Evaluating results from the multiple myeloma patient subset treated with denosumab or zoledronic acid in a randomized phase 3 trial.
Identifieur interne : 002488 ( PubMed/Corpus ); précédent : 002487; suivant : 002489Evaluating results from the multiple myeloma patient subset treated with denosumab or zoledronic acid in a randomized phase 3 trial.
Auteurs : N. Raje ; S. Vadhan-Raj ; W. Willenbacher ; E. Terpos ; V. Hungria ; A. Spencer ; Y. Alexeeva ; T. Facon ; A K Stewart ; A. Feng ; A. Braun ; A. Balakumaran ; G D RoodmanSource :
- Blood cancer journal [ 2044-5385 ] ; 2016.
English descriptors
- KwdEn :
- Aged, Antineoplastic Combined Chemotherapy Protocols (therapeutic use), Bone Density Conservation Agents (therapeutic use), Bone Neoplasms (drug therapy), Bone Neoplasms (secondary), Denosumab (administration & dosage), Denosumab (adverse effects), Denosumab (therapeutic use), Diphosphonates (administration & dosage), Diphosphonates (adverse effects), Diphosphonates (therapeutic use), Female, Hematopoietic Stem Cell Transplantation, Humans, Imidazoles (administration & dosage), Imidazoles (adverse effects), Imidazoles (therapeutic use), Male, Middle Aged, Multiple Myeloma (diagnosis), Multiple Myeloma (drug therapy), Multiple Myeloma (mortality), Neoplasm Metastasis, Neoplasm Staging, Neoplasms (pathology), Transplantation, Autologous, Treatment Outcome.
- MESH :
- chemical , administration & dosage : Denosumab, Diphosphonates, Imidazoles.
- chemical , adverse effects : Denosumab, Diphosphonates, Imidazoles.
- chemical , therapeutic use : Bone Density Conservation Agents, Denosumab, Diphosphonates, Imidazoles.
- diagnosis : Multiple Myeloma.
- drug therapy : Bone Neoplasms, Multiple Myeloma.
- mortality : Multiple Myeloma.
- pathology : Neoplasms.
- secondary : Bone Neoplasms.
- therapeutic use : Antineoplastic Combined Chemotherapy Protocols.
- Aged, Female, Hematopoietic Stem Cell Transplantation, Humans, Male, Middle Aged, Neoplasm Metastasis, Neoplasm Staging, Transplantation, Autologous, Treatment Outcome.
Abstract
In a phase 3 trial of denosumab vs zoledronic acid in patients (n=1776) with bone metastases and solid tumors or multiple myeloma, denosumab was superior to zoledronic acid for the primary end point of prevention of skeletal-related events. There was no difference in overall survival between the two groups; however, an ad hoc overall survival analysis in the multiple myeloma subset of patients (n=180) favored zoledronic acid (hazard ratio (HR) 2.26; 95% confidence interval (CI) 1.13-4.50; P=0.014). In the present analysis, we found imbalances between the groups with respect to baseline risk characteristics. HRs with two-sided 95% CIs were estimated using the Cox model. After adjustment in a covariate analysis, the CI crossed unity (HR 1.86; 95% CI 0.90-3.84; P=0.0954). Furthermore, we found a higher rate of early withdrawals for the reasons of lost to follow-up and withdrawal of consent in the zoledronic acid group; after accounting for these, the HR was 1.31 (95% CI 0.80-2.15; P=0.278). In conclusion, the survival results in multiple myeloma patients in this trial were confounded and will eventually be resolved by an ongoing phase 3 trial.
