Effect of Finasteride on Serum Androstenedione and Risk of Prostate Cancer Within the Prostate Cancer Prevention Trial: Differential Effect on High- and Low-grade Disease

Objective To evaluate the effect of finasteride on serum androst-4-ene-3,17-dione (androstenedione) and its association with prostate cancer risk among subjects who participated in the Prostate Cancer Prevention Trial. Methods We analyzed serum androstenedione levels in 317 prostate cancer cases and...

Full description

Saved in:
Bibliographic Details
Published in:Urology (Ridgewood, N.J.) N.J.), 2015-03, Vol.85 (3), p.616-620
Main Authors: Hoque, Ashraful, Yao, Song, Till, Cathee, Kristal, Alan R, Goodman, Phyllis J, Hsing, Ann W, Tangen, Catherine M, Platz, Elizabeth A, Stanczyk, Frank Z, Reichardt, Juergen K.V, vanBokhoven, Adrie, Neuhouser, Marian L, Santella, Regina M, Figg, William D, Price, Douglas K, Parnes, Howard L, Lippman, Scott M, Ambrosone, Christine B, Thompson, Ian M
Format: Article
Language:English
Subjects:
Androstenedione - blood
Case-Control Studies
Double-Blind Method
Finasteride - pharmacology
Finasteride - therapeutic use
Humans
Male
Middle Aged
Neoplasm Grading
Prostatic Neoplasms - epidemiology
Prostatic Neoplasms - pathology
Prostatic Neoplasms - prevention & control
Risk Assessment
Urology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by cdi_FETCH-LOGICAL-c522t-d304251e0b0073c36f9d95ac27c2787ce6fd32c478f94cad80903fb8a358f683
cites cdi_FETCH-LOGICAL-c522t-d304251e0b0073c36f9d95ac27c2787ce6fd32c478f94cad80903fb8a358f683
container_end_page 620
container_issue 3
container_start_page 616
container_title Urology (Ridgewood, N.J.)
container_volume 85
creator Hoque, Ashraful
Yao, Song
Till, Cathee
Kristal, Alan R
Goodman, Phyllis J
Hsing, Ann W
Tangen, Catherine M
Platz, Elizabeth A
Stanczyk, Frank Z
Reichardt, Juergen K.V
vanBokhoven, Adrie
Neuhouser, Marian L
Santella, Regina M
Figg, William D
Price, Douglas K
Parnes, Howard L
Lippman, Scott M
Ambrosone, Christine B
Thompson, Ian M
description Objective To evaluate the effect of finasteride on serum androst-4-ene-3,17-dione (androstenedione) and its association with prostate cancer risk among subjects who participated in the Prostate Cancer Prevention Trial. Methods We analyzed serum androstenedione levels in 317 prostate cancer cases and 353 controls, nested in the Prostate Cancer Prevention Trial, a randomized placebo-controlled trial that found finasteride decreased prostate cancer risk. Androstenedione is the second most important circulating androgen in men besides testosterone and also a substrate for 5α-reductase enzyme. Results We observed a 22% increase in androstenedione levels compared with the baseline values in subjects who were treated with finasteride for 3 years. This significant increase did not vary by case-control status. Adjusted odds ratio and 95% confidence interval for the third tertile of absolute change in androstenedione levels compared with the first tertile were 0.42 (95% confidence interval, 0.19-0.94) for low-grade (Gleason score 
doi_str_mv 10.1016/j.urology.2014.11.024
format article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4348556</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S009042951401320X</els_id><sourcerecordid>1660651660</sourcerecordid><originalsourceid>FETCH-LOGICAL-c522t-d304251e0b0073c36f9d95ac27c2787ce6fd32c478f94cad80903fb8a358f683</originalsourceid><addsrcrecordid>eNqFUl1v0zAUjRCIlcFPAPmRlwR_xE7Cw9DUbQyp0iZWCd4s175p3aX2ZidF_Uv8ShzaTcAekCxbuvfcc4_OcZa9JbggmIgP62IIvvPLXUExKQtCCkzLZ9mEcFrlTdPw59kE4wbnJW34UfYqxjXGWAhRvcyOKK8Yo1U5yX6ety3oHvkWXVinYg_BGkDeoRsIwwadOhN8qjow1jtAyhn01cbbceB67Kge0FQ5DQF9s_3KOtSv4EnrOsAWXJ8o0DxY1X1EZzYtDmNNdehBhEOXdrnKf2-Z-R_5Mqgk5sxGUBFeZy9a1UV4c3iPs_nF-Xx6mc-uPn-Zns5yzSntc8NwSTkBvMC4YpqJtjENV5pW6dSVBtEaRnVZ1W1TamXqZBJrF7VivG5FzY6zkz3t3bDYgNFJYlCdvAt2o8JOemXl3x1nV3Lpt7JkZc25SATvDwTB3w8Qe7mxUUPXKQd-iJIIgQUf7wTle6hOfsUA7eMaguUYs1zLQ8xyjFkSIlPMae7dnxofpx5yTYBPewAko7YWgozaQorC2JCclsbb_644-YdBd9ZZrbpb2EFc-yG4lIIkMlKJ5c3418avRkpMGMXf2S8dDdQ8</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1660651660</pqid></control><display><type>article</type><title>Effect