Risk of gastric cancer in the second decade of follow-up after Helicobacter pylori eradication
Background and aims Eradication of Helicobacter pylori reduces the risk of gastric cancer. In this study, we investigated the risk beyond 10 years after eradication of H. pylori . Methods We conducted a retrospective cohort study of 2737 patients who had yearly endoscopic follow-up after cure of H....
Gespeichert in:
| Veröffentlicht in: | Journal of gastroenterology 2020-03, Vol.55 (3), p.281-288 |
|---|---|
| Hauptverfasser: | , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 288 |
|---|---|
| container_issue | 3 |
| container_start_page | 281 |
| container_title | Journal of gastroenterology |
| container_volume | 55 |
| creator | Take, Susumu Mizuno, Motowo Ishiki, Kuniharu Kusumoto, Chiaki Imada, Takayuki Hamada, Fumihiro Yoshida, Tomowo Yokota, Kenji Mitsuhashi, Toshiharu Okada, Hiroyuki |
| description | Background and aims
Eradication of
Helicobacter pylori
reduces the risk of gastric cancer. In this study, we investigated the risk beyond 10 years after eradication of
H. pylori
.
Methods
We conducted a retrospective cohort study of 2737 patients who had yearly endoscopic follow-up after cure of
H. pylori
infection. For comparison of gastric cancer risk in the second decade of follow-up with that in the first decade, we calculated standardized incidence ratios (SIRs) by dividing the number of observed cases of gastric cancer in the second decade of follow-up by that of expected cases which was estimated using the incidence rate ratio of age in the first decade.
Results
During the follow-up for as long as 21.4 years (mean 7.1 years), gastric cancer developed in 68 patients (0.35% per year). The SIRs for diffuse-type gastric cancer was infinity (0 expected case and 4 observed cases) in patients with mild gastric mucosal atrophy and 10.9 (95% confidence interval 4.53–26.1) with moderate atrophy, whereas no significant increase of SIRs was observed in intestinal-type cancer regardless of the grade of baseline gastric atrophy or in diffuse-type cancer in patients with severe atrophy even though who had the highest risk.
Conclusions
The longer the follow-up, the greater the risk of developing diffuse-type gastric cancer becomes in patients with mild-to-moderate gastric atrophy at baseline. Endoscopic surveillance should be continued beyond 10 years after cure of
H. pylori
irrespective of the severity of gastric atrophy. |
| doi_str_mv | 10.1007/s00535-019-01639-w |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7026240</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A714582935</galeid><sourcerecordid>A714582935</sourcerecordid><originalsourceid>FETCH-LOGICAL-c631t-4a8b1a60c3dfdd848e102175f8a8a2c920b0cf5a7507ca9c55a4f4240c2a5c0c3</originalsourceid><addsrcrecordid>eNp9kl1rFTEQhoMo9lj9A17IgjfebJ187ceNUIpaoSCI3hrmzCanqXuSY7Lrof_erKfWVsSLEDLzvG-Y4WXsOYcTDtC-zgBa6hp4X04j-3r_gK24KiXdC_GQraBXqua8VUfsSc5XAFyC7h6zI8mbptVds2JfP_n8rYqu2mCekqeKMJBNlQ_VdGmrbCmGoRos4WAXzMVxjPt63lXopsKd29FTXCMtj931GJOvbMLBE04-hqfskcMx22c39zH78u7t57Pz-uLj-w9npxc1NZJPtcJuzbEBkoMbhk51loPgrXYddiioF7AGchpbDS1hT1qjckooIIGaiuyYvTn47ub11g5kw5RwNLvkt5iuTURv7neCvzSb-MO0IJriUwxe3Rik-H22eTJbn8mOIwYb52yE5NByKZumoC__Qq_inEIZr1C6UR3v4Q61wdEaH1ws_9Jiak5brnQneqkLdfIPCpdtb8teg3W-1O8JxEFAKeacrLudkYNZUmEOqTAlFeZXKsy-iF7c3c6t5HcMCiAPQC6tsLHpz0j_sf0JNEnCmA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2356481906</pqid></control><display><type>article</type><title>Risk of gastric cancer in the second decade of follow-up after Helicobacter pylori eradication</title><source>SpringerLink Journals - AutoHoldings</source><creator>Take, Susumu ; Mizuno, Motowo ; Ishiki, Kuniharu ; Kusumoto, Chiaki ; Imada, Takayuki ; Hamada, Fumihiro ; Yoshida, Tomowo ; Yokota, Kenji ; Mitsuhashi, Toshiharu ; Okada, Hiroyuki</creator><creatorcontrib>Take, Susumu ; Mizuno, Motowo ; Ishiki, Kuniharu ; Kusumoto, Chiaki ; Imada, Takayuki ; Hamada, Fumihiro ; Yoshida, Tomowo ; Yokota, Kenji ; Mitsuhashi, Toshiharu ; Okada, Hiroyuki</creatorcontrib><description>Background and aims
Eradication of
Helicobacter pylori
reduces the risk of gastric cancer. In this study, we investigated the risk beyond 10 years after eradication of
H. pylori
.
