Tozadenant (SYN115) in patients with Parkinson's disease who have motor fluctuations on levodopa: a phase 2b, double-blind, randomised trial.
Identifieur interne : 000620 ( PubMed/Checkpoint ); précédent : 000619; suivant : 000621Tozadenant (SYN115) in patients with Parkinson's disease who have motor fluctuations on levodopa: a phase 2b, double-blind, randomised trial.
Auteurs : Robert A. Hauser [États-Unis] ; C Warren Olanow [États-Unis] ; Karl D. Kieburtz [États-Unis] ; Emmanuelle Pourcher [Canada] ; Any Docu-Axelerad [Roumanie] ; Mark Lew [États-Unis] ; Olexandr Kozyolkin [Ukraine] ; Ann Neale [États-Unis] ; Chris Resburg [États-Unis] ; Uwe Meya [États-Unis] ; Christopher Kenney [États-Unis] ; Stephen Bandak [États-Unis]Source :
- The Lancet. Neurology [ 1474-4465 ] ; 2014.
English descriptors
- KwdEn :
- Adenosine A2 Receptor Antagonists (adverse effects), Aged, Antiparkinson Agents (adverse effects), Benzothiazoles (adverse effects), Cross-Over Studies, Double-Blind Method, Dyskinesia, Drug-Induced (diagnosis), Dyskinesia, Drug-Induced (epidemiology), Female, Humans, Internationality, Levodopa (adverse effects), Male, Middle Aged, Parkinson Disease (diagnosis), Parkinson Disease (drug therapy), Parkinson Disease (epidemiology).
- MESH :
- chemical , adverse effects : Adenosine A2 Receptor Antagonists, Antiparkinson Agents, Benzothiazoles, Levodopa.
- diagnosis : Dyskinesia, Drug-Induced, Parkinson Disease.
- drug therapy : Parkinson Disease.
- epidemiology : Dyskinesia, Drug-Induced, Parkinson Disease.
- Aged, Cross-Over Studies, Double-Blind Method, Female, Humans, Internationality, Male, Middle Aged.
Abstract
Many patients with Parkinson's disease have motor fluctuations despite treatment with available drugs. Tozadenant (SYN115) is an oral, selective adenosine A2A receptor antagonist that improves motor function in animal models of Parkinson's disease. We aimed to assess the safety and efficacy of tozadenant as an adjunct to levodopa in patients with Parkinson's disease who have motor fluctuations on levodopa.
DOI: 10.1016/S1474-4422(14)70148-6
PubMed: 25008546
Affiliations:
- Canada, Roumanie, Ukraine, États-Unis
- Californie, Floride, État de New York
- Los Angeles
- Université de Californie du Sud
Links toward previous steps (curation, corpus...)
Links to Exploration step
pubmed:25008546Le document en format XML
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Hauser</name><affiliation wicri:level="2"><nlm:affiliation>University of South Florida Parkinson's Disease and Movement Disorders Center, National Parkinson Foundation Center of Excellence, Tampa, FL, USA. Electronic address: rhauser@health.usf.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>University of South Florida Parkinson's Disease and Movement Disorders Center, National Parkinson Foundation Center of Excellence, Tampa, FL</wicri:regionArea><placeName><region type="state">Floride</region></placeName></affiliation></author><author><name sortKey="Olanow, C Warren" sort="Olanow, C Warren" uniqKey="Olanow C" first="C Warren" last="Olanow">C Warren Olanow</name><affiliation wicri:level="2"><nlm:affiliation>Department of Neurology, Mount Sinai School of Medicine, New York, NY, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Mount Sinai School of Medicine, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Kieburtz, Karl D" sort="Kieburtz, Karl D" uniqKey="Kieburtz K" first="Karl D" last="Kieburtz">Karl D. Kieburtz</name><affiliation wicri:level="2"><nlm:affiliation>University of Rochester School of Medicine, Rochester, NY, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>University of Rochester School of Medicine, Rochester, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Pourcher, Emmanuelle" sort="Pourcher, Emmanuelle" uniqKey="Pourcher E" first="Emmanuelle" last="Pourcher">Emmanuelle Pourcher</name><affiliation wicri:level="1"><nlm:affiliation>Clinique Sainte-Anne Mémoire et Mouvement, Faculty of Medicine, Laval University, Quebec, QC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Clinique Sainte-Anne Mémoire et Mouvement, Faculty of Medicine, Laval University, Quebec, QC</wicri:regionArea><wicri:noRegion>QC</wicri:noRegion></affiliation></author><author><name sortKey="Docu Axelerad, Any" sort="Docu Axelerad, Any" uniqKey="Docu Axelerad A" first="Any" last="Docu-Axelerad">Any Docu-Axelerad</name><affiliation wicri:level="1"><nlm:affiliation>Department of General Medicine, Ovidius University of Constanta, Constanta, Romania.