Loading…
A combination of hydroxytyrosol, omega-3 fatty acids and curcumin improves pain and inflammation among early stage breast cancer patients receiving adjuvant hormonal therapy: results of a pilot study
Purpose Breast cancer patients receiving hormonal therapies face risks of relapse, increased rates of cardiovascular events, and toxicities of therapy such as aromatase inhibitor (AI)-associated musculoskeletal symptoms (AIMSS). C-reactive protein (CRP), a marker for inflammation, is associated with...
Saved in:
Published in: | Clinical & translational oncology 2019-04, Vol.21 (4), p.489-498 |
---|---|
Main Authors: | , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
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-c344t-3ae07af63b8880da43ab369e5e7471cd162a2e4990b8d5d0396709471ebda8273 |
---|---|
cites | cdi_FETCH-LOGICAL-c344t-3ae07af63b8880da43ab369e5e7471cd162a2e4990b8d5d0396709471ebda8273 |
container_end_page | 498 |
container_issue | 4 |
container_start_page | 489 |
container_title | Clinical & translational oncology |
container_volume | 21 |
creator | Martínez, N. Herrera, M. Frías, L. Provencio, M. Pérez-Carrión, R. Díaz, V. Morse, Michael Crespo, M. C. |
description | Purpose
Breast cancer patients receiving hormonal therapies face risks of relapse, increased rates of cardiovascular events, and toxicities of therapy such as aromatase inhibitor (AI)-associated musculoskeletal symptoms (AIMSS). C-reactive protein (CRP), a marker for inflammation, is associated with breast cancer outcomes. We evaluated whether the olive-derived polyphenol hydroxytyrosol combined with omega-3 fatty acids and curcumin would reduce CRP and musculoskeletal symptoms in breast cancer patients receiving adjuvant hormonal therapies.
Experimental design
This prospective, multicenter, open-label, single arm, clinical trial enrolled post-menopausal breast cancer patients (
n
= 45) with elevated C-reactive protein (CRP) taking predominantly aromatase inhibitors to receive a combination of hydroxytyrosol, omega-3 fatty acids, and curcumin for 1 month. CRP, other inflammation-associated cytokines, and pain scores on the Brief Pain Inventory were measured before therapy, at the end of therapy and 1 month after completion of therapy.
Results
CRP levels declined during the therapy [from 8.2 ± 6.4 mg/L at baseline to 5.3 ± 3.2 mg/L (
p
= 0.014) at 30 days of treatment], and remained decreased during the additional 1 month off therapy. Subjects with the highest baseline CRP levels had the greatest decrease with the therapy. Pain scores also decreased during the therapy. There were no significant adverse events.
Conclusions
The combination of hydroxytyrosol, omega-3 fatty acids, and curcumin reduced inflammation as indicated by a reduction in CRP and reduced pain in patients with aromatase-induced musculoskeletal symptoms. Longer studies comparing this combination to other anti-inflammatories in larger groups of patients with clinical outcome endpoints are warranted. |
doi_str_mv | 10.1007/s12094-018-1950-0 |
format | article |
fullrecord | <record><control><sourceid>pubmed_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1007_s12094_018_1950_0</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>30293230</sourcerecordid><originalsourceid>FETCH-LOGICAL-c344t-3ae07af63b8880da43ab369e5e7471cd162a2e4990b8d5d0396709471ebda8273</originalsourceid><addsrcrecordid>eNp9kcuO1DAQRS0EYh7wAWxQfQABO87L7EYjHiONxAYkdlHFrnS7ldiR7bTIF_JbuJWBJSuXXedeueoy9kbw94Lz9kMUJVdVwUVXCFXzgj9j16JRqpC8rp8_1bzqfl6xmxhPPL82QrxkV5KXSpaSX7Pfd6D9PFiHyXoHfoTjZoL_taUt-Oind-BnOmAhYcSUNkBtTQR0BvQa9DpbB3Zegj9ThAXz7dKybpxwnndLnL07AGGYNogJDwRDIIwJNDpNIauSJZciBNJkzzbDaE7rGV2Cow9ZjROkIwVcto8ZiuuU4fxRhMVOPmXT1Wyv2IsRp0ivn85b9uPzp-_3X4vHb18e7u8eCy2rKhUSibc4NnLouo4brCQOslFUU1u1QhvRlFhSpRQfOlMbLlXT5hW3ggaDXdnKWyZ2X53XEwON_RLsjGHrBe8vofR7KH0Opb-E0vOsebtrlnWYyfxT_E0hA-UOxNxyBwr9ya8hzx3_4_oHJqGdLw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>A combination of hydroxytyrosol, omega-3 fatty acids and curcumin improves pain and inflammation among early stage breast cancer patients receiving adjuvant hormonal therapy: results of a pilot study</title><source>Springer Nature:Jisc Collections:Springer Nature Read and Publish 2023-2025: Springer Reading List</source><creator>Martínez, N. ; Herrera, M. ; Frías, L. ; Provencio, M. ; Pérez-Carrión, R. ; Díaz, V. ; Morse, Michael ; Crespo, M. C.</creator><creatorcontrib>Martínez, N. ; Herrera, M. ; Frías, L. ; Provencio, M. ; Pérez-Carrión, R. ; Díaz, V. ; Morse, Michael ; Crespo, M. C.</creatorcontrib><description>Purpose
