Cold-adapted live influenza vaccine versus inactivated vaccine: systemic vaccine reactions, local and systemic antibody response, and vaccine efficacy. A meta-analysis.
Identifieur interne : 000320 ( PubMed/Checkpoint ); précédent : 000319; suivant : 000321Cold-adapted live influenza vaccine versus inactivated vaccine: systemic vaccine reactions, local and systemic antibody response, and vaccine efficacy. A meta-analysis.
Auteurs : W E P. Beyer [Pays-Bas] ; A M Palache ; J C De Jong ; A D M E. OsterhausSource :
- Vaccine [ 0264-410X ] ; 2002.
Descripteurs français
- KwdFr :
- Adaptation physiologique, Administration par voie nasale, Adolescent, Adulte, Adulte d'âge moyen, Anticorps antiviraux (sang), Basse température, Enfant, Enfant d'âge préscolaire, Grippe humaine (), Humains, Immunoglobuline A (sang), Injections musculaires, Nourrisson, Sujet âgé, Vaccins antigrippaux (administration et posologie), Vaccins antigrippaux (effets indésirables), Vaccins antigrippaux (immunologie), Vaccins inactivés (immunologie).
- MESH :
- administration et posologie : Vaccins antigrippaux.
- effets indésirables : Vaccins antigrippaux.
- immunologie : Vaccins antigrippaux, Vaccins inactivés.
- sang : Anticorps antiviraux, Immunoglobuline A.
- Adaptation physiologique, Administration par voie nasale, Adolescent, Adulte, Adulte d'âge moyen, Basse température, Enfant, Enfant d'âge préscolaire, Grippe humaine, Humains, Injections musculaires, Nourrisson, Sujet âgé.
English descriptors
- KwdEn :
- Adaptation, Physiological, Administration, Intranasal, Adolescent, Adult, Aged, Antibodies, Viral (blood), Child, Child, Preschool, Cold Temperature, Humans, Immunoglobulin A (blood), Infant, Influenza Vaccines (administration & dosage), Influenza Vaccines (adverse effects), Influenza Vaccines (immunology), Influenza, Human (prevention & control), Injections, Intramuscular, Middle Aged, Vaccines, Inactivated (immunology).
- MESH :
- chemical , administration & dosage : Influenza Vaccines.
- chemical , adverse effects : Influenza Vaccines.
- chemical , blood : Antibodies, Viral, Immunoglobulin A.
- chemical , immunology : Influenza Vaccines, Vaccines, Inactivated.
- prevention & control : Influenza, Human.
- Adaptation, Physiological, Administration, Intranasal, Adolescent, Adult, Aged, Child, Child, Preschool, Cold Temperature, Humans, Infant, Injections, Intramuscular, Middle Aged.
Abstract
Since the 1940s, influenza vaccines are inactivated and purified virus or virus subunit preparations (IIV) administered by the intramuscular route. Since decades, attempts have been made to construct, as an alternative, attenuated live influenza vaccines (LIV) for intranasal administration. Presently, the most successful LIV is derived from the cold-adapted master strains A/Ann Arbor/6/60 (H2N2) and B/Ann Arbor/1/66 (AA-LIV, for Ann-Arbor-derived live influenza vaccine). It has been claimed that AA-LIV is more efficacious than IIV. In order to assess differences between the two vaccines with respect to systemic reactogenicity, antibody response, and efficacy, we performed a meta-analysis on eighteen randomised comparative clinical trials involving a total of 5000 vaccinees of all ages. Pooled odds ratios (AA-LIV versus IIV) were calculated according to the random effects model. The two vaccines were associated with similarly low frequencies of systemic vaccine reactions (pooled odds ratio: 0.96, 95% confidence interval: 0.74-1.24). AA-LIV induced significantly lower levels of serum haemagglutination inhibiting antibody and significantly greater levels of local IgA antibody (influenza virus-specific respiratory IgA assayed by ELISA in nasal wash specimens) than IIV. Yet, although they predominantly stimulate different antibody compartments, the two vaccines were similarly efficacious in preventing culture-positive influenza illness. In all trials assessing clinical efficacy, the odds ratios were not significantly different from one (point of equivalence). The pooled odds ratio for influenza A-H3N2 was 1.50 (95% CI: 0.80-2.82), and for A-H1N1, 1.03 (95% CI: 0.58-1.82). The choice between the two vaccine types should be based on weighing the advantage of the attractive non-invasive mode of administration of AA-LIV, against serious concerns about the biological risks inherent to large-scale use of infectious influenza virus, in particular the hazard of gene reassortment with non-human influenza virus strains.
DOI: 10.1016/s0264-410x(01)00471-6
PubMed: 11818152
Affiliations:
Links toward previous steps (curation, corpus...)