of Finasteride on Serum Androstenedione and Risk of Prostate Cancer Within the Prostate Cancer Prevention Trial: Differential Effect on High- and Low-grade Disease</title><source>ScienceDirect Freedom Collection 2022-2024</source><creator>Hoque, Ashraful ; Yao, Song ; Till, Cathee ; Kristal, Alan R ; Goodman, Phyllis J ; Hsing, Ann W ; Tangen, Catherine M ; Platz, Elizabeth A ; Stanczyk, Frank Z ; Reichardt, Juergen K.V ; vanBokhoven, Adrie ; Neuhouser, Marian L ; Santella, Regina M ; Figg, William D ; Price, Douglas K ; Parnes, Howard L ; Lippman, Scott M ; Ambrosone, Christine B ; Thompson, Ian M</creator><creatorcontrib>Hoque, Ashraful ; Yao, Song ; Till, Cathee ; Kristal, Alan R ; Goodman, Phyllis J ; Hsing, Ann W ; Tangen, Catherine M ; Platz, Elizabeth A ; Stanczyk, Frank Z ; Reichardt, Juergen K.V ; vanBokhoven, Adrie ; Neuhouser, Marian L ; Santella, Regina M ; Figg, William D ; Price, Douglas K ; Parnes, Howard L ; Lippman, Scott M ; Ambrosone, Christine B ; Thompson, Ian M</creatorcontrib><description>Objective To evaluate the effect of finasteride on serum androst-4-ene-3,17-dione (androstenedione) and its association with prostate cancer risk among subjects who participated in the Prostate Cancer Prevention Trial. Methods We analyzed serum androstenedione levels in 317 prostate cancer cases and 353 controls, nested in the Prostate Cancer Prevention Trial, a randomized placebo-controlled trial that found finasteride decreased prostate cancer risk. Androstenedione is the second most important circulating androgen in men besides testosterone and also a substrate for 5α-reductase enzyme. Results We observed a 22% increase in androstenedione levels compared with the baseline values in subjects who were treated with finasteride for 3 years. This significant increase did not vary by case-control status. Adjusted odds ratio and 95% confidence interval for the third tertile of absolute change in androstenedione levels compared with the first tertile were 0.42 (95% confidence interval, 0.19-0.94) for low-grade (Gleason score &lt;7) cases. Similar results were observed when analyzed using percent change. There were no significant associations between serum androstenedione levels and the risk of high-grade disease. Conclusion The results of this nested case-control study confirm that finasteride blocks the conversion of testosterone to dihydrotestosterone (DHT) and of androstenedione to 5α-androstanedione-3,17-dione, which also leads to the reduction of DHT formation. This decrease in DHT may help reduce the risk of low-grade prostate cancer in men. Our data on a differential effect of androstenedione also suggest that some high-grade prostate cancers may not require androgen for progression.</description><identifier>ISSN: 0090-4295</identifier><identifier>EISSN: 1527-9995</identifier><identifier>DOI: 10.1016/j.urology.2014.11.024</identifier><identifier>PMID: 25733274</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Androstenedione - blood ; Case-Control Studies ; Double-Blind Method ; Finasteride - pharmacology ; Finasteride - therapeutic use ; Humans ; Male ; Middle Aged ; Neoplasm Grading ; Prostatic Neoplasms - epidemiology ; Prostatic Neoplasms - pathology ; Prostatic Neoplasms - prevention &amp; control ; Risk Assessment ; Urology</subject><ispartof>Urology (Ridgewood, N.J.), 2015-03, Vol.85 (3), p.616-620</ispartof><rights>Elsevier Inc.</rights><rights>2015 Elsevier Inc.</rights><rights>Copyright © 2015 Elsevier Inc. All rights reserved.</rights><rights>2014 Elsevier Inc. All rights reserved. 