Breast cancer patients receiving hormonal therapies face risks of relapse, increased rates of cardiovascular events, and toxicities of therapy such as aromatase inhibitor (AI)-associated musculoskeletal symptoms (AIMSS). C-reactive protein (CRP), a marker for inflammation, is associated with breast cancer outcomes. We evaluated whether the olive-derived polyphenol hydroxytyrosol combined with omega-3 fatty acids and curcumin would reduce CRP and musculoskeletal symptoms in breast cancer patients receiving adjuvant hormonal therapies.
Experimental design
This prospective, multicenter, open-label, single arm, clinical trial enrolled post-menopausal breast cancer patients (
n
= 45) with elevated C-reactive protein (CRP) taking predominantly aromatase inhibitors to receive a combination of hydroxytyrosol, omega-3 fatty acids, and curcumin for 1 month. CRP, other inflammation-associated cytokines, and pain scores on the Brief Pain Inventory were measured before therapy, at the end of therapy and 1 month after completion of therapy.
Results
CRP levels declined during the therapy [from 8.2 ± 6.4 mg/L at baseline to 5.3 ± 3.2 mg/L (
p
= 0.014) at 30 days of treatment], and remained decreased during the additional 1 month off therapy. Subjects with the highest baseline CRP levels had the greatest decrease with the therapy. Pain scores also decreased during the therapy. There were no significant adverse events.
Conclusions
The combination of hydroxytyrosol, omega-3 fatty acids, and curcumin reduced inflammation as indicated by a reduction in CRP and reduced pain in patients with aromatase-induced musculoskeletal symptoms. Longer studies comparing this combination to other anti-inflammatories in larger groups of patients with clinical outcome endpoints are warranted.</description><identifier>ISSN: 1699-048X</identifier><identifier>EISSN: 1699-3055</identifier><identifier>DOI: 10.1007/s12094-018-1950-0</identifier><identifier>PMID: 30293230</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Aromatase Inhibitors - adverse effects ; Aromatase Inhibitors - therapeutic use ; Breast Neoplasms - drug therapy ; Breast Neoplasms - pathology ; C-Reactive Protein - metabolism ; Chemotherapy, Adjuvant - adverse effects ; Curcumin - administration & dosage ; Curcumin - adverse effects ; Drug Combinations ; Fatty Acids, Omega-3 - administration & dosage ; Fatty Acids, Omega-3 - adverse effects ; Female ; Humans ; Inflammation - chemically induced ; Inflammation - drug therapy ; Inflammation - metabolism ; Medicine ; Medicine & Public Health ; Middle Aged ; Musculoskeletal Pain - chemically induced ; Musculoskeletal Pain - drug therapy ; Musculoskeletal Pain - pathology ; Oncology ; Phenylethyl Alcohol - administration & dosage ; Phenylethyl Alcohol - adverse effects ; Phenylethyl Alcohol - analogs & derivatives ; Pilot Projects ; Postmenopause ; Prospective Studies ; Research Article</subject><ispartof>Clinical & translational oncology, 2019-04, Vol.21 (4), p.489-498</ispartof><rights>Federación de Sociedades Españolas de Oncología (FESEO) 2018</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c344t-3ae07af63b8880da43ab369e5e7471cd162a2e4990b8d5d0396709471ebda8273</citedby><cites>FETCH-LOGICAL-c344t-3ae07af63b8880da43ab369e5e7471cd162a2e4990b8d5d0396709471ebda8273</cites><orcidid>0000-0002-5725-4533</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30293230$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Martínez, N.</creatorcontrib><creatorcontrib>Herrera, M.</creatorcontrib><creatorcontrib>Frías, L.</creatorcontrib><creatorcontrib>Provencio, M.</creatorcontrib><creatorcontrib>Pérez-Carrión, R.</creatorcontrib><creatorcontrib>Díaz, V.</creatorcontrib><creatorcontrib>Morse, Michael</creatorcontrib><creatorcontrib>Crespo, M. C.</creatorcontrib><title>A combination of hydroxytyrosol, omega-3 fatty acids and curcumin improves pain and inflammation among early stage breast cancer patients receiving adjuvant hormonal therapy: results of a pilot study</title><title>Clinical & translational oncology</title><addtitle>Clin Transl Oncol</addtitle><addtitle>Clin Transl Oncol</addtitle><description>Purpose
Breast cancer patients receiving hormonal therapies face risks of relapse, increased rates of cardiovascular events, and toxicities of therapy such as aromatase inhibitor (AI)-associated musculoskeletal symptoms (AIMSS). C-reactive protein (CRP), a marker for inflammation, is associated with breast cancer outcomes. We evaluated whether the olive-derived polyphenol hydroxytyrosol combined with omega-3 fatty acids and curcumin would reduce CRP and musculoskeletal symptoms in breast cancer patients receiving adjuvant hormonal therapies.
Experimental design
This prospective, multicenter, open-label, single arm, clinical trial enrolled post-menopausal breast cancer patients (
n
= 45) with elevated C-reactive protein (CRP) taking predominantly aromatase inhibitors to receive a combination of hydroxytyrosol, omega-3 fatty acids, and curcumin for 1 month. CRP, other inflammation-associated cytokines, and pain scores on the Brief Pain Inventory were measured before therapy, at the end of therapy and 1 month after completion of therapy.
Results
CRP levels declined during the therapy [from 8.2 ± 6.4 mg/L at baseline to 5.3 ± 3.2 mg/L (
p
= 0.014) at 30 days of treatment], and remained decreased during the additional 1 month off therapy. Subjects with the highest baseline CRP levels had the greatest decrease with the therapy. Pain scores also decreased during the therapy. There were no significant adverse events.
Conclusions
The combination of hydroxytyrosol, omega-3 fatty acids, and curcumin reduced inflammation as indicated by a reduction in CRP and reduced pain in patients with aromatase-induced musculoskeletal symptoms. Longer studies comparing this combination to other anti-inflammatories in larger groups of patients with clinical outcome endpoints are warranted.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Aromatase Inhibitors - adverse effects</subject><subject>Aromatase Inhibitors - therapeutic use</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Breast Neoplasms - pathology</subject><subject>C-Reactive Protein - metabolism</subject><subject>Chemotherapy, Adjuvant - adverse effects</subject><subject>Curcumin - administration & dosage</subject><subject>Curcumin - adverse effects</subject><subject>Drug Combinations</subject><subject>Fatty Acids, Omega-3 - administration & dosage</subject><subject>Fatty Acids, Omega-3 - adverse effects</subject><subject>Female</subject><subject>Humans</subject><subject>Inflammation - chemically induced</subject><subject>Inflammation - drug therapy</subject><subject>Inflammation - metabolism</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Musculoskeletal Pain - chemically induced</subject><subject>Musculoskeletal Pain - drug therapy</subject><subject>Musculoskeletal Pain - pathology</subject><subject>Oncology</subject><subject>Phenylethyl Alcohol - administration & dosage</subject><subject>Phenylethyl Alcohol - adverse effects</subject><subject>Phenylethyl Alcohol - analogs & derivatives</subject><subject>Pilot Projects</subject><subject>Postmenopause</subject><subject>Prospective Studies</subject><subject>Research Article</subject><issn>1699-048X</issn><issn>1699-3055</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp9kcuO1DAQRS0EYh7wAWxQfQABO87L7EYjHiONxAYkdlHFrnS7ldiR7bTIF_JbuJWBJSuXXedeueoy9kbw94Lz9kMUJVdVwUVXCFXzgj9j16JRqpC8rp8_1bzqfl6xmxhPPL82QrxkV5KXSpaSX7Pfd6D9PFiHyXoHfoTjZoL_taUt-Oind-BnOmAhYcSUNkBtTQR0BvQa9DpbB3Zegj9ThAXz7dKybpxwnndLnL07AGGYNogJDwRDIIwJNDpNIauSJZciBNJkzzbDaE7rGV2Cow9ZjROkIwVcto8ZiuuU4fxRhMVOPmXT1Wyv2IsRp0ivn85b9uPzp-_3X4vHb18e7u8eCy2rKhUSibc4NnLouo4brCQOslFUU1u1QhvRlFhSpRQfOlMbLlXT5hW3ggaDXdnKWyZ2X53XEwON_RLsjGHrBe8vofR7KH0Opb-E0vOsebtrlnWYyfxT_E0hA-UOxNxyBwr9ya8hzx3_4_oHJqGdLw</recordid><startdate>20190401</startdate><enddate>20190401</enddate><creator>Martínez, N.