Methods
We conducted a retrospective cohort study of 2737 patients who had yearly endoscopic follow-up after cure of
H. pylori
infection. For comparison of gastric cancer risk in the second decade of follow-up with that in the first decade, we calculated standardized incidence ratios (SIRs) by dividing the number of observed cases of gastric cancer in the second decade of follow-up by that of expected cases which was estimated using the incidence rate ratio of age in the first decade.
Results
During the follow-up for as long as 21.4 years (mean 7.1 years), gastric cancer developed in 68 patients (0.35% per year). The SIRs for diffuse-type gastric cancer was infinity (0 expected case and 4 observed cases) in patients with mild gastric mucosal atrophy and 10.9 (95% confidence interval 4.53–26.1) with moderate atrophy, whereas no significant increase of SIRs was observed in intestinal-type cancer regardless of the grade of baseline gastric atrophy or in diffuse-type cancer in patients with severe atrophy even though who had the highest risk.
Conclusions
The longer the follow-up, the greater the risk of developing diffuse-type gastric cancer becomes in patients with mild-to-moderate gastric atrophy at baseline. Endoscopic surveillance should be continued beyond 10 years after cure of
H. pylori
irrespective of the severity of gastric atrophy.</description><identifier>ISSN: 0944-1174</identifier><identifier>EISSN: 1435-5922</identifier><identifier>DOI: 10.1007/s00535-019-01639-w</identifier><identifier>PMID: 31667586</identifier><language>eng</language><publisher>Singapore: Springer Singapore</publisher><subject>Abdominal Surgery ; Atrophy ; Cancer ; Colorectal Surgery ; Comparative analysis ; Development and progression ; Endoscopy ; Eradication ; Gastric cancer ; Gastroenterology ; Health aspects ; Health risk assessment ; Helicobacter infections ; Helicobacter pylori ; Hepatology ; Infection ; Intestine ; Medical colleges ; Medicine ; Medicine & Public Health ; Mucosa ; Oncology, Experimental ; Original Article—Alimentary Tract ; Original —Alimentary Tract ; Prevention ; Risk factors ; Stomach cancer ; Surgical Oncology</subject><ispartof>Journal of gastroenterology, 2020-03, Vol.55 (3), p.281-288</ispartof><rights>The Author(s) 2019</rights><rights>COPYRIGHT 2020 Springer</rights><rights>Journal of Gastroenterology is a copyright of Springer, (2019). All Rights Reserved. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c631t-4a8b1a60c3dfdd848e102175f8a8a2c920b0cf5a7507ca9c55a4f4240c2a5c0c3</citedby><cites>FETCH-LOGICAL-c631t-4a8b1a60c3dfdd848e102175f8a8a2c920b0cf5a7507ca9c55a4f4240c2a5c0c3</cites><orcidid>0000-0001-6974-4401</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00535-019-01639-w$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00535-019-01639-w$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,27923,27924,41487,42556,51318</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31667586$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Take, Susumu</creatorcontrib><creatorcontrib>Mizuno, Motowo</creatorcontrib><creatorcontrib>Ishiki, Kuniharu</creatorcontrib><creatorcontrib>Kusumoto, Chiaki</creatorcontrib><creatorcontrib>Imada, Takayuki</creatorcontrib><creatorcontrib>Hamada, Fumihiro</creatorcontrib><creatorcontrib>Yoshida, Tomowo</creatorcontrib><creatorcontrib>Yokota, Kenji</creatorcontrib><creatorcontrib>Mitsuhashi, Toshiharu</creatorcontrib><creatorcontrib>Okada, Hiroyuki</creatorcontrib><title>Risk of gastric cancer in the second decade of follow-up after Helicobacter pylori eradication</title><title>Journal of gastroenterology</title><addtitle>J Gastroenterol</addtitle><addtitle>J Gastroenterol</addtitle><description>Background and aims
Eradication of
Helicobacter pylori
reduces the risk of gastric cancer. In this study, we investigated the risk beyond 10 years after eradication of
H. pylori
.
Methods
We conducted a retrospective cohort study of 2737 patients who had yearly endoscopic follow-up after cure of
H. pylori
infection. For comparison of gastric cancer risk in the second decade of follow-up with that in the first decade, we calculated standardized incidence ratios (SIRs) by dividing the number of observed cases of gastric cancer in the second decade of follow-up by that of expected cases which was estimated using the incidence rate ratio of age in the first decade.
