Tryptophan and Kynurenine Levels and Its Association With Sleep, Nonphysical Fatigue, and Depression in Chronic Hemodialysis Patients
Objective Sleep and mood disorders are common in hemodialysis (HD) patients and the pathophysiology is still unclear. Tryptophan (TRP) and its metabolites may play a prominent role in neural pathways related to sleep, fatigue, and depression. Here, we sought to compare the levels of TRP and its meta...
Gespeichert in:
| Veröffentlicht in: | Journal of renal nutrition 2017-07, Vol.27 (4), p.260-266 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 266 |
|---|---|
| container_issue | 4 |
| container_start_page | 260 |
| container_title | Journal of renal nutrition |
| container_volume | 27 |
| creator | Malhotra, Rakesh, MD, MPH Persic, Vanja, MD Zhang, Weifang, MS Brown, Jill, MS Tao, Xia, MD, PhD Rosales, Laura, MD Thijssen, Stephan, MD Finkelstein, Fredric O., MD Unruh, Mark L., MD Ikizler, Alp, MD Garimella, Pranav S., MD, MPH Ix, Joachim H., MD Kooman, Jeroen, MD Levin, Nathan W., MD Handelman, Garry J., PhD Kotanko, Peter, MD |
| description | Objective Sleep and mood disorders are common in hemodialysis (HD) patients and the pathophysiology is still unclear. Tryptophan (TRP) and its metabolites may play a prominent role in neural pathways related to sleep, fatigue, and depression. Here, we sought to compare the levels of TRP and its metabolites between HD patients and healthy subjects and examine their association with sleep, fatigue, and depression in HD patients. The design was cross-sectional analysis. Subjects Ninety-nine adult patients on stable thrice weekly HD schedule between September 2011 and March 2014 and 10 healthy controls. Intervention Venous blood samples were drawn in healthy subjects and immediately before dialysis in chronic HD patients. TRP and kynurenine (KYN) metabolites were measured by high-performance liquid chromatography. The Medical Outcomes Study Sleep Scale, the PROMIS Short form Fatigue, and the Patient Health Questionnaire were administered concurrently. Main Outcome Measure Sleep, fatigue, and depression as assessed by subjective questionnaire. Results TRP levels were significantly lower (52.4 ± 15.2 vs. 67.9 ± 3.1 μmol/L; P |
| doi_str_mv | 10.1053/j.jrn.2017.01.024 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1883839046</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S1051227617300535</els_id><sourcerecordid>1883839046</sourcerecordid><originalsourceid>FETCH-LOGICAL-c408t-7608d9a164307838b59f62c3551a428b49bed3b15b77ae5b2d89c3a5b68299443</originalsourceid><addsrcrecordid>eNp9kctu1DAUhiMEoqXwAGyQlyyawdfEERJSNdCLGAFSi1hajnOG8ZCxU5-k0jwA712nU1iwYHWs4-__F98piteMLhhV4t12sU1hwSmrF5QtKJdPimOmBC-1ouJpflPFSs7r6qh4gbillDGl-fPiiGtRVVLK4-L3TdoPYxw2NhAbOvJ5H6YEwQcgK7iDHh-2VyOSM8TovB19DOSHHzfkugcYTsmXGIbNHr2zPTnP3z8nOH0IfYQhAeLM-0CWmxSDd-QSdrHzts8JJN8yD2HEl8Wzte0RXj3Ok-L7-aeb5WW5-npxtTxblU5SPZZ1RXXXWFZJQWstdKuadcWdUIpZyXUrmxY60TLV1rUF1fJON05Y1VaaN42U4qR4e-gdUrydAEez8-ig722AOKFhOreKhsoqo-yAuhQRE6zNkPzOpr1h1Mz2zdZk-2a2bygz2X7OvHmsn9oddH8Tf3Rn4P0ByGLhzkMy6LIAB51P4EbTRf_f-g__pF3vwyz-F-wBt3FKIdszzCA31FzP55-vz2pBc6MS924dqsI</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1883839046</pqid></control><display><type>article</type><title>Tryptophan and Kynurenine Levels and Its Association With Sleep, Nonphysical Fatigue, and Depression in Chronic Hemodialysis Patients</title><source>MEDLINE</source><source>Access via ScienceDirect (Elsevier)</source><creator>Malhotra, Rakesh, MD, MPH ; Persic, Vanja, MD ; Zhang, Weifang, MS ; Brown, Jill, MS ; Tao, Xia, MD, PhD ; Rosales, Laura, MD ; Thijssen, Stephan, MD ; Finkelstein, Fredric O., MD ; Unruh, Mark L., MD ; Ikizler, Alp, MD ; Garimella, Pranav S., MD, MPH ; Ix, Joachim H., MD ; Kooman, Jeroen, MD ; Levin, Nathan W., MD ; Handelman, Garry J., PhD ; Kotanko, Peter, MD</creator><creatorcontrib>Malhotra, Rakesh, MD, MPH ; Persic, Vanja, MD ; Zhang, Weifang, MS ; Brown, Jill, MS ; Tao, Xia, MD, PhD ; Rosales, Laura, MD ; Thijssen, Stephan, MD ; Finkelstein, Fredric O., MD ; Unruh, Mark L., MD ; Ikizler, Alp, MD ; Garimella, Pranav S., MD, MPH ; Ix, Joachim H., MD ; Kooman, Jeroen, MD ; Levin, Nathan W., MD ; Handelman, Garry J., PhD ; Kotanko, Peter, MD</creatorcontrib><description>Objective Sleep and mood disorders are common in hemodialysis (HD) patients and the pathophysiology is still unclear. Tryptophan (TRP) and its metabolites may play a prominent role in neural pathways related to sleep, fatigue, and depression. Here, we sought to compare the levels of TRP and its metabolites between HD patients and healthy subjects and examine their association with sleep, fatigue, and depression in HD patients. The design was cross-sectional analysis. Subjects Ninety-nine adult patients on stable thrice weekly HD schedule between September 2011 and March 2014 and 10 healthy controls. Intervention Venous blood samples were drawn in healthy subjects and immediately before dialysis in chronic HD patients. TRP and kynurenine (KYN) metabolites were measured by high-performance liquid chromatography. The Medical Outcomes Study Sleep Scale, the PROMIS Short form Fatigue, and the Patient Health Questionnaire were administered concurrently. Main Outcome Measure Sleep, fatigue, and depression as assessed by subjective questionnaire. Results TRP levels were significantly lower (52.4 ± 15.2 vs. 67.9 ± 3.1 μmol/L; P < .0001) and KYN (3.2 ± 1.2 vs. 1.4 ± 0.1 μmol/L; P < .0001) were significantly higher in the 99 HD patients relative to 10 healthy controls. In HD patients, higher KYN levels were correlated with worse depression and fatigue scores ( r2 = 0.23 and 0.21; P ≤ .05, respectively). We found no association between TRP and KYN/TRP ratio with sleep disturbances, fatigue, and depression in HD patients. Conclusions Our study indicates disturbed TRP metabolism in HD patients, but low TRP levels were not related with sleep disturbances, depression, and fatigue. In contrast, KYN levels, a metabolite of TRP, were much higher in HD patients compared with controls, and higher KYN associated with depression and fatigue. Further studies exploring the biological and functional consequences of increased TRP catabolism in HD patients are warranted.</description><identifier>ISSN: 1051-2276</identifier><identifier>EISSN: 1532-8503</identifier><identifier>DOI: 10.1053/j.jrn.2017.01.024</identifier><identifier>PMID: 28366444</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adult ; Aged ; Body Mass Index ; Case-Control Studies ; Cross-Sectional Studies ; Depression - blood ; Depression - diagnosis ; Fatigue - blood ; Fatigue - diagnosis ; Female ; Humans ; Kynurenine - blood ; Male ; Middle Aged ; Nephrology ; Renal Dialysis ; Reproducibility of Results ; Sleep - physiology ; Surveys and Questionnaires ; Tryptophan - blood</subject><ispartof>Journal of renal nutrition, 2017-07, Vol.27 (4), p.260-266</ispartof><rights>National Kidney Foundation, Inc.</rights><rights>2017 National Kidney Foundation, Inc.</rights><rights>Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c408t-7608d9a164307838b59f62c3551a428b49bed3b15b77ae5b2d89c3a5b68299443</citedby><cites>FETCH-LOGICAL-c408t-7608d9a164307838b59f62c3551a428b49bed3b15b77ae5b2d89c3a5b68299443</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1053/j.jrn.2017.01.024$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,781,785,3551,27929,27930,46000</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28366444$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Malhotra, Rakesh, MD, MPH</creatorcontrib><creatorcontrib>Persic, Vanja, MD</creatorcontrib><creatorcontrib>Zhang, Weifang, MS</creatorcontrib><creatorcontrib>Brown, Jill, MS</creatorcontrib><creatorcontrib>Tao, Xia, MD, PhD</creatorcontrib><creatorcontrib>Rosales, Laura, MD</creatorcontrib><creatorcontrib>Thijssen, Stephan, MD</creatorcontrib><creatorcontrib>Finkelstein, Fredric