Efficacy of pharmacological therapies in patients with IBS with diarrhoea or mixed stool pattern: systematic review and network meta-analysis.
Identifieur interne : 000228 ( Main/Exploration ); précédent : 000227; suivant : 000229Efficacy of pharmacological therapies in patients with IBS with diarrhoea or mixed stool pattern: systematic review and network meta-analysis.
Auteurs : Christopher J. Black [Royaume-Uni] ; Nicholas E. Burr [Royaume-Uni] ; Michael Camilleri [États-Unis] ; David L. Earnest [États-Unis] ; Eamonn Mm Quigley [États-Unis] ; Paul Moayyedi [Canada] ; Lesley A. Houghton [Royaume-Uni] ; Alexander C. Ford [Royaume-Uni]Source :
- Gut [ 1468-3288 ] ; 2020.
Descripteurs français
- KwdFr :
- Agents gastro-intestinaux (effets indésirables), Agents gastro-intestinaux (usage thérapeutique), Diarrhée (traitement médicamenteux), Diarrhée (étiologie), Douleur abdominale (traitement médicamenteux), Douleur abdominale (étiologie), Détermination du point final (normes), Essais contrôlés randomisés comme sujet (méthodes), Gestion de la douleur (normes), Humains (MeSH), Résultat thérapeutique (MeSH), Syndrome du côlon irritable (complications), Syndrome du côlon irritable (traitement médicamenteux), Échec thérapeutique (MeSH).
- MESH :
- effets indésirables : Agents gastro-intestinaux, Syndrome du côlon irritable.
- méthodes : Essais contrôlés randomisés comme sujet.
- normes : Détermination du point final, Gestion de la douleur.
- traitement médicamenteux : Diarrhée, Douleur abdominale, Syndrome du côlon irritable.
- usage thérapeutique : Agents gastro-intestinaux.
- étiologie : Diarrhée, Douleur abdominale.
- Humains, Résultat thérapeutique, Échec thérapeutique.
English descriptors
- KwdEn :
- Abdominal Pain (drug therapy), Abdominal Pain (etiology), Diarrhea (drug therapy), Diarrhea (etiology), Endpoint Determination (standards), Gastrointestinal Agents (adverse effects), Gastrointestinal Agents (therapeutic use), Humans (MeSH), Irritable Bowel Syndrome (complications), Irritable Bowel Syndrome (drug therapy), Pain Management (standards), Randomized Controlled Trials as Topic (methods), Treatment Failure (MeSH), Treatment Outcome (MeSH).
- MESH :
- chemical , adverse effects : Gastrointestinal Agents.
- complications : Irritable Bowel Syndrome.
- drug therapy : Abdominal Pain, Diarrhea, Irritable Bowel Syndrome.
- etiology : Abdominal Pain, Diarrhea.
- methods : Randomized Controlled Trials as Topic.
- standards : Endpoint Determination, Pain Management.
- chemical , therapeutic use : Gastrointestinal Agents.
- Humans, Treatment Failure, Treatment Outcome.
Abstract
OBJECTIVE
Over half of patients with IBS have either diarrhoea (IBS-D) or a mixed stool pattern (IBS-M). The relative efficacy of licenced pharmacological therapies is unclear in the absence of head-to-head trials. We conducted a network meta-analysis to resolve this uncertainty.
DESIGN
We searched MEDLINE, Embase, Embase Classic, the Cochrane central register of controlled trials, and Clinicaltrials.gov through January 2019 to identify randomised controlled trials (RCTs) assessing the efficacy of licenced pharmacological therapies (alosetron, eluxadoline, ramosetron and rifaximin) in adults with IBS-D or IBS-M. Trials included in the analysis reported a dichotomous assessment of overall response to therapy, and data were pooled using a random effects model. Efficacy and safety of all pharmacological therapies were reported as a pooled relative risk with 95% CIs to summarise the effect of each comparison tested. Treatments were ranked according to their p score.
RESULTS
We identified 18 eligible RCTs (seven alosetron, five ramosetron, two rifaximin and four eluxadoline), containing 9844 patients. All were superior to placebo for the treatment of IBS-D or IBS-M at 12 weeks, according to the Food and Drug Administration (FDA)-recommended endpoint for trials in IBS. Alosetron 1 mg twice daily was ranked first for efficacy, based on the FDA-recommended composite endpoint of improvement in both abdominal pain and stool consistency, effect on global symptoms of IBS and effect on stool consistency. Ramosetron 2.5µg once daily was ranked first for effect on abdominal pain. Total numbers of adverse events were significantly greater with alosetron 1 mg twice daily and ramosetron 2.5µg once daily, compared with placebo. Rifaximin 550 mg three times daily ranked first for safety. Constipation was significantly more common with all drugs, except rifaximin 550 mg three times daily.
CONCLUSION
In a network meta-analysis of RCTs of pharmacological therapies for IBS-D and IBS-M, we found all drugs to be superior to placebo, but alosetron and ramosetron appeared to be the most effective.
DOI: 10.1136/gutjnl-2018-318160
PubMed: 30996042
Affiliations:
- Canada, Royaume-Uni, États-Unis
- Angleterre, Arizona, Minnesota, Ontario, Texas, Yorkshire-et-Humber
- Hamilton (Ontario), Leeds
- Université McMaster, Université de Leeds
Links toward previous steps (curation, corpus...)
Le document en format XML
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Earnest</name><affiliation wicri:level="2"><nlm:affiliation>Division of Gastroenterology, The University of Arizona College of Medicine, Tucson, Arizona, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Gastroenterology, The University of Arizona College of Medicine, Tucson, Arizona</wicri:regionArea><placeName><region type="state">Arizona</region></placeName></affiliation></author><author><name sortKey="Quigley, Eamonn Mm" sort="Quigley, Eamonn Mm" uniqKey="Quigley E" first="Eamonn Mm" last="Quigley">Eamonn Mm Quigley</name><affiliation wicri:level="2"><nlm:affiliation>Division of Gastroenterology and Hepatology, The Methodist Hospital, Weill Cornell Medical College, Houston, Texas, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Gastroenterology and Hepatology, The Methodist Hospital, Weill Cornell Medical College, Houston, Texas</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Moayyedi, Paul" sort="Moayyedi, Paul" uniqKey="Moayyedi P" first="Paul" last="Moayyedi">Paul Moayyedi</name><affiliation wicri:level="4"><nlm:affiliation>Department of Gastroenterology, McMaster University, Hamilton, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Gastroenterology, McMaster University, Hamilton, Ontario</wicri:regionArea><orgName type="university">Université McMaster</orgName><placeName><settlement type="city">Hamilton (Ontario)</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Houghton, Lesley A" sort="Houghton, Lesley A" uniqKey="Houghton L" first="Lesley A" last="Houghton">Lesley A. 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Ford</name><affiliation wicri:level="4"><nlm:affiliation>Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds</wicri:regionArea><orgName type="university">Université de Leeds</orgName><placeName><settlement type="city">Leeds</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Yorkshire-et-Humber</region></placeName></affiliation><affiliation wicri:level="1"><nlm:affiliation>Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Leeds Gastroenterology Institute, St. James's University Hospital, Leeds</wicri:regionArea><wicri:noRegion>Leeds</wicri:noRegion></affiliation></author></analytic><series><title level="j">Gut</title><idno type="eISSN">1468-3288</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Abdominal Pain (drug therapy)</term><term>Abdominal Pain (etiology)</term><term>Diarrhea (drug therapy)</term><term>Diarrhea (etiology)</term><term>Endpoint Determination (standards)</term><term>Gastrointestinal Agents (adverse effects)</term><term>Gastrointestinal Agents (therapeutic use)</term><term>Humans (MeSH)</term><term>Irritable Bowel Syndrome (complications)</term><term>Irritable Bowel Syndrome (drug therapy)</term><term>Pain Management (standards)</term><term>Randomized Controlled Trials as Topic (methods)</term><term>Treatment Failure (MeSH)</term><term>Treatment Outcome (MeSH)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Agents gastro-intestinaux (effets indésirables)</term><term>Agents gastro-intestinaux (usage thérapeutique)</term><term>Diarrhée (traitement médicamenteux)</term><term>Diarrhée (étiologie)</term><term>Douleur abdominale (traitement médicamenteux)</term><term>Douleur abdominale (étiologie)</term><term>Détermination du point final (normes)</term><term>Essais contrôlés randomisés comme sujet (méthodes)</term><term>Gestion de la douleur (normes)</term><term>Humains (MeSH)</term><term>Résultat thérapeutique (MeSH)</term><term>Syndrome du côlon irritable (complications)</term><term>Syndrome du côlon irritable (traitement médicamenteux)</term><term>Échec thérapeutique (MeSH)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Gastrointestinal Agents</term></keywords><keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>Irritable Bowel Syndrome</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Abdominal Pain</term><term>Diarrhea</term><term>Irritable Bowel Syndrome</term></keywords><keywords scheme="MESH" qualifier="effets indésirables" xml:lang="fr"><term>Agents gastro-intestinaux</term><term>Syndrome du côlon