DOI: 10.1038/bcj.2015.96
PubMed: 26745852
Links to Exploration step
pubmed:26745852Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Evaluating results from the multiple myeloma patient subset treated with denosumab or zoledronic acid in a randomized phase 3 trial.</title><author><name sortKey="Raje, N" sort="Raje, N" uniqKey="Raje N" first="N" last="Raje">N. Raje</name><affiliation><nlm:affiliation>Center for Multiple Myeloma, Massachusetts General Hospital Cancer Center, Boston, MA, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Vadhan Raj, S" sort="Vadhan Raj, S" uniqKey="Vadhan Raj S" first="S" last="Vadhan-Raj">S. Vadhan-Raj</name><affiliation><nlm:affiliation>University of Texas, MD Anderson Cancer Center, Houston, TX, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Willenbacher, W" sort="Willenbacher, W" uniqKey="Willenbacher W" first="W" last="Willenbacher">W. Willenbacher</name><affiliation><nlm:affiliation>Internal Medicine V, Haematology and Oncology, Medical University of Innsbruck, Innsbruck, Austria.</nlm:affiliation></affiliation></author><author><name sortKey="Terpos, E" sort="Terpos, E" uniqKey="Terpos E" first="E" last="Terpos">E. Terpos</name><affiliation><nlm:affiliation>Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece.</nlm:affiliation></affiliation></author><author><name sortKey="Hungria, V" sort="Hungria, V" uniqKey="Hungria V" first="V" last="Hungria">V. Hungria</name><affiliation><nlm:affiliation>Irmandade da Santa Casa de Misericordia de Sao Paulo, São Paulo, Brazil.</nlm:affiliation></affiliation></author><author><name sortKey="Spencer, A" sort="Spencer, A" uniqKey="Spencer A" first="A" last="Spencer">A. Spencer</name><affiliation><nlm:affiliation>The Alfred Hospital, Melbourne, Victoria, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Alexeeva, Y" sort="Alexeeva, Y" uniqKey="Alexeeva Y" first="Y" last="Alexeeva">Y. Alexeeva</name><affiliation><nlm:affiliation>City Hospital No. 31, Saint Petersburg, Russia.</nlm:affiliation></affiliation></author><author><name sortKey="Facon, T" sort="Facon, T" uniqKey="Facon T" first="T" last="Facon">T. Facon</name><affiliation><nlm:affiliation>Hôpital Claude Huriez, Lille, France.</nlm:affiliation></affiliation></author><author><name sortKey="Stewart, A K" sort="Stewart, A K" uniqKey="Stewart A" first="A K" last="Stewart">A K Stewart</name><affiliation><nlm:affiliation>Mayo Clinic, Scottsdale, AZ, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Feng, A" sort="Feng, A" uniqKey="Feng A" first="A" last="Feng">A. 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Balakumaran</name><affiliation><nlm:affiliation>Amgen Inc., Thousand Oaks, CA, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Roodman, G D" sort="Roodman, G D" uniqKey="Roodman G" first="G D" last="Roodman">G D Roodman</name><affiliation><nlm:affiliation>Indiana University School of Medicine, Indianapolis, IN, USA.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2016">2016</date><idno type="RBID">pubmed:26745852</idno><idno type="pmid">26745852</idno><idno type="doi">10.1038/bcj.2015.96</idno><idno type="wicri:Area/PubMed/Corpus">002488</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002488</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Evaluating results from the multiple myeloma patient subset treated with denosumab or zoledronic acid in a randomized phase 3 trial.</title><author><name sortKey="Raje, N" sort="Raje, N" uniqKey="Raje N" first="N" last="Raje">N. Raje</name><affiliation><nlm:affiliation>Center for Multiple Myeloma, Massachusetts General Hospital Cancer Center, Boston, MA, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Vadhan Raj, S" sort="Vadhan Raj, S" uniqKey="Vadhan Raj S" first="S" last="Vadhan-Raj">S. Vadhan-Raj</name><affiliation><nlm:affiliation>University of Texas, MD Anderson Cancer Center, Houston, TX, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Willenbacher, W" sort="Willenbacher, W" uniqKey="Willenbacher W" first="W" last="Willenbacher">W. Willenbacher</name><affiliation><nlm:affiliation>Internal Medicine V, Haematology and Oncology, Medical University of Innsbruck, Innsbruck, Austria.</nlm:affiliation></affiliation></author><author><name sortKey="Terpos, E" sort="Terpos, E" uniqKey="Terpos E" first="E" last="Terpos">E. Terpos</name><affiliation><nlm:affiliation>Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece.</nlm:affiliation></affiliation></author><author><name sortKey="Hungria, V" sort="Hungria, V" uniqKey="Hungria V" first="V" last="Hungria">V. Hungria</name><affiliation><nlm:affiliation>Irmandade da Santa Casa de Misericordia de Sao Paulo, São Paulo, Brazil.</nlm:affiliation></affiliation></author><author><name sortKey="Spencer, A" sort="Spencer, A" uniqKey="Spencer A" first="A" last="Spencer">A. Spencer</name><affiliation><nlm:affiliation>The Alfred Hospital, Melbourne, Victoria, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Alexeeva, Y" sort="Alexeeva, Y" uniqKey="Alexeeva Y" first="Y" last="Alexeeva">Y. Alexeeva</name><affiliation><nlm:affiliation>City Hospital No. 31, Saint Petersburg, Russia.</nlm:affiliation></affiliation></author><author><name sortKey="Facon, T" sort="Facon, T" uniqKey="Facon T" first="T" last="Facon">T. Facon</name><affiliation><nlm:affiliation>Hôpital Claude Huriez, Lille, France.</nlm:affiliation></affiliation></author><author><name sortKey="Stewart, A K" sort="Stewart, A K" uniqKey="Stewart A" first="A K" last="Stewart">A K Stewart</name><affiliation><nlm:affiliation>Mayo Clinic, Scottsdale, AZ, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Feng, A" sort="Feng, A" uniqKey="Feng A" first="A" last="Feng">A. Feng</name><affiliation><nlm:affiliation>Amgen Inc., Thousand Oaks, CA, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Braun, A" sort="Braun, A" uniqKey="Braun A" first="A" last="Braun">A. Braun</name><affiliation><nlm:affiliation>Amgen Inc., Thousand Oaks, CA, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Balakumaran, A" sort="Balakumaran, A" uniqKey="Balakumaran A" first="A" last="Balakumaran">A. Balakumaran</name><affiliation><nlm:affiliation>Amgen Inc., Thousand Oaks, CA, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Roodman, G D" sort="Roodman, G D" uniqKey="Roodman G" first="G D" last="Roodman">G D Roodman</name><affiliation><nlm:affiliation>Indiana University School of Medicine, Indianapolis, IN, USA.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Blood cancer journal</title><idno type="eISSN">2044-5385</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aged</term><term>Antineoplastic Combined Chemotherapy Protocols (therapeutic use)</term><term>Bone Density Conservation Agents (therapeutic use)</term><term>Bone Neoplasms (drug therapy)</term><term>Bone Neoplasms (secondary)</term><term>Denosumab (administration & dosage)</term><term>Denosumab (adverse effects)</term><term>Denosumab (therapeutic use)</term><term>Diphosphonates (administration & dosage)</term><term>Diphosphonates (adverse effects)</term><term>Diphosphonates (therapeutic use)</term><term>Female</term><term>Hematopoietic Stem Cell Transplantation</term><term>Humans</term><term>Imidazoles (administration & dosage)</term><term>Imidazoles (adverse effects)</term><term>Imidazoles (therapeutic use)</term><term>Male</term><term>Middle Aged</term><term>Multiple Myeloma (diagnosis)</term><term>Multiple Myeloma (drug therapy)</term><term>Multiple Myeloma (mortality)</term><term>Neoplasm Metastasis</term><term>Neoplasm Staging</term><term>Neoplasms (pathology)</term><term>Transplantation, Autologous</term><term>Treatment Outcome</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Denosumab</term><term>Diphosphonates</term><term>Imidazoles</term></keywords><keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Denosumab</term><term>Diphosphonates</term><term>Imidazoles</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Bone Density Conservation Agents</term><term>Denosumab</term><term>Diphosphonates</term><term>Imidazoles</term></keywords><keywords scheme="MESH" qualifier="diagnosis" xml:lang="en"><term>Multiple Myeloma</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Bone Neoplasms</term><term>Multiple Myeloma</term></keywords><keywords scheme="MESH" qualifier="mortality" xml:lang="en"><term>Multiple Myeloma</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Neoplasms</term></keywords><keywords scheme="MESH" qualifier="secondary" xml:lang="en"><term>Bone Neoplasms</term></keywords><keywords scheme="MESH" qualifier="therapeutic use" xml:lang="en"><term>Antineoplastic Combined Chemotherapy Protocols</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Aged</term><term>Female</term><term>Hematopoietic Stem Cell