Results
During the follow-up for as long as 21.4 years (mean 7.1 years), gastric cancer developed in 68 patients (0.35% per year). The SIRs for diffuse-type gastric cancer was infinity (0 expected case and 4 observed cases) in patients with mild gastric mucosal atrophy and 10.9 (95% confidence interval 4.53–26.1) with moderate atrophy, whereas no significant increase of SIRs was observed in intestinal-type cancer regardless of the grade of baseline gastric atrophy or in diffuse-type cancer in patients with severe atrophy even though who had the highest risk.
Conclusions
The longer the follow-up, the greater the risk of developing diffuse-type gastric cancer becomes in patients with mild-to-moderate gastric atrophy at baseline. Endoscopic surveillance should be continued beyond 10 years after cure of
H. pylori
irrespective of the severity of gastric atrophy.</description><subject>Abdominal Surgery</subject><subject>Atrophy</subject><subject>Cancer</subject><subject>Colorectal Surgery</subject><subject>Comparative analysis</subject><subject>Development and progression</subject><subject>Endoscopy</subject><subject>Eradication</subject><subject>Gastric cancer</subject><subject>Gastroenterology</subject><subject>Health aspects</subject><subject>Health risk assessment</subject><subject>Helicobacter infections</subject><subject>Helicobacter pylori</subject><subject>Hepatology</subject><subject>Infection</subject><subject>Intestine</subject><subject>Medical colleges</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mucosa</subject><subject>Oncology, Experimental</subject><subject>Original Article—Alimentary Tract</subject><subject>Original —Alimentary Tract</subject><subject>Prevention</subject><subject>Risk factors</subject><subject>Stomach cancer</subject><subject>Surgical Oncology</subject><issn>0944-1174</issn><issn>1435-5922</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp9kl1rFTEQhoMo9lj9A17IgjfebJ187ceNUIpaoSCI3hrmzCanqXuSY7Lrof_erKfWVsSLEDLzvG-Y4WXsOYcTDtC-zgBa6hp4X04j-3r_gK24KiXdC_GQraBXqua8VUfsSc5XAFyC7h6zI8mbptVds2JfP_n8rYqu2mCekqeKMJBNlQ_VdGmrbCmGoRos4WAXzMVxjPt63lXopsKd29FTXCMtj931GJOvbMLBE04-hqfskcMx22c39zH78u7t57Pz-uLj-w9npxc1NZJPtcJuzbEBkoMbhk51loPgrXYddiioF7AGchpbDS1hT1qjckooIIGaiuyYvTn47ub11g5kw5RwNLvkt5iuTURv7neCvzSb-MO0IJriUwxe3Rik-H22eTJbn8mOIwYb52yE5NByKZumoC__Qq_inEIZr1C6UR3v4Q61wdEaH1ws_9Jiak5brnQneqkLdfIPCpdtb8teg3W-1O8JxEFAKeacrLudkYNZUmEOqTAlFeZXKsy-iF7c3c6t5HcMCiAPQC6tsLHpz0j_sf0JNEnCmA</recordid><startdate>20200301</startdate><enddate>20200301</enddate><creator>Take, Susumu</creator><creator>Mizuno, Motowo</creator><creator>Ishiki, Kuniharu</creator><creator>Kusumoto, Chiaki</creator><creator>Imada, Takayuki</creator><creator>Hamada, Fumihiro</creator><creator>Yoshida, Tomowo</creator><creator>Yokota, Kenji</creator><creator>Mitsuhashi, Toshiharu</creator><creator>Okada, Hiroyuki</creator><general>Springer Singapore</general><general>Springer</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-6974-4401</orcidid></search><sort><creationdate>20200301</creationdate><title>Risk of gastric cancer in the second decade of follow-up after Helicobacter pylori eradication</title><author>Take, Susumu ; Mizuno, Motowo ; Ishiki, Kuniharu ; Kusumoto, Chiaki ; Imada, Takayuki ; Hamada, Fumihiro ; Yoshida, Tomowo ; Yokota, Kenji ; Mitsuhashi, Toshiharu ; Okada, Hiroyuki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c631t-4a8b1a60c3dfdd848e102175f8a8a2c920b0cf5a7507ca9c55a4f4240c2a5c0c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Abdominal Surgery</topic><topic>Atrophy</topic><topic>Cancer</topic><topic>Colorectal Surgery</topic><topic>Comparative analysis</topic><topic>Development and progression</topic><topic>Endoscopy</topic><topic>Eradication</topic><topic>Gastric cancer</topic><topic>Gastroenterology</topic><topic>Health aspects</topic><topic>Health risk assessment</topic><topic>Helicobacter infections</topic><topic>Helicobacter pylori</topic><topic>Hepatology</topic><topic>Infection</topic><topic>Intestine</topic><topic>Medical colleges</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Mucosa</topic><topic>Oncology, Experimental</topic><topic>Original Article—Alimentary Tract</topic><topic>Original —Alimentary Tract</topic><topic>Prevention</topic><topic>Risk factors</topic><topic>Stomach cancer</topic><topic>Surgical Oncology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Take, Susumu</creatorcontrib><creatorcontrib>Mizuno, Motowo</creatorcontrib><creatorcontrib>Ishiki, Kuniharu</creatorcontrib><creatorcontrib>Kusumoto, Chiaki</creatorcontrib><creatorcontrib>Imada, Takayuki</creatorcontrib><creatorcontrib>Hamada, Fumihiro</creatorcontrib><creatorcontrib>Yoshida, Tomowo</creatorcontrib><creatorcontrib>Yokota, Kenji</creatorcontrib><creatorcontrib>Mitsuhashi, Toshiharu</creatorcontrib><creatorcontrib>Okada, Hiroyuki</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of gastroenterology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Take, Susumu</au><au>Mizuno, Motowo</au><au>Ishiki, Kuniharu</au><au>Kusumoto, Chiaki</au><au>Imada, Takayuki</au><au>Hamada, Fumihiro</au><au>Yoshida, Tomowo</au><au>Yokota, Kenji</au><au>Mitsuhashi, Toshiharu</au><au>Okada, Hiroyuki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Risk of gastric cancer in the second decade of follow-up after Helicobacter pylori eradication</atitle><jtitle>Journal of gastroenterology</jtitle><stitle>J Gastroenterol</stitle><addtitle>J Gastroenterol</addtitle><date>2020-03-01</date><risdate>2020</risdate><volume>55</volume><issue>3</issue><spage>281</spage><epage>288</epage><pages>281-288</pages><issn>0944-1174</issn><eissn>1435-5922</eissn><abstract>Background and aims
Eradication of
Helicobacter pylori
reduces the risk of gastric cancer. In this study, we investigated the risk beyond 10 years after eradication of
H. pylori
.
Methods
We conducted a retrospective cohort study of 2737 patients who had yearly endoscopic follow-up after cure of
H. pylori
infection. For comparison of gastric cancer risk in the second decade of follow-up with that in the first decade, we calculated standardized incidence ratios (SIRs) by dividing the number of observed cases of gastric cancer in the second decade of follow-up by that of expected cases which was estimated using the incidence rate ratio of age in the first decade.
Results
During the follow-up for as long as 21.4 years (mean 7.1 years), gastric cancer developed in 68 patients (0.35% per year). The SIRs for diffuse-type gastric cancer was infinity (0 expected case and 4 observed cases) in patients with mild gastric mucosal atrophy and 10.9 (95% confidence interval 4.53–26.1) with moderate atrophy, whereas no significant increase of SIRs was observed in intestinal-type cancer regardless of the grade of baseline gastric atrophy or in diffuse-type cancer in patients with severe atrophy even though who had the highest risk.
Conclusions
The longer the follow-up, the greater the risk of developing diffuse-type gastric cancer becomes in patients with mild-to-moderate gastric atrophy at baseline. Endoscopic surveillance should be continued beyond 10 years after cure of
H. pylori
irrespective of the severity of gastric atrophy.</abstract><cop>Singapore</cop><pub>Springer Singapore</pub><pmid>31667586</pmid><doi>10.1007/s00535-019-01639-w</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0001-6974-4401</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0944-1174 |
| ispartof | Journal of gastroenterology, 2020-03, Vol.55 (3), p.281-288 |
| issn | 0944-1174 1435-5922 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7026240 |
| source | SpringerLink Journals - AutoHoldings |
| subjects | Abdominal Surgery Atrophy Cancer Colorectal Surgery Comparative analysis Development and progression Endoscopy Eradication Gastric cancer Gastroenterology Health aspects Health risk assessment Helicobacter infections Helicobacter pylori Hepatology Infection Intestine Medical colleges Medicine Medicine & Public Health Mucosa Oncology, Experimental Original Article—Alimentary Tract Original —Alimentary Tract Prevention Risk factors Stomach cancer Surgical Oncology |
| title | Risk of gastric cancer in the second decade of follow-up after Helicobacter pylori eradication |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-12T03%3A15%3A52IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Risk%20of%20gastric%20cancer%20in%20the%20second%20decade%20of%20follow-up%20after%20Helicobacter%20pylori%20eradication&rft.jtitle=Journal%20of%20gastroenterology&rft.au=Take,%20Susumu&rft.date=2020-03-01&rft.volume=55&rft.issue=3&rft.spage=281&rft.epage=288&rft.pages=281-288&rft.issn=0944-1174&rft.eissn=1435-5922&rft_id=info:doi/10.1007/s00535-019-01639-w&rft_dat=%3Cgale_pubme%3EA714582935%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2356481906&rft_id=info:pmid/31667586&rft_galeid=A714582935&rfr_iscdi=true |