Association of Increased Urinary Albumin With Risk of Incident Clinical Fracture and Rate of Hip Bone Loss: the Osteoporotic Fractures in Men Study
ABSTRACT Prior studies suggest that increased urine albumin is associated with a heightened fracture risk in women, but results in men are unclear. We used data from Osteoporotic Fractures in Men (MrOS), a prospective cohort study of community‐dwelling men aged ≥65 years, to evaluate the association...
Gespeichert in:
Veröffentlicht in: | Journal of bone and mineral research 2017-05, Vol.32 (5), p.1090-1099 |
---|---|
Hauptverfasser: | , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 1099 |
---|---|
container_issue | 5 |
container_start_page | 1090 |
container_title | Journal of bone and mineral research |
container_volume | 32 |
creator | Fink, Howard A Vo, Tien N Langsetmo, Lisa Barzilay, Joshua I Cauley, Jane A Schousboe, John T Orwoll, Eric S Canales, Muna T Ishani, Areef Lane, Nancy E Ensrud, Kristine E |
description | ABSTRACT
Prior studies suggest that increased urine albumin is associated with a heightened fracture risk in women, but results in men are unclear. We used data from Osteoporotic Fractures in Men (MrOS), a prospective cohort study of community‐dwelling men aged ≥65 years, to evaluate the association of increased urine albumin with subsequent fractures and annualized rate of hip bone loss. We calculated albumin/creatinine ratio (ACR) from urine collected at the 2003–2005 visit. Subsequent clinical fractures were ascertained from triannual questionnaires and centrally adjudicated by review of radiographic reports. Total hip BMD was measured by DXA at the 2003–2005 visit and again an average of 3.5 years later. We estimated risk of incident clinical fracture using Cox proportional hazards models, and annualized BMD change using ANCOVA. Of 2982 men with calculable ACR, 9.4% had ACR ≥30 mg/g (albuminuria) and 1.0% had ACR ≥300 mg/g (macroalbuminuria). During a mean of 8.7 years of follow‐up, 20.0% of men had an incident clinical fracture. In multivariate‐adjusted models, neither higher ACR quintile (p for trend 0.75) nor albuminuria (HR versus no albuminuria, 0.89; 95% CI, 0.65 to 1.20) was associated with increased risk of incident clinical fracture. Increased urine albumin had a borderline significant, multivariate‐adjusted, positive association with rate of total hip bone loss when modeled in ACR quintiles (p = 0.06), but not when modeled as albuminuria versus no albuminuria. Macroalbuminuria was associated with a higher rate of annualized hip bone loss compared to no albuminuria (–1.8% more annualized loss than in men with ACR |
doi_str_mv | 10.1002/jbmr.3065 |
format | Article |
fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5413394</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1895050240</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4435-25a2bcb6bfd770efa3b8432bccebbc99118e1bb1fb3345fe590895e0f11c303d3</originalsourceid><addsrcrecordid>eNp1kc1uEzEYRS0EoqGw4AWQJTawmNY_4_lhUSmNKC1KVSlQsbRszzfEYWIH2wPKc_DCOCREgMTKkn18_F1fhJ5TckYJYecrvQ5nnFTiAZpQwXhRVg19iCakacqClJyeoCcxrgjJSFU9RiesIZQxWk_Qj2mM3liVrHfY9_jGmQAqQofvg3UqbPF00OPaOvzJpiVe2PjlgNkOXMKzwTpr1ICvgjJpDICV6_BCJdhh13aDL70DPPcxvsFpCfguJvAbH3yy5ngp4vzALTj8IY3d9il61KshwrPDeorur95-nF0X87t3N7PpvDBlyUXBhGLa6Er3XV0T6BXXTcnzlgGtTdtS2gDVmvaa81L0IFrStAJIT6nhhHf8FF3svZtRr6EzOU9Qg9wEu87BpVdW_n3i7FJ-9t-kKCnnbZkFrw6C4L-OEJNc22hgGJQDP0ZJG8Hqpqo5y-jLf9CVH4PL8TLVCiIIK0mmXu8pE_KHBeiPw1Aid1XLXdVyV3VmX_w5_ZH83W0GzvfAdzvA9v8m-f7ydvFL-RMgVbWj</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1895050240</pqid></control><display><type>article</type><title>Association of Increased Urinary Albumin With Risk of Incident Clinical Fracture and Rate of Hip Bone Loss: the Osteoporotic Fractures in Men Study</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Access via Wiley Online Library</source><source>Oxford University Press Journals All Titles (1996-Current)</source><creator>Fink, Howard A ; Vo, Tien N ; Langsetmo, Lisa ; Barzilay, Joshua I ; Cauley, Jane A ; Schousboe, John T ; Orwoll, Eric S ; Canales, Muna T ; Ishani, Areef ; Lane, Nancy E ; Ensrud, Kristine E</creator><creatorcontrib>Fink, Howard A ; Vo, Tien N ; Langsetmo, Lisa ; Barzilay, Joshua I ; Cauley, Jane A ; Schousboe, John T ; Orwoll, Eric S ; Canales, Muna T ; Ishani, Areef ; Lane, Nancy E ; Ensrud, Kristine E</creatorcontrib><description>ABSTRACT
