Antifactor Xa activity in critically ill patients receiving antithrombotic prophylaxis with standard dosages of certoparin: a prospective, clinical study

Deep venous thrombosis with subsequent pulmonary embolism or post-thrombotic syndrome is a feared complication in the intensive care unit. Therefore, routine prophylactic anticoagulation is widely recommended. Aside from unfractionated heparin, low molecular weight heparins, such as certoparin, have...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Critical care (London, England) England), 2005, Vol.9 (5), p.R541-R548, Article R541
Hauptverfasser: Jochberger, Stefan, Mayr, Viktoria, Luckner, Günter, Fries, Dietmar R, Mayr, Andreas J, Friesenecker, Barbara E, Lorenz, Ingo, Hasibeder, Walter R, Ulmer, Hanno, Schobersberger, Wolfgang, Dünser, Martin W
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page R548
container_issue 5
container_start_page R541
container_title Critical care (London, England)
container_volume 9
creator Jochberger, Stefan
Mayr, Viktoria
Luckner, Günter
Fries, Dietmar R
Mayr, Andreas J
Friesenecker, Barbara E
Lorenz, Ingo
Hasibeder, Walter R
Ulmer, Hanno
Schobersberger, Wolfgang
Dünser, Martin W
description Deep venous thrombosis with subsequent pulmonary embolism or post-thrombotic syndrome is a feared complication in the intensive care unit. Therefore, routine prophylactic anticoagulation is widely recommended. Aside from unfractionated heparin, low molecular weight heparins, such as certoparin, have become increasingly used for prophylactic anticoagulation in critically ill patients. In this prospective study, we evaluated the potency of 3,000 IU certoparin administered once daily to reach antithrombotic antifactor Xa (aFXa) levels of 0.1 to 0.3 IU/ml in 62 critically ill patients. AFXa levels were determined 4, 12 and 24 h after injection of certoparin. Prothrombin time, activated partial thromboplastin time, antithrombin, fibrinogen, hemoglobin, platelet count, serum urea and creatinine concentrations were documented before and 12 and 24 h after injection of certoparin. Four hours after certoparin injection (n = 32), 28% of patients were within the antithrombotic aFXa range. After 12 and 24 h, 6% achieved antithrombotic aFXa levels. Because of a severe pulmonary embolism in one study patient, an interim analysis was performed, and the dosage of certoparin was increased to 3,000 IU twice daily. This regime attained recommended antithrombotic aFXa levels in 47%, 27%, 40% and 30% of patients at 4, 12, 16 and 24 h, respectively, after twice daily certoparin injection (n = 30). Antithrombin and fibrinogen concentrations slightly increased during the observation period. Low antithrombin concentrations before certoparin were independently correlated with underdosing of certoparin. Patients with aFXa levels
doi_str_mv 10.1186/cc3792
format Article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_1297619</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2034903701</sourcerecordid><originalsourceid>FETCH-LOGICAL-b410t-ca21dd50d2089476534bb9939aa3aa0d9d84c94ce73ea2eb399f5394162ac93b3</originalsourceid><addsrcrecordid>eNp1Ud1uFCEUJkZjf9RHMMSLXjkKAwODF02axrYmTbzRpHfkDDC7NLMwArvtPopvK5vdWHvhFYd8f_nOQegdJZ8o7cVnY5hU7Qt0TLkQjSDq7mWdmeBN37HuCJ3kfE8Ilb1gr9ERFa2Ukopj9PsiFD-CKTHhO8B18BtfttgHbJIv3sA01d804RmKd6FknJxxlRQWGKq2LFNcDbEy8ZzivNxO8OgzfqgAzgWChWSxjRkWLuM4YuNSiTMkH75g2Eny7Hah7iM2kw-7wKpb2-0b9GqEKbu3h_cU_bz6-uPyprn9fv3t8uK2GTglpTHQUms7YlvSKy5Fx_gwKMUUAAMgVtmeG8WNk8xB6wam1NgxxesKwCg2sFN0vved18PKWVM7Jpj0nPwK0lZH8Po5EvxSL-JG01ZJQVU1UHuDwcf_GDxHTFzp_b2q9sMhPMVfa5eLvo_rFGpf3fZ9SyXjpJLO9iRTt5WTG_96U6J3139ye_9vlSfa4dzsD3QrsWA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>288217340</pqid></control><display><type>article</type><title>Antifactor Xa activity in critically ill patients receiving antithrombotic prophylaxis with standard dosages of certoparin: a prospective, clinical study</title><source>Springer Open Access</source><source>MEDLINE</source><source>Springer