Predicting Out-of-Office Blood Pressure in the Clinic (PROOF-BP): Derivation and Validation of a Tool to Improve the Accuracy of Blood Pressure Measurement in Clinical Practice

Patients often have lower (white coat effect) or higher (masked effect) ambulatory/home blood pressure readings compared with clinic measurements, resulting in misdiagnosis of hypertension. The present study assessed whether blood pressure and patient characteristics from a single clinic visit can a...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Hypertension (Dallas, Tex. 1979) Tex. 1979), 2016-05, Vol.67 (5), p.941-950
Hauptverfasser: Sheppard, James P, Stevens, Richard, Gill, Paramjit, Martin, Una, Godwin, Marshall, Hanley, Janet, Heneghan, Carl, Hobbs, F.D Richard, Mant, Jonathan, McKinstry, Brian, Myers, Martin, Nunan, David, Ward, Alison, Williams, Bryan, McManus, Richard J
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 950
container_issue 5
container_start_page 941
container_title Hypertension (Dallas, Tex. 1979)
container_volume 67
creator Sheppard, James P
Stevens, Richard
Gill, Paramjit
Martin, Una
Godwin, Marshall
Hanley, Janet
Heneghan, Carl
Hobbs, F.D Richard
Mant, Jonathan
McKinstry, Brian
Myers, Martin
Nunan, David
Ward, Alison
Williams, Bryan
McManus, Richard J
description Patients often have lower (white coat effect) or higher (masked effect) ambulatory/home blood pressure readings compared with clinic measurements, resulting in misdiagnosis of hypertension. The present study assessed whether blood pressure and patient characteristics from a single clinic visit can accurately predict the difference between ambulatory/home and clinic blood pressure readings (the home–clinic difference). A linear regression model predicting the home–clinic blood pressure difference was derived in 2 data sets measuring automated clinic and ambulatory/home blood pressure (n=991) using candidate predictors identified from a literature review. The model was validated in 4 further data sets (n=1172) using area under the receiver operator characteristic curve analysis. A masked effect was associated with male sex, a positive clinic blood pressure change (difference between consecutive measurements during a single visit), and a diagnosis of hypertension. Increasing age, clinic blood pressure level, and pulse pressure were associated with a white coat effect. The model showed good calibration across data sets (Pearson correlation, 0.48–0.80) and performed well-predicting ambulatory hypertension (area under the receiver operator characteristic curve, 0.75; 95% confidence interval, 0.72–0.79 [systolic]; 0.87; 0.85–0.89 [diastolic]). Used as a triaging tool for ambulatory monitoring, the model improved classification of a patient’s blood pressure status compared with other guideline recommended approaches (93% [92% to 95%] classified correctly; United States, 73% [70% to 75%]; Canada, 74% [71% to 77%]; United Kingdom, 78% [76% to 81%]). This study demonstrates that patient characteristics from a single clinic visit can accurately predict a patient’s ambulatory blood pressure. Usage of this prediction tool for triaging of ambulatory monitoring could result in more accurate diagnosis of hypertension and hence more appropriate treatment.
doi_str_mv 10.1161/HYPERTENSIONAHA.115.07108
format Article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4905620</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1781537908</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3708-ba54a20f94b7eb95ad184148d8c6c6470465ac19f29cb51bc445c599a3f409273</originalsourceid><addsrcrecordid>eNqNkdFu0zAUhi0EYmXwCsjcjYsMO7GTGAmkrnS00liqURBcWY5jrx5OXOyk096KR8RdxgS74urY53zn_4_0A_AKo2OMc_xm8X01v1jPzz8vq_PpYhqb9BgVGJWPwATTlCSE5tljMEGYkYRh_O0APAvhCiFMCCmegoO0iO-UsQn4tfKqMbI33SWshj5xOqm0NlLBE-tcA-M4hMEraDrYbxScWdMZCY9WF1V1mpysXr-FH5Q3O9Eb10HRNfCrsKYZv05DAdfOWdg7uGy33u3UrcpUysELebMnHvh8UmJfW9X1e8_RT9gIiHilVM_BEy1sUC_u6iH4cjpfzxbJWfVxOZueJTIrUJnUghKRIs1IXaiaUdHgkmBSNqXMZU4KRHIqJGY6ZbKmuJaEUEkZE5kmiKVFdgjej7rboW5VI-M9Xli-9aYV_oY7Yfi_k85s-KXbccIQzVMUBY7uBLz7OajQ89YEqawVnXJD4LgoMc0KhsqIshGV3oXglb63wYjvE-cPEo9Nym8Tj7sv_77zfvNPxBF4NwLXzvbKhx92uFaeb5Sw_eY_DH4Do3G-5A</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1781537908</pqid></control><display><type>article</type><title>Predicting