Prior studies suggest that increased urine albumin is associated with a heightened fracture risk in women, but results in men are unclear. We used data from Osteoporotic Fractures in Men (MrOS), a prospective cohort study of community‐dwelling men aged ≥65 years, to evaluate the association of increased urine albumin with subsequent fractures and annualized rate of hip bone loss. We calculated albumin/creatinine ratio (ACR) from urine collected at the 2003–2005 visit. Subsequent clinical fractures were ascertained from triannual questionnaires and centrally adjudicated by review of radiographic reports. Total hip BMD was measured by DXA at the 2003–2005 visit and again an average of 3.5 years later. We estimated risk of incident clinical fracture using Cox proportional hazards models, and annualized BMD change using ANCOVA. Of 2982 men with calculable ACR, 9.4% had ACR ≥30 mg/g (albuminuria) and 1.0% had ACR ≥300 mg/g (macroalbuminuria). During a mean of 8.7 years of follow‐up, 20.0% of men had an incident clinical fracture. In multivariate‐adjusted models, neither higher ACR quintile (p for trend 0.75) nor albuminuria (HR versus no albuminuria, 0.89; 95% CI, 0.65 to 1.20) was associated with increased risk of incident clinical fracture. Increased urine albumin had a borderline significant, multivariate‐adjusted, positive association with rate of total hip bone loss when modeled in ACR quintiles (p = 0.06), but not when modeled as albuminuria versus no albuminuria. Macroalbuminuria was associated with a higher rate of annualized hip bone loss compared to no albuminuria (–1.8% more annualized loss than in men with ACR <30 mg/g; p < 0.001), but the limited prevalence of macroalbuminuria precluded reliable estimates of its fracture associations. In these community‐dwelling older men, we found no association between urine albumin levels and risk of incident clinical fracture, but found a borderline significant, positive association with rate of hip bone loss. © 2016 American Society for Bone and Mineral Research.</description><identifier>ISSN: 0884-0431</identifier><identifier>EISSN: 1523-4681</identifier><identifier>DOI: 10.1002/jbmr.3065</identifier><identifier>PMID: 28012217</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Aged ; Aged, 80 and over ; Albumin ; ALBUMINURIA ; Albuminuria - epidemiology ; Bone loss ; Bone mineral density ; Creatinine ; Dual energy X-ray absorptiometry ; FRACTURE ; Fractures ; Fractures, Bone - epidemiology ; Fractures, Bone - urine ; Health risk assessment ; Hip ; Humans ; Incidence ; MALE ; OSTEOPOROSIS ; Osteoporosis - epidemiology ; Osteoporosis - urine ; Proportional Hazards Models ; Prospective Studies ; Risk Factors ; Urine</subject><ispartof>Journal of bone and mineral research, 2017-05, Vol.32 (5), p.1090-1099</ispartof><rights>2016 American Society for Bone and Mineral Research</rights><rights>2016 American Society for Bone and Mineral Research.