</nlm:affiliation><country xml:lang="fr">Roumanie</country><wicri:regionArea>Department of General Medicine, Ovidius University of Constanta, Constanta</wicri:regionArea><wicri:noRegion>Constanta</wicri:noRegion></affiliation></author><author><name sortKey="Lew, Mark" sort="Lew, Mark" uniqKey="Lew M" first="Mark" last="Lew">Mark Lew</name><affiliation wicri:level="4"><nlm:affiliation>Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA</wicri:regionArea><placeName><region type="state">Californie</region><settlement type="city">Los Angeles</settlement></placeName><orgName type="university">Université de Californie du Sud</orgName></affiliation></author><author><name sortKey="Kozyolkin, Olexandr" sort="Kozyolkin, Olexandr" uniqKey="Kozyolkin O" first="Olexandr" last="Kozyolkin">Olexandr Kozyolkin</name><affiliation wicri:level="1"><nlm:affiliation>Department of General Neurology, Zaporizhzhya State Medical University, Zaporizhzhya, Ukraine.</nlm:affiliation><country xml:lang="fr">Ukraine</country><wicri:regionArea>Department of General Neurology, Zaporizhzhya State Medical University, Zaporizhzhya</wicri:regionArea><wicri:noRegion>Zaporizhzhya</wicri:noRegion></affiliation></author><author><name sortKey="Neale, Ann" sort="Neale, Ann" uniqKey="Neale A" first="Ann" last="Neale">Ann Neale</name><affiliation wicri:level="2"><nlm:affiliation>Biotie Therapies, South San Francisco, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Biotie Therapies, South San Francisco, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Resburg, Chris" sort="Resburg, Chris" uniqKey="Resburg C" first="Chris" last="Resburg">Chris Resburg</name><affiliation wicri:level="2"><nlm:affiliation>Biotie Therapies, South San Francisco, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Biotie Therapies, South San Francisco, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Meya, Uwe" sort="Meya, Uwe" uniqKey="Meya U" first="Uwe" last="Meya">Uwe Meya</name><affiliation wicri:level="2"><nlm:affiliation>Biotie Therapies, South San Francisco, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Biotie Therapies, South San Francisco, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Kenney, Christopher" sort="Kenney, Christopher" uniqKey="Kenney C" first="Christopher" last="Kenney">Christopher Kenney</name><affiliation wicri:level="2"><nlm:affiliation>Biotie Therapies, South San Francisco, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Biotie Therapies, South San Francisco, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Bandak, Stephen" sort="Bandak, Stephen" uniqKey="Bandak S" first="Stephen" last="Bandak">Stephen Bandak</name><affiliation wicri:level="2"><nlm:affiliation>Biotie Therapies, South San Francisco, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Biotie Therapies, South San Francisco, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author></analytic><series><title level="j">The Lancet. Neurology</title><idno type="eISSN">1474-4465</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adenosine A2 Receptor Antagonists (adverse effects)</term><term>Aged</term><term>Antiparkinson Agents (adverse effects)</term><term>Benzothiazoles (adverse effects)</term><term>Cross-Over Studies</term><term>Double-Blind Method</term><term>Dyskinesia, Drug-Induced (diagnosis)</term><term>Dyskinesia, Drug-Induced (epidemiology)</term><term>Female</term><term>Humans</term><term>Internationality</term><term>Levodopa (adverse effects)</term><term>Male</term><term>Middle Aged</term><term>Parkinson Disease (diagnosis)</term><term>Parkinson Disease (drug therapy)</term><term>Parkinson Disease (epidemiology)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Adenosine A2 Receptor Antagonists</term><term>Antiparkinson Agents</term><term>Benzothiazoles</term><term>Levodopa</term></keywords><keywords