Links to Exploration step
pubmed:11818152Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Cold-adapted live influenza vaccine versus inactivated vaccine: systemic vaccine reactions, local and systemic antibody response, and vaccine efficacy. A meta-analysis.</title><author><name sortKey="Beyer, W E P" sort="Beyer, W E P" uniqKey="Beyer W" first="W E P" last="Beyer">W E P. Beyer</name><affiliation wicri:level="3"><nlm:affiliation>WHO National Influenza Centre, Institute of Virology, Erasmus University Rotterdam, P.O. Box 1738, NL-3000 DR, Rotterdam, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>WHO National Influenza Centre, Institute of Virology, Erasmus University Rotterdam, P.O. Box 1738, NL-3000 DR, Rotterdam</wicri:regionArea><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Palache, A M" sort="Palache, A M" uniqKey="Palache A" first="A M" last="Palache">A M Palache</name></author><author><name sortKey="De Jong, J C" sort="De Jong, J C" uniqKey="De Jong J" first="J C" last="De Jong">J C De Jong</name></author><author><name sortKey="Osterhaus, A D M E" sort="Osterhaus, A D M E" uniqKey="Osterhaus A" first="A D M E" last="Osterhaus">A D M E. Osterhaus</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2002">2002</date><idno type="RBID">pubmed:11818152</idno><idno type="pmid">11818152</idno><idno type="doi">10.1016/s0264-410x(01)00471-6</idno><idno type="wicri:Area/PubMed/Corpus">000354</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000354</idno><idno type="wicri:Area/PubMed/Curation">000354</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000354</idno><idno type="wicri:Area/PubMed/Checkpoint">000320</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000320</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Cold-adapted live influenza vaccine versus inactivated vaccine: systemic vaccine reactions, local and systemic antibody response, and vaccine efficacy. A meta-analysis.</title><author><name sortKey="Beyer, W E P" sort="Beyer, W E P" uniqKey="Beyer W" first="W E P" last="Beyer">W E P. Beyer</name><affiliation wicri:level="3"><nlm:affiliation>WHO National Influenza Centre, Institute of Virology, Erasmus University Rotterdam, P.O. Box 1738, NL-3000 DR, Rotterdam, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>WHO National Influenza Centre, Institute of Virology, Erasmus University Rotterdam, P.O. Box 1738, NL-3000 DR, Rotterdam</wicri:regionArea><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Palache, A M" sort="Palache, A M" uniqKey="Palache A" first="A M" last="Palache">A M Palache</name></author><author><name sortKey="De Jong, J C" sort="De Jong, J C" uniqKey="De Jong J" first="J C" last="De Jong">J C De Jong</name></author><author><name sortKey="Osterhaus, A D M E" sort="Osterhaus, A D M E" uniqKey="Osterhaus A" first="A D M E" last="Osterhaus">A D M E. Osterhaus</name></author></analytic><series><title level="j">Vaccine</title><idno type="ISSN">0264-410X</idno><imprint><date when="2002" type="published">2002</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adaptation, Physiological</term><term>Administration, Intranasal</term><term>Adolescent</term><term>Adult</term><term>Aged</term><term>Antibodies, Viral (blood)</term><term>Child</term><term>Child, Preschool</term><term>Cold Temperature</term><term>Humans</term><term>Immunoglobulin A (blood)</term><term>Infant</term><term>Influenza Vaccines (administration & dosage)</term><term>Influenza Vaccines (adverse effects)</term><term>Influenza Vaccines (immunology)</term><term>Influenza, Human (prevention & control)</term><term>Injections, Intramuscular</term><term>Middle Aged</term><term>Vaccines, Inactivated (immunology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adaptation physiologique</term><term>Administration par voie nasale</term><term>Adolescent</term><term>Adulte</term><term>Adulte d'âge moyen</term><term>Anticorps antiviraux (sang)</term><term>Basse température</term><term>Enfant</term><term>Enfant d'âge préscolaire</term><term>Grippe humaine ()</term><term>Humains</term><term>Immunoglobuline A (sang)</term><term>Injections musculaires</term><term>Nourrisson</term><term>Sujet âgé</term><term>Vaccins antigrippaux (administration et posologie)</term><term>Vaccins antigrippaux (effets indésirables)</term><term>Vaccins antigrippaux (immunologie)</term><term>Vaccins inactivés (immunologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Influenza Vaccines</term></keywords><keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Influenza Vaccines</term></keywords><keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Antibodies, Viral</term><term>Immunoglobulin A</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Influenza Vaccines</term><term>Vaccines, Inactivated</term></keywords><keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Vaccins antigrippaux</term></keywords><keywords scheme="MESH" qualifier="effets indésirables" xml:lang="fr"><term>Vaccins antigrippaux</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Vaccins antigrippaux</term><term>Vaccins inactivés</term></keywords><keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Influenza, Human</term></keywords><keywords scheme="MESH" qualifier="sang" xml:lang="fr"><term>Anticorps antiviraux</term><term>Immunoglobuline