journals</source><source>PubMed Central</source><source>Directory of Open Access Journals</source><source>Alma/SFX Local Collection</source><source>EZB Electronic Journals Library</source><creator>Jochberger, Stefan ; Mayr, Viktoria ; Luckner, Günter ; Fries, Dietmar R ; Mayr, Andreas J ; Friesenecker, Barbara E ; Lorenz, Ingo ; Hasibeder, Walter R ; Ulmer, Hanno ; Schobersberger, Wolfgang ; Dünser, Martin W</creator><creatorcontrib>Jochberger, Stefan ; Mayr, Viktoria ; Luckner, Günter ; Fries, Dietmar R ; Mayr, Andreas J ; Friesenecker, Barbara E ; Lorenz, Ingo ; Hasibeder, Walter R ; Ulmer, Hanno ; Schobersberger, Wolfgang ; Dünser, Martin W</creatorcontrib><description>Deep venous thrombosis with subsequent pulmonary embolism or post-thrombotic syndrome is a feared complication in the intensive care unit. Therefore, routine prophylactic anticoagulation is widely recommended. Aside from unfractionated heparin, low molecular weight heparins, such as certoparin, have become increasingly used for prophylactic anticoagulation in critically ill patients. In this prospective study, we evaluated the potency of 3,000 IU certoparin administered once daily to reach antithrombotic antifactor Xa (aFXa) levels of 0.1 to 0.3 IU/ml in 62 critically ill patients. AFXa levels were determined 4, 12 and 24 h after injection of certoparin. Prothrombin time, activated partial thromboplastin time, antithrombin, fibrinogen, hemoglobin, platelet count, serum urea and creatinine concentrations were documented before and 12 and 24 h after injection of certoparin. Four hours after certoparin injection (n = 32), 28% of patients were within the antithrombotic aFXa range. After 12 and 24 h, 6% achieved antithrombotic aFXa levels. Because of a severe pulmonary embolism in one study patient, an interim analysis was performed, and the dosage of certoparin was increased to 3,000 IU twice daily. This regime attained recommended antithrombotic aFXa levels in 47%, 27%, 40% and 30% of patients at 4, 12, 16 and 24 h, respectively, after twice daily certoparin injection (n = 30). Antithrombin and fibrinogen concentrations slightly increased during the observation period. Low antithrombin concentrations before certoparin were independently correlated with underdosing of certoparin. Patients with aFXa levels &lt;0.1 IU/ml 4 h after certoparin injection required vasopressors more often and had lower serum concentrations of creatinine and urea than patients with antithrombotic aFXa levels. Standard dosages of certoparin of 3,000 IU given once or twice daily are ineffective for attaining the recommended aFXa levels of 0.1 to 0.3 IU/ml in critically ill patients. Low antithrombin levels before certoparin administration were independently associated with low aFXa levels. Renal function and vasopressor therapy may further influence the effectiveness of certoparin in ensuring adequate antithrombotic prophylaxis.</description><identifier>ISSN: 1364-8535</identifier><identifier>EISSN: 1466-609X</identifier><identifier>EISSN: 1364-8535</identifier><identifier>DOI: 10.1186/cc3792</identifier><identifier>PMID: 16277716</identifier><language>eng</language><publisher>England: National Library of Medicine - MEDLINE Abstracts</publisher><subject>Aged ; Anticoagulants - therapeutic use ; Dose-Response Relationship, Drug ; Epidemiologic Methods ; Factor Xa - drug effects ; Factor Xa - metabolism ; Female ; Fibrinolytic Agents - therapeutic use ; Heparin, Low-Molecular-Weight - therapeutic use ; Humans ; Male ; Middle Aged ; Risk Factors ; Venous Thrombosis - blood ; Venous Thrombosis - drug therapy ; Venous Thrombosis - prevention &amp; control</subject><ispartof>Critical care (London, England), 2005, Vol.9 (5), p.R541-R548, Article R541</ispartof><rights>Copyright National Library of Medicine - MEDLINE Abstracts Oct 5, 2005</rights><rights>Copyright © 2005 Jochberger et al.; licensee BioMed