Fluid overload is associated with an increased risk for 90-day mortality in critically ill patients with renal replacement therapy: data from the prospective FINNAKI study
Positive fluid balance has been associated with an increased risk for mortality in critically ill patients with acute kidney injury with or without renal replacement therapy (RRT). Data on fluid accumulation prior to RRT initiation and mortality are limited. We aimed to study the association between...
Gespeichert in:
Veröffentlicht in: | Critical care (London, England) England), 2012-10, Vol.16 (5), p.R197-R197, Article R197 |
---|---|
Hauptverfasser: | , , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | R197 |
---|---|
container_issue | 5 |
container_start_page | R197 |
container_title | Critical care (London, England) |
container_volume | 16 |
creator | Vaara, Suvi T Korhonen, Anna-Maija Kaukonen, Kirsi-Maija Nisula, Sara Inkinen, Outi Hoppu, Sanna Laurila, Jouko J Mildh, Leena Reinikainen, Matti Lund, Vesa Parviainen, Ilkka Pettilä, Ville |
description | Positive fluid balance has been associated with an increased risk for mortality in critically ill patients with acute kidney injury with or without renal replacement therapy (RRT). Data on fluid accumulation prior to RRT initiation and mortality are limited. We aimed to study the association between fluid accumulation at RRT initiation and 90-day mortality.
We conducted a prospective, multicenter, observational cohort study in 17 Finnish intensive care units (ICUs) during a five-month period. We collected data on patient characteristics, RRT timing, and parameters at RRT initiation. We studied the association of parameters at RRT initiation, including fluid overload (defined as cumulative fluid accumulation > 10% of baseline weight) with 90-day mortality.
We included 296 RRT-treated critically ill patients. Of 283 patients with complete data on fluid balance, 76 (26.9%) patients had fluid overload. The median (interquartile range) time from ICU admission to RRT initiation was 14 (3.3 to 41.5) hours. The 90-day mortality rate of the whole cohort was 116 of 296 (39.2%; 95% confidence interval 38.6 to 39.8%). The crude 90-day mortality of patients with or without fluid overload was 45 of 76 (59.2%) vs. 65 of 207 (31.4%), P < 0.001. In logistic regression, fluid overload was associated with an increased risk for 90-day mortality (odds ratio 2.6) after adjusting for disease severity, time of RRT initiation, initial RRT modality, and sepsis. Of the 168 survivors with data on RRT use at 90 days, 34 (18.9%, 95% CI 13.2 to 24.6%) were still dependent on RRT.
Patients with fluid overload at RRT initiation had twice as high crude 90-day mortality compared to those without. Fluid overload was associated with increased risk for 90-day mortality even after adjustments. |
doi_str_mv | 10.1186/cc11682 |
format | Article |
fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3682299</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A534371031</galeid><sourcerecordid>A534371031</sourcerecordid><originalsourceid>FETCH-LOGICAL-c436t-9b7599ccfa97ba15b7d7491d8a7128287ccaadc2769350a917343dbea5ee0343</originalsourceid><addsrcrecordid>eNptktGO1CAUhhujcdfV-AaGxAu96VpKKcULk8nG0Ymb9WYvvCNn4HQHpaUCHdNn8iVlMuPGTQwJHH6-8-cApyhe0uqS0q59pzWlbVc_Ks5p07ZlW8lvj3PM2qbsOONnxbMYv1cVFV3LnhZnNasEb7g8L36v3WwN8XsMzoMhNhKI0WsLCQ35ZdOOwEjsqANCzEqw8QfpfSCyKg0sZPAhgbNpyQzRwSarwbm8c45MkCyOKR5tAo7g8jw50DhknaQdBpiW98RAAtIHPxwkMgUfJ9TJ7pGsNzc3qy8bEtNslufFkx5cxBen9aK4XX-8vfpcXn_9tLlaXZe6YW0q5VZwKbXuQYotUL4VRjSSmg4Erbu6E1oDGF2LVjJegaSCNcxsEThilcOL4sPRdpq3AxqdSw3g1BTsAGFRHqx6eDLanbrze8XyD9RSZoO3J4Pgf84Ykxps1OgcjOjnqCjnlNUif0JGXx_RO3Co7Nj77KgPuFrxXIugFaOZuvwPlYfBwWo_Ym-z_iDhzTFB57eMAfv76mmlDg2jTg2TyVf_Xvae-9sh7A8t5L3W</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1551327230</pqid></control><display><type>article</type><title>Fluid overload is associated with an increased risk for 90-day mortality in critically ill patients with renal replacement therapy: data from the prospective FINNAKI