A</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adaptation, Physiological</term><term>Administration, Intranasal</term><term>Adolescent</term><term>Adult</term><term>Aged</term><term>Child</term><term>Child, Preschool</term><term>Cold Temperature</term><term>Humans</term><term>Infant</term><term>Injections, Intramuscular</term><term>Middle Aged</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adaptation physiologique</term><term>Administration par voie nasale</term><term>Adolescent</term><term>Adulte</term><term>Adulte d'âge moyen</term><term>Basse température</term><term>Enfant</term><term>Enfant d'âge préscolaire</term><term>Grippe humaine</term><term>Humains</term><term>Injections musculaires</term><term>Nourrisson</term><term>Sujet âgé</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Since the 1940s, influenza vaccines are inactivated and purified virus or virus subunit preparations (IIV) administered by the intramuscular route. Since decades, attempts have been made to construct, as an alternative, attenuated live influenza vaccines (LIV) for intranasal administration. Presently, the most successful LIV is derived from the cold-adapted master strains A/Ann Arbor/6/60 (H2N2) and B/Ann Arbor/1/66 (AA-LIV, for Ann-Arbor-derived live influenza vaccine). It has been claimed that AA-LIV is more efficacious than IIV. In order to assess differences between the two vaccines with respect to systemic reactogenicity, antibody response, and efficacy, we performed a meta-analysis on eighteen randomised comparative clinical trials involving a total of 5000 vaccinees of all ages. Pooled odds ratios (AA-LIV versus IIV) were calculated according to the random effects model. The two vaccines were associated with similarly low frequencies of systemic vaccine reactions (pooled odds ratio: 0.96, 95% confidence interval: 0.74-1.24). AA-LIV induced significantly lower levels of serum haemagglutination inhibiting antibody and significantly greater levels of local IgA antibody (influenza virus-specific respiratory IgA assayed by ELISA in nasal wash specimens) than IIV. Yet, although they predominantly stimulate different antibody compartments, the two vaccines were similarly efficacious in preventing culture-positive influenza illness. In all trials assessing clinical efficacy, the odds ratios were not significantly different from one (point of equivalence). The pooled odds ratio for influenza A-H3N2 was 1.50 (95% CI: 0.80-2.82), and for A-H1N1, 1.03 (95% CI: 0.58-1.82). The choice between the two vaccine types should be based on weighing the advantage of the attractive non-invasive mode of administration of AA-LIV, against serious concerns about the biological risks inherent to large-scale use of infectious influenza virus, in particular the hazard of gene reassortment with non-human influenza virus strains.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">11818152</PMID><DateCompleted><Year>2002</Year><Month>04</Month><Day>25</Day></DateCompleted><DateRevised><Year>2019</Year><Month>07</Month><Day>28</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0264-410X</ISSN><JournalIssue CitedMedium="Print"><Volume>20</Volume><Issue>9-10</Issue><PubDate><Year>2002</Year><Month>Jan</Month><Day>31</Day></PubDate></JournalIssue><Title>Vaccine</Title><ISOAbbreviation>Vaccine</ISOAbbreviation></Journal><ArticleTitle>Cold-adapted live influenza vaccine versus inactivated vaccine: systemic vaccine reactions, local and systemic antibody response, and vaccine efficacy. A meta-analysis.</ArticleTitle><Pagination><MedlinePgn>1340-53</MedlinePgn></Pagination><Abstract><AbstractText>Since the 1940s, influenza vaccines are inactivated and purified virus or virus subunit preparations (IIV) administered by the intramuscular route. Since decades, attempts have been made to construct, as an alternative, attenuated live influenza vaccines (LIV) for intranasal administration. Presently, the most successful LIV is derived from the cold-adapted master strains A/Ann Arbor/6/60 (H2N2) and B/Ann Arbor/1/66 (AA-LIV, for Ann-Arbor-derived live influenza vaccine). It has been claimed that AA-LIV is more efficacious than IIV. In order to assess differences between the two vaccines with respect to systemic reactogenicity, antibody response, and efficacy, we performed a meta-analysis on eighteen randomised comparative clinical trials involving a total of 5000 vaccinees of all ages. Pooled odds ratios (AA-LIV versus IIV) were calculated according to the random effects model. The two vaccines were associated with similarly low frequencies of systemic vaccine reactions (pooled odds ratio: 0.96, 95% confidence interval: 0.74-1.24). AA-LIV induced significantly lower levels of serum haemagglutination inhibiting antibody and significantly greater levels of local IgA antibody (influenza virus-specific respiratory IgA assayed by ELISA in nasal wash specimens) than IIV. Yet, although they predominantly stimulate different antibody compartments, the two vaccines were similarly efficacious in preventing culture-positive influenza illness. In all trials assessing clinical efficacy, the odds ratios were not significantly different from one (point of equivalence). The pooled odds ratio for influenza A-H3N2 was 1.50 (95% CI: 0.80-2.82), and for A-H1N1, 1.03 (95% CI: 0.58-1.82). The choice between the two vaccine types should be based on weighing the advantage of the attractive non-invasive mode of administration of AA-LIV, against serious concerns about the biological risks inherent to large-scale use of infectious influenza virus, in particular the hazard of gene reassortment with non-human influenza virus strains.