{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T02:51:22Z","timestamp":1791859882067,"version":"4.3.4"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2022,4,5]],"date-time":"2022-04-05T00:00:00Z","timestamp":1649116800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"This study received funding from the Sigrid Jus\u00e9lius Foundation"},{"DOI":"10.13039\/100015738","name":"Mary and Georg C. Ehrnrooth Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100015738","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,5,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Non-operative management of uncomplicated acute appendicitis is an option, but omission of antibiotics from the regimen has not been tested.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A double-blind, placebo-controlled, superiority RCT in adults with CT-confirmed uncomplicated acute appendicitis was designed to compare placebo with antibiotics (intravenous ertapenem followed by oral levofloxacin and metronidazole). The primary endpoint was treatment success (resolution resulting in discharge without appendicectomy within 10 days); secondary outcomes included pain scores, complications, hospital stay, and return to work.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>From May 2017 to September 2020, 72 patients with a mean(s.d.) age of 37.5 (11.1) years were recruited at five hospitals. Six were excluded after randomization (5 early consent withdrawals, 1 randomization protocol violation), 35 were assigned to receive antibiotics, and 31 to receive placebo. Enrolment challenges (including hospital pharmacy resources in an acute-care surgery setting) meant that only the lowest sample size of three predefined scenarios was achieved. The 10-day treatment success rate was 87 (95 per cent c.i. 75 to 99) per cent for placebo and 97 (92 to 100) per cent for antibiotics. This clinical difference of 10 (90 per cent c.i. \u22120.9 to 21) per cent was not statistically different for the primary outcome (1-sided P = 0.142), and secondary outcomes were similar.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>The lack of antibiotic superiority statistically suggests that a non-inferiority trial against placebo is warranted in adults with CT-confirmed mild appendicitis. Registration number: EudraCT 2015-003634-26 (https:\/\/eudract.ema.europa.eu\/eudract-web\/index.faces), NCT03234296 (http:\/\/www.clinicaltrials.gov).<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bjs\/znac086","type":"journal-article","created":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T20:11:54Z","timestamp":1646770314000},"page":"503-509","source":"Crossref","is-referenced-by-count":56,"title":["Antibiotics <i>versus<\/i> placebo in adults with CT-confirmed uncomplicated acute appendicitis (APPAC III): randomized double-blind superiority trial"],"prefix":"10.1093","volume":"109","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6435-9264","authenticated-orcid":false,"given":"Paulina","family":"Salminen","sequence":"first","affiliation":[{"name":"Division of Digestive Surgery and Urology, Turku University Hospital , Turku, Finland"},{"name":"Department of Surgery, University of Turku , Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suvi","family":"Sippola","sequence":"additional","affiliation":[{"name":"Division of Digestive Surgery and Urology, Turku University Hospital , Turku, Finland"},{"name":"Department of Surgery, University of Turku , Turku, Finland"},{"name":"Department of Surgery, Jyv\u00e4skyl\u00e4 Central Hospital , Jyv\u00e4skyl\u00e4, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jussi","family":"Haijanen","sequence":"additional","affiliation":[{"name":"Division of Digestive Surgery and Urology, Turku University Hospital , Turku, Finland"},{"name":"Department of Surgery, University of Turku , Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pia","family":"Nordstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital , Tampere, Finland"},{"name":"Faculty of Medicine and Health Technology, University of Tampere , Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuomo","family":"Rantanen","sequence":"additional","affiliation":[{"name":"Department of Surgery, Kuopio University Hospital , Kuopio, Finland"},{"name":"Department of Surgery, Institute of Clinical Medicine, University of Eastern Finland , Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tero","family":"Rautio","sequence":"additional","affiliation":[{"name":"Department of Surgery, Oulu University Hospital , Oulu, Finland"},{"name":"Medical Research Centre Oulu, University of Oulu , Oulu, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5394-4169","authenticated-orcid":false,"given":"Ville","family":"Sallinen","sequence":"additional","affiliation":[{"name":"Gastroenterological Surgery, Helsinki University Hospital and University of Helsinki , Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliisa","family":"L\u00f6yttyniemi","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of Turku , Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saija","family":"Hurme","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of Turku , Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ville","family":"Tammilehto","sequence":"additional","affiliation":[{"name":"Department