O., MD</creatorcontrib><creatorcontrib>Unruh, Mark L., MD</creatorcontrib><creatorcontrib>Ikizler, Alp, MD</creatorcontrib><creatorcontrib>Garimella, Pranav S., MD, MPH</creatorcontrib><creatorcontrib>Ix, Joachim H., MD</creatorcontrib><creatorcontrib>Kooman, Jeroen, MD</creatorcontrib><creatorcontrib>Levin, Nathan W., MD</creatorcontrib><creatorcontrib>Handelman, Garry J., PhD</creatorcontrib><creatorcontrib>Kotanko, Peter, MD</creatorcontrib><title>Tryptophan and Kynurenine Levels and Its Association With Sleep, Nonphysical Fatigue, and Depression in Chronic Hemodialysis Patients</title><title>Journal of renal nutrition</title><addtitle>J Ren Nutr</addtitle><description>Objective Sleep and mood disorders are common in hemodialysis (HD) patients and the pathophysiology is still unclear. Tryptophan (TRP) and its metabolites may play a prominent role in neural pathways related to sleep, fatigue, and depression. Here, we sought to compare the levels of TRP and its metabolites between HD patients and healthy subjects and examine their association with sleep, fatigue, and depression in HD patients. The design was cross-sectional analysis. Subjects Ninety-nine adult patients on stable thrice weekly HD schedule between September 2011 and March 2014 and 10 healthy controls. Intervention Venous blood samples were drawn in healthy subjects and immediately before dialysis in chronic HD patients. TRP and kynurenine (KYN) metabolites were measured by high-performance liquid chromatography. The Medical Outcomes Study Sleep Scale, the PROMIS Short form Fatigue, and the Patient Health Questionnaire were administered concurrently. Main Outcome Measure Sleep, fatigue, and depression as assessed by subjective questionnaire. Results TRP levels were significantly lower (52.4 ± 15.2 vs. 67.9 ± 3.1 μmol/L; P < .0001) and KYN (3.2 ± 1.2 vs. 1.4 ± 0.1 μmol/L; P < .0001) were significantly higher in the 99 HD patients relative to 10 healthy controls. In HD patients, higher KYN levels were correlated with worse depression and fatigue scores ( r2 = 0.23 and 0.21; P ≤ .05, respectively). We found no association between TRP and KYN/TRP ratio with sleep disturbances, fatigue, and depression in HD patients. Conclusions Our study indicates disturbed TRP metabolism in HD patients, but low TRP levels were not related with sleep disturbances, depression, and fatigue. In contrast, KYN levels, a metabolite of TRP, were much higher in HD patients compared with controls, and higher KYN associated with depression and fatigue. Further studies exploring the biological and functional consequences of increased TRP catabolism in HD patients are warranted.</description><subject>Adult</subject><subject>Aged</subject><subject>Body Mass Index</subject><subject>Case-Control Studies</subject><subject>Cross-Sectional Studies</subject><subject>Depression - blood</subject><subject>Depression - diagnosis</subject><subject>Fatigue - blood</subject><subject>Fatigue - diagnosis</subject><subject>Female</subject><subject>Humans</subject><subject>Kynurenine - blood</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Nephrology</subject><subject>Renal Dialysis</subject><subject>Reproducibility of Results</subject><subject>Sleep - physiology</subject><subject>Surveys and Questionnaires</subject><subject>Tryptophan - blood</subject><issn>1051-2276</issn><issn>1532-8503</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kctu1DAUhiMEoqXwAGyQlyyawdfEERJSNdCLGAFSi1hajnOG8ZCxU5-k0jwA712nU1iwYHWs4-__F98piteMLhhV4t12sU1hwSmrF5QtKJdPimOmBC-1ouJpflPFSs7r6qh4gbillDGl-fPiiGtRVVLK4-L3TdoPYxw2NhAbOvJ5H6YEwQcgK7iDHh-2VyOSM8TovB19DOSHHzfkugcYTsmXGIbNHr2zPTnP3z8nOH0IfYQhAeLM-0CWmxSDd-QSdrHzts8JJN8yD2HEl8Wzte0RXj3Ok-L7-aeb5WW5-npxtTxblU5SPZZ1RXXXWFZJQWstdKuadcWdUIpZyXUrmxY60TLV1rUF1fJON05Y1VaaN42U4qR4e-gdUrydAEez8-ig722AOKFhOreKhsoqo-yAuhQRE6zNkPzOpr1h1Mz2zdZk-2a2bygz2X7OvHmsn9oddH8Tf3Rn4P0ByGLhzkMy6LIAB51P4EbTRf_f-g__pF3vwyz-F-wBt3FKIdszzCA31FzP55-vz2pBc6MS924dqsI</recordid><startdate>20170701</startdate><enddate>20170701</enddate><creator>Malhotra, Rakesh, MD, MPH</creator><creator>Persic, Vanja, MD</creator><creator>Zhang, Weifang, MS</creator><creator>Brown, Jill, MS</creator><creator>Tao, Xia, MD, PhD</creator><creator>Rosales, Laura, MD</creator><creator>Thijssen, Stephan, MD</creator><creator>Finkelstein, Fredric O., MD</creator><creator>Unruh, Mark L., MD</creator><creator>Ikizler, Alp, MD</creator><creator>Garimella, Pranav S., MD, MPH</creator><creator>Ix, Joachim H., MD</creator><creator>Kooman, Jeroen, MD</creator><creator>Levin, Nathan W., MD</creator><creator>Handelman, Garry J., PhD</creator><creator>Kotanko, Peter, MD</creator><general>Elsevier Inc</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></search><sort><creationdate>20170701</creationdate><title>Tryptophan and Kynurenine Levels and Its Association With Sleep, Nonphysical Fatigue, and Depression in Chronic Hemodialysis Patients</title><author>Malhotra, Rakesh, MD, MPH ; Persic, Vanja, MD ; Zhang, Weifang, MS ; Brown, Jill, MS ; Tao, Xia, MD, PhD ; Rosales, Laura, MD ; Thijssen, Stephan, MD ; Finkelstein, Fredric O., MD ; Unruh, Mark L., MD ; Ikizler, Alp, MD ; Garimella, Pranav S., MD, MPH ; Ix, Joachim H., MD ; Kooman, Jeroen, MD ; Levin, Nathan W., MD ; Handelman, Garry J., PhD ; Kotanko, Peter, MD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c408t-7608d9a164307838b59f62c3551a428b49bed3b15b77ae5b2d89c3a5b68299443</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Body Mass Index</topic><topic>Case-Control Studies</topic><topic>Cross-Sectional Studies</topic><topic>Depression - blood</topic><topic>Depression - diagnosis</topic><topic>Fatigue - blood</topic><topic>Fatigue - diagnosis</topic><topic>Female</topic><topic>Humans</topic><topic>Kynurenine - blood</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Nephrology</topic><topic>Renal Dialysis</topic><topic>Reproducibility of Results</topic><topic>Sleep - physiology</topic><topic>Surveys and Questionnaires</topic><topic>Tryptophan - blood</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Malhotra, Rakesh, MD, MPH</creatorcontrib><creatorcontrib>Persic, Vanja, MD</creatorcontrib><creatorcontrib>Zhang, Weifang, MS</creatorcontrib><creatorcontrib>Brown, Jill, MS</creatorcontrib><creatorcontrib>Tao, Xia, MD, PhD</creatorcontrib><creatorcontrib>Rosales, Laura, MD</creatorcontrib><creatorcontrib>Thijssen, Stephan, MD</creatorcontrib><creatorcontrib>Finkelstein, Fredric O., MD</creatorcontrib><creatorcontrib>Unruh, Mark L., MD</creatorcontrib><creatorcontrib>Ikizler, Alp, MD</creatorcontrib><creatorcontrib>Garimella, Pranav S., MD, MPH</creatorcontrib><creatorcontrib>Ix, Joachim H., MD</creatorcontrib><creatorcontrib>Kooman, Jeroen, MD</creatorcontrib><creatorcontrib>Levin, Nathan W., MD</creatorcontrib><creatorcontrib>Handelman, Garry J., PhD</creatorcontrib><creatorcontrib>Kotanko, Peter, MD</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><jtitle>Journal of renal nutrition</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Malhotra, Rakesh, MD, MPH</au><au>Persic, Vanja, MD</au><au>Zhang, Weifang, MS</au><au>Brown, Jill, MS</au><au>Tao, Xia, MD, PhD</au><au>Rosales, Laura, MD</au><au>Thijssen, Stephan, MD</au><au>Finkelstein, Fredric O., MD</au><au>Unruh, Mark L., MD</au><au>Ikizler, Alp, MD</au><au>Garimella, Pranav S., MD, MPH</au><au>Ix, Joachim H., MD</au><au>Kooman, Jeroen, MD</au><au>Levin, Nathan W., MD</au><au>Handelman, Garry J., PhD</au><au>Kotanko, Peter, MD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tryptophan and Kynurenine Levels and Its Association With Sleep, Nonphysical Fatigue, and