scheme="MESH" qualifier="diagnosis" xml:lang="en"><term>Dyskinesia, Drug-Induced</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="epidemiology" xml:lang="en"><term>Dyskinesia, Drug-Induced</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Aged</term><term>Cross-Over Studies</term><term>Double-Blind Method</term><term>Female</term><term>Humans</term><term>Internationality</term><term>Male</term><term>Middle Aged</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Many patients with Parkinson's disease have motor fluctuations despite treatment with available drugs. Tozadenant (SYN115) is an oral, selective adenosine A2A receptor antagonist that improves motor function in animal models of Parkinson's disease. We aimed to assess the safety and efficacy of tozadenant as an adjunct to levodopa in patients with Parkinson's disease who have motor fluctuations on levodopa.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">25008546</PMID><DateCreated><Year>2014</Year><Month>07</Month><Day>17</Day></DateCreated><DateCompleted><Year>2014</Year><Month>09</Month><Day>15</Day></DateCompleted><DateRevised><Year>2016</Year><Month>07</Month><Day>01</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1474-4465</ISSN><JournalIssue CitedMedium="Internet"><Volume>13</Volume><Issue>8</Issue><PubDate><Year>2014</Year><Month>Aug</Month></PubDate></JournalIssue><Title>The Lancet. Neurology</Title><ISOAbbreviation>Lancet Neurol</ISOAbbreviation></Journal><ArticleTitle>Tozadenant (SYN115) in patients with Parkinson's disease who have motor fluctuations on levodopa: a phase 2b, double-blind, randomised trial.</ArticleTitle><Pagination><MedlinePgn>767-76</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/S1474-4422(14)70148-6</ELocationID><ELocationID EIdType="pii" ValidYN="Y">S1474-4422(14)70148-6</ELocationID><Abstract><AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">Many patients with Parkinson's disease have motor fluctuations despite treatment with available drugs. Tozadenant (SYN115) is an oral, selective adenosine A2A receptor antagonist that improves motor function in animal models of Parkinson's disease. We aimed to assess the safety and efficacy of tozadenant as an adjunct to levodopa in patients with Parkinson's disease who have motor fluctuations on levodopa.</AbstractText><AbstractText Label="METHODS" NlmCategory="METHODS">We did an international, multicentre, phase 2b, randomised, double-blind, placebo-controlled, parallel-group, dose-finding clinical trial of tozadenant in levodopa-treated patients with Parkinson's disease who had motor fluctuations (at least 2·5 h off-time per day). Eligible patients were randomly assigned via a computer-generated randomisation schedule to receive tozadenant 60, 120, 180, or 240 mg or matching placebo twice daily for 12 weeks. All study management, site personnel, and patients were masked to treatment assignment. The primary outcome was change from baseline to week 12 in hours per day spent in the off-state (assessed from Parkinson's disease diaries completed by patients). This study is registered at ClinicalTrials.gov, number NCT01283594.</AbstractText><AbstractText Label="FINDINGS" NlmCategory="RESULTS">Of 420 randomised patients (mean age 63·3 [SD 8·3] years; mean duration of Parkinson's disease 8·7 [4·7] years), 403 provided post-baseline diary data and 337 completed study treatment. Compared with placebo, mean daily off-time was significantly reduced in the combined tozadenant 120 mg twice-daily and 180 mg twice-daily group (-1·1 h, 95% CI -1·8 to -0·5; p=0·0006), the tozadenant 120 mg twice-daily group (-1·1 h, -1·8 to -0·4; p=0.0039), and the tozadenant 180 mg twice-daily group (-1·2 h, -1·9 to -0·4; p=0·0039). The most common adverse events in these groups were dyskinesia (seven [8%] of 84 patients in the placebo group, 13 [16%] of 82 in the 120 mg twice-daily group, and 17 [20%] of 85 in the 180 mg twice-daily group), nausea (three [4%], 9 [11%], and ten [12%]), and dizziness (one [1%], four [5%], and 11 [13%]). Tozadenant 60 mg twice daily was not associated with a significant reduction in off-time, and tozadenant 240 mg twice daily was associated with an increased rate of discontinuation because of adverse events (17 [20%] of 84 patients).