of Radiology, Turku University Hospital , Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Laukkarinen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital , Tampere, Finland"},{"name":"Faculty of Medicine and Health Technology, University of Tampere , Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heini","family":"Savolainen","sequence":"additional","affiliation":[{"name":"Department of Surgery, Kuopio University Hospital , Kuopio, Finland"},{"name":"Department of Surgery, Institute of Clinical Medicine, University of Eastern Finland , Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanna","family":"Meril\u00e4inen","sequence":"additional","affiliation":[{"name":"Department of Surgery, Oulu University Hospital , Oulu, Finland"},{"name":"Medical Research Centre Oulu, University of Oulu , Oulu, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ari","family":"Lepp\u00e4niemi","sequence":"additional","affiliation":[{"name":"Gastroenterological Surgery, Helsinki University Hospital and University of Helsinki , Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juha","family":"Gr\u00f6nroos","sequence":"additional","affiliation":[{"name":"Division of Digestive Surgery and Urology, Turku University Hospital , Turku, Finland"},{"name":"Department of Surgery, University of Turku , Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,4,6]]},"reference":[{"key":"2023063011091710200_znac086-B1","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1056\/NEJMoa2014320","article-title":"A randomized trial comparing antibiotics with appendectomy for appendicitis","volume":"383","author":"Flum","year":"2020","journal-title":"N Engl J Med"},{"key":"2023063011091710200_znac086-B2","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1001\/jama.2020.10888","article-title":"Association of nonoperative management using antibiotic therapy vs laparoscopic appendectomy with treatment success and disability days in children with uncomplicated appendicitis","volume":"324","author":"Minneci","year":"2020","journal-title":"JAMA"},{"key":"2023063011091710200_znac086-B3","doi-asserted-by":"crossref","first-page":"2340","DOI":"10.1001\/jama.2015.6154","article-title":"Antibiotic therapy vs appendectomy for treatment of uncomplicated acute appendicitis: the APPAC randomized clinical trial","volume":"313","author":"Salminen","year":"2015","journal-title":"JAMA"},{"key":"2023063011091710200_znac086-B4","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1001\/jama.2018.13201","article-title":"Five-year follow-up of antibiotic therapy for uncomplicated acute appendicitis in the APPAC randomized clinical trial","volume":"320","author":"Salminen","year":"2018","journal-title":"JAMA"},{"key":"2023063011091710200_znac086-B5","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1001\/jama.2020.23525","article-title":"Effect of oral moxifloxacin vs intravenous ertapenem plus oral levofloxacin for treatment of uncomplicated acute appendicitis: the APPAC II randomized clinical trial","volume":"325","author":"Sippola","year":"2021","journal-title":"JAMA"},{"key":"2023063011091710200_znac086-B6","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1001\/jamasurg.2019.6028","article-title":"Quality of life and patient satisfaction at 7-year follow-up of antibiotic therapy vs appendectomy for uncomplicated acute appendicitis: a secondary analysis of a randomized clinical trial","volume":"155","author":"Sippola","year":"2020","journal-title":"JAMA Surg"},{"key":"2023063011091710200_znac086-B7","volume-title":"COVID 19: Elective Case Triage Guidelines for Surgical Care","author":"American College of Surgeons","year":"2020"},{"key":"2023063011091710200_znac086-B8","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1001\/jamasurg.2018.4373","article-title":"Risk of appendiceal neoplasm in periappendicular abscess in patients treated with interval appendectomy vs follow-up with magnetic resonance imaging: 1-year outcomes of the Peri-Appendicitis Acuta randomized clinical trial","volume":"154","author":"Mallinen","year":"2019","journal-title":"JAMA Surg"},{"key":"2023063011091710200_znac086-B9","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1002\/bjs.10873","article-title":"Meta-analysis of in-hospital delay before surgery as a risk factor for complications in patients with acute appendicitis","volume":"105","author":"van Dijk","year":"2018","journal-title":"Br J Surg"},{"key":"2023063011091710200_znac086-B10","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1177\/14574969211008330","article-title":"Diagnosis of uncomplicated and complicated appendicitis in adults","volume":"110","author":"Bom","year":"2021","journal-title":"Scand J Surg"},{"key":"2023063011091710200_znac086-B11","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1016\/S0140-6736(11)60410-8","article-title":"Amoxicillin plus clavulanic acid versus appendicectomy for treatment of acute uncomplicated appendicitis: an open-label, non-inferiority, randomised controlled trial","volume":"377","author":"Vons","year":"2011","journal-title":"Lancet"},{"key":"2023063011091710200_znac086-B12","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1002\/bjs.8688","article-title":"Randomized clinical trial of antibiotics in acute uncomplicated diverticulitