Effect of Losmapimod on Cardiovascular Outcomes in Patients Hospitalized With Acute Myocardial Infarction: A Randomized Clinical Trial.
Identifieur interne : 003358 ( Ncbi/Merge ); précédent : 003357; suivant : 003359Effect of Losmapimod on Cardiovascular Outcomes in Patients Hospitalized With Acute Myocardial Infarction: A Randomized Clinical Trial.
Auteurs : Michelle L. O'Donoghue [États-Unis] ; Ruchira Glaser [États-Unis] ; Matthew A. Cavender [États-Unis] ; Philip E. Aylward [Australie] ; Marc P. Bonaca [États-Unis] ; Andrzej Budaj [Pologne] ; Richard Y. Davies [États-Unis] ; Mikael Dellborg [Suède] ; Keith A A. Fox [Royaume-Uni] ; Jorge Antonio T. Gutierrez [États-Unis] ; Christian Hamm [Allemagne] ; Robert G. Kiss [Hongrie] ; František Kovar ; Julia F. Kuder [États-Unis] ; Kyung Ah Im [États-Unis] ; John J. Lepore [États-Unis] ; Jose L. Lopez-Sendon [Espagne] ; Ton Oude Ophuis [Pays-Bas] ; Alexandr Parkhomenko [Ukraine] ; Jennifer B. Shannon [États-Unis] ; Jindrich Spinar [République tchèque] ; Jean-Francois Tanguay [Canada] ; Mikhail Ruda [Russie] ; P Gabriel Steg [France] ; Pierre Theroux [Canada] ; Stephen D. Wiviott [États-Unis] ; Ian Laws [États-Unis] ; Marc S. Sabatine [États-Unis] ; David A. Morrow [États-Unis]Source :
- JAMA [ 1538-3598 ] ; 2016.
Descripteurs français
- KwdFr :
- Adulte d'âge moyen, Algorithmes, Calendrier d'administration des médicaments, Cyclopropanes (effets indésirables), Cyclopropanes (usage thérapeutique), Femelle, Hospitalisation, Humains, Infarctus du myocarde (enzymologie), Infarctus du myocarde (mortalité), Infarctus du myocarde (traitement médicamenteux), Inhibiteurs de protéines kinases (effets indésirables), Inhibiteurs de protéines kinases (usage thérapeutique), Ischémie myocardique (), Mâle, Méthode en double aveugle, Protéine C-réactive (analyse), Prévention secondaire, Pyridines (effets indésirables), Pyridines (usage thérapeutique), Revascularisation myocardique, Récidive, Sujet âgé, p38 Mitogen-Activated Protein Kinases (antagonistes et inhibiteurs), Échec thérapeutique.
- MESH :
- analyse : Protéine C-réactive.
- antagonistes et inhibiteurs : p38 Mitogen-Activated Protein Kinases.
- effets indésirables : Cyclopropanes, Inhibiteurs de protéines kinases, Pyridines.
- enzymologie : Infarctus du myocarde.
- mortalité : Infarctus du myocarde.
- traitement médicamenteux : Infarctus du myocarde.
- usage thérapeutique : Cyclopropanes, Inhibiteurs de protéines kinases, Pyridines.
- Adulte d'âge moyen, Algorithmes, Calendrier d'administration des médicaments, Femelle, Hospitalisation, Humains, Ischémie myocardique, Mâle, Méthode en double aveugle, Prévention secondaire, Revascularisation myocardique, Récidive, Sujet âgé, Échec thérapeutique.
English descriptors
- KwdEn :
- Aged, Algorithms, C-Reactive Protein (analysis), Cyclopropanes (adverse effects), Cyclopropanes (therapeutic use), Double-Blind Method, Drug Administration Schedule, Female, Hospitalization, Humans, Male, Middle Aged, Myocardial Infarction (drug therapy), Myocardial Infarction (enzymology), Myocardial Infarction (mortality), Myocardial Ischemia (prevention & control), Myocardial Ischemia (surgery), Myocardial Revascularization, Protein Kinase Inhibitors (adverse effects), Protein Kinase Inhibitors (therapeutic use), Pyridines (adverse effects), Pyridines (therapeutic use), Recurrence, Secondary Prevention, Treatment Failure, p38 Mitogen-Activated Protein Kinases (antagonists & inhibitors).
