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Elbasvir/Grazoprevir for Patients With Hepatitis C Virus Infection and Inherited Blood Disorders: A Phase III Study.

Identifieur interne : 000D42 ( PubMed/Checkpoint ); précédent : 000D41; suivant : 000D43

Elbasvir/Grazoprevir for Patients With Hepatitis C Virus Infection and Inherited Blood Disorders: A Phase III Study.

Auteurs : Christophe Hézode [France] ; Massimo Colombo [Italie] ; Marc Bourlière [France] ; Ulrich Spengler [Allemagne] ; Ziv Ben-Ari [Israël] ; Simone I. Strasser [Australie] ; William M. Lee [États-Unis] ; Leslie Morgan [États-Unis] ; Jingjun Qiu [États-Unis] ; Peggy Hwang [États-Unis] ; Michael Robertson [États-Unis] ; Bach-Yen Nguyen [États-Unis] ; Eliav Barr [États-Unis] ; Janice Wahl [États-Unis] ; Barbara Haber [États-Unis] ; Robert Chase [États-Unis] ; Rohit Talwani [États-Unis] ; Vito Di Marco [Italie]

Source :

RBID : pubmed:28256747

Descripteurs français

English descriptors

Abstract

Direct-acting antiviral agents have not been studied exclusively in patients with inherited blood disorders and hepatitis C virus (HCV) infection. The objective of the randomized, placebo-controlled, phase III C-EDGE IBLD study was to assess the safety and efficacy of elbasvir/grazoprevir (EBR/GZR) in patients with inherited bleeding disorders and HCV infection. One hundred fifty-nine adults with HCV infection and sickle cell anemia, thalassemia, or hemophilia A/B or von Willebrand disease were enrolled at 31 study sites in the United States, Europe, Australia, Canada, Israel, and Thailand. Patients were given an oral, once-daily, fixed-dose combination of EBR/GZR 50 mg/100 mg for 12 weeks and randomized to the immediate-treatment group (ITG) or deferred-treatment group (DTG; placebo followed by active treatment). The primary endpoints were the proportion of patients in the ITG with unquantifiable HCV RNA 12 weeks posttreatment (sustained virological response 12 weeks after completion of study treatment; SVR12) and the comparison of safety in the ITG and DTG. In the ITG, 100 of 107 patients (93.5%) achieved SVR12, 6 relapsed, and 1 was lost to follow-up. SVR12 was achieved in 94.7% (18 of 19), 97.6% (40 of 41), and 89.4% (42 of 47) of patients with sickle cell disease, β-thalassemia, and hemophilia A/B or von Willebrand disease, respectively. Serious adverse events were reported by 2.8% (n = 3) and 11.5% (n = 6) of patients in the ITG and DTG, respectively. Hemoglobin levels and international normalized ratio values were similar in patients receiving EBR/GZR and placebo; among patients with hemoglobinopathies, change in mean hemoglobin levels was similar in those receiving EBR/GZR compared to those receiving placebo.