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c522t-d304251e0b0073c36f9d95ac27c2787ce6fd32c478f94cad80903fb8a358f683</citedby><cites>FETCH-LOGICAL-c522t-d304251e0b0073c36f9d95ac27c2787ce6fd32c478f94cad80903fb8a358f683</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25733274$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hoque, Ashraful</creatorcontrib><creatorcontrib>Yao, Song</creatorcontrib><creatorcontrib>Till, Cathee</creatorcontrib><creatorcontrib>Kristal, Alan R</creatorcontrib><creatorcontrib>Goodman, Phyllis J</creatorcontrib><creatorcontrib>Hsing, Ann W</creatorcontrib><creatorcontrib>Tangen, Catherine M</creatorcontrib><creatorcontrib>Platz, Elizabeth A</creatorcontrib><creatorcontrib>Stanczyk, Frank Z</creatorcontrib><creatorcontrib>Reichardt, Juergen K.V</creatorcontrib><creatorcontrib>vanBokhoven, Adrie</creatorcontrib><creatorcontrib>Neuhouser, Marian L</creatorcontrib><creatorcontrib>Santella, Regina M</creatorcontrib><creatorcontrib>Figg, William D</creatorcontrib><creatorcontrib>Price, Douglas K</creatorcontrib><creatorcontrib>Parnes, Howard L</creatorcontrib><creatorcontrib>Lippman, Scott M</creatorcontrib><creatorcontrib>Ambrosone, Christine B</creatorcontrib><creatorcontrib>Thompson, Ian M</creatorcontrib><title>Effect of Finasteride on Serum Androstenedione and Risk of Prostate Cancer Within the Prostate Cancer Prevention Trial: Differential Effect on High- and Low-grade Disease</title><title>Urology (Ridgewood, N.J.)</title><addtitle>Urology</addtitle><description>Objective To evaluate the effect of finasteride on serum androst-4-ene-3,17-dione (androstenedione) and its association with prostate cancer risk among subjects who participated in the Prostate Cancer Prevention Trial. Methods We analyzed serum androstenedione levels in 317 prostate cancer cases and 353 controls, nested in the Prostate Cancer Prevention Trial, a randomized placebo-controlled trial that found finasteride decreased prostate cancer risk. Androstenedione is the second most important circulating androgen in men besides testosterone and also a substrate for 5α-reductase enzyme. Results We observed a 22% increase in androstenedione levels compared with the baseline values in subjects who were treated with finasteride for 3 years. This significant increase did not vary by case-control status. Adjusted odds ratio and 95% confidence interval for the third tertile of absolute change in androstenedione levels compared with the first tertile were 0.42 (95% confidence interval, 0.19-0.94) for low-grade (Gleason score &lt;7) cases. Similar results were observed when analyzed using percent change. There were no significant associations between serum androstenedione levels and the risk of high-grade disease. Conclusion The results of this nested case-control study confirm that finasteride blocks the conversion of testosterone to dihydrotestosterone (DHT) and of androstenedione to 5α-androstanedione-3,17-dione, which also leads to the reduction of DHT formation. This decrease in DHT may help reduce the risk of low-grade prostate cancer in men. Our data on a differential effect of androstenedione also suggest that some high-grade prostate cancers may not require androgen for progression.</description><subject>Androstenedione - blood</subject><subject>Case-Control Studies</subject><subject>Double-Blind Method</subject><subject>Finasteride - pharmacology</subject><subject>Finasteride - therapeutic use</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Neoplasm Grading</subject><subject>Prostatic Neoplasms - epidemiology</subject><subject>Prostatic Neoplasms - pathology</subject><subject>Prostatic Neoplasms - prevention &amp; control</subject><subject>Risk