Transplantation</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Neoplasm Metastasis</term><term>Neoplasm Staging</term><term>Transplantation, Autologous</term><term>Treatment Outcome</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">In a phase 3 trial of denosumab vs zoledronic acid in patients (n=1776) with bone metastases and solid tumors or multiple myeloma, denosumab was superior to zoledronic acid for the primary end point of prevention of skeletal-related events. There was no difference in overall survival between the two groups; however, an ad hoc overall survival analysis in the multiple myeloma subset of patients (n=180) favored zoledronic acid (hazard ratio (HR) 2.26; 95% confidence interval (CI) 1.13-4.50; P=0.014). In the present analysis, we found imbalances between the groups with respect to baseline risk characteristics. HRs with two-sided 95% CIs were estimated using the Cox model. After adjustment in a covariate analysis, the CI crossed unity (HR 1.86; 95% CI 0.90-3.84; P=0.0954). Furthermore, we found a higher rate of early withdrawals for the reasons of lost to follow-up and withdrawal of consent in the zoledronic acid group; after accounting for these, the HR was 1.31 (95% CI 0.80-2.15; P=0.278). In conclusion, the survival results in multiple myeloma patients in this trial were confounded and will eventually be resolved by an ongoing phase 3 trial.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">26745852</PMID><DateCreated><Year>2016</Year><Month>01</Month><Day>09</Day></DateCreated><DateCompleted><Year>2016</Year><Month>10</Month><Day>13</Day></DateCompleted><DateRevised><Year>2017</Year><Month>04</Month><Day>21</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">2044-5385</ISSN><JournalIssue CitedMedium="Internet"><Volume>6</Volume><PubDate><Year>2016</Year><Month>Jan</Month><Day>08</Day></PubDate></JournalIssue><Title>Blood cancer journal</Title><ISOAbbreviation>Blood Cancer J</ISOAbbreviation></Journal><ArticleTitle>Evaluating results from the multiple myeloma patient subset treated with denosumab or zoledronic acid in a randomized phase 3 trial.</ArticleTitle><Pagination><MedlinePgn>e378</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1038/bcj.2015.96</ELocationID><Abstract><AbstractText>In a phase 3 trial of denosumab vs zoledronic acid in patients (n=1776) with bone metastases and solid tumors or multiple myeloma, denosumab was superior to zoledronic acid for the primary end point of prevention of skeletal-related events. There was no difference in overall survival between the two groups; however, an ad hoc overall survival analysis in the multiple myeloma subset of patients (n=180) favored zoledronic acid (hazard ratio (HR) 2.26; 95% confidence interval (CI) 1.13-4.50; P=0.014). In the present analysis, we found imbalances between the groups with respect to baseline risk characteristics. HRs with two-sided 95% CIs were estimated using the Cox model. After adjustment in a covariate analysis, the CI crossed unity (HR 1.86; 95% CI 0.90-3.84; P=0.0954). Furthermore, we found a higher rate of early withdrawals for the reasons of lost to follow-up and withdrawal of consent in the zoledronic acid group; after accounting for these, the HR was 1.31 (95% CI 0.80-2.15; P=0.278). In conclusion, the survival results in multiple myeloma patients in this trial were confounded and will eventually be resolved by an ongoing phase 3 trial.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Raje</LastName><ForeName>N</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Center for Multiple Myeloma, Massachusetts General Hospital Cancer Center, Boston, MA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Vadhan-Raj</LastName><ForeName>S</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>University of Texas, MD Anderson Cancer Center, Houston, TX, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Willenbacher</LastName><ForeName>W</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>Internal Medicine V, Haematology and Oncology, Medical University of Innsbruck, Innsbruck, Austria.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Terpos</LastName><ForeName>E</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hungria</LastName><ForeName>V</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>Irmandade da Santa Casa de Misericordia de Sao Paulo, São Paulo, Brazil.