DOI: 10.1002/hep.29139
PubMed: 28256747


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pubmed:28256747

Le document en format XML

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<name sortKey="Marco, Vito Di" sort="Marco, Vito Di" uniqKey="Marco V" first="Vito Di" last="Marco">Vito Di Marco</name>
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<orgName type="university">Université de Sydney</orgName>
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<settlement type="city">Sydney</settlement>
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<region type="state">Texas</region>
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<wicri:cityArea>University of Texas Southwestern Medical Center, Dallas</wicri:cityArea>
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<name sortKey="Morgan, Leslie" sort="Morgan, Leslie" uniqKey="Morgan L" first="Leslie" last="Morgan">Leslie Morgan</name>
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<nlm:affiliation>Merck & Co., Inc, Kenilworth, NJ.</nlm:affiliation>
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<nlm:affiliation>Merck & Co., Inc, Kenilworth, NJ.</nlm:affiliation>
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<name sortKey="Robertson, Michael" sort="Robertson, Michael" uniqKey="Robertson M" first="Michael" last="Robertson">Michael Robertson</name>
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<nlm:affiliation>Merck & Co., Inc, Kenilworth, NJ.</nlm:affiliation>
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<name sortKey="Nguyen, Bach Yen" sort="Nguyen, Bach Yen" uniqKey="Nguyen B" first="Bach-Yen" last="Nguyen">Bach-Yen Nguyen</name>
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<nlm:affiliation>Merck & Co., Inc, Kenilworth, NJ.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
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<region type="state">New Jersey</region>
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<name sortKey="Barr, Eliav" sort="Barr, Eliav" uniqKey="Barr E" first="Eliav" last="Barr">Eliav Barr</name>
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<nlm:affiliation>Merck & Co., Inc, Kenilworth, NJ.</nlm:affiliation>
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<name sortKey="Wahl, Janice" sort="Wahl, Janice" uniqKey="Wahl J" first="Janice" last="Wahl">Janice Wahl</name>
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<nlm:affiliation>Merck & Co., Inc, Kenilworth, NJ.</nlm:affiliation>
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<wicri:cityArea>Merck & Co., Inc, Kenilworth</wicri:cityArea>
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<name sortKey="Haber, Barbara" sort="Haber, Barbara" uniqKey="Haber B" first="Barbara" last="Haber">Barbara Haber</name>
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<nlm:affiliation>Merck & Co., Inc, Kenilworth, NJ.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
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<region type="state">New Jersey</region>
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<wicri:cityArea>Merck & Co., Inc, Kenilworth</wicri:cityArea>
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<name sortKey="Chase, Robert" sort="Chase, Robert" uniqKey="Chase R" first="Robert" last="Chase">Robert Chase</name>
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<nlm:affiliation>Merck & Co., Inc, Kenilworth, NJ.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
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<region type="state">New Jersey</region>
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<wicri:cityArea>Merck & Co., Inc, Kenilworth</wicri:cityArea>
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<name sortKey="Talwani, Rohit" sort="Talwani, Rohit" uniqKey="Talwani R" first="Rohit" last="Talwani">Rohit Talwani</name>
<affiliation wicri:level="2">
<nlm:affiliation>Merck & Co., Inc, Kenilworth, NJ.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">New Jersey</region>
</placeName>
<wicri:cityArea>Merck & Co., Inc, Kenilworth</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Marco, Vito Di" sort="Marco, Vito Di" uniqKey="Marco V" first="Vito Di" last="Marco">Vito Di Marco</name>
<affiliation wicri:level="1">
<nlm:affiliation>University of Palermo, Palermo, Italy.</nlm:affiliation>
<country xml:lang="fr">Italie</country>
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<wicri:noRegion>Palermo</wicri:noRegion>
</affiliation>
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<series>
<title level="j">Hepatology (Baltimore, Md.)</title>
<idno type="eISSN">1527-3350</idno>
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<date when="2017" type="published">2017</date>
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<term>Imidazoles (administration & dosage)</term>
<term>Immunohistochemistry</term>
<term>Liver Function Tests</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Quinoxalines (administration & dosage)</term>
<term>Reference Values</term>
<term>Severity of Illness Index</term>
<term>Treatment Outcome</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>Administration par voie orale</term>
<term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Association de médicaments</term>
<term>Benzofuranes (administration et posologie)</term>
<term>Calendrier d'administration des médicaments</term>
<term>Femelle</term>
<term>Hepacivirus ()</term>
<term>Humains</term>
<term>Hépatite C chronique ()</term>
<term>Hépatite C chronique (diagnostic)</term>
<term>Hépatite C chronique (traitement médicamenteux)</term>