study</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>SpringerLink Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Springer Nature OA Free Journals</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><creator>Vaara, Suvi T ; Korhonen, Anna-Maija ; Kaukonen, Kirsi-Maija ; Nisula, Sara ; Inkinen, Outi ; Hoppu, Sanna ; Laurila, Jouko J ; Mildh, Leena ; Reinikainen, Matti ; Lund, Vesa ; Parviainen, Ilkka ; Pettilä, Ville</creator><creatorcontrib>Vaara, Suvi T ; Korhonen, Anna-Maija ; Kaukonen, Kirsi-Maija ; Nisula, Sara ; Inkinen, Outi ; Hoppu, Sanna ; Laurila, Jouko J ; Mildh, Leena ; Reinikainen, Matti ; Lund, Vesa ; Parviainen, Ilkka ; Pettilä, Ville ; FINNAKI Study Group ; The FINNAKI study group</creatorcontrib><description>Positive fluid balance has been associated with an increased risk for mortality in critically ill patients with acute kidney injury with or without renal replacement therapy (RRT). Data on fluid accumulation prior to RRT initiation and mortality are limited. We aimed to study the association between fluid accumulation at RRT initiation and 90-day mortality.
We conducted a prospective, multicenter, observational cohort study in 17 Finnish intensive care units (ICUs) during a five-month period. We collected data on patient characteristics, RRT timing, and parameters at RRT initiation. We studied the association of parameters at RRT initiation, including fluid overload (defined as cumulative fluid accumulation > 10% of baseline weight) with 90-day mortality.
We included 296 RRT-treated critically ill patients. Of 283 patients with complete data on fluid balance, 76 (26.9%) patients had fluid overload. The median (interquartile range) time from ICU admission to RRT initiation was 14 (3.3 to 41.5) hours. The 90-day mortality rate of the whole cohort was 116 of 296 (39.2%; 95% confidence interval 38.6 to 39.8%). The crude 90-day mortality of patients with or without fluid overload was 45 of 76 (59.2%) vs. 65 of 207 (31.4%), P < 0.001. In logistic regression, fluid overload was associated with an increased risk for 90-day mortality (odds ratio 2.6) after adjusting for disease severity, time of RRT initiation, initial RRT modality, and sepsis. Of the 168 survivors with data on RRT use at 90 days, 34 (18.9%, 95% CI 13.2 to 24.6%) were still dependent on RRT.
Patients with fluid overload at RRT initiation had twice as high crude 90-day mortality compared to those without. Fluid overload was associated with increased risk for 90-day mortality even after adjustments.</description><identifier>ISSN: 1364-8535</identifier><identifier>EISSN: 1466-609X</identifier><identifier>EISSN: 1364-8535</identifier><identifier>DOI: 10.1186/cc11682</identifier><identifier>PMID: 23075459</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Aged ; Catastrophic illness ; Cohort Studies ; Critical Illness - mortality ; Critical Illness - therapy ; Female ; Finland - epidemiology ; Health aspects ; Hospital Mortality - trends ; Humans ; Male ; Middle Aged ; Mortality ; Osmoregulation ; Patient outcomes ; Prospective Studies ; Renal Replacement Therapy - adverse effects ; Renal Replacement Therapy - mortality ; Renal Replacement Therapy - trends ; Risk Factors ; Time Factors ; Water-Electrolyte Balance - physiology</subject><ispartof>Critical care (London, England), 2012-10, Vol.16 (5), p.R197-R197, Article R197</ispartof><rights>COPYRIGHT 2012 BioMed Central Ltd.</rights><rights>Copyright ©2012 Vaara et al.; licensee BioMed Central Ltd. 2012 Vaara et al.; licensee BioMed Central Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c436t-9b7599ccfa97ba15b7d7491d8a7128287ccaadc2769350a917343dbea5ee0343</citedby><cites>FETCH-LOGICAL-c436t-9b7599ccfa97ba15b7d7491d8a7128287ccaadc2769350a917343dbea5ee0343</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/PMC3682299/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682299/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,861,882,27905,27906,53772,53774</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23075459$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Vaara, Suvi