{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T13:19:26Z","timestamp":1784121566707,"version":"3.55.0"},"reference-count":51,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,3,18]],"date-time":"2019-03-18T00:00:00Z","timestamp":1552867200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pain"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and objective<\/jats:title><jats:p>We explored how systematic reviews evaluated paracetamol and ibuprofen for treating pain in children, as these two non\u2010opioid analgesics are well\u2010established medicines included in most national essential medicines lists.<\/jats:p><\/jats:sec><jats:sec><jats:title>Databases and data treatment<\/jats:title><jats:p>We carried out an overview of systematic reviews (SRs) of randomized controlled trials (RCTs) of interventions (PROSPERO registration: 42016045367). We searched MEDLINE, EMBASE, Cochrane Database of Systematic Reviews (CDSR) and Database of Reviews of Effects (DARE) up to 23 August 2017. We used AMSTAR checklist to analyse methodological quality of included SRs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found 17 SRs with 72 unique RCTs; the majority of those trials included under 100 children. Positive conclusive evidence was found in only one SR, regarding safety of paracetamol. Conclusions of other SRs for efficacy and safety of ibuprofen and paracetamol were inconclusive, unclear, or there was no opinion. Only one SR analysed efficacy of ibuprofen and other non\u2010steroidal anti\u2010inflammatory drugs (NSAIDs) in chronic pain and the conclusion was that there was no evidence from RCTs that NSAIDs were effective for chronic non\u2010cancer pain in children and adolescents. Most of the SRs addressed very narrow questions, included few trials, with few children and were of low or medium methodological quality.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Most SRs on two relevant medicines have inconsistent conclusions and doubt upon their effectiveness. Instead of focusing on very narrow questions, SRs should examine more comprehensive research topics to obtain a general sense of consistency, particularly when analysing established medicines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Evidence behind two analgesics\u2014ibuprofen and paracetamol\u2014that are well\u2010established medicines for children in most countries appears limited, judging by the systematic reviews. The discrepancy between clinical use and the extensive evidence we reviewed may be a result of the selective criteria in the reviews examined. We need new, and better evidence syntheses supporting the use of these two medicines in wide indications regarding pain in children.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ejp.1380","type":"journal-article","created":{"date-parts":[[2019,2,22]],"date-time":"2019-02-22T04:13:12Z","timestamp":1550808792000},"page":"1071-1082","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Revisiting established medicines: An overview of systematic reviews about ibuprofen and paracetamol for treating pain in children"],"prefix":"10.1002","volume":"23","author":[{"given":"Marija","family":"Radman","sequence":"first","affiliation":[{"name":"Split\u2010Dalmatia County Pharmacy Split Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrija","family":"Babic","sequence":"additional","affiliation":[{"name":"Institute of Emergency Medicine in Split\u2010Dalmatia County Split Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edita","family":"Runjic","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University Hospital Split Split Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia","family":"Jelicic Kadic","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University Hospital Split Split Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milka","family":"Jeric","sequence":"additional","affiliation":[{"name":"Department of Dermatovenerology General Hospital Zadar Zadar Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Moja","sequence":"additional","affiliation":[{"name":"Unit of Clinical Epidemiology IRCCS Istituto Ortopedico Galeazzi Milan Italy"},{"name":"Department of Biomedical Sciences for Public Health Universit\u00e0 degli Studi di Milano Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8467-6061","authenticated-orcid":false,"given":"Livia","family":"Puljak","sequence":"additional","affiliation":[{"name":"Center for Evidence\u2010Based Medicine and Health Care Catholic University of Croatia Zagreb Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,3,18]]},"reference":[{"issue":"4","key":"e_1_2_7_2_1","first-page":"140","article-title":"Antipyretic activity of ibuprofen and paracetamol in children with pyrexia","volume":"39","author":"Amdekar Y. 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