{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T20:16:50Z","timestamp":1769199410405,"version":"3.49.0"},"reference-count":12,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,12,17]],"date-time":"2018-12-17T00:00:00Z","timestamp":1545004800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacoepidemiology and Drug"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>Drug\u2010induced aseptic meningitis (DIAM) is an inflammation of the membranes of the central nervous system caused by certain medications. It is a rare clinical entity whose risk factors are not yet fully elucidated. A local pattern of disproportionality within a global database of suspected adverse drug reactions (ADRs) revealed an increased reporting of aseptic meningitis and amoxicillin\u2010clavulanic acid (AC) in males. The aim of this report is to explore the clinical probability of a higher risk in males to support the use of statistical methods to identify subgroups at risk for adverse drug reactions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Disproportionality analysis was performed for all drug\u2010adverse event (AE) pairs in the entire database and for the subsets of males and females. AC\u2010aseptic meningitis was highlighted for an increased disproportionality in the male subgroup in the absence of an elevated disproportionality measure for the database overall. A clinical review was undertaken.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Clinical review revealed a similar statistical pattern of gender difference observed for amoxicillin, evidence to suggest a delayed type 4 hypersensitivity reaction with Th1 cells as a mechanism for amoxicillin\u2010aseptic meningitis, the existence of sex differences in immune responses (Th1\/Th2), and an analogous increased risk of drug\u2010induced liver injury by AC in males.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Subgroup disproportionality analysis has revealed a larger than expected number of reports of aseptic meningitis after amoxicillin and AC in males. Evidence synthesis supports the statistical finding. Further exploration of spontaneous databases with more extensive analyses could usher in a new era of \u201cprecision pharmacovigilance.\u201d<\/jats:p><\/jats:sec>","DOI":"10.1002\/pds.4707","type":"journal-article","created":{"date-parts":[[2018,12,17]],"date-time":"2018-12-17T12:39:55Z","timestamp":1545050395000},"page":"389-395","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Increased risk for aseptic meningitis after amoxicillin or amoxicillin\u2010clavulanic acid in males: A signal revealed by subset disproportionality analysis within a global database of suspected adverse drug reactions"],"prefix":"10.1002","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9334-9046","authenticated-orcid":false,"given":"Rebecca E.","family":"Chandler","sequence":"first","affiliation":[{"name":"Research Section Uppsala Monitoring Centre  Uppsala Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,12,17]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.159.11.1185"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2014.2918"},{"key":"e_1_2_9_4_1","doi-asserted-by":"crossref","unstructured":"HopstadiusJ Nor\u00e9nGN.Robust discovery of local patterns: subsets and stratification in adverse drug reaction surveillance. Proceedings of the 2nd ACM SIGHIT International Health Informatics SymposiumACM:Miami FL 2012:265\u2013274.","DOI":"10.1145\/2110363.2110395"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.2165\/00002018-200022030-00005"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.74.5.690"},{"key":"e_1_2_9_7_1","first-page":"120","article-title":"Meningencefalite asseptica recorrente induzida por amoxicilina","volume":"14","author":"Militao A","year":"2014","journal-title":"Sinapse"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2010.07.122"},{"key":"e_1_2_9_9_1","unstructured":"AlarconE SansostiA BoetyE et al.Drug\u2010induced aseptic meningitis due to amoxicillin. 34th Annual Congress of the European Academy of Allergy and Clinical Immunology.2015."},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2017.11.034"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2016.90"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-016-4121-6"},{"key":"e_1_2_9_13_1","unstructured":"Electronic Medicines Compendium.Summary of Product Characteristics for amoxicillin;clavulanic acid(Augmentin\u00ae). Available from:https:\/\/www.medicines.org.uk\/emc\/product\/280\/smpc. Accessed 12 September 2018."}],"container-title":["Pharmacoepidemiology and Drug Safety"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpds.4707","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pds.4707","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T02:13:58Z","timestamp":1694657638000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pds.4707"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,17]]},"references-count":12,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2019,3]]}},"alternative-id":["10.1002\/pds.4707"],"URL":"https:\/\/doi.org\/10.1002\/pds.4707","archive":["Portico"],"relation":{},"ISSN":["1053-8569","1099-1557"],"issn-type":[{"value":"1053-8569","type":"print"},{"value":"1099-1557","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,12,17]]},"assertion":[{"value":"2018-11-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-11-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-12-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}