{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T08:19:55Z","timestamp":1791879595048,"version":"4.3.4"},"reference-count":138,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,6,21]],"date-time":"2021-06-21T00:00:00Z","timestamp":1624233600000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Translational All"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Patients with a penicillin allergy label tend to have worse clinical outcomes and increased healthcare use. Drug provocation tests (DPT) are the gold\u2010standard in the diagnostic workup of penicillin allergy, but safety concerns may hinder their performance. We aimed to assess the frequency of severe reactions following a DPT in patients with reported allergy to penicillins or other\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010lactams.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a systematic review, searching MEDLINE, Scopus, and Web of Science. We included primary studies assessing participants with a penicillin allergy label who underwent a DPT. We performed a Bayesian meta\u2010analysis to estimate the pooled frequency of severe reactions to penicillin DPTs. Sources of heterogeneity were explored by subgroup and metaregression analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We included 112 primary studies which included a total of 26,595 participants. The pooled frequency of severe reactions was estimated at 0.06% (95% credible interval [95% CrI]\u00a0=\u00a00.01%\u20130.13%;\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u00a0=\u00a057.9%). Most severe reactions (80\/93; 86.0%) consisted of anaphylaxis. Compared to studies where the index reaction was immediate, we observed a lower frequency of severe reactions for studies assessing non\u2010immediate index reactions (OR\u00a0=\u00a00.05; 95% CrI\u00a0=\u00a00\u20100.31). Patients reporting anaphylaxis as their index reaction were found to be at increased risk of developing severe reactions (OR\u00a0=\u00a013.5; 95% CrI\u00a0=\u00a07.7\u201321.5;\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u00a0=\u00a00.3%). Performance of direct DPTs in low\u2010risk patients or testing with the suspected culprit drug were not associated with clinically relevant increased risk of severe reactions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In patients with a penicillin allergy label, severe reactions resulting from DPTs are rare. Therefore, except for patients with potentially life\u2010threatening index reactions or patients with positive skin tests\u2014who were mostly not assessed in this analysis \u2010, the safety of DPTs supports their performance in the diagnostic assessment of penicillin allergy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/clt2.12008","type":"journal-article","created":{"date-parts":[[2021,6,21]],"date-time":"2021-06-21T07:57:27Z","timestamp":1624262247000},"source":"Crossref","is-referenced-by-count":37,"title":["Frequency of severe reactions following penicillin drug provocation tests: A Bayesian meta\u2010analysis"],"prefix":"10.1002","volume":"11","author":[{"given":"Ant\u00f3nio","family":"Cardoso\u2010Fernandes","sequence":"first","affiliation":[{"name":"Department of Community Medicine, Information and Health Decision Sciences (MEDCIDS) Faculty of Medicine, University of Porto  Porto Portugal"},{"name":"Center for Health Technology and Services Research (CINTESIS) Faculty of Medicine, University of Porto  Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly G.","family":"Blumenthal","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Allergy, and Immunology, Department of Medicine Massachusetts General Hospital  Boston Massachusetts USA"},{"name":"Harvard Medical School Harvard University  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anca Mirela","family":"Chiriac","sequence":"additional","affiliation":[{"name":"Department of Pulmonology Division of Allergy, H\u00f4pital Arnaud de Villeneuve University Hospital of Montpellier  Montpellier France"},{"name":"UMR\u2010S 1136 INSERM\u2010Sorbonne Universit\u00e9 Equipe Epid\u00e9miologie des Maladies Allergiques et Respiratoires (EPAR) Institut Pierre Louis d\u2019Epid\u00e9miologie et de Sant\u00e9 Publique  Paris 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Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1277-3401","authenticated-orcid":false,"given":"Bernardo","family":"Sousa\u2010Pinto","sequence":"additional","affiliation":[{"name":"Department of Community Medicine, Information and Health Decision Sciences (MEDCIDS) Faculty of Medicine, University of Porto  Porto Portugal"},{"name":"Center for Health Technology and Services Research (CINTESIS) Faculty of Medicine, University of Porto  Porto Portugal"},{"name":"Basic and Clinical Immunology Unit, Department of Pathology, Faculty of Medicine University of Porto  Porto 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