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Beyer</LastName><ForeName>W E P</ForeName><Initials>WE</Initials><AffiliationInfo><Affiliation>WHO National Influenza Centre, Institute of Virology, Erasmus University Rotterdam, P.O. Box 1738, NL-3000 DR, Rotterdam, The Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Palache</LastName><ForeName>A M</ForeName><Initials>AM</Initials></Author><Author ValidYN="Y"><LastName>de Jong</LastName><ForeName>J C</ForeName><Initials>JC</Initials></Author><Author ValidYN="Y"><LastName>Osterhaus</LastName><ForeName>A D M E</ForeName><Initials>AD</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D003160">Comparative Study</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D017418">Meta-Analysis</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>Netherlands</Country><MedlineTA>Vaccine</MedlineTA><NlmUniqueID>8406899</NlmUniqueID><ISSNLinking>0264-410X</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000914">Antibodies, Viral</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D007070">Immunoglobulin A</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D007252">Influenza Vaccines</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D015164">Vaccines, Inactivated</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections RefType="CommentIn"><RefSource>Vaccine. 2002 Oct 4;20(29-30):3429-30</RefSource><PMID Version="1">12297386</PMID></CommentsCorrections></CommentsCorrectionsList><MeshHeadingList><MeshHeading><DescriptorName UI="D000222" MajorTopicYN="N">Adaptation, Physiological</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000281" MajorTopicYN="N">Administration, Intranasal</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000293" MajorTopicYN="N">Adolescent</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000368" MajorTopicYN="N">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000914" MajorTopicYN="N">Antibodies, Viral</DescriptorName><QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002648" MajorTopicYN="N">Child</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002675" MajorTopicYN="N">Child, Preschool</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D003080" MajorTopicYN="N">Cold Temperature</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007070" MajorTopicYN="N">Immunoglobulin A</DescriptorName><QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007223" MajorTopicYN="N">Infant</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007252" MajorTopicYN="N">Influenza Vaccines</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName><QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007251" MajorTopicYN="N">Influenza, Human</DescriptorName><QualifierName UI="Q000517" MajorTopicYN="N">prevention & control</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007273" MajorTopicYN="N">Injections, Intramuscular</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015164" MajorTopicYN="N">Vaccines, Inactivated</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2002</Year><Month>1</Month><Day>31</Day><Hour>10</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2002</Year><Month>4</Month><Day>26</Day><Hour>10</Hour><Minute>1</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2002</Year><Month>1</Month><Day>31</Day><Hour>10</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">11818152</ArticleId><ArticleId IdType="pii">S0264410X01004716</ArticleId><ArticleId IdType="doi">10.1016/s0264-410x(01)00471-6</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Pays-Bas</li></country><region><li>Hollande-Méridionale</li></region><settlement><li>Rotterdam</li></settlement></list><tree><noCountry><name sortKey="De Jong, J C" sort="De Jong, J C" uniqKey="De Jong J" first="J C" last="De Jong">J C De Jong</name><name sortKey="Osterhaus, A D M E" sort="Osterhaus, A D M E" uniqKey="Osterhaus A" first="A D M E" last="Osterhaus">A D M E. Osterhaus</name><name sortKey="Palache, A M" sort="Palache, A M" uniqKey="Palache A" first="A M" last="Palache">A M Palache</name></noCountry><country name="Pays-Bas"><region name="Hollande-Méridionale"><name sortKey="Beyer, W E P" sort="Beyer, W E P" uniqKey="Beyer W" first="W E P" last="Beyer">W E P. Beyer</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/H2N2V1/Data/PubMed/Checkpoint
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000320 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/PubMed/Checkpoint/biblio.hfd -nk 000320 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= H2N2V1
|flux= PubMed
|étape= Checkpoint
|type= RBID
|clé= pubmed:11818152
|texte= Cold-adapted live influenza vaccine versus inactivated vaccine: systemic vaccine reactions, local and systemic antibody response, and vaccine efficacy. A meta-analysis.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/PubMed/Checkpoint/RBID.i -Sk "pubmed:11818152" \
| HfdSelect -Kh $EXPLOR_AREA/Data/PubMed/Checkpoint/biblio.hfd \
| NlmPubMed2Wicri -a H2N2V1
| This area was generated with Dilib version V0.6.33. |  |