<term>Imidazoles (administration et posologie)</term>
<term>Immunohistochimie</term>
<term>Indice de gravité médicale</term>
<term>Mâle</term>
<term>Ponction-biopsie à l'aiguille</term>
<term>Quinoxalines (administration et posologie)</term>
<term>Relation dose-effet des médicaments</term>
<term>Résultat thérapeutique</term>
<term>Tests de la fonction hépatique</term>
<term>Troubles héréditaires de la coagulation sanguine ()</term>
<term>Troubles héréditaires de la coagulation sanguine (diagnostic)</term>
<term>Troubles héréditaires de la coagulation sanguine (traitement médicamenteux)</term>
<term>Valeurs de référence</term>
<term>Études de suivi</term>
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<term>Benzofurans</term>
<term>Imidazoles</term>
<term>Quinoxalines</term>
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<term>Benzofuranes</term>
<term>Imidazoles</term>
<term>Quinoxalines</term>
</keywords>
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<term>Blood Coagulation Disorders, Inherited</term>
<term>Hepatitis C, Chronic</term>
</keywords>
<keywords scheme="MESH" qualifier="diagnosis" xml:lang="en">
<term>Blood Coagulation Disorders, Inherited</term>
<term>Hepatitis C, Chronic</term>
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<term>Hépatite C chronique</term>
<term>Troubles héréditaires de la coagulation sanguine</term>
</keywords>
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<term>Hepacivirus</term>
</keywords>
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<term>Blood Coagulation Disorders, Inherited</term>
<term>Hepatitis C, Chronic</term>
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<term>Hépatite C chronique</term>
<term>Troubles héréditaires de la coagulation sanguine</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Administration, Oral</term>
<term>Adult</term>
<term>Biopsy, Needle</term>
<term>Dose-Response Relationship, Drug</term>
<term>Drug Administration Schedule</term>
<term>Drug Therapy, Combination</term>
<term>Female</term>
<term>Follow-Up Studies</term>
<term>Humans</term>
<term>Immunohistochemistry</term>
<term>Liver Function Tests</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Reference Values</term>
<term>Severity of Illness Index</term>
<term>Treatment Outcome</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Administration par voie orale</term>
<term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Association de médicaments</term>
<term>Calendrier d'administration des médicaments</term>
<term>Femelle</term>
<term>Hepacivirus</term>
<term>Humains</term>
<term>Hépatite C chronique</term>
<term>Immunohistochimie</term>
<term>Indice de gravité médicale</term>
<term>Mâle</term>
<term>Ponction-biopsie à l'aiguille</term>
<term>Relation dose-effet des médicaments</term>
<term>Résultat thérapeutique</term>
<term>Tests de la fonction hépatique</term>
<term>Troubles héréditaires de la coagulation sanguine</term>
<term>Valeurs de référence</term>
<term>Études de suivi</term>
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<front>
<div type="abstract" xml:lang="en">Direct-acting antiviral agents have not been studied exclusively in patients with inherited blood disorders and hepatitis C virus (HCV) infection. The objective of the randomized, placebo-controlled, phase III C-EDGE IBLD study was to assess the safety and efficacy of elbasvir/grazoprevir (EBR/GZR) in patients with inherited bleeding disorders and HCV infection. One hundred fifty-nine adults with HCV infection and sickle cell anemia, thalassemia, or hemophilia A/B or von Willebrand disease were enrolled at 31 study sites in the United States, Europe, Australia, Canada, Israel, and Thailand. Patients were given an oral, once-daily, fixed-dose combination of EBR/GZR 50 mg/100 mg for 12 weeks and randomized to the immediate-treatment group (ITG) or deferred-treatment group (DTG; placebo followed by active treatment). The primary endpoints were the proportion of patients in the ITG with unquantifiable HCV RNA 12 weeks posttreatment (sustained virological response 12 weeks after completion of study treatment; SVR12) and the comparison of safety in the ITG and DTG. In the ITG, 100 of 107 patients (93.5%) achieved SVR12, 6 relapsed, and 1 was lost to follow-up. SVR12 was achieved in 94.7% (18 of 19), 97.6% (40 of 41), and 89.4% (42 of 47) of patients with sickle cell disease, β-thalassemia, and hemophilia A/B or von Willebrand disease, respectively. Serious adverse events were reported by 2.8% (n = 3) and 11.5% (n = 6) of patients in the ITG and DTG, respectively. Hemoglobin levels and international normalized ratio values were similar in patients receiving EBR/GZR and placebo; among patients with hemoglobinopathies, change in mean hemoglobin levels was similar in those receiving EBR/GZR compared to those receiving placebo.</div>
</front>
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<DateCreated>
<Year>2017</Year>
<Month>03</Month>
<Day>03</Day>
</DateCreated>
<DateCompleted>
<Year>2017</Year>
<Month>10</Month>
<Day>04</Day>
</DateCompleted>
<DateRevised>
<Year>2017</Year>
<Month>10</Month>
<Day>04</Day>
</DateRevised>
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<ISSN IssnType="Electronic">1527-3350</ISSN>
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<Volume>66</Volume>
<Issue>3</Issue>
<PubDate>
<Year>2017</Year>
<Month>Sep</Month>
</PubDate>
</JournalIssue>
<Title>Hepatology (Baltimore, Md.)</Title>
<ISOAbbreviation>Hepatology</ISOAbbreviation>
</Journal>
<ArticleTitle>Elbasvir/Grazoprevir for Patients With Hepatitis C Virus Infection and Inherited Blood Disorders: A Phase III Study.</ArticleTitle>