T</creatorcontrib><creatorcontrib>Korhonen, Anna-Maija</creatorcontrib><creatorcontrib>Kaukonen, Kirsi-Maija</creatorcontrib><creatorcontrib>Nisula, Sara</creatorcontrib><creatorcontrib>Inkinen, Outi</creatorcontrib><creatorcontrib>Hoppu, Sanna</creatorcontrib><creatorcontrib>Laurila, Jouko J</creatorcontrib><creatorcontrib>Mildh, Leena</creatorcontrib><creatorcontrib>Reinikainen, Matti</creatorcontrib><creatorcontrib>Lund, Vesa</creatorcontrib><creatorcontrib>Parviainen, Ilkka</creatorcontrib><creatorcontrib>Pettilä, Ville</creatorcontrib><creatorcontrib>FINNAKI Study Group</creatorcontrib><creatorcontrib>The FINNAKI study group</creatorcontrib><title>Fluid overload is associated with an increased risk for 90-day mortality in critically ill patients with renal replacement therapy: data from the prospective FINNAKI study</title><title>Critical care (London, England)</title><addtitle>Crit Care</addtitle><description>Positive fluid balance has been associated with an increased risk for mortality in critically ill patients with acute kidney injury with or without renal replacement therapy (RRT). Data on fluid accumulation prior to RRT initiation and mortality are limited. We aimed to study the association between fluid accumulation at RRT initiation and 90-day mortality.
We conducted a prospective, multicenter, observational cohort study in 17 Finnish intensive care units (ICUs) during a five-month period. We collected data on patient characteristics, RRT timing, and parameters at RRT initiation. We studied the association of parameters at RRT initiation, including fluid overload (defined as cumulative fluid accumulation > 10% of baseline weight) with 90-day mortality.
We included 296 RRT-treated critically ill patients. Of 283 patients with complete data on fluid balance, 76 (26.9%) patients had fluid overload. The median (interquartile range) time from ICU admission to RRT initiation was 14 (3.3 to 41.5) hours. The 90-day mortality rate of the whole cohort was 116 of 296 (39.2%; 95% confidence interval 38.6 to 39.8%). The crude 90-day mortality of patients with or without fluid overload was 45 of 76 (59.2%) vs. 65 of 207 (31.4%), P < 0.001. In logistic regression, fluid overload was associated with an increased risk for 90-day mortality (odds ratio 2.6) after adjusting for disease severity, time of RRT initiation, initial RRT modality, and sepsis. Of the 168 survivors with data on RRT use at 90 days, 34 (18.9%, 95% CI 13.2 to 24.6%) were still dependent on RRT.
Patients with fluid overload at RRT initiation had twice as high crude 90-day mortality compared to those without. Fluid overload was associated with increased risk for 90-day mortality even after adjustments.</description><subject>Aged</subject><subject>Catastrophic illness</subject><subject>Cohort Studies</subject><subject>Critical Illness - mortality</subject><subject>Critical Illness - therapy</subject><subject>Female</subject><subject>Finland - epidemiology</subject><subject>Health aspects</subject><subject>Hospital Mortality - trends</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Mortality</subject><subject>Osmoregulation</subject><subject>Patient outcomes</subject><subject>Prospective Studies</subject><subject>Renal Replacement Therapy - adverse effects</subject><subject>Renal Replacement Therapy - mortality</subject><subject>Renal Replacement Therapy - trends</subject><subject>Risk Factors</subject><subject>Time Factors</subject><subject>Water-Electrolyte Balance - physiology</subject><issn>1364-8535</issn><issn>1466-609X</issn><issn>1364-8535</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptktGO1CAUhhujcdfV-AaGxAu96VpKKcULk8nG0Ymb9WYvvCNn4HQHpaUCHdNn8iVlMuPGTQwJHH6-8-cApyhe0uqS0q59pzWlbVc_Ks5p07ZlW8lvj3PM2qbsOONnxbMYv1cVFV3LnhZnNasEb7g8L36v3WwN8XsMzoMhNhKI0WsLCQ35ZdOOwEjsqANCzEqw8QfpfSCyKg0sZPAhgbNpyQzRwSarwbm8c45MkCyOKR5tAo7g8jw50DhknaQdBpiW98RAAtIHPxwkMgUfJ9TJ7pGsNzc3qy8bEtNslufFkx5cxBen9aK4XX-8vfpcXn_9tLlaXZe6YW0q5VZwKbXuQYotUL4VRjSSmg4Erbu6E1oDGF2LVjJegaSCNcxsEThilcOL4sPRdpq3AxqdSw3g1BTsAGFRHqx6eDLanbrze8XyD9RSZoO3J4Pgf84Ykxps1OgcjOjnqCjnlNUif0JGXx_RO3Co7Nj77KgPuFrxXIugFaOZuvwPlYfBwWo_Ym-z_iDhzTFB57eMAfv76mmlDg2jTg2TyVf_Xvae-9sh7A8t5L3W</recordid><startdate>20121017</startdate><enddate>20121017</enddate><creator>Vaara, Suvi