Assessment</subject><subject>Urology</subject><issn>0090-4295</issn><issn>1527-9995</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><recordid>eNqFUl1v0zAUjRCIlcFPAPmRlwR_xE7Cw9DUbQyp0iZWCd4s175p3aX2ZidF_Uv8ShzaTcAekCxbuvfcc4_OcZa9JbggmIgP62IIvvPLXUExKQtCCkzLZ9mEcFrlTdPw59kE4wbnJW34UfYqxjXGWAhRvcyOKK8Yo1U5yX6ety3oHvkWXVinYg_BGkDeoRsIwwadOhN8qjow1jtAyhn01cbbceB67Kge0FQ5DQF9s_3KOtSv4EnrOsAWXJ8o0DxY1X1EZzYtDmNNdehBhEOXdrnKf2-Z-R_5Mqgk5sxGUBFeZy9a1UV4c3iPs_nF-Xx6mc-uPn-Zns5yzSntc8NwSTkBvMC4YpqJtjENV5pW6dSVBtEaRnVZ1W1TamXqZBJrF7VivG5FzY6zkz3t3bDYgNFJYlCdvAt2o8JOemXl3x1nV3Lpt7JkZc25SATvDwTB3w8Qe7mxUUPXKQd-iJIIgQUf7wTle6hOfsUA7eMaguUYs1zLQ8xyjFkSIlPMae7dnxofpx5yTYBPewAko7YWgozaQorC2JCclsbb_644-YdBd9ZZrbpb2EFc-yG4lIIkMlKJ5c3418avRkpMGMXf2S8dDdQ8</recordid><startdate>20150301</startdate><enddate>20150301</enddate><creator>Hoque, Ashraful</creator><creator>Yao, Song</creator><creator>Till, Cathee</creator><creator>Kristal, Alan R</creator><creator>Goodman, Phyllis J</creator><creator>Hsing, Ann W</creator><creator>Tangen, Catherine M</creator><creator>Platz, Elizabeth A</creator><creator>Stanczyk, Frank Z</creator><creator>Reichardt, Juergen K.V</creator><creator>vanBokhoven, Adrie</creator><creator>Neuhouser, Marian L</creator><creator>Santella, Regina M</creator><creator>Figg, William D</creator><creator>Price, Douglas K</creator><creator>Parnes, Howard L</creator><creator>Lippman, Scott M</creator><creator>Ambrosone, Christine B</creator><creator>Thompson, Ian M</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><scope>5PM</scope></search><sort><creationdate>20150301</creationdate><title>Effect of Finasteride on Serum Androstenedione and Risk of Prostate Cancer Within the Prostate Cancer Prevention Trial: Differential Effect on High- and Low-grade Disease</title><author>Hoque, Ashraful ; Yao, Song ; Till, Cathee ; Kristal, Alan R ; Goodman, Phyllis J ; Hsing, Ann W ; Tangen, Catherine M ; Platz, Elizabeth A ; Stanczyk, Frank Z ; Reichardt, Juergen K.V ; vanBokhoven, Adrie ; Neuhouser, Marian L ; Santella, Regina M ; Figg, William D ; Price, Douglas K ; Parnes, Howard L ; Lippman, Scott M ; Ambrosone, Christine B ; Thompson, Ian M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c522t-d304251e0b0073c36f9d95ac27c2787ce6fd32c478f94cad80903fb8a358f683</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Androstenedione - blood</topic><topic>Case-Control Studies</topic><topic>Double-Blind Method</topic><topic>Finasteride - pharmacology</topic><topic>Finasteride - therapeutic use</topic><topic>Humans</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Neoplasm Grading</topic><topic>Prostatic Neoplasms - epidemiology</topic><topic>Prostatic Neoplasms - pathology</topic><topic>Prostatic Neoplasms - prevention &amp; control</topic><topic>Risk Assessment</topic><topic>Urology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hoque, Ashraful</creatorcontrib><creatorcontrib>Yao, Song</creatorcontrib><creatorcontrib>Till, Cathee</creatorcontrib><creatorcontrib>Kristal, Alan R</creatorcontrib><creatorcontrib>Goodman, Phyllis J</creatorcontrib><creatorcontrib>Hsing, Ann W</creatorcontrib><creatorcontrib>Tangen, Catherine M</creatorcontrib><creatorcontrib>Platz, Elizabeth A</creatorcontrib><creatorcontrib>Stanczyk, Frank Z</creatorcontrib><creatorcontrib>Reichardt, Juergen K.V</creatorcontrib><creatorcontrib>vanBokhoven, Adrie</creatorcontrib><creatorcontrib>Neuhouser, Marian L</creatorcontrib><creatorcontrib>Santella, Regina M</creatorcontrib><creatorcontrib>Figg, William D</creatorcontrib><creatorcontrib>Price, Douglas K</creatorcontrib><creatorcontrib>Parnes, Howard L</creatorcontrib><creatorcontrib>Lippman, Scott M</creatorcontrib><creatorcontrib>Ambrosone, Christine B</creatorcontrib><creatorcontrib>Thompson, Ian M</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>Urology (Ridgewood, N.J.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hoque, Ashraful</au><au>Yao, Song</au><au>Till, Cathee</au><au>Kristal, Alan R</au><au>Goodman, Phyllis J</au><au>Hsing, Ann W</au><au>Tangen, Catherine M</au><au>Platz, Elizabeth A</au><au>Stanczyk, Frank Z</au><au>Reichardt, Juergen K.V</au><au>vanBokhoven, Adrie</au><au>Neuhouser, Marian L</au><au>Santella, Regina M</au><au>Figg, William D</au><au>Price, Douglas K</au><au>Parnes, Howard L</au><au>Lippman, Scott M</au><au>Ambrosone, Christine B</au><au>Thompson, Ian M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of Finasteride on Serum Androstenedione and Risk of Prostate Cancer Within the Prostate Cancer Prevention Trial: Differential Effect on High- and Low-grade Disease</atitle><jtitle>Urology (Ridgewood, N.J.)