- MESH :
- chemical , adverse effects : Cyclopropanes, Protein Kinase Inhibitors, Pyridines.
- chemical , analysis : C-Reactive Protein.
- chemical , antagonists & inhibitors : p38 Mitogen-Activated Protein Kinases.
- chemical , therapeutic use : Cyclopropanes, Protein Kinase Inhibitors, Pyridines.
- drug therapy : Myocardial Infarction.
- enzymology : Myocardial Infarction.
- mortality : Myocardial Infarction.
- prevention & control : Myocardial Ischemia.
- surgery : Myocardial Ischemia.
- Aged, Algorithms, Double-Blind Method, Drug Administration Schedule, Female, Hospitalization, Humans, Male, Middle Aged, Myocardial Revascularization, Recurrence, Secondary Prevention, Treatment Failure.
Abstract
p38 Mitogen-activated protein kinase (MAPK)-stimulated inflammation is implicated in atherogenesis, plaque destabilization, and maladaptive processes in myocardial infarction (MI). Pilot data in a phase 2 trial in non-ST elevation MI indicated that the p38 MAPK inhibitor losmapimod attenuates inflammation and may improve outcomes.
DOI: 10.1001/jama.2016.3609
PubMed: 27043082
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pubmed:27043082Le document en format XML
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Effect of Losmapimod on Cardiovascular Outcomes in Patients Hospitalized With Acute Myocardial Infarction: A Randomized Clinical Trial.</title>
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<country>Royaume-Uni</country>
<placeName><region type="country">Écosse</region>
</placeName>
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<author><name sortKey="Steg, P Gabriel" sort="Steg, P Gabriel" uniqKey="Steg P" first="P Gabriel" last="Steg">P Gabriel Steg</name>
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<author><name sortKey="Theroux, Pierre" sort="Theroux, Pierre" uniqKey="Theroux P" first="Pierre" last="Theroux">Pierre Theroux</name>
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<author><name sortKey="Wiviott, Stephen D" sort="Wiviott, Stephen D" uniqKey="Wiviott S" first="Stephen D" last="Wiviott">Stephen D. Wiviott</name>
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<front><div type="abstract" xml:lang="en">p38 Mitogen-activated protein kinase (MAPK)-stimulated inflammation is implicated in atherogenesis, plaque destabilization, and maladaptive processes in myocardial infarction (MI). Pilot data in a phase 2 trial in non-ST elevation MI indicated that the p38 MAPK inhibitor losmapimod attenuates inflammation and may improve outcomes.</div>
</front>
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<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">27043082</PMID>
<DateCreated><Year>2016</Year>
<Month>04</Month>
<Day>20</Day>
</DateCreated>
<DateCompleted><Year>2016</Year>
<Month>05</Month>
<Day>01</Day>
</DateCompleted>
<DateRevised><Year>2016</Year>
<Month>10</Month>
<Day>17</Day>
</DateRevised>
<Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1538-3598</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>315</Volume>
<Issue>15</Issue>
<PubDate><Year>2016</Year>
<Month>Apr</Month>
<Day>19</Day>
</PubDate>
</JournalIssue>
<Title>JAMA</Title>
<ISOAbbreviation>JAMA</ISOAbbreviation>
</Journal>
<ArticleTitle>Effect of Losmapimod on Cardiovascular Outcomes in Patients Hospitalized With Acute Myocardial Infarction: A Randomized Clinical Trial.</ArticleTitle>
<Pagination><MedlinePgn>1591-9</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1001/jama.2016.3609</ELocationID>
<Abstract><AbstractText Label="IMPORTANCE" NlmCategory="OBJECTIVE">p38 Mitogen-activated protein kinase (MAPK)-stimulated inflammation is implicated in atherogenesis, plaque destabilization, and maladaptive processes in myocardial infarction (MI). Pilot data in a phase 2 trial in non-ST elevation MI indicated that the p38 MAPK inhibitor losmapimod attenuates inflammation and may improve outcomes.</AbstractText>
<AbstractText Label="OBJECTIVE" NlmCategory="OBJECTIVE">To evaluate the efficacy and safety of losmapimod on cardiovascular outcomes in patients hospitalized with an acute myocardial infarction.</AbstractText>
<AbstractText Label="DESIGN, SETTING, AND PATIENTS" NlmCategory="METHODS">LATITUDE-TIMI 60, a randomized, placebo-controlled, double-blind, parallel-group trial conducted at 322 sites in 34 countries from June 3, 2014, until December 8, 2015. Part A consisted of a leading cohort (n = 3503) to provide an initial assessment of safety and exploratory efficacy before considering progression to part B (approximately 22,000 patients). Patients were considered potentially eligible for enrollment if they had been hospitalized with an acute MI and had at least 1 additional predictor of cardiovascular risk.</AbstractText>
<AbstractText Label="INTERVENTIONS" NlmCategory="METHODS">Patients were randomized to either twice-daily losmapimod (7.5 mg; n = 1738) or matching placebo (n = 1765) on a background of guideline-recommended therapy. Patients were treated for 12 weeks and followed up for an additional 12 weeks.</AbstractText>
<AbstractText Label="MAIN OUTCOMES AND MEASURES" NlmCategory="METHODS">The primary end point was the composite of cardiovascular death, MI, or severe recurrent ischemia requiring urgent coronary revascularization with the principal analysis specified at week 12.</AbstractText>
<AbstractText Label="RESULTS" NlmCategory="RESULTS">In part A, among the 3503 patients randomized (median age, 66 years; 1036 [29.6%] were women), 99.1% had complete ascertainment for the primary outcome. The primary end point occurred by 12 weeks in 123 patients treated with placebo (7.0%) and 139 patients treated with losmapimod (8.1%; hazard ratio, 1.16; 95% CI, 0.91-1.47; P = .24). The on-treatment rates of serious adverse events were 16.0% with losmapimod and 14.2% with placebo.</AbstractText>
<AbstractText Label="CONCLUSIONS AND RELEVANCE" NlmCategory="CONCLUSIONS">Among patients with acute MI, use of losmapimod compared with placebo did not reduce the risk of major ischemic cardiovascular events. The results of this exploratory efficacy study did not justify proceeding to a larger efficacy trial in the existing patient population.</AbstractText>
<AbstractText Label="TRIAL REGISTRATION" NlmCategory="BACKGROUND">clinicaltrials.gov Identifier: NCT02145468.</AbstractText>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>O'Donoghue</LastName>
<ForeName>Michelle L</ForeName>
<Initials>ML</Initials>
<AffiliationInfo><Affiliation>TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Glaser</LastName>
<ForeName>Ruchira</ForeName>
<Initials>R</Initials>
<AffiliationInfo><Affiliation>Metabolic Pathways and Cardiovascular Unit, Research and Development, GlaxoSmithKline, Collegeville, Pennsylvania.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Cavender</LastName>
<ForeName>Matthew A</ForeName>
<Initials>MA</Initials>
<AffiliationInfo><Affiliation>TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Aylward</LastName>
<ForeName>Philip E</ForeName>
<Initials>PE</Initials>
<AffiliationInfo><Affiliation>South Australian Health and Medical Research Institute, Flinders University Medical Centre, Adelaide, South Australia, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Bonaca</LastName>
<ForeName>Marc P</ForeName>
<Initials>MP</Initials>
<AffiliationInfo><Affiliation>TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Budaj</LastName>
<ForeName>Andrzej</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>Postgraduate Medical School, Grochowski Hospital, Warsaw, Poland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Davies</LastName>
<ForeName>Richard Y</ForeName>
<Initials>RY</Initials>
<AffiliationInfo><Affiliation>Metabolic Pathways and Cardiovascular Unit, Research and Development, GlaxoSmithKline, Collegeville, Pennsylvania.</Affiliation>
</AffiliationInfo>
</Author>
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<CommentsCorrectionsList><CommentsCorrections RefType="CommentIn"><RefSource>J Thorac Dis. 2016 Sep;8(9):2328-2330</RefSource>
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<ForeName>Soeren Lind</ForeName>
<Initials>SL</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Skov Jensen</LastName>
<ForeName>Jan</ForeName>
<Initials>J</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Hedman</LastName>
<ForeName>Anu</ForeName>
<Initials>A</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Reinmets</LastName>
<ForeName>Julia</ForeName>
<Initials>J</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Soopold</LastName>
<ForeName>Ullar</ForeName>
<Initials>U</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Agraou</LastName>
<ForeName>Benaissa</ForeName>
<Initials>B</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Cottin</LastName>
<ForeName>Yves</ForeName>
<Initials>Y</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>De Labriolle</LastName>
<ForeName>Axel</ForeName>
<Initials>A</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Decoulx</LastName>
<ForeName>Eric</ForeName>
<Initials>E</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Delarche</LastName>
<ForeName>Nicolas</ForeName>
<Initials>N</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Elbaz</LastName>
<ForeName>Meyer</ForeName>
<Initials>M</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Ohlmann</LastName>
<ForeName>Patrick</ForeName>
<Initials>P</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Probst</LastName>
<ForeName>Vincent</ForeName>
<Initials>V</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Schiele</LastName>
<ForeName>François</ForeName>
<Initials>F</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Steg</LastName>
<ForeName>Gabriel</ForeName>
<Initials>G</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Appel</LastName>
<ForeName>Karl-Friedrich</ForeName>
<Initials>KF</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Bavendiek</LastName>
<ForeName>Udo</ForeName>
<Initials>U</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Butter</LastName>
<ForeName>Christian</ForeName>
<Initials>C</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Fuisting</LastName>
<ForeName>Jan</ForeName>
<Initials>J</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Ghanem</LastName>
<ForeName>Alexander</ForeName>
<Initials>A</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Groenefeld</LastName>
<ForeName>Gerian</ForeName>
<Initials>G</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Hamm</LastName>
<ForeName>Christian</ForeName>
<Initials>C</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Hoffman</LastName>
<ForeName>Ursula</ForeName>
<Initials>U</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Kadel</LastName>
<ForeName>Christoph</ForeName>
<Initials>C</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Karakas</LastName>
<ForeName>Mahir</ForeName>
<Initials>M</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Leschke</LastName>
<ForeName>Matthias</ForeName>
<Initials>M</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Mangner</LastName>
<ForeName>Norman</ForeName>
<Initials>N</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Moellmann</LastName>
<ForeName>Helge</ForeName>
<Initials>H</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Olbrich</LastName>
<ForeName>Hans-Georg</ForeName>
<Initials>HG</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Reith</LastName>
<ForeName>Sebastian</ForeName>
<Initials>S</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Schwimmbeck</LastName>
<ForeName>Peter</ForeName>
<Initials>P</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Sechtem</LastName>
<ForeName>Udo</ForeName>
<Initials>U</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Smettan</LastName>
<ForeName>Jan</ForeName>
<Initials>J</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Stellbrink</LastName>
<ForeName>Christoph</ForeName>
<Initials>C</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>vom Dahl</LastName>
<ForeName>Juergen</ForeName>
<Initials>J</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Vorpahl</LastName>
<ForeName>Marc</ForeName>
<Initials>M</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Werner</LastName>
<ForeName>Nikos</ForeName>
<Initials>N</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Zeh</LastName>
<ForeName>Wolfgang</ForeName>
<Initials>W</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Zirlik</LastName>
<ForeName>Andreas</ForeName>
<Initials>A</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Kanakakis</LastName>
<ForeName>Ioannis</ForeName>
<Initials>I</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Kyriakides</LastName>
<ForeName>Zenon</ForeName>
<Initials>Z</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Mantas</LastName>
<ForeName>Ioannis</ForeName>
<Initials>I</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Styliadis</LastName>
<ForeName>Ioannis</ForeName>
<Initials>I</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Tziakas</LastName>
<ForeName>Dimitrios</ForeName>
<Initials>D</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Zarifis</LastName>
<ForeName>Ioannis</ForeName>
<Initials>I</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Chan</LastName>
<ForeName>Kwok Keung</ForeName>
<Initials>KK</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Wong</LastName>
<ForeName>Chi Yuen</ForeName>
<Initials>CY</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Yan</LastName>
<ForeName>Ping Yen Bryan</ForeName>
<Initials>PY</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Benczúr</LastName>
<ForeName>Béla</ForeName>
<Initials>B</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Faluközy</LastName>
<ForeName>József</ForeName>
<Initials>J</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Kiss</LastName>
<ForeName>Róbert Gábor</ForeName>
<Initials>RG</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Lupkovics</LastName>
<ForeName>Géza</ForeName>
<Initials>G</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Merkely</LastName>
<ForeName>Béla</ForeName>
<Initials>B</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Atar</LastName>
<ForeName>Shaul</ForeName>
<Initials>S</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Banai</LastName>
<ForeName>Shmuel</ForeName>
<Initials>S</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Katz</LastName>
<ForeName>Amos</ForeName>
<Initials>A</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Meisel</LastName>
<ForeName>Simcha</ForeName>
<Initials>S</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Mosseri</LastName>
<ForeName>Morris</ForeName>
<Initials>M</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Ardissino</LastName>
<ForeName>Diego</ForeName>
<Initials>D</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Cavallini</LastName>
<ForeName>Claudio</ForeName>
<Initials>C</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Maria De Biase</LastName>
<ForeName>Anna</ForeName>
<Initials>A</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Morocutti</LastName>
<ForeName>Giorgio</ForeName>
<Initials>G</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Musumeci</LastName>
<ForeName>Giuseppe</ForeName>
<Initials>G</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Pirelli</LastName>
<ForeName>Salvatore</ForeName>
<Initials>S</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Salvioni</LastName>
<ForeName>Alessandro</ForeName>
<Initials>A</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Hong</LastName>
<ForeName>Bum Kee</ForeName>
<Initials>BK</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Jeong</LastName>
<ForeName>Jin-Ok</ForeName>
<Initials>JO</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Jeong</LastName>
<ForeName>MyungHo</ForeName>
<Initials>M</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Kim</LastName>
<ForeName>Chong-Jin</ForeName>
<Initials>CJ</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Kim</LastName>
<ForeName>Hyo-Soo</ForeName>
<Initials>HS</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Rha</LastName>
<ForeName>SeungWoon</ForeName>
<Initials>S</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Seung</LastName>
<ForeName>Ki-Bae</ForeName>
<Initials>KB</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Yoon</LastName>
<ForeName>Junghan</ForeName>
<Initials>J</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Carrillo-Calvillo</LastName>
<ForeName>Jorge</ForeName>
<Initials>J</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Esturau-Santalo</LastName>
<ForeName>Ramon-Miguel</ForeName>
<Initials>RM</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Dirksen</LastName>
<ForeName>Maurits</ForeName>
<Initials>M</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Gosselink</LastName>
<ForeName>Antonius</ForeName>
<Initials>A</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Hamer</LastName>
<ForeName>Barnabas J B</ForeName>
<Initials>BJ</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Magro</LastName>
<ForeName>Michael</ForeName>
<Initials>M</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Nierop</LastName>
<ForeName>Pieter</ForeName>
<Initials>P</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Oude Ophuis</LastName>
</Investigator>
<Investigator ValidYN="Y"><LastName>Perik</LastName>
<ForeName>Patrick J</ForeName>
<Initials>PJ</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Prins</LastName>
<ForeName>Fransisco J</ForeName>
<Initials>FJ</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Rensing</LastName>
<ForeName>Bernard J W M</ForeName>
<Initials>BJ</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Ronner</LastName>
<ForeName>Eelko</ForeName>
<Initials>E</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Slagboom</LastName>
<ForeName>Ton</ForeName>
<Initials>T</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Troquay</LastName>
<ForeName>Roland</ForeName>
<Initials>R</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>van Daele</LastName>
<ForeName>Marcus</ForeName>
<Initials>M</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>van der Heijden</LastName>
<ForeName>Robert</ForeName>
<Initials>R</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Devlin</LastName>
<ForeName>Gerard</ForeName>
<Initials>G</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Elliott</LastName>
<ForeName>John</ForeName>
<Initials>J</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Harding</LastName>
<ForeName>Scott</ForeName>
<Initials>S</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Scott</LastName>
<ForeName>Douglas</ForeName>
<Initials>D</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Stewart</LastName>
<ForeName>Ralph</ForeName>
<Initials>R</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Ternouth</LastName>
<ForeName>Ian</ForeName>
<Initials>I</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Atar</LastName>
<ForeName>Dan</ForeName>
<Initials>D</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Høgalmen</LastName>
<ForeName>Geir</ForeName>
<Initials>G</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Hysing</LastName>
<ForeName>Jan</ForeName>
<Initials>J</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Larsen</LastName>
<ForeName>Alf</ForeName>
<Initials>A</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Trovik</LastName>
<ForeName>Thor</ForeName>
<Initials>T</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Añonuevo</LastName>
<ForeName>John</ForeName>
<Initials>J</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Hay</LastName>
<ForeName>Eduardo Tin</ForeName>
<Initials>ET</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Marañon</LastName>
<ForeName>Donato</ForeName>
<Initials>D</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Miranda</LastName>
<ForeName>Ariel</ForeName>
<Initials>A</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Bujaj</LastName>
<ForeName>Andrzej</ForeName>
<Initials>A</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Gessek</LastName>
<ForeName>Jacek</ForeName>
<Initials>J</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Jaworska</LastName>
<ForeName>Krystyna</ForeName>
<Initials>K</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Kubica</LastName>
<ForeName>Jacek</ForeName>
<Initials>J</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Miekus</LastName>
<ForeName>Pawel</ForeName>
<Initials>P</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Mysiak</LastName>
<ForeName>Andrzej</ForeName>
<Initials>A</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Przewlocki</LastName>
<ForeName>Tadeusz</ForeName>
<Initials>T</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Raczak</LastName>
<ForeName>Grzegorz</ForeName>
<Initials>G</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Serafin</LastName>
<ForeName>Ryszard</ForeName>
<Initials>R</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Trebacz</LastName>
<ForeName>Jaroslaw</ForeName>
<Initials>J</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Tyllo</LastName>
<ForeName>Mateusz</ForeName>
<Initials>M</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Wlodarczak</LastName>
<ForeName>Adrian</ForeName>
<Initials>A</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Wojcik</LastName>
<ForeName>Jaroslaw</ForeName>
<Initials>J</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Cinteza</LastName>
<ForeName>Mircea</ForeName>
<Initials>M</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Dorobantu</LastName>
<ForeName>Maria</ForeName>
<Initials>M</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Musetescu</LastName>
<ForeName>Rodica</ForeName>
<Initials>R</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Aksentyev</LastName>
<ForeName>Sergey</ForeName>
<Initials>S</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Apartsin</LastName>
<ForeName>Konstantin</ForeName>
<Initials>K</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Barbarash</LastName>
<ForeName>Olga</ForeName>
<Initials>O</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Berns</LastName>
<ForeName>Svetlana</ForeName>
<Initials>S</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Bessonova</LastName>
<ForeName>Nina</ForeName>
<Initials>N</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Duda</LastName>
<ForeName>Alexey</ForeName>
<Initials>A</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Duplyakov</LastName>
<ForeName>Dmitry</ForeName>
<Initials>D</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Ermoshkina</LastName>
<ForeName>Lyudmila</ForeName>
<Initials>L</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Gordeev</LastName>
<ForeName>Ivan</ForeName>
<Initials>I</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Kobalava</LastName>
<ForeName>Zhanna</ForeName>
<Initials>Z</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Kostenko</LastName>
<ForeName>Victor</ForeName>
<Initials>V</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Lapin</LastName>
<ForeName>Oleg</ForeName>
<Initials>O</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Markov</LastName>
<ForeName>Valentin</ForeName>
<Initials>V</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Orlikova</LastName>
<ForeName>Olga</ForeName>
<Initials>O</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Rebrov</LastName>
<ForeName>Andrey</ForeName>
<Initials>A</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Ruda</LastName>
<ForeName>Mikhail</ForeName>
<Initials>M</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Shalaev</LastName>
<ForeName>Sergey</ForeName>
<Initials>S</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Tsyba</LastName>
<ForeName>Larisa</ForeName>
<Initials>L</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Vishnevsky</LastName>
<ForeName>Alexander</ForeName>
<Initials>A</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Yakushin</LastName>
<ForeName>Sergey</ForeName>
<Initials>S</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Hranai</LastName>
<ForeName>Marian</ForeName>
<Initials>M</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Hricak</LastName>
<ForeName>Vasil</ForeName>
<Initials>V</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Juhas</LastName>
<ForeName>Stanislav</ForeName>
<Initials>S</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Kovar</LastName>
<ForeName>Frantisek</ForeName>
<Initials>F</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Abelson</LastName>
<ForeName>Mark</ForeName>
<Initials>M</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Basson</LastName>
<ForeName>Matthys</ForeName>
<Initials>M</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Cyster</LastName>
<ForeName>H P</ForeName>
<Initials>HP</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Dalby</LastName>
<ForeName>Anthony</ForeName>
<Initials>A</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Dawood</LastName>
<ForeName>Saleem</ForeName>
<Initials>S</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Horak</LastName>
<ForeName>Adrian</ForeName>
<Initials>A</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Saaiman</LastName>
<ForeName>Jan</ForeName>
<Initials>J</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Barrabes Riu</LastName>
<ForeName>José Antonio</ForeName>
<Initials>JA</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Cequier Fillat</LastName>
<ForeName>Angel</ForeName>
<Initials>A</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Delia</LastName>
<ForeName>Manuel Almendro</ForeName>
<Initials>MA</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Fernández-Avilés Díaz</LastName>
<ForeName>Francisco</ForeName>
<Initials>F</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Genover</LastName>
<ForeName>Xavier Bosch</ForeName>
<Initials>XB</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>González Juanatey</LastName>
<ForeName>José Ramón</ForeName>
<Initials>JR</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Lekuona Goya</LastName>
<ForeName>Iñaki</ForeName>
<Initials>I</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>López de Sa</LastName>
<ForeName>Esteban</ForeName>
<Initials>E</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Macaya</LastName>
<ForeName>Carlos</ForeName>
<Initials>C</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Navarro</LastName>
<ForeName>Manuel Jiménez</ForeName>
<Initials>MJ</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Ortega Marcos</LastName>
<ForeName>Javier</ForeName>
<Initials>J</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Zamorano</LastName>
<ForeName>José Luis</ForeName>
<Initials>JL</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Bandh</LastName>
<ForeName>Stellan</ForeName>
<Initials>S</Initials>
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