</AbstractText><AbstractText Label="INTERPRETATION" NlmCategory="CONCLUSIONS">Tozadenant at 120 or 180 mg twice daily was generally well tolerated and was effective at reducing off-time. Further investigation of tozadenant treatment in phase 3 trials is warranted.</AbstractText><AbstractText Label="FUNDING" NlmCategory="BACKGROUND">Biotie Therapies.</AbstractText><CopyrightInformation>Copyright © 2014 Elsevier Ltd. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Hauser</LastName><ForeName>Robert A</ForeName><Initials>RA</Initials><AffiliationInfo><Affiliation>University of South Florida Parkinson's Disease and Movement Disorders Center, National Parkinson Foundation Center of Excellence, Tampa, FL, USA. Electronic address: rhauser@health.usf.edu.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Olanow</LastName><ForeName>C Warren</ForeName><Initials>CW</Initials><AffiliationInfo><Affiliation>Department of Neurology, Mount Sinai School of Medicine, New York, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kieburtz</LastName><ForeName>Karl D</ForeName><Initials>KD</Initials><AffiliationInfo><Affiliation>University of Rochester School of Medicine, Rochester, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pourcher</LastName><ForeName>Emmanuelle</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Clinique Sainte-Anne Mémoire et Mouvement, Faculty of Medicine, Laval University, Quebec, QC, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Docu-Axelerad</LastName><ForeName>Any</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of General Medicine, Ovidius University of Constanta, Constanta, Romania.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lew</LastName><ForeName>Mark</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kozyolkin</LastName><ForeName>Olexandr</ForeName><Initials>O</Initials><AffiliationInfo><Affiliation>Department of General Neurology, Zaporizhzhya State Medical University, Zaporizhzhya, Ukraine.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Neale</LastName><ForeName>Ann</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Biotie Therapies, South San Francisco, CA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Resburg</LastName><ForeName>Chris</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Biotie Therapies, South San Francisco, CA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Meya</LastName><ForeName>Uwe</ForeName><Initials>U</Initials><AffiliationInfo><Affiliation>Biotie Therapies, South San Francisco, CA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kenney</LastName><ForeName>Christopher</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Biotie Therapies, South San Francisco, CA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bandak</LastName><ForeName>Stephen</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Biotie Therapies, South San Francisco, CA, USA.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><DataBankList CompleteYN="Y"><DataBank><DataBankName>ClinicalTrials.gov</DataBankName><AccessionNumberList><AccessionNumber>NCT01283594</AccessionNumber></AccessionNumberList></DataBank></DataBankList><PublicationTypeList><PublicationType UI="D017427">Clinical Trial, Phase II</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D016448">Multicenter Study</PublicationType><PublicationType UI="D016449">Randomized Controlled Trial</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2014</Year><Month>07</Month><Day>06</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Lancet Neurol</MedlineTA><NlmUniqueID>101139309</NlmUniqueID><ISSNLinking>1474-4422</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D058917">Adenosine A2 Receptor Antagonists</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000978">Antiparkinson Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D052160">Benzothiazoles</NameOfSubstance></Chemical><Chemical><RegistryNumber>46627O600J</RegistryNumber><NameOfSubstance UI="D007980">Levodopa</NameOfSubstance></Chemical><Chemical><RegistryNumber>D9K857J81I</RegistryNumber><NameOfSubstance UI="C000593256">tozadenant</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections RefType="CommentIn"><RefSource>Lancet Neurol. 