</rights><rights>2017 American Society for Bone and Mineral Research</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4435-25a2bcb6bfd770efa3b8432bccebbc99118e1bb1fb3345fe590895e0f11c303d3</citedby><cites>FETCH-LOGICAL-c4435-25a2bcb6bfd770efa3b8432bccebbc99118e1bb1fb3345fe590895e0f11c303d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjbmr.3065$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjbmr.3065$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,780,784,885,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28012217$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fink, Howard A</creatorcontrib><creatorcontrib>Vo, Tien N</creatorcontrib><creatorcontrib>Langsetmo, Lisa</creatorcontrib><creatorcontrib>Barzilay, Joshua I</creatorcontrib><creatorcontrib>Cauley, Jane A</creatorcontrib><creatorcontrib>Schousboe, John T</creatorcontrib><creatorcontrib>Orwoll, Eric S</creatorcontrib><creatorcontrib>Canales, Muna T</creatorcontrib><creatorcontrib>Ishani, Areef</creatorcontrib><creatorcontrib>Lane, Nancy E</creatorcontrib><creatorcontrib>Ensrud, Kristine E</creatorcontrib><title>Association of Increased Urinary Albumin With Risk of Incident Clinical Fracture and Rate of Hip Bone Loss: the Osteoporotic Fractures in Men Study</title><title>Journal of bone and mineral research</title><addtitle>J Bone Miner Res</addtitle><description>ABSTRACT
Prior studies suggest that increased urine albumin is associated with a heightened fracture risk in women, but results in men are unclear. We used data from Osteoporotic Fractures in Men (MrOS), a prospective cohort study of community‐dwelling men aged ≥65 years, to evaluate the association of increased urine albumin with subsequent fractures and annualized rate of hip bone loss. We calculated albumin/creatinine ratio (ACR) from urine collected at the 2003–2005 visit. Subsequent clinical fractures were ascertained from triannual questionnaires and centrally adjudicated by review of radiographic reports. Total hip BMD was measured by DXA at the 2003–2005 visit and again an average of 3.5 years later. We estimated risk of incident clinical fracture using Cox proportional hazards models, and annualized BMD change using ANCOVA. Of 2982 men with calculable ACR, 9.4% had ACR ≥30 mg/g (albuminuria) and 1.0% had ACR ≥300 mg/g (macroalbuminuria). During a mean of 8.7 years of follow‐up, 20.0% of men had an incident clinical fracture. In multivariate‐adjusted models, neither higher ACR quintile (p for trend 0.75) nor albuminuria (HR versus no albuminuria, 0.89; 95% CI, 0.65 to 1.20) was associated with increased risk of incident clinical fracture. Increased urine albumin had a borderline significant, multivariate‐adjusted, positive association with rate of total hip bone loss when modeled in ACR quintiles (p = 0.06), but not when modeled as albuminuria versus no albuminuria. Macroalbuminuria was associated with a higher rate of annualized hip bone loss compared to no albuminuria (–1.8% more annualized loss than in men with ACR <30 mg/g; p < 0.001), but the limited prevalence of macroalbuminuria precluded reliable estimates of its fracture associations. In these community‐dwelling older men, we found no association between urine albumin levels and risk of incident clinical fracture, but found a borderline significant, positive association with rate of hip bone loss. © 2016 American Society for Bone and Mineral Research.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Albumin</subject><subject>ALBUMINURIA</subject><subject>Albuminuria - epidemiology</subject><subject>Bone loss</subject><subject>Bone mineral density</subject><subject>Creatinine</subject><subject>Dual energy X-ray absorptiometry</subject><subject>FRACTURE</subject><subject>Fractures</subject><subject>Fractures, Bone - epidemiology</subject><subject>Fractures, Bone - urine</subject><subject>Health risk assessment</subject><subject>Hip</subject><subject>Humans</subject><subject>Incidence</subject><subject>MALE</subject><subject>OSTEOPOROSIS</subject><subject>Osteoporosis - epidemiology</subject><subject>Osteoporosis - urine</subject><subject>Proportional Hazards Models</subject><subject>Prospective Studies</subject><subject>Risk