Out-of-Office Blood Pressure in the Clinic (PROOF-BP): Derivation and Validation of a Tool to Improve the Accuracy of Blood Pressure Measurement in Clinical Practice</title><source>MEDLINE</source><source>American Heart Association Journals</source><source>Journals@Ovid Complete</source><source>EZB-FREE-00999 freely available EZB journals</source><creator>Sheppard, James P ; Stevens, Richard ; Gill, Paramjit ; Martin, Una ; Godwin, Marshall ; Hanley, Janet ; Heneghan, Carl ; Hobbs, F.D Richard ; Mant, Jonathan ; McKinstry, Brian ; Myers, Martin ; Nunan, David ; Ward, Alison ; Williams, Bryan ; McManus, Richard J</creator><creatorcontrib>Sheppard, James P ; Stevens, Richard ; Gill, Paramjit ; Martin, Una ; Godwin, Marshall ; Hanley, Janet ; Heneghan, Carl ; Hobbs, F.D Richard ; Mant, Jonathan ; McKinstry, Brian ; Myers, Martin ; Nunan, David ; Ward, Alison ; Williams, Bryan ; McManus, Richard J</creatorcontrib><description>Patients often have lower (white coat effect) or higher (masked effect) ambulatory/home blood pressure readings compared with clinic measurements, resulting in misdiagnosis of hypertension. The present study assessed whether blood pressure and patient characteristics from a single clinic visit can accurately predict the difference between ambulatory/home and clinic blood pressure readings (the home–clinic difference). A linear regression model predicting the home–clinic blood pressure difference was derived in 2 data sets measuring automated clinic and ambulatory/home blood pressure (n=991) using candidate predictors identified from a literature review. The model was validated in 4 further data sets (n=1172) using area under the receiver operator characteristic curve analysis. A masked effect was associated with male sex, a positive clinic blood pressure change (difference between consecutive measurements during a single visit), and a diagnosis of hypertension. Increasing age, clinic blood pressure level, and pulse pressure were associated with a white coat effect. The model showed good calibration across data sets (Pearson correlation, 0.48–0.80) and performed well-predicting ambulatory hypertension (area under the receiver operator characteristic curve, 0.75; 95% confidence interval, 0.72–0.79 [systolic]; 0.87; 0.85–0.89 [diastolic]). Used as a triaging tool for ambulatory monitoring, the model improved classification of a patient’s blood pressure status compared with other guideline recommended approaches (93% [92% to 95%] classified correctly; United States, 73% [70% to 75%]; Canada, 74% [71% to 77%]; United Kingdom, 78% [76% to 81%]). This study demonstrates that patient characteristics from a single clinic visit can accurately predict a patient’s ambulatory blood pressure. Usage of this prediction tool for triaging of ambulatory monitoring could result in more accurate diagnosis of hypertension and hence more appropriate treatment.</description><identifier>ISSN: 0194-911X</identifier><identifier>EISSN: 1524-4563</identifier><identifier>DOI: 10.1161/HYPERTENSIONAHA.115.07108</identifier><identifier>PMID: 27001299</identifier><language>eng</language><publisher>United States: American Heart Association, Inc</publisher><subject>Adult ; Aged ; Algorithms ; Blood Pressure Determination - methods ; Blood Pressure Monitoring, Ambulatory - methods ; Canada ; Circadian Rhythm ; Cohort Studies ; Databases, Factual ; Female ; Humans ; Linear Models ; Male ; Masked Hypertension - diagnosis ; Middle Aged ; Office Visits ; Original ; Predictive Value of Tests ; Risk Assessment ; ROC Curve ; Sensitivity and Specificity ; United Kingdom ; United States ; White Coat Hypertension - diagnosis</subject><ispartof>Hypertension (Dallas, Tex. 1979), 2016-05, Vol.67 (5), p.941-950</ispartof><rights>2016 American Heart Association, Inc</rights><rights>2016 The Authors.</rights><rights>2016 The Authors. 