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Spencer</LastName><ForeName>A</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>The Alfred Hospital, Melbourne, Victoria, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Alexeeva</LastName><ForeName>Y</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>City Hospital No. 31, Saint Petersburg, Russia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Facon</LastName><ForeName>T</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Hôpital Claude Huriez, Lille, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Stewart</LastName><ForeName>A K</ForeName><Initials>AK</Initials><AffiliationInfo><Affiliation>Mayo Clinic, Scottsdale, AZ, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Feng</LastName><ForeName>A</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Amgen Inc., Thousand Oaks, CA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Braun</LastName><ForeName>A</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Amgen Inc., Thousand Oaks, CA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Balakumaran</LastName><ForeName>A</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Amgen Inc., Thousand Oaks, CA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Roodman</LastName><ForeName>G D</ForeName><Initials>GD</Initials><AffiliationInfo><Affiliation>Indiana University School of Medicine, Indianapolis, IN, USA.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>P30 CA016672</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D017428">Clinical Trial, Phase III</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D016449">Randomized Controlled Trial</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2016</Year><Month>01</Month><Day>08</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Blood Cancer J</MedlineTA><NlmUniqueID>101568469</NlmUniqueID><ISSNLinking>2044-5385</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D050071">Bone Density Conservation Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D004164">Diphosphonates</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D007093">Imidazoles</NameOfSubstance></Chemical><Chemical><RegistryNumber>4EQZ6YO2HI</RegistryNumber><NameOfSubstance UI="D000069448">Denosumab</NameOfSubstance></Chemical><Chemical><RegistryNumber>6XC1PAD3KF</RegistryNumber><NameOfSubstance UI="C088658">zoledronic acid</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections RefType="Cites"><RefSource>N Engl J Med. 2003 Dec 25;349(26):2495-502</RefSource><PMID Version="1">14695409</PMID></CommentsCorrections><CommentsCorrections 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MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009101" MajorTopicYN="N">Multiple Myeloma</DescriptorName><QualifierName UI="Q000175" MajorTopicYN="Y">diagnosis</QualifierName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName><QualifierName UI="Q000401" MajorTopicYN="N">mortality</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D009362" MajorTopicYN="N">Neoplasm Metastasis</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009367" MajorTopicYN="N">Neoplasm Staging</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009369" MajorTopicYN="N">Neoplasms</DescriptorName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014182" MajorTopicYN="N">Transplantation, Autologous</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016896" MajorTopicYN="N">Treatment Outcome</DescriptorName></MeshHeading></MeshHeadingList><OtherID Source="NLM">PMC4742634</OtherID></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2015</Year><Month>04</Month><Day>14</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2015</Year><Month>08</Month><Day>18</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2015</Year><Month>09</Month><Day>02</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2016</Year><Month>1</Month><Day>9</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2016</Year><Month>1</Month><Day>9</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2016</Year><Month>10</Month><Day>14</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">26745852</ArticleId><ArticleId IdType="pii">bcj201596</ArticleId><ArticleId IdType="doi">10.1038/bcj.2015.96</ArticleId><ArticleId IdType="pmc">PMC4742634</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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