</creator><creator>Herrera, M.</creator><creator>Frías, L.</creator><creator>Provencio, M.</creator><creator>Pérez-Carrión, R.</creator><creator>Díaz, V.</creator><creator>Morse, Michael</creator><creator>Crespo, M. C.</creator><general>Springer International Publishing</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><orcidid>https://orcid.org/0000-0002-5725-4533</orcidid></search><sort><creationdate>20190401</creationdate><title>A combination of hydroxytyrosol, omega-3 fatty acids and curcumin improves pain and inflammation among early stage breast cancer patients receiving adjuvant hormonal therapy: results of a pilot study</title><author>Martínez, N. ; Herrera, M. ; Frías, L. ; Provencio, M. ; Pérez-Carrión, R. ; Díaz, V. ; Morse, Michael ; Crespo, M. C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c344t-3ae07af63b8880da43ab369e5e7471cd162a2e4990b8d5d0396709471ebda8273</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Aromatase Inhibitors - adverse effects</topic><topic>Aromatase Inhibitors - therapeutic use</topic><topic>Breast Neoplasms - drug therapy</topic><topic>Breast Neoplasms - pathology</topic><topic>C-Reactive Protein - metabolism</topic><topic>Chemotherapy, Adjuvant - adverse effects</topic><topic>Curcumin - administration & dosage</topic><topic>Curcumin - adverse effects</topic><topic>Drug Combinations</topic><topic>Fatty Acids, Omega-3 - administration & dosage</topic><topic>Fatty Acids, Omega-3 - adverse effects</topic><topic>Female</topic><topic>Humans</topic><topic>Inflammation - chemically induced</topic><topic>Inflammation - drug therapy</topic><topic>Inflammation - metabolism</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>Musculoskeletal Pain - chemically induced</topic><topic>Musculoskeletal Pain - drug therapy</topic><topic>Musculoskeletal Pain - pathology</topic><topic>Oncology</topic><topic>Phenylethyl Alcohol - administration & dosage</topic><topic>Phenylethyl Alcohol - adverse effects</topic><topic>Phenylethyl Alcohol - analogs & derivatives</topic><topic>Pilot Projects</topic><topic>Postmenopause</topic><topic>Prospective Studies</topic><topic>Research Article</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Martínez, N.</creatorcontrib><creatorcontrib>Herrera, M.</creatorcontrib><creatorcontrib>Frías, L.</creatorcontrib><creatorcontrib>Provencio, M.</creatorcontrib><creatorcontrib>Pérez-Carrión, R.</creatorcontrib><creatorcontrib>Díaz, V.</creatorcontrib><creatorcontrib>Morse, Michael</creatorcontrib><creatorcontrib>Crespo, M. C.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Clinical & translational oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Martínez, N.</au><au>Herrera, M.</au><au>Frías, L.</au><au>Provencio, M.</au><au>Pérez-Carrión, R.</au><au>Díaz, V.</au><au>Morse, Michael</au><au>Crespo, M. C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A combination of hydroxytyrosol, omega-3 fatty acids and curcumin improves pain and inflammation among early stage breast cancer patients receiving adjuvant hormonal therapy: results of a pilot study</atitle><jtitle>Clinical & translational oncology</jtitle><stitle>Clin Transl Oncol</stitle><addtitle>Clin Transl Oncol</addtitle><date>2019-04-01</date><risdate>2019</risdate><volume>21</volume><issue>4</issue><spage>489</spage><epage>498</epage><pages>489-498</pages><issn>1699-048X</issn><eissn>1699-3055</eissn><abstract>Purpose
Breast cancer patients receiving hormonal therapies face risks of relapse, increased rates of cardiovascular events, and toxicities of therapy such as aromatase inhibitor (AI)-associated musculoskeletal symptoms (AIMSS). C-reactive protein (CRP), a marker for inflammation, is associated with breast cancer outcomes. We evaluated whether the olive-derived polyphenol hydroxytyrosol combined with omega-3 fatty acids and curcumin would reduce CRP and musculoskeletal symptoms in breast cancer patients receiving adjuvant hormonal therapies.