Factors</subject><subject>Urine</subject><issn>0884-0431</issn><issn>1523-4681</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kc1uEzEYRS0EoqGw4AWQJTawmNY_4_lhUSmNKC1KVSlQsbRszzfEYWIH2wPKc_DCOCREgMTKkn18_F1fhJ5TckYJYecrvQ5nnFTiAZpQwXhRVg19iCakacqClJyeoCcxrgjJSFU9RiesIZQxWk_Qj2mM3liVrHfY9_jGmQAqQofvg3UqbPF00OPaOvzJpiVe2PjlgNkOXMKzwTpr1ICvgjJpDICV6_BCJdhh13aDL70DPPcxvsFpCfguJvAbH3yy5ngp4vzALTj8IY3d9il61KshwrPDeorur95-nF0X87t3N7PpvDBlyUXBhGLa6Er3XV0T6BXXTcnzlgGtTdtS2gDVmvaa81L0IFrStAJIT6nhhHf8FF3svZtRr6EzOU9Qg9wEu87BpVdW_n3i7FJ-9t-kKCnnbZkFrw6C4L-OEJNc22hgGJQDP0ZJG8Hqpqo5y-jLf9CVH4PL8TLVCiIIK0mmXu8pE_KHBeiPw1Aid1XLXdVyV3VmX_w5_ZH83W0GzvfAdzvA9v8m-f7ydvFL-RMgVbWj</recordid><startdate>201705</startdate><enddate>201705</enddate><creator>Fink, Howard A</creator><creator>Vo, Tien N</creator><creator>Langsetmo, Lisa</creator><creator>Barzilay, Joshua I</creator><creator>Cauley, Jane A</creator><creator>Schousboe, John T</creator><creator>Orwoll, Eric S</creator><creator>Canales, Muna T</creator><creator>Ishani, Areef</creator><creator>Lane, Nancy E</creator><creator>Ensrud, Kristine E</creator><general>Wiley Subscription Services, 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>7QP</scope><scope>7TS</scope><scope>K9.</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201705</creationdate><title>Association of Increased Urinary Albumin With Risk of Incident Clinical Fracture and Rate of Hip Bone Loss: the Osteoporotic Fractures in Men Study</title><author>Fink, Howard A ; Vo, Tien N ; Langsetmo, Lisa ; Barzilay, Joshua I ; Cauley, Jane A ; Schousboe, John T ; Orwoll, Eric S ; Canales, Muna T ; Ishani, Areef ; Lane, Nancy E ; Ensrud, Kristine E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4435-25a2bcb6bfd770efa3b8432bccebbc99118e1bb1fb3345fe590895e0f11c303d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Albumin</topic><topic>ALBUMINURIA</topic><topic>Albuminuria - epidemiology</topic><topic>Bone loss</topic><topic>Bone mineral density</topic><topic>Creatinine</topic><topic>Dual energy X-ray absorptiometry</topic><topic>FRACTURE</topic><topic>Fractures</topic><topic>Fractures, Bone - epidemiology</topic><topic>Fractures, Bone - urine</topic><topic>Health risk assessment</topic><topic>Hip</topic><topic>Humans</topic><topic>Incidence</topic><topic>MALE</topic><topic>OSTEOPOROSIS</topic><topic>Osteoporosis - epidemiology</topic><topic>Osteoporosis - urine</topic><topic>Proportional Hazards Models</topic><topic>Prospective Studies</topic><topic>Risk Factors</topic><topic>Urine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fink, Howard A</creatorcontrib><creatorcontrib>Vo, Tien N</creatorcontrib><creatorcontrib>Langsetmo, Lisa</creatorcontrib><creatorcontrib>Barzilay, Joshua I</creatorcontrib><creatorcontrib>Cauley, Jane A</creatorcontrib><creatorcontrib>Schousboe, John T</creatorcontrib><creatorcontrib>Orwoll, Eric S</creatorcontrib><creatorcontrib>Canales, Muna T</creatorcontrib><creatorcontrib>Ishani, Areef</creatorcontrib><creatorcontrib>Lane, Nancy E</creatorcontrib><creatorcontrib>Ensrud, Kristine E</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Physical Education Index</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of bone and mineral research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fink, Howard A</au><au>Vo, Tien N</au><au>Langsetmo, Lisa</au><au>Barzilay, Joshua I</au><au>Cauley, Jane A</au><au>Schousboe, John T</au><au>Orwoll, Eric S</au><au>Canales, Muna T</au><au>Ishani, Areef</au><au>Lane, Nancy E</au><au>Ensrud, Kristine E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association of Increased Urinary Albumin With Risk of Incident Clinical Fracture and Rate of Hip Bone Loss: the Osteoporotic Fractures in Men Study</atitle><jtitle>Journal of bone and mineral research</jtitle><addtitle>J Bone Miner Res</addtitle><date>2017-05</date><risdate>2017</risdate><volume>32</volume><issue>5</issue><spage>1090</spage><epage>1099</epage><pages>1090-1099</pages><issn>0884-0431</issn><eissn>1523-4681</eissn><abstract>ABSTRACT