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c3708-ba54a20f94b7eb95ad184148d8c6c6470465ac19f29cb51bc445c599a3f409273</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,3687,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27001299$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sheppard, James P</creatorcontrib><creatorcontrib>Stevens, Richard</creatorcontrib><creatorcontrib>Gill, Paramjit</creatorcontrib><creatorcontrib>Martin, Una</creatorcontrib><creatorcontrib>Godwin, Marshall</creatorcontrib><creatorcontrib>Hanley, Janet</creatorcontrib><creatorcontrib>Heneghan, Carl</creatorcontrib><creatorcontrib>Hobbs, F.D Richard</creatorcontrib><creatorcontrib>Mant, Jonathan</creatorcontrib><creatorcontrib>McKinstry, Brian</creatorcontrib><creatorcontrib>Myers, Martin</creatorcontrib><creatorcontrib>Nunan, David</creatorcontrib><creatorcontrib>Ward, Alison</creatorcontrib><creatorcontrib>Williams, Bryan</creatorcontrib><creatorcontrib>McManus, Richard J</creatorcontrib><title>Predicting Out-of-Office Blood Pressure in the Clinic (PROOF-BP): Derivation and Validation of a Tool to Improve the Accuracy of Blood Pressure Measurement in Clinical Practice</title><title>Hypertension (Dallas, Tex. 1979)</title><addtitle>Hypertension</addtitle><description>Patients often have lower (white coat effect) or higher (masked effect) ambulatory/home blood pressure readings compared with clinic measurements, resulting in misdiagnosis of hypertension. The present study assessed whether blood pressure and patient characteristics from a single clinic visit can accurately predict the difference between ambulatory/home and clinic blood pressure readings (the home–clinic difference). A linear regression model predicting the home–clinic blood pressure difference was derived in 2 data sets measuring automated clinic and ambulatory/home blood pressure (n=991) using candidate predictors identified from a literature review. The model was validated in 4 further data sets (n=1172) using area under the receiver operator characteristic curve analysis. A masked effect was associated with male sex, a positive clinic blood pressure change (difference between consecutive measurements during a single visit), and a diagnosis of hypertension. Increasing age, clinic blood pressure level, and pulse pressure were associated with a white coat effect. The model showed good calibration across data sets (Pearson correlation, 0.48–0.80) and performed well-predicting ambulatory hypertension (area under the receiver operator characteristic curve, 0.75; 95% confidence interval, 0.72–0.79 [systolic]; 0.87; 0.85–0.89 [diastolic]). Used as a triaging tool for ambulatory monitoring, the model improved classification of a patient’s blood pressure status compared with other guideline recommended approaches (93% [92% to 95%] classified correctly; United States, 73% [70% to 75%]; Canada, 74% [71% to 77%]; United Kingdom, 78% [76% to 81%]). This study demonstrates that patient characteristics from a single clinic visit can accurately predict a patient’s ambulatory blood pressure. Usage of this prediction tool for triaging of ambulatory monitoring could result in more accurate diagnosis of hypertension and hence more appropriate treatment.</description><subject>Adult</subject><subject>Aged</subject><subject>Algorithms</subject><subject>Blood Pressure Determination - methods</subject><subject>Blood Pressure Monitoring, Ambulatory - methods</subject><subject>Canada</subject><subject>Circadian Rhythm</subject><subject>Cohort Studies</subject><subject>Databases, Factual</subject><subject>Female</subject><subject>Humans</subject><subject>Linear Models</subject><subject>Male</subject><subject>Masked Hypertension - diagnosis</subject><subject>Middle Aged</subject><subject>Office Visits</subject><subject>Original</subject><subject>Predictive Value of Tests</subject><subject>Risk Assessment</subject><subject>ROC Curve</subject><subject>Sensitivity and Specificity</subject><subject>United Kingdom</subject><subject>United States</subject><subject>White Coat Hypertension - diagnosis</subject><issn>0194-911X</issn><issn>1524-4563</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkdFu0zAUhi0EYmXwCsjcjYsMO7GTGAmkrnS00liqURBcWY5jrx5OXOyk096KR8RdxgS74urY53zn_4_0A_AKo2OMc_xm8X01v1jPzz8vq_PpYhqb9BgVGJWPwATTlCSE5tljMEGYkYRh_O0APAvhCiFMCCmegoO0iO-UsQn4tfKqMbI33SWshj5xOqm0NlLBE-tcA-M4hMEraDrYbxScWdMZCY9WF1V1mpysXr-FH5Q3O9Eb10HRNfCrsKYZv05DAdfOWdg7uGy33u3UrcpUysELebMnHvh8UmJfW9X1e8_RT9gIiHilVM_BEy1sUC_u6iH4cjpfzxbJWfVxOZueJTIrUJnUghKRIs1IXaiaUdHgkmBSNqXMZU4KRHIqJGY6ZbKmuJaEUEkZE5kmiKVFdgjej7rboW5VI-M9Xli-9aYV_oY7Yfi_k85s-KXbccIQzVMUBY7uBLz7OajQ89YEqawVnXJD4LgoMc0KhsqIshGV3oXglb63wYjvE-cPEo9Nym8Tj7sv_77zfvNPxBF4NwLXzvbKhx92uFaeb5Sw_eY_DH4Do3G-5A</recordid><startdate>201605</startdate><enddate>201605</enddate><creator>Sheppard, James P</creator><creator>Stevens, Richard</creator><creator>Gill, Paramjit</creator><creator>Martin, Una</creator><creator>Godwin, Marshall</creator><creator>Hanley, Janet</creator><creator>Heneghan, Carl</creator><creator>Hobbs, F.D Richard</creator><creator>Mant, Jonathan</creator><creator>McKinstry, Brian</creator><creator>Myers, Martin</creator><creator>Nunan, David</creator><creator>Ward, Alison</creator><creator>Williams, Bryan</creator><creator>McManus, Richard J</creator><general>American Heart Association, Inc</general><general>Lippincott, Williams &amp; Wilkins</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>201605</creationdate><title>Predicting Out-of-Office Blood Pressure in the Clinic (PROOF-BP): Derivation and Validation of a Tool to Improve the Accuracy of Blood Pressure Measurement in Clinical Practice</title><author>Sheppard, James P ; Stevens, Richard ; Gill, Paramjit ; Martin, Una ; Godwin, Marshall ; Hanley, Janet ; Heneghan, Carl ; Hobbs, F.D Richard ; Mant, Jonathan ; McKinstry, Brian ; Myers, Martin ; Nunan, David ; Ward, Alison ; Williams, Bryan ; McManus, Richard J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3708-ba54a20f94b7eb95ad184148d8c6c6470465ac19f29cb51bc445c599a3f409273</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Algorithms</topic><topic>Blood Pressure Determination - methods</topic><topic>Blood Pressure Monitoring, Ambulatory - methods</topic><topic>Canada</topic><topic>Circadian Rhythm</topic><topic>Cohort Studies</topic><topic>Databases, Factual</topic><topic>Female</topic><topic>Humans</topic><topic>Linear Models</topic><topic>Male</topic><topic>Masked Hypertension - diagnosis</topic><topic>Middle Aged</topic><topic>Office Visits</topic><topic>Original</topic><topic>Predictive Value of Tests</topic><topic>Risk Assessment</topic><topic>ROC Curve</topic><topic>Sensitivity and Specificity</topic><topic>United Kingdom</topic><topic>United States</topic><topic>White Coat Hypertension - diagnosis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sheppard, James P</creatorcontrib><creatorcontrib>Stevens, Richard</creatorcontrib><creatorcontrib>Gill, Paramjit</creatorcontrib><creatorcontrib>Martin, Una</creatorcontrib><creatorcontrib>Godwin, Marshall</creatorcontrib><creatorcontrib>Hanley, Janet</creatorcontrib><creatorcontrib>Heneghan, Carl</creatorcontrib><creatorcontrib>Hobbs, F.D Richard</creatorcontrib><creatorcontrib>Mant, Jonathan</creatorcontrib><creatorcontrib>McKinstry, Brian</creatorcontrib><creatorcontrib>Myers, Martin</creatorcontrib><creatorcontrib>Nunan, David</creatorcontrib><creatorcontrib>Ward, Alison</creatorcontrib><creatorcontrib>Williams, Bryan</creatorcontrib><creatorcontrib>McManus, Richard J</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>Hypertension (Dallas, Tex. 1979)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sheppard, James P</au><au>Stevens, Richard</au><au>Gill, Paramjit</au><au>Martin, Una</au><au>Godwin, Marshall</au><au>Hanley, Janet</au><au>Heneghan, Carl</au><au>Hobbs, F.D Richard</au><au>Mant, Jonathan</au><au>McKinstry, Brian</au><au>Myers, Martin</au><au>Nunan, David</au><au>Ward, Alison</au><au>Williams, Bryan</au><au>McManus, Richard J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Predicting Out-of-Office Blood Pressure in the Clinic (PROOF-BP): Derivation and Validation of a Tool to Improve the Accuracy of Blood Pressure Measurement