<Pagination>
<MedlinePgn>736-745</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1002/hep.29139</ELocationID>
<Abstract>
<AbstractText>Direct-acting antiviral agents have not been studied exclusively in patients with inherited blood disorders and hepatitis C virus (HCV) infection. The objective of the randomized, placebo-controlled, phase III C-EDGE IBLD study was to assess the safety and efficacy of elbasvir/grazoprevir (EBR/GZR) in patients with inherited bleeding disorders and HCV infection. One hundred fifty-nine adults with HCV infection and sickle cell anemia, thalassemia, or hemophilia A/B or von Willebrand disease were enrolled at 31 study sites in the United States, Europe, Australia, Canada, Israel, and Thailand. Patients were given an oral, once-daily, fixed-dose combination of EBR/GZR 50 mg/100 mg for 12 weeks and randomized to the immediate-treatment group (ITG) or deferred-treatment group (DTG; placebo followed by active treatment). The primary endpoints were the proportion of patients in the ITG with unquantifiable HCV RNA 12 weeks posttreatment (sustained virological response 12 weeks after completion of study treatment; SVR12) and the comparison of safety in the ITG and DTG. In the ITG, 100 of 107 patients (93.5%) achieved SVR12, 6 relapsed, and 1 was lost to follow-up. SVR12 was achieved in 94.7% (18 of 19), 97.6% (40 of 41), and 89.4% (42 of 47) of patients with sickle cell disease, β-thalassemia, and hemophilia A/B or von Willebrand disease, respectively. Serious adverse events were reported by 2.8% (n = 3) and 11.5% (n = 6) of patients in the ITG and DTG, respectively. Hemoglobin levels and international normalized ratio values were similar in patients receiving EBR/GZR and placebo; among patients with hemoglobinopathies, change in mean hemoglobin levels was similar in those receiving EBR/GZR compared to those receiving placebo.</AbstractText>
<AbstractText Label="CONCLUSION" NlmCategory="CONCLUSIONS">These results add to the expanding pool of data available for EBR/GZR, indicating a high level of efficacy and favorable tolerability in patients with HCV infection. (Hepatology 2017;66:736-745).</AbstractText>
<CopyrightInformation>© 2017 by the American Association for the Study of Liver Diseases.</CopyrightInformation>
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<LastName>Hézode</LastName>
<ForeName>Christophe</ForeName>
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<LastName>Colombo</LastName>
<ForeName>Massimo</ForeName>
<Initials>M</Initials>
<AffiliationInfo>
<Affiliation>Humanitas Clinical and Research Center, Rozzano, Italy.</Affiliation>
</AffiliationInfo>
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<ForeName>Marc</ForeName>
<Initials>M</Initials>
<AffiliationInfo>
<Affiliation>Hôpital Saint Joseph, Marseille, France.</Affiliation>
</AffiliationInfo>
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<LastName>Spengler</LastName>
<ForeName>Ulrich</ForeName>
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<Affiliation>University Hospital Bonn, Bonn, Germany.</Affiliation>
</AffiliationInfo>
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<LastName>Ben-Ari</LastName>
<ForeName>Ziv</ForeName>
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<Affiliation>Sheba Medical Center, Ramat Gan, Israel.</Affiliation>
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</AffiliationInfo>
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<ForeName>Leslie</ForeName>
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</AffiliationInfo>
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</AffiliationInfo>
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<LastName>Hwang</LastName>
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</AffiliationInfo>
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</AffiliationInfo>
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</AffiliationInfo>
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</AffiliationInfo>
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<ForeName>Rohit</ForeName>
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</AffiliationInfo>
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<LastName>Marco</LastName>
<ForeName>Vito Di</ForeName>
<Initials>VD</Initials>
<AffiliationInfo>
<Affiliation>University of Palermo, Palermo, Italy.</Affiliation>
</AffiliationInfo>
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<Month>07</Month>
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<name sortKey="Robertson, Michael" sort="Robertson, Michael" uniqKey="Robertson M" first="Michael" last="Robertson">Michael Robertson</name>
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<name sortKey="Wahl, Janice" sort="Wahl, Janice" uniqKey="Wahl J" first="Janice" last="Wahl">Janice Wahl</name>
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Ou

HfdSelect -h $EXPLOR_AREA/Data/PubMed/Checkpoint/biblio.hfd -nk 000D42 | SxmlIndent | more

Pour mettre un lien sur cette page dans le réseau Wicri

{{Explor lien
   |wiki=    Wicri/Asie
   |area=    AustralieFrV1
   |flux=    PubMed
   |étape=   Checkpoint
   |type=    RBID
   |clé=     pubmed:28256747
   |texte=   Elbasvir/Grazoprevir for Patients With Hepatitis C Virus Infection and Inherited Blood Disorders: A Phase III Study.
}}

Pour générer des pages wiki

HfdIndexSelect -h $EXPLOR_AREA/Data/PubMed/Checkpoint/RBID.i   -Sk "pubmed:28256747" \
       | HfdSelect -Kh $EXPLOR_AREA/Data/PubMed/Checkpoint/biblio.hfd   \
       | NlmPubMed2Wicri -a AustralieFrV1 

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