Experimental design
This prospective, multicenter, open-label, single arm, clinical trial enrolled post-menopausal breast cancer patients (
n
= 45) with elevated C-reactive protein (CRP) taking predominantly aromatase inhibitors to receive a combination of hydroxytyrosol, omega-3 fatty acids, and curcumin for 1 month. CRP, other inflammation-associated cytokines, and pain scores on the Brief Pain Inventory were measured before therapy, at the end of therapy and 1 month after completion of therapy.
Results
CRP levels declined during the therapy [from 8.2 ± 6.4 mg/L at baseline to 5.3 ± 3.2 mg/L (
p
= 0.014) at 30 days of treatment], and remained decreased during the additional 1 month off therapy. Subjects with the highest baseline CRP levels had the greatest decrease with the therapy. Pain scores also decreased during the therapy. There were no significant adverse events.
Conclusions
The combination of hydroxytyrosol, omega-3 fatty acids, and curcumin reduced inflammation as indicated by a reduction in CRP and reduced pain in patients with aromatase-induced musculoskeletal symptoms. Longer studies comparing this combination to other anti-inflammatories in larger groups of patients with clinical outcome endpoints are warranted.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>30293230</pmid><doi>10.1007/s12094-018-1950-0</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-5725-4533</orcidid></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1699-048X |
ispartof | Clinical & translational oncology, 2019-04, Vol.21 (4), p.489-498 |
issn | 1699-048X 1699-3055 |
language | eng |
recordid | cdi_crossref_primary_10_1007_s12094_018_1950_0 |
source | Springer Nature:Jisc Collections:Springer Nature Read and Publish 2023-2025: Springer Reading List |
subjects | Adult Aged Aged, 80 and over Aromatase Inhibitors - adverse effects Aromatase Inhibitors - therapeutic use Breast Neoplasms - drug therapy Breast Neoplasms - pathology C-Reactive Protein - metabolism Chemotherapy, Adjuvant - adverse effects Curcumin - administration & dosage Curcumin - adverse effects Drug Combinations Fatty Acids, Omega-3 - administration & dosage Fatty Acids, Omega-3 - adverse effects Female Humans Inflammation - chemically induced Inflammation - drug therapy Inflammation - metabolism Medicine Medicine & Public Health Middle Aged Musculoskeletal Pain - chemically induced Musculoskeletal Pain - drug therapy Musculoskeletal Pain - pathology Oncology Phenylethyl Alcohol - administration & dosage Phenylethyl Alcohol - adverse effects Phenylethyl Alcohol - analogs & derivatives Pilot Projects Postmenopause Prospective Studies Research Article |
title | A combination of hydroxytyrosol, omega-3 fatty acids and curcumin improves pain and inflammation among early stage breast cancer patients receiving adjuvant hormonal therapy: results of a pilot study |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T02%3A27%3A30IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-pubmed_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20combination%20of%20hydroxytyrosol,%20omega-3%20fatty%20acids%20and%20curcumin%20improves%20pain%20and%20inflammation%20among%20early%20stage%20breast%20cancer%20patients%20receiving%20adjuvant%20hormonal%20therapy:%20results%20of%20a%20pilot%20study&rft.jtitle=Clinical%20&%20translational%20oncology&rft.au=Mart%C3%ADnez,%20N.&rft.date=2019-04-01&rft.volume=21&rft.issue=4&rft.spage=489&rft.epage=498&rft.pages=489-498&rft.issn=1699-048X&rft.eissn=1699-3055&rft_id=info:doi/10.1007/s12094-018-1950-0&rft_dat=%3Cpubmed_cross%3E30293230%3C/pubmed_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c344t-3ae07af63b8880da43ab369e5e7471cd162a2e4990b8d5d0396709471ebda8273%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_id=info:pmid/30293230&rfr_iscdi=true |