Central Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b410t-ca21dd50d2089476534bb9939aa3aa0d9d84c94ce73ea2eb399f5394162ac93b3</citedby><cites>FETCH-LOGICAL-b410t-ca21dd50d2089476534bb9939aa3aa0d9d84c94ce73ea2eb399f5394162ac93b3</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/PMC1297619/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1297619/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,4024,27923,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16277716$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jochberger, Stefan</creatorcontrib><creatorcontrib>Mayr, Viktoria</creatorcontrib><creatorcontrib>Luckner, Günter</creatorcontrib><creatorcontrib>Fries, Dietmar R</creatorcontrib><creatorcontrib>Mayr, Andreas J</creatorcontrib><creatorcontrib>Friesenecker, Barbara E</creatorcontrib><creatorcontrib>Lorenz, Ingo</creatorcontrib><creatorcontrib>Hasibeder, Walter R</creatorcontrib><creatorcontrib>Ulmer, Hanno</creatorcontrib><creatorcontrib>Schobersberger, Wolfgang</creatorcontrib><creatorcontrib>Dünser, Martin W</creatorcontrib><title>Antifactor Xa activity in critically ill patients receiving antithrombotic prophylaxis with standard dosages of certoparin: a prospective, clinical study</title><title>Critical care (London, England)</title><addtitle>Crit Care</addtitle><description>Deep venous thrombosis with subsequent pulmonary embolism or post-thrombotic syndrome is a feared complication in the intensive care unit. Therefore, routine prophylactic anticoagulation is widely recommended. Aside from unfractionated heparin, low molecular weight heparins, such as certoparin, have become increasingly used for prophylactic anticoagulation in critically ill patients. In this prospective study, we evaluated the potency of 3,000 IU certoparin administered once daily to reach antithrombotic antifactor Xa (aFXa) levels of 0.1 to 0.3 IU/ml in 62 critically ill patients. AFXa levels were determined 4, 12 and 24 h after injection of certoparin. Prothrombin time, activated partial thromboplastin time, antithrombin, fibrinogen, hemoglobin, platelet count, serum urea and creatinine concentrations were documented before and 12 and 24 h after injection of certoparin. Four hours after certoparin injection (n = 32), 28% of patients were within the antithrombotic aFXa range. After 12 and 24 h, 6% achieved antithrombotic aFXa levels. Because of a severe pulmonary embolism in one study patient, an interim analysis was performed, and the dosage of certoparin was increased to 3,000 IU twice daily. This regime attained recommended antithrombotic aFXa levels in 47%, 27%, 40% and 30% of patients at 4, 12, 16 and 24 h, respectively, after twice daily certoparin injection (n = 30). Antithrombin and fibrinogen concentrations slightly increased during the observation period. Low antithrombin concentrations before certoparin were independently correlated with underdosing of certoparin. Patients with aFXa levels &lt;0.1 IU/ml 4 h after certoparin injection required vasopressors more often and had lower serum concentrations of creatinine and urea than patients with antithrombotic aFXa levels. Standard dosages of certoparin of 3,000 IU given once or twice daily are ineffective for attaining the recommended aFXa levels of 0.1 to 0.3 IU/ml in critically ill patients. Low antithrombin levels before certoparin administration were independently associated with low aFXa levels. Renal function and vasopressor therapy may further influence the effectiveness of certoparin in ensuring adequate antithrombotic prophylaxis.