T</creator><creator>Korhonen, Anna-Maija</creator><creator>Kaukonen, Kirsi-Maija</creator><creator>Nisula, Sara</creator><creator>Inkinen, Outi</creator><creator>Hoppu, Sanna</creator><creator>Laurila, Jouko J</creator><creator>Mildh, Leena</creator><creator>Reinikainen, Matti</creator><creator>Lund, Vesa</creator><creator>Parviainen, Ilkka</creator><creator>Pettilä, Ville</creator><general>BioMed Central Ltd</general><general>BioMed Central</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></search><sort><creationdate>20121017</creationdate><title>Fluid overload is associated with an increased risk for 90-day mortality in critically ill patients with renal replacement therapy: data from the prospective FINNAKI study</title><author>Vaara, Suvi T ; Korhonen, Anna-Maija ; Kaukonen, Kirsi-Maija ; Nisula, Sara ; Inkinen, Outi ; Hoppu, Sanna ; Laurila, Jouko J ; Mildh, Leena ; Reinikainen, Matti ; Lund, Vesa ; Parviainen, Ilkka ; Pettilä, Ville</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c436t-9b7599ccfa97ba15b7d7491d8a7128287ccaadc2769350a917343dbea5ee0343</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Aged</topic><topic>Catastrophic illness</topic><topic>Cohort Studies</topic><topic>Critical Illness - mortality</topic><topic>Critical Illness - therapy</topic><topic>Female</topic><topic>Finland - epidemiology</topic><topic>Health aspects</topic><topic>Hospital Mortality - trends</topic><topic>Humans</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Mortality</topic><topic>Osmoregulation</topic><topic>Patient outcomes</topic><topic>Prospective Studies</topic><topic>Renal Replacement Therapy - adverse effects</topic><topic>Renal Replacement Therapy - mortality</topic><topic>Renal Replacement Therapy - trends</topic><topic>Risk Factors</topic><topic>Time Factors</topic><topic>Water-Electrolyte Balance - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Vaara, Suvi T</creatorcontrib><creatorcontrib>Korhonen, Anna-Maija</creatorcontrib><creatorcontrib>Kaukonen, Kirsi-Maija</creatorcontrib><creatorcontrib>Nisula, Sara</creatorcontrib><creatorcontrib>Inkinen, Outi</creatorcontrib><creatorcontrib>Hoppu, Sanna</creatorcontrib><creatorcontrib>Laurila, Jouko J</creatorcontrib><creatorcontrib>Mildh, Leena</creatorcontrib><creatorcontrib>Reinikainen, Matti</creatorcontrib><creatorcontrib>Lund, Vesa</creatorcontrib><creatorcontrib>Parviainen, Ilkka</creatorcontrib><creatorcontrib>Pettilä, Ville</creatorcontrib><creatorcontrib>FINNAKI Study Group</creatorcontrib><creatorcontrib>The FINNAKI study group</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><jtitle>Critical care (London, England)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vaara, Suvi T</au><au>Korhonen, Anna-Maija</au><au>Kaukonen, Kirsi-Maija</au><au>Nisula, Sara</au><au>Inkinen, Outi</au><au>Hoppu, Sanna</au><au>Laurila, Jouko J</au><au>Mildh, Leena</au><au>Reinikainen, Matti</au><au>Lund, Vesa</au><au>Parviainen, Ilkka</au><au>Pettilä, Ville</au><aucorp>FINNAKI Study Group</aucorp><aucorp>The FINNAKI study group</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Fluid overload is associated with an increased risk for 90-day mortality in critically ill patients with renal replacement therapy: data from the prospective FINNAKI study</atitle><jtitle>Critical care (London, England)</jtitle><addtitle>Crit Care</addtitle><date>2012-10-17</date><risdate>2012</risdate><volume>16</volume><issue>5</issue><spage>R197</spage><epage>R197</epage><pages>R197-R197</pages><artnum>R197</artnum><issn>1364-8535</issn><eissn>1466-609X</eissn><eissn>1364-8535</eissn><abstract>Positive fluid balance has been associated with an increased risk for mortality in critically ill patients with acute kidney injury with or without renal replacement therapy (RRT). Data on fluid accumulation prior to RRT initiation and mortality are limited. We aimed to study the association between fluid accumulation at RRT initiation and 90-day mortality.