</jtitle><addtitle>Urology</addtitle><date>2015-03-01</date><risdate>2015</risdate><volume>85</volume><issue>3</issue><spage>616</spage><epage>620</epage><pages>616-620</pages><issn>0090-4295</issn><eissn>1527-9995</eissn><abstract>Objective To evaluate the effect of finasteride on serum androst-4-ene-3,17-dione (androstenedione) and its association with prostate cancer risk among subjects who participated in the Prostate Cancer Prevention Trial. Methods We analyzed serum androstenedione levels in 317 prostate cancer cases and 353 controls, nested in the Prostate Cancer Prevention Trial, a randomized placebo-controlled trial that found finasteride decreased prostate cancer risk. Androstenedione is the second most important circulating androgen in men besides testosterone and also a substrate for 5α-reductase enzyme. Results We observed a 22% increase in androstenedione levels compared with the baseline values in subjects who were treated with finasteride for 3 years. This significant increase did not vary by case-control status. Adjusted odds ratio and 95% confidence interval for the third tertile of absolute change in androstenedione levels compared with the first tertile were 0.42 (95% confidence interval, 0.19-0.94) for low-grade (Gleason score &lt;7) cases. Similar results were observed when analyzed using percent change. There were no significant associations between serum androstenedione levels and the risk of high-grade disease. Conclusion The results of this nested case-control study confirm that finasteride blocks the conversion of testosterone to dihydrotestosterone (DHT) and of androstenedione to 5α-androstanedione-3,17-dione, which also leads to the reduction of DHT formation. This decrease in DHT may help reduce the risk of low-grade prostate cancer in men. Our data on a differential effect of androstenedione also suggest that some high-grade prostate cancers may not require androgen for progression.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>25733274</pmid><doi>10.1016/j.urology.2014.11.024</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0090-4295
ispartof Urology (Ridgewood, N.J.), 2015-03, Vol.85 (3), p.616-620
issn 0090-4295
1527-9995
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4348556
source ScienceDirect Freedom Collection 2022-2024
subjects Androstenedione - blood
Case-Control Studies
Double-Blind Method
Finasteride - pharmacology
Finasteride - therapeutic use
Humans
Male
Middle Aged
Neoplasm Grading
Prostatic Neoplasms - epidemiology
Prostatic Neoplasms - pathology
Prostatic Neoplasms - prevention & control
Risk Assessment
Urology
title Effect of Finasteride on Serum Androstenedione and Risk of Prostate Cancer Within the Prostate Cancer Prevention Trial: Differential Effect on High- and Low-grade Disease
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-01T04%3A51%3A52IST&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=Effect%20of%20Finasteride%20on%20Serum%20Androstenedione%20and%20Risk%20of%20Prostate%20Cancer%20Within%20the%20Prostate%20Cancer%20Prevention%20Trial:%20Differential%20Effect%20on%20High-%20and%20Low-grade%20Disease&rft.jtitle=Urology%20(Ridgewood,%20N.J.)&rft.au=Hoque,%20Ashraful&rft.date=2015-03-01&rft.volume=85&rft.issue=3&rft.spage=616&rft.epage=620&rft.pages=616-620&rft.issn=0090-4295&rft.eissn=1527-9995&rft_id=info:doi/10.1016/j.urology.2014.11.024&rft_dat=%3Cproquest_pubme%3E1660651660%3C/proquest_pubme%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c522t-d304251e0b0073c36f9d95ac27c2787ce6fd32c478f94cad80903fb8a358f683%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1660651660&rft_id=info:pmid/25733274&rfr_iscdi=true