2014 Aug;13(8):748-9</RefSource><PMID Version="1">25008550</PMID></CommentsCorrections></CommentsCorrectionsList><MeshHeadingList><MeshHeading><DescriptorName UI="D058917" MajorTopicYN="N">Adenosine A2 Receptor Antagonists</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="Y">adverse effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000368" MajorTopicYN="N">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000978" MajorTopicYN="N">Antiparkinson Agents</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="Y">adverse effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D052160" MajorTopicYN="N">Benzothiazoles</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="Y">adverse effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018592" MajorTopicYN="N">Cross-Over Studies</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004311" MajorTopicYN="N">Double-Blind Method</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004409" MajorTopicYN="N">Dyskinesia, Drug-Induced</DescriptorName><QualifierName UI="Q000175" MajorTopicYN="Y">diagnosis</QualifierName><QualifierName UI="Q000453" MajorTopicYN="N">epidemiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D038622" MajorTopicYN="N">Internationality</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007980" MajorTopicYN="N">Levodopa</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="Y">adverse effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010300" MajorTopicYN="N">Parkinson Disease</DescriptorName><QualifierName UI="Q000175" MajorTopicYN="Y">diagnosis</QualifierName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName><QualifierName UI="Q000453" MajorTopicYN="N">epidemiology</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2014</Year><Month>7</Month><Day>11</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2014</Year><Month>7</Month><Day>11</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2014</Year><Month>9</Month><Day>16</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">25008546</ArticleId><ArticleId IdType="pii">S1474-4422(14)70148-6</ArticleId><ArticleId IdType="doi">10.1016/S1474-4422(14)70148-6</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Canada</li><li>Roumanie</li><li>Ukraine</li><li>États-Unis</li></country><region><li>Californie</li><li>Floride</li><li>État de New York</li></region><settlement><li>Los Angeles</li></settlement><orgName><li>Université de Californie du Sud</li></orgName></list><tree><country name="États-Unis"><region name="Floride"><name sortKey="Hauser, Robert A" sort="Hauser, Robert A" uniqKey="Hauser R" first="Robert A" last="Hauser">Robert A. Hauser</name></region><name sortKey="Bandak, Stephen" sort="Bandak, Stephen" uniqKey="Bandak S" first="Stephen" last="Bandak">Stephen Bandak</name><name sortKey="Kenney, Christopher" sort="Kenney, Christopher" uniqKey="Kenney C" first="Christopher" last="Kenney">Christopher Kenney</name><name sortKey="Kieburtz, Karl D" sort="Kieburtz, Karl D" uniqKey="Kieburtz K" first="Karl D" last="Kieburtz">Karl D. Kieburtz</name><name sortKey="Lew, Mark" sort="Lew, Mark" uniqKey="Lew M" first="Mark" last="Lew">Mark Lew</name><name sortKey="Meya, Uwe" sort="Meya, Uwe" uniqKey="Meya U" first="Uwe" last="Meya">Uwe Meya</name><name sortKey="Neale, Ann" sort="Neale, Ann" uniqKey="Neale A" first="Ann" last="Neale">Ann Neale</name><name sortKey="Olanow, C Warren" sort="Olanow, C Warren" uniqKey="Olanow C" first="C Warren" last="Olanow">C Warren Olanow</name><name sortKey="Resburg, Chris" sort="Resburg, Chris" uniqKey="Resburg C" first="Chris" last="Resburg">Chris Resburg</name></country><country name="Canada"><noRegion><name sortKey="Pourcher, Emmanuelle" sort="Pourcher, Emmanuelle" uniqKey="Pourcher E" first="Emmanuelle" last="Pourcher">Emmanuelle Pourcher</name></noRegion></country><country name="Roumanie"><noRegion><name sortKey="Docu Axelerad, Any" sort="Docu Axelerad, Any" uniqKey="Docu Axelerad A" first="Any" last="Docu-Axelerad">Any Docu-Axelerad</name></noRegion></country><country name="Ukraine"><noRegion><name sortKey="Kozyolkin, Olexandr" sort="Kozyolkin, Olexandr" uniqKey="Kozyolkin O" first="Olexandr" last="Kozyolkin">Olexandr Kozyolkin</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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