We conducted a prospective, multicenter, observational cohort study in 17 Finnish intensive care units (ICUs) during a five-month period. We collected data on patient characteristics, RRT timing, and parameters at RRT initiation. We studied the association of parameters at RRT initiation, including fluid overload (defined as cumulative fluid accumulation > 10% of baseline weight) with 90-day mortality.
We included 296 RRT-treated critically ill patients. Of 283 patients with complete data on fluid balance, 76 (26.9%) patients had fluid overload. The median (interquartile range) time from ICU admission to RRT initiation was 14 (3.3 to 41.5) hours. The 90-day mortality rate of the whole cohort was 116 of 296 (39.2%; 95% confidence interval 38.6 to 39.8%). The crude 90-day mortality of patients with or without fluid overload was 45 of 76 (59.2%) vs. 65 of 207 (31.4%), P < 0.001. In logistic regression, fluid overload was associated with an increased risk for 90-day mortality (odds ratio 2.6) after adjusting for disease severity, time of RRT initiation, initial RRT modality, and sepsis. Of the 168 survivors with data on RRT use at 90 days, 34 (18.9%, 95% CI 13.2 to 24.6%) were still dependent on RRT.
Patients with fluid overload at RRT initiation had twice as high crude 90-day mortality compared to those without. Fluid overload was associated with increased risk for 90-day mortality even after adjustments.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>23075459</pmid><doi>10.1186/cc11682</doi><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1364-8535 |
ispartof | Critical care (London, England), 2012-10, Vol.16 (5), p.R197-R197, Article R197 |
issn | 1364-8535 1466-609X 1364-8535 |
language | eng |
recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3682299 |
source | MEDLINE; DOAJ Directory of Open Access Journals; SpringerLink Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Springer Nature OA Free Journals; PubMed Central; Alma/SFX Local Collection |
subjects | Aged Catastrophic illness Cohort Studies Critical Illness - mortality Critical Illness - therapy Female Finland - epidemiology Health aspects Hospital Mortality - trends Humans Male Middle Aged Mortality Osmoregulation Patient outcomes Prospective Studies Renal Replacement Therapy - adverse effects Renal Replacement Therapy - mortality Renal Replacement Therapy - trends Risk Factors Time Factors Water-Electrolyte Balance - physiology |
title | Fluid overload is associated with an increased risk for 90-day mortality in critically ill patients with renal replacement therapy: data from the prospective FINNAKI study |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-19T08%3A10%3A41IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Fluid%20overload%20is%20associated%20with%20an%20increased%20risk%20for%2090-day%20mortality%20in%20critically%20ill%20patients%20with%20renal%20replacement%20therapy:%20data%20from%20the%20prospective%20FINNAKI%20study&rft.jtitle=Critical%20care%20(London,%20England)&rft.au=Vaara,%20Suvi%20T&rft.aucorp=FINNAKI%20Study%20Group&rft.date=2012-10-17&rft.volume=16&rft.issue=5&rft.spage=R197&rft.epage=R197&rft.pages=R197-R197&rft.artnum=R197&rft.issn=1364-8535&rft.eissn=1466-609X&rft_id=info:doi/10.1186/cc11682&rft_dat=%3Cgale_pubme%3EA534371031%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1551327230&rft_id=info:pmid/23075459&rft_galeid=A534371031&rfr_iscdi=true |