories</subject><subject>Male</subject><subject>Malnutrition</subject><subject>Malnutrition - complications</subject><subject>Medicine and Health Sciences</subject><subject>Morbidity</subject><subject>Mortality</subject><subject>Oxygen</subject><subject>Oxygen content</subject><subject>Oxygen saturation</subject><subject>Patient outcomes</subject><subject>Patients</subject><subject>Pediatrics</subject><subject>Physical Sciences</subject><subject>Pneumonia</subject><subject>Pneumonia - complications</subject><subject>Pneumonia - diagnosis</subject><subject>Pneumonia - drug therapy</subject><subject>Pneumonia - epidemiology</subject><subject>Prognosis</subject><subject>Prospective Studies</subject><subject>Statistical models</subject><subject>Tanzania</subject><subject>Treatment Failure</subject><subject>Vital signs</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</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>eNqNk11rFDEUhgdRbK3-A9FAQRS6azLJZHa8ENbiR6GlotXbkMmc7KbMJNt8tNZ_5z8z025LV3ohc5Ehed73TU5yiuI5wVNCa_L21CVvZT9dOQtTXDLKKX9QbJOGlhNeYvrwzv9W8SSEU4wrOuP8cbFFKcW8Lsvt4s9XD51R0fmApO2QS1G5AZDTSBsfIuqNBRQ9yDiAjUhL0ycPSA7OLlCyHfiJNueA1NL0nQeLLkxcouwxJGviJZLqLJmcgQKcQxauLKSsNRLJiD6kRQ516Gjcg-zRfo7wsIeOLqT9LffQyThk9h2ao5V3YQUqXoW5pfMRhZi6y6fFIy37AM_W407x49PHk_0vk8Pjzwf788OJqhmNEyZJB1XL66ZmquqqrtZlxVldVW0rKaGM0pnGmHVEYdbkZVW1oDSpMSdSzwjdKV5e-656F8S6-kGUjDcVqbJRJg6uic7JU7HyZpD-UjhpxNWE8wshfTSqB9HwsqVydM7Jis9aWmtScY4J5k2jm-z1fp2W2gE6NRZG9hummyvWLMXCnYu6piVuWDZ4vTbw7ixBiGIwQUHfSwsujfuuMaZs1tQZ3f0Hvf90a2oh8wGM1S7nqtFUzDnLHGXVuO_pPVT-OhiMyk9Vmzy_IXizIchMhF9xIVMI4uD7t_9nj39usq_usEuQfVwG16donA2bILsGVX5gwYO-LTLBYuy0m2qIsdPEutOy7MXdC7oV3bQW_Qu5GyaA</recordid><startdate>20201211</startdate><enddate>20201211</enddate><creator>Muro, Restituta Phabian</creator><creator>Masoza, Tulla Sylvester</creator><creator>Kasanga, Godfrey</creator><creator>Kayange, Neema</creator><creator>Kidenya, Benson R</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>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/0000-0002-3856-8908</orcidid></search><sort><creationdate>20201211</creationdate><title>Predictors and outcome of first line treatment failure among under-five children with community acquired severe pneumonia at Bugando Medical Centre, Mwanza, Tanzania: A prospective cohort study</title><author>Muro, Restituta Phabian ; Masoza, Tulla Sylvester ; Kasanga, Godfrey ; Kayange, Neema ; Kidenya, Benson R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c743t-4a1de5b67974c5d5d7f2564755bba3134338f004d1c0495d7c5becf17061af813</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Age</topic><topic>Anti-Bacterial Agents - therapeutic use</topic><topic>Antibiotics</topic><topic>Antibodies</topic><topic>Biology and Life Sciences</topic><topic>Breastfeeding & lactation</topic><topic>Care and treatment</topic><topic>Chest</topic><topic>Child, Preschool</topic><topic>Childhood pneumonia</topic><topic>Children</topic><topic>Children & youth</topic><topic>Childrens health</topic><topic>Clinical trials</topic><topic>Cohort analysis</topic><topic>Community-acquired infections</topic><topic>Community-Acquired Infections - complications</topic><topic>Community-Acquired Infections - diagnosis</topic><topic>Community-Acquired Infections - drug therapy</topic><topic>Community-Acquired Infections - epidemiology</topic><topic>Consent</topic><topic>Convulsions</topic><topic>Cyanosis</topic><topic>Ethics</topic><topic>Failure</topic><topic>Female</topic><topic>Generalized linear models</topic><topic>Health care facilities</topic><topic>Health services</topic><topic>HIV</topic><topic>HIV Infections - complications</topic><topic>Hospitals</topic><topic>Human immunodeficiency virus</topic><topic>Humans</topic><topic>Infant</topic><topic>Infections</topic><topic>Laboratories</topic><topic>Male</topic><topic>Malnutrition</topic><topic>Malnutrition - 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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>Muro, Restituta Phabian</au><au>Masoza, Tulla Sylvester</au><au>Kasanga, Godfrey</au><au>Kayange, Neema</au><au>Kidenya, Benson R</au><au>Berkley, James A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Predictors and outcome of first line treatment failure among under-five children with community acquired severe pneumonia at Bugando Medical Centre, Mwanza, Tanzania: A prospective cohort study</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2020-12-11</date><risdate>2020</risdate><volume>15</volume><issue>12</issue><spage>e0243636</spage><epage>e0243636</epage><pages>e0243636-e0243636</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Despite recent advances in management and preventive strategies, high rates of first line antibiotics treatment failure and case fatality for Severe Community Acquired Pneumonia (SCAP) continue to occur in children in low and middle-income countries. This study aimed to identify the predictors and outcome of first line antibiotics treatment failure among children under-five years of age with SCAP admitted at Bugando Medical Centre (BMC) in Mwanza, Tanzania.