Prior studies suggest that increased urine albumin is associated with a heightened fracture risk in women, but results in men are unclear. We used data from Osteoporotic Fractures in Men (MrOS), a prospective cohort study of community‐dwelling men aged ≥65 years, to evaluate the association of increased urine albumin with subsequent fractures and annualized rate of hip bone loss. We calculated albumin/creatinine ratio (ACR) from urine collected at the 2003–2005 visit. Subsequent clinical fractures were ascertained from triannual questionnaires and centrally adjudicated by review of radiographic reports. Total hip BMD was measured by DXA at the 2003–2005 visit and again an average of 3.5 years later. We estimated risk of incident clinical fracture using Cox proportional hazards models, and annualized BMD change using ANCOVA. Of 2982 men with calculable ACR, 9.4% had ACR ≥30 mg/g (albuminuria) and 1.0% had ACR ≥300 mg/g (macroalbuminuria). During a mean of 8.7 years of follow‐up, 20.0% of men had an incident clinical fracture. In multivariate‐adjusted models, neither higher ACR quintile (p for trend 0.75) nor albuminuria (HR versus no albuminuria, 0.89; 95% CI, 0.65 to 1.20) was associated with increased risk of incident clinical fracture. Increased urine albumin had a borderline significant, multivariate‐adjusted, positive association with rate of total hip bone loss when modeled in ACR quintiles (p = 0.06), but not when modeled as albuminuria versus no albuminuria. Macroalbuminuria was associated with a higher rate of annualized hip bone loss compared to no albuminuria (–1.8% more annualized loss than in men with ACR <30 mg/g; p < 0.001), but the limited prevalence of macroalbuminuria precluded reliable estimates of its fracture associations. In these community‐dwelling older men, we found no association between urine albumin levels and risk of incident clinical fracture, but found a borderline significant, positive association with rate of hip bone loss. © 2016 American Society for Bone and Mineral Research.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>28012217</pmid><doi>10.1002/jbmr.3065</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0884-0431 |
ispartof | Journal of bone and mineral research, 2017-05, Vol.32 (5), p.1090-1099 |
issn | 0884-0431 1523-4681 |
language | eng |
recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5413394 |
source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Access via Wiley Online Library; Oxford University Press Journals All Titles (1996-Current) |
subjects | Aged Aged, 80 and over Albumin ALBUMINURIA Albuminuria - epidemiology Bone loss Bone mineral density Creatinine Dual energy X-ray absorptiometry FRACTURE Fractures Fractures, Bone - epidemiology Fractures, Bone - urine Health risk assessment Hip Humans Incidence MALE OSTEOPOROSIS Osteoporosis - epidemiology Osteoporosis - urine Proportional Hazards Models Prospective Studies Risk Factors Urine |
title | Association of Increased Urinary Albumin With Risk of Incident Clinical Fracture and Rate of Hip Bone Loss: the Osteoporotic Fractures in Men Study |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T17%3A03%3A02IST&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=Association%20of%20Increased%20Urinary%20Albumin%20With%20Risk%20of%20Incident%20Clinical%20Fracture%20and%20Rate%20of%20Hip%20Bone%20Loss:%20the%20Osteoporotic%20Fractures%20in%20Men%20Study&rft.jtitle=Journal%20of%20bone%20and%20mineral%20research&rft.au=Fink,%20Howard%20A&rft.date=2017-05&rft.volume=32&rft.issue=5&rft.spage=1090&rft.epage=1099&rft.pages=1090-1099&rft.issn=0884-0431&rft.eissn=1523-4681&rft_id=info:doi/10.1002/jbmr.3065&rft_dat=%3Cproquest_pubme%3E1895050240%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=1895050240&rft_id=info:pmid/28012217&rfr_iscdi=true |