in Clinical Practice</atitle><jtitle>Hypertension (Dallas, Tex. 1979)</jtitle><addtitle>Hypertension</addtitle><date>2016-05</date><risdate>2016</risdate><volume>67</volume><issue>5</issue><spage>941</spage><epage>950</epage><pages>941-950</pages><issn>0194-911X</issn><eissn>1524-4563</eissn><abstract>Patients often have lower (white coat effect) or higher (masked effect) ambulatory/home blood pressure readings compared with clinic measurements, resulting in misdiagnosis of hypertension. The present study assessed whether blood pressure and patient characteristics from a single clinic visit can accurately predict the difference between ambulatory/home and clinic blood pressure readings (the home–clinic difference). A linear regression model predicting the home–clinic blood pressure difference was derived in 2 data sets measuring automated clinic and ambulatory/home blood pressure (n=991) using candidate predictors identified from a literature review. The model was validated in 4 further data sets (n=1172) using area under the receiver operator characteristic curve analysis. A masked effect was associated with male sex, a positive clinic blood pressure change (difference between consecutive measurements during a single visit), and a diagnosis of hypertension. Increasing age, clinic blood pressure level, and pulse pressure were associated with a white coat effect. The model showed good calibration across data sets (Pearson correlation, 0.48–0.80) and performed well-predicting ambulatory hypertension (area under the receiver operator characteristic curve, 0.75; 95% confidence interval, 0.72–0.79 [systolic]; 0.87; 0.85–0.89 [diastolic]). Used as a triaging tool for ambulatory monitoring, the model improved classification of a patient’s blood pressure status compared with other guideline recommended approaches (93% [92% to 95%] classified correctly; United States, 73% [70% to 75%]; Canada, 74% [71% to 77%]; United Kingdom, 78% [76% to 81%]). This study demonstrates that patient characteristics from a single clinic visit can accurately predict a patient’s ambulatory blood pressure. Usage of this prediction tool for triaging of ambulatory monitoring could result in more accurate diagnosis of hypertension and hence more appropriate treatment.</abstract><cop>United States</cop><pub>American Heart Association, Inc</pub><pmid>27001299</pmid><doi>10.1161/HYPERTENSIONAHA.115.07108</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0194-911X
ispartof Hypertension (Dallas, Tex. 1979), 2016-05, Vol.67 (5), p.941-950
issn 0194-911X
1524-4563
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4905620
source MEDLINE; American Heart Association Journals; Journals@Ovid Complete; EZB-FREE-00999 freely available EZB journals
subjects Adult
Aged
Algorithms
Blood Pressure Determination - methods
Blood Pressure Monitoring, Ambulatory - methods
Canada
Circadian Rhythm
Cohort Studies
Databases, Factual
Female
Humans
Linear Models
Male
Masked Hypertension - diagnosis
Middle Aged
Office Visits
Original
Predictive Value of Tests
Risk Assessment
ROC Curve
Sensitivity and Specificity
United Kingdom
United States
White Coat Hypertension - diagnosis
title Predicting Out-of-Office Blood Pressure in the Clinic (PROOF-BP): Derivation and Validation of a Tool to Improve the Accuracy of Blood Pressure Measurement in Clinical Practice
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-22T10%3A20%3A21IST&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=Predicting%20Out-of-Office%20Blood%20Pressure%20in%20the%20Clinic%20(PROOF-BP):%20Derivation%20and%20Validation%20of%20a%20Tool%20to%20Improve%20the%20Accuracy%20of%20Blood%20Pressure%20Measurement%20in%20Clinical%20Practice&rft.jtitle=Hypertension%20(Dallas,%20Tex.%201979)&rft.au=Sheppard,%20James%20P&rft.date=2016-05&rft.volume=67&rft.issue=5&rft.spage=941&rft.epage=950&rft.pages=941-950&rft.issn=0194-911X&rft.eissn=1524-4563&rft_id=info:doi/10.1161/HYPERTENSIONAHA.115.07108&rft_dat=%3Cproquest_pubme%3E1781537908%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=1781537908&rft_id=info:pmid/27001299&rfr_iscdi=true