irritable</term></keywords><keywords scheme="MESH" qualifier="etiology" xml:lang="en"><term>Abdominal Pain</term><term>Diarrhea</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Randomized Controlled Trials as Topic</term></keywords><keywords scheme="MESH" qualifier="méthodes" xml:lang="fr"><term>Essais contrôlés randomisés comme sujet</term></keywords><keywords scheme="MESH" qualifier="normes" xml:lang="fr"><term>Détermination du point final</term><term>Gestion de la douleur</term></keywords><keywords scheme="MESH" qualifier="standards" xml:lang="en"><term>Endpoint Determination</term><term>Pain Management</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Gastrointestinal Agents</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Diarrhée</term><term>Douleur abdominale</term><term>Syndrome du côlon irritable</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Agents gastro-intestinaux</term></keywords><keywords scheme="MESH" qualifier="étiologie" xml:lang="fr"><term>Diarrhée</term><term>Douleur abdominale</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Humans</term><term>Treatment Failure</term><term>Treatment Outcome</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Humains</term><term>Résultat thérapeutique</term><term>Échec thérapeutique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><b>OBJECTIVE</b></p><p>Over half of patients with IBS have either diarrhoea (IBS-D) or a mixed stool pattern (IBS-M). The relative efficacy of licenced pharmacological therapies is unclear in the absence of head-to-head trials. We conducted a network meta-analysis to resolve this uncertainty.</p></div><div type="abstract" xml:lang="en"><p><b>DESIGN</b></p><p>We searched MEDLINE, Embase, Embase Classic, the Cochrane central register of controlled trials, and Clinicaltrials.gov through January 2019 to identify randomised controlled trials (RCTs) assessing the efficacy of licenced pharmacological therapies (alosetron, eluxadoline, ramosetron and rifaximin) in adults with IBS-D or IBS-M. Trials included in the analysis reported a dichotomous assessment of overall response to therapy, and data were pooled using a random effects model. Efficacy and safety of all pharmacological therapies were reported as a pooled relative risk with 95% CIs to summarise the effect of each comparison tested. Treatments were ranked according to their p score.</p></div><div type="abstract" xml:lang="en"><p><b>RESULTS</b></p><p>We identified 18 eligible RCTs (seven alosetron, five ramosetron, two rifaximin and four eluxadoline), containing 9844 patients. All were superior to placebo for the treatment of IBS-D or IBS-M at 12 weeks, according to the Food and Drug Administration (FDA)-recommended endpoint for trials in IBS. Alosetron 1 mg twice daily was ranked first for efficacy, based on the FDA-recommended composite endpoint of improvement in both abdominal pain and stool consistency, effect on global symptoms of IBS and effect on stool consistency. Ramosetron 2.5µg once daily was ranked first for effect on abdominal pain. Total numbers of adverse events were significantly greater with alosetron 1 mg twice daily and ramosetron 2.5µg once daily, compared with placebo. Rifaximin 550 mg three times daily ranked first for safety. Constipation was significantly more common with all drugs, except rifaximin 550 mg three times daily.</p></div><div type="abstract" xml:lang="en"><p><b>CONCLUSION</b></p><p>In a network meta-analysis of RCTs of pharmacological therapies for IBS-D and IBS-M, we found all drugs to be superior to placebo, but alosetron and ramosetron appeared to be the most effective.</p></div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">30996042</PMID><DateCompleted><Year>2019</Year><Month>12</Month><Day>16</Day></DateCompleted><DateRevised><Year>2019</Year><Month>12</Month><Day>17</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1468-3288</ISSN><JournalIssue CitedMedium="Internet"><Volume>69</Volume><Issue>1</Issue><PubDate><Year>2020</Year><Month>01</Month></PubDate></JournalIssue><Title>Gut</Title><ISOAbbreviation>Gut</ISOAbbreviation></Journal><ArticleTitle>Efficacy of pharmacological therapies in patients with IBS with diarrhoea or mixed stool pattern: systematic review and network meta-analysis.</ArticleTitle><Pagination><MedlinePgn>74-82</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1136/gutjnl-2018-318160</ELocationID><Abstract><AbstractText Label="OBJECTIVE">Over half of patients with IBS have either diarrhoea (IBS-D) or a mixed stool pattern (IBS-M). The relative efficacy of licenced pharmacological therapies is unclear in the absence of head-to-head trials. We conducted a network meta-analysis to resolve this uncertainty.</AbstractText><AbstractText Label="DESIGN">We searched MEDLINE, Embase, Embase Classic, the Cochrane central register of controlled trials, and Clinicaltrials.gov through January 2019 to identify randomised controlled trials (RCTs) assessing the efficacy of licenced pharmacological therapies (alosetron, eluxadoline, ramosetron and rifaximin) in adults with IBS-D or IBS-M. Trials included in the analysis reported a dichotomous assessment of overall response to therapy, and data were pooled using a random effects model. Efficacy and safety of all pharmacological therapies were reported as a pooled relative risk with 95% CIs to summarise the effect of each comparison tested. Treatments were ranked according to their p score.</AbstractText><AbstractText Label="RESULTS">We identified 18 eligible RCTs (seven alosetron, five ramosetron, two rifaximin and four eluxadoline), containing 9844 patients. All were superior to placebo for the treatment of IBS-D or IBS-M at 12 weeks, according to the Food and Drug Administration (FDA)-recommended endpoint for trials in IBS. Alosetron 1 mg twice daily was ranked first for efficacy, based on the FDA-recommended composite endpoint of improvement in both abdominal pain and stool consistency, effect on global symptoms of IBS and effect on stool consistency. Ramosetron 2.5µg once daily was ranked first for effect on abdominal pain. Total numbers of adverse events were significantly greater with alosetron 1 mg twice daily and ramosetron 2.5µg once daily, compared with placebo. Rifaximin 550 mg three times daily ranked first for safety. Constipation was significantly more common with all drugs, except rifaximin 550 mg three times daily.</AbstractText><AbstractText Label="CONCLUSION">In a network meta-analysis of RCTs of pharmacological therapies for IBS-D and IBS-M, we found all drugs to be superior to placebo, but alosetron and ramosetron appeared to be the most effective.</AbstractText><CopyrightInformation>© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Black</LastName><ForeName>Christopher J</ForeName><Initials>CJ</Initials><AffiliationInfo><Affiliation>Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Burr</LastName><ForeName>Nicholas E</ForeName><Initials>NE</Initials><AffiliationInfo><Affiliation>Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Camilleri</LastName><ForeName>Michael</ForeName><Initials>M</Initials><Identifier Source="ORCID">0000-0001-6472-7514</Identifier><AffiliationInfo><Affiliation>Mayo Clinic, Rochester, Minnesota, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Earnest</LastName><ForeName>David L</ForeName><Initials>DL</Initials><AffiliationInfo><Affiliation>Division of Gastroenterology, The University of Arizona College of Medicine, Tucson, Arizona, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Quigley</LastName><ForeName>Eamonn Mm</ForeName><Initials>EM</Initials><AffiliationInfo><Affiliation>Division of Gastroenterology and Hepatology, The Methodist Hospital, Weill Cornell Medical College, Houston, Texas, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Moayyedi</LastName><ForeName>Paul</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Department of Gastroenterology, McMaster University, Hamilton, Ontario, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Houghton</LastName><ForeName>Lesley A</ForeName><Initials>LA</Initials><AffiliationInfo><Affiliation>Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ford</LastName><ForeName>Alexander C</ForeName><Initials>AC</Initials><Identifier Source="ORCID">0000-0001-6371-4359</Identifier><AffiliationInfo><Affiliation>Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D017418">Meta-Analysis</PublicationType><PublicationType UI="D000078182">Systematic Review</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>04</Month><Day>17</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Gut</MedlineTA><NlmUniqueID>2985108R</NlmUniqueID><ISSNLinking>0017-5749</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D005765">Gastrointestinal Agents</NameOfSubstance></Chemical></ChemicalList><CitationSubset>AIM</CitationSubset><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D015746" MajorTopicYN="N">Abdominal Pain</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="N">drug therapy</QualifierName><QualifierName UI="Q000209" MajorTopicYN="N">etiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003967" MajorTopicYN="N">Diarrhea</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName><QualifierName UI="Q000209" MajorTopicYN="N">etiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D023381" MajorTopicYN="N">Endpoint Determination</DescriptorName><QualifierName UI="Q000592" MajorTopicYN="N">standards</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005765" MajorTopicYN="N">Gastrointestinal Agents</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D043183" MajorTopicYN="N">Irritable Bowel Syndrome</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="N">complications</QualifierName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D059408" MajorTopicYN="N">Pain Management</DescriptorName><QualifierName UI="Q000592" MajorTopicYN="N">standards</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D016032" MajorTopicYN="N">Randomized Controlled Trials as Topic</DescriptorName><QualifierName UI="Q000379" MajorTopicYN="N">methods</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D017211" MajorTopicYN="N">Treatment Failure</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016896" MajorTopicYN="N">Treatment Outcome</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">diarrhoea</Keyword><Keyword MajorTopicYN="Y">effectiveness</Keyword><Keyword MajorTopicYN="Y">stool consistency</Keyword><Keyword MajorTopicYN="Y">treatment response</Keyword></KeywordList><CoiStatement>Competing interests: MC has received research funding from Allergan. DLE has acted as a consultant for Prometheus Laboratories. EMMQ has acted as a consultant to Almirall, Synergy and Salix. PM has received honoraria from Allergan and Salix, and research funding from Allergan. LAH has acted as a consultant for, and received research funding from Takeda, USA, and has acted as a consultant for Pfizer, USA. ACF has acted as a consultant for and received researching funding from Almirall.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2018</Year><Month>12</Month><Day>26</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2019</Year><Month>02</Month><Day>04</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2019</Year><Month>04</Month><Day>02</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2019</Year><Month>4</Month><Day>19</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2019</Year><Month>12</Month><Day>18</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2019</Year><Month>4</Month><Day>19</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">30996042</ArticleId><ArticleId IdType="pii">gutjnl-2018-318160</ArticleId><ArticleId IdType="doi">10.1136/gutjnl-2018-318160</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Canada</li><li>Royaume-Uni</li><li>États-Unis</li></country><region><li>Angleterre</li><li>Arizona</li><li>Minnesota</li><li>Ontario</li><li>Texas</li><li>Yorkshire-et-Humber</li></region><settlement><li>Hamilton (Ontario)</li><li>Leeds</li></settlement><orgName><li>Université McMaster</li><li>Université de Leeds</li></orgName></list><tree><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Black, Christopher J" sort="Black, Christopher J" uniqKey="Black C" first="Christopher J" last="Black">Christopher J. Black</name></region><name sortKey="Black, Christopher J" sort="Black, Christopher J" uniqKey="Black C" first="Christopher J" last="Black">Christopher J. Black</name><name sortKey="Burr, Nicholas E" sort="Burr, Nicholas E" uniqKey="Burr N" first="Nicholas E" last="Burr">Nicholas E. Burr</name><name sortKey="Burr, Nicholas E" sort="Burr, Nicholas E" uniqKey="Burr N" first="Nicholas E" last="Burr">Nicholas E. Burr</name><name sortKey="Ford, Alexander C" sort="Ford, Alexander C" uniqKey="Ford A" first="Alexander C" last="Ford">Alexander C. Ford</name><name sortKey="Ford, Alexander C" sort="Ford, Alexander C" uniqKey="Ford A" first="Alexander C" last="Ford">Alexander C. Ford</name><name sortKey="Houghton, Lesley A" sort="Houghton, Lesley A" uniqKey="Houghton L" first="Lesley A" last="Houghton">Lesley A. Houghton</name></country><country name="États-Unis"><region name="Minnesota"><name sortKey="Camilleri, Michael" sort="Camilleri, Michael" uniqKey="Camilleri M" first="Michael" last="Camilleri">Michael Camilleri</name></region><name sortKey="Earnest, David L" sort="Earnest, David L" uniqKey="Earnest D" first="David L" last="Earnest">David L. Earnest</name><name sortKey="Quigley, Eamonn Mm" sort="Quigley, Eamonn Mm" uniqKey="Quigley E" first="Eamonn Mm" last="Quigley">Eamonn Mm Quigley</name></country><country name="Canada"><region name="Ontario"><name sortKey="Moayyedi, Paul" sort="Moayyedi, Paul" uniqKey="Moayyedi P" first="Paul" last="Moayyedi">Paul Moayyedi</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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