Depression in Chronic Hemodialysis Patients</atitle><jtitle>Journal of renal nutrition</jtitle><addtitle>J Ren Nutr</addtitle><date>2017-07-01</date><risdate>2017</risdate><volume>27</volume><issue>4</issue><spage>260</spage><epage>266</epage><pages>260-266</pages><issn>1051-2276</issn><eissn>1532-8503</eissn><abstract>Objective Sleep and mood disorders are common in hemodialysis (HD) patients and the pathophysiology is still unclear. Tryptophan (TRP) and its metabolites may play a prominent role in neural pathways related to sleep, fatigue, and depression. Here, we sought to compare the levels of TRP and its metabolites between HD patients and healthy subjects and examine their association with sleep, fatigue, and depression in HD patients. The design was cross-sectional analysis. Subjects Ninety-nine adult patients on stable thrice weekly HD schedule between September 2011 and March 2014 and 10 healthy controls. Intervention Venous blood samples were drawn in healthy subjects and immediately before dialysis in chronic HD patients. TRP and kynurenine (KYN) metabolites were measured by high-performance liquid chromatography. The Medical Outcomes Study Sleep Scale, the PROMIS Short form Fatigue, and the Patient Health Questionnaire were administered concurrently. Main Outcome Measure Sleep, fatigue, and depression as assessed by subjective questionnaire. Results TRP levels were significantly lower (52.4 ± 15.2 vs. 67.9 ± 3.1 μmol/L; P < .0001) and KYN (3.2 ± 1.2 vs. 1.4 ± 0.1 μmol/L; P < .0001) were significantly higher in the 99 HD patients relative to 10 healthy controls. In HD patients, higher KYN levels were correlated with worse depression and fatigue scores ( r2 = 0.23 and 0.21; P ≤ .05, respectively). We found no association between TRP and KYN/TRP ratio with sleep disturbances, fatigue, and depression in HD patients. Conclusions Our study indicates disturbed TRP metabolism in HD patients, but low TRP levels were not related with sleep disturbances, depression, and fatigue. In contrast, KYN levels, a metabolite of TRP, were much higher in HD patients compared with controls, and higher KYN associated with depression and fatigue. Further studies exploring the biological and functional consequences of increased TRP catabolism in HD patients are warranted.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>28366444</pmid><doi>10.1053/j.jrn.2017.01.024</doi><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1051-2276 |
| ispartof | Journal of renal nutrition, 2017-07, Vol.27 (4), p.260-266 |
| issn | 1051-2276 1532-8503 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1883839046 |
| source | MEDLINE; Access via ScienceDirect (Elsevier) |
| subjects | Adult Aged Body Mass Index Case-Control Studies Cross-Sectional Studies Depression - blood Depression - diagnosis Fatigue - blood Fatigue - diagnosis Female Humans Kynurenine - blood Male Middle Aged Nephrology Renal Dialysis Reproducibility of Results Sleep - physiology Surveys and Questionnaires Tryptophan - blood |
| title | Tryptophan and Kynurenine Levels and Its Association With Sleep, Nonphysical Fatigue, and Depression in Chronic Hemodialysis Patients |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-11T08%3A40%3A16IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Tryptophan%20and%20Kynurenine%20Levels%20and%20Its%20Association%20With%20Sleep,%20Nonphysical%20Fatigue,%20and%20Depression%20in%20Chronic%20Hemodialysis%20Patients&rft.jtitle=Journal%20of%20renal%20nutrition&rft.au=Malhotra,%20Rakesh,%20MD,%20MPH&rft.date=2017-07-01&rft.volume=27&rft.issue=4&rft.spage=260&rft.epage=266&rft.pages=260-266&rft.issn=1051-2276&rft.eissn=1532-8503&rft_id=info:doi/10.1053/j.jrn.2017.01.024&rft_dat=%3Cproquest_cross%3E1883839046%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1883839046&rft_id=info:pmid/28366444&rft_els_id=S1051227617300535&rfr_iscdi=true |