The study involved under-five children admitted with SCAP, treated with first line antibiotics as recommended by WHO. Patients with treatment failure at 48 hours were shifted to second line of antibiotics treatment and followed up for 7 days. Generalized linear model was used to determine predictors of first line antibiotics treatment failure for SCAP.
A total of 250 children with SCAP with a median age of 18 [IQR 9-36] months were enrolled, 8.4% had HIV infection and 28% had acute malnutrition. The percentage of first line antibiotics treatment failure for the children with SCAP was 50.4%. Predictors of first line treatment failure were; presentation with convulsion (RR 1.55; 95% CI [1.11-2.16]; p-value 0.009), central cyanosis (RR 1.55; 95% CI [1.16-2.07]; p-value 0.003), low oxygen saturation (RR 1.28; 95% CI [1.01-1.62]; p-value 0.04), abnormal chest X-ray (RR 1.71; 95% CI [1.28-2.29]; p-value <0.001), HIV infection (RR 1.80; 95% CI [1.42-2.27]; p-value 0.001), moderate acute malnutrition (RR 1.48; 95% CI [1.04-2.12]; p-value = 0.030) and severe acute malnutrition (RR 2.02; 95% CI [1.56-2.61]; p-value<0.001). Mortality in children who failed first line treatment was 4.8%.
Half of the children with SCAP at this tertiary center had first line antibiotics treatment failure. HIV infection, acute malnutrition, low oxygen saturation, convulsions, central cyanosis, and abnormal chest X-ray were independently predictive of first line treatment failure. We recommend consideration of second line treatment and clinical trials for patients with SCAP to reduce associated morbidity and mortality.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>33306722</pmid><doi>10.1371/journal.pone.0243636</doi><tpages>e0243636</tpages><orcidid>https://orcid.org/0000-0002-3856-8908</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2020-12, Vol.15 (12), p.e0243636-e0243636 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2469515475 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Age Anti-Bacterial Agents - therapeutic use Antibiotics Antibodies Biology and Life Sciences Breastfeeding & lactation Care and treatment Chest Child, Preschool Childhood pneumonia Children Children & youth Childrens health Clinical trials Cohort analysis Community-acquired infections Community-Acquired Infections - complications Community-Acquired Infections - diagnosis Community-Acquired Infections - drug therapy Community-Acquired Infections - epidemiology Consent Convulsions Cyanosis Ethics Failure Female Generalized linear models Health care facilities Health services HIV HIV Infections - complications Hospitals Human immunodeficiency virus Humans Infant Infections Laboratories Male Malnutrition Malnutrition - complications Medicine and Health Sciences Morbidity Mortality Oxygen Oxygen content Oxygen saturation Patient outcomes Patients Pediatrics Physical Sciences Pneumonia Pneumonia - complications Pneumonia - diagnosis Pneumonia - drug therapy Pneumonia - epidemiology Prognosis Prospective Studies Statistical models Tanzania Treatment Failure Vital signs |
| title | Predictors and outcome of first line treatment failure among under-five children with community acquired severe pneumonia at Bugando Medical Centre, Mwanza, Tanzania: A prospective cohort study |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T20%3A52%3A33IST&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=Predictors%20and%20outcome%20of%20first%20line%20treatment%20failure%20among%20under-five%20children%20with%20community%20acquired%20severe%20pneumonia%20at%20Bugando%20Medical%20Centre,%20Mwanza,%20Tanzania:%20A%20prospective%20cohort%20study&rft.jtitle=PloS%20one&rft.au=Muro,%20Restituta%20Phabian&rft.date=2020-12-11&rft.volume=15&rft.issue=12&rft.spage=e0243636&rft.epage=e0243636&rft.pages=e0243636-e0243636&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0243636&rft_dat=%3Cgale_plos_%3EA644693459%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=2469515475&rft_id=info:pmid/33306722&rft_galeid=A644693459&rft_doaj_id=oai_doaj_org_article_962b3a61af134c68b37f1566010699f9&rfr_iscdi=true |