</description><subject>Aged</subject><subject>Anticoagulants - therapeutic use</subject><subject>Dose-Response Relationship, Drug</subject><subject>Epidemiologic Methods</subject><subject>Factor Xa - drug effects</subject><subject>Factor Xa - metabolism</subject><subject>Female</subject><subject>Fibrinolytic Agents - therapeutic use</subject><subject>Heparin, Low-Molecular-Weight - therapeutic use</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Risk Factors</subject><subject>Venous Thrombosis - blood</subject><subject>Venous Thrombosis - drug therapy</subject><subject>Venous Thrombosis - prevention &amp; control</subject><issn>1364-8535</issn><issn>1466-609X</issn><issn>1364-8535</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1Ud1uFCEUJkZjf9RHMMSLXjkKAwODF02axrYmTbzRpHfkDDC7NLMwArvtPopvK5vdWHvhFYd8f_nOQegdJZ8o7cVnY5hU7Qt0TLkQjSDq7mWdmeBN37HuCJ3kfE8Ilb1gr9ERFa2Ukopj9PsiFD-CKTHhO8B18BtfttgHbJIv3sA01d804RmKd6FknJxxlRQWGKq2LFNcDbEy8ZzivNxO8OgzfqgAzgWChWSxjRkWLuM4YuNSiTMkH75g2Eny7Hah7iM2kw-7wKpb2-0b9GqEKbu3h_cU_bz6-uPyprn9fv3t8uK2GTglpTHQUms7YlvSKy5Fx_gwKMUUAAMgVtmeG8WNk8xB6wam1NgxxesKwCg2sFN0vved18PKWVM7Jpj0nPwK0lZH8Po5EvxSL-JG01ZJQVU1UHuDwcf_GDxHTFzp_b2q9sMhPMVfa5eLvo_rFGpf3fZ9SyXjpJLO9iRTt5WTG_96U6J3139ye_9vlSfa4dzsD3QrsWA</recordid><startdate>2005</startdate><enddate>2005</enddate><creator>Jochberger, Stefan</creator><creator>Mayr, Viktoria</creator><creator>Luckner, Günter</creator><creator>Fries, Dietmar R</creator><creator>Mayr, Andreas J</creator><creator>Friesenecker, Barbara E</creator><creator>Lorenz, Ingo</creator><creator>Hasibeder, Walter R</creator><creator>Ulmer, Hanno</creator><creator>Schobersberger, Wolfgang</creator><creator>Dünser, Martin W</creator><general>National Library of Medicine - MEDLINE Abstracts</general><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>K9.</scope><scope>5PM</scope></search><sort><creationdate>2005</creationdate><title>Antifactor Xa activity in critically ill patients receiving antithrombotic prophylaxis with standard dosages of certoparin: a prospective, clinical study</title><author>Jochberger, Stefan ; Mayr, Viktoria ; Luckner, Günter ; Fries, Dietmar R ; Mayr, Andreas J ; Friesenecker, Barbara E ; Lorenz, Ingo ; Hasibeder, Walter R ; Ulmer, Hanno ; Schobersberger, Wolfgang ; Dünser, Martin W</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b410t-ca21dd50d2089476534bb9939aa3aa0d9d84c94ce73ea2eb399f5394162ac93b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Aged</topic><topic>Anticoagulants - therapeutic use</topic><topic>Dose-Response Relationship, Drug</topic><topic>Epidemiologic Methods</topic><topic>Factor Xa - drug effects</topic><topic>Factor Xa - metabolism</topic><topic>Female</topic><topic>Fibrinolytic Agents - therapeutic use</topic><topic>Heparin, Low-Molecular-Weight - therapeutic use</topic><topic>Humans</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Risk Factors</topic><topic>Venous Thrombosis - blood</topic><topic>Venous Thrombosis - drug therapy</topic><topic>Venous Thrombosis - prevention &amp; control</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jochberger, Stefan</creatorcontrib><creatorcontrib>Mayr, Viktoria</creatorcontrib><creatorcontrib>Luckner, Günter</creatorcontrib><creatorcontrib>Fries, Dietmar R</creatorcontrib><creatorcontrib>Mayr, Andreas J</creatorcontrib><creatorcontrib>Friesenecker, Barbara E</creatorcontrib><creatorcontrib>Lorenz, Ingo</creatorcontrib><creatorcontrib>Hasibeder, Walter R</creatorcontrib><creatorcontrib>Ulmer, Hanno</creatorcontrib><creatorcontrib>Schobersberger, Wolfgang</creatorcontrib><creatorcontrib>Dünser, Martin W</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</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>Jochberger, Stefan</au><au>Mayr, Viktoria</au><au>Luckner, Günter</au><au>Fries, Dietmar R</au><au>Mayr, Andreas J</au><au>Friesenecker, Barbara E</au><au>Lorenz, Ingo</au><au>Hasibeder, Walter R</au><au>Ulmer, Hanno</au><au>Schobersberger, Wolfgang</au><au>Dünser, Martin W</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antifactor Xa activity in critically ill patients receiving antithrombotic prophylaxis with standard dosages of certoparin: a prospective, clinical study</atitle><jtitle>Critical care (London, England)</jtitle><addtitle>Crit Care</addtitle><date>2005</date><risdate>2005</risdate><volume>9</volume><issue>5</issue><spage>R541</spage><epage>R548</epage><pages>R541-R548</pages><artnum>R541</artnum><issn>1364-8535</issn><eissn>1466-609X</eissn><eissn>1364-8535</eissn><abstract>Deep venous thrombosis with subsequent pulmonary embolism or post-thrombotic syndrome is a feared complication in the intensive care unit. Therefore, routine prophylactic anticoagulation is widely recommended. Aside from unfractionated heparin, low molecular weight heparins, such as certoparin, have become increasingly used for prophylactic anticoagulation in critically ill patients. In this prospective study, we evaluated the potency of 3,000 IU certoparin administered once daily to reach antithrombotic antifactor Xa (aFXa) levels of 0.1 to 0.3 IU/ml in 62 critically ill patients. AFXa levels were determined 4, 12 and 24 h after injection of certoparin. Prothrombin time, activated partial thromboplastin time, antithrombin, fibrinogen, hemoglobin, platelet count, serum urea and creatinine concentrations were documented before and 12 and 24 h after injection of certoparin. Four hours after certoparin injection (n = 32), 28% of patients were within the antithrombotic aFXa range. After 12 and 24 h, 6% achieved antithrombotic aFXa levels. Because of a severe pulmonary embolism in one study patient, an interim analysis was performed, and the dosage of certoparin was increased to 3,000 IU twice daily. This regime attained recommended antithrombotic aFXa levels in 47%, 27%, 40% and 30% of patients at 4, 12, 16 and 24 h, respectively, after twice daily certoparin injection (n = 30). Antithrombin and fibrinogen concentrations slightly increased during the observation period. Low antithrombin concentrations before certoparin were independently correlated with underdosing of certoparin. Patients with aFXa levels &lt;0.1 IU/ml 4 h after certoparin injection required vasopressors more often and had lower serum concentrations of creatinine and urea than patients with antithrombotic aFXa levels. Standard dosages of certoparin of 3,000 IU given once or twice daily are ineffective for attaining the recommended aFXa levels of 0.1 to 0.3 IU/ml in critically ill patients. Low antithrombin levels before certoparin administration were independently associated with low aFXa levels. Renal function and vasopressor therapy may further influence the effectiveness of certoparin in ensuring adequate antithrombotic prophylaxis.</abstract><cop>England</cop><pub>National Library of Medicine - MEDLINE Abstracts</pub><pmid>16277716</pmid><doi>10.1186/cc3792</doi><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1364-8535
ispartof Critical care (London, England), 2005, Vol.9 (5), p.R541-R548, Article R541
issn 1364-8535
1466-609X
1364-8535
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_1297619
source Springer Open Access; MEDLINE; Springer journals; PubMed Central; Directory of Open Access Journals; Alma/SFX Local Collection; EZB Electronic Journals Library
subjects Aged
Anticoagulants - therapeutic use
Dose-Response Relationship, Drug
Epidemiologic Methods
Factor Xa - drug effects
Factor Xa - metabolism
Female
Fibrinolytic Agents - therapeutic use
Heparin, Low-Molecular-Weight - therapeutic use
Humans
Male
Middle Aged
Risk Factors
Venous Thrombosis - blood
Venous Thrombosis - drug therapy
Venous Thrombosis - prevention & control
title Antifactor Xa activity in critically ill patients receiving antithrombotic prophylaxis with standard dosages of certoparin: a prospective, clinical study
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-20T19%3A10%3A50IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Antifactor%20Xa%20activity%20in%20critically%20ill%20patients%20receiving%20antithrombotic%20prophylaxis%20with%20standard%20dosages%20of%20certoparin:%20a%20prospective,%20clinical%20study&rft.jtitle=Critical%20care%20(London,%20England)&rft.au=Jochberger,%20Stefan&rft.date=2005&rft.volume=9&rft.issue=5&rft.spage=R541&rft.epage=R548&rft.pages=R541-R548&rft.artnum=R541&rft.issn=1364-8535&rft.eissn=1466-609X&rft_id=info:doi/10.1186/cc3792&rft_dat=%3Cproquest_pubme%3E2034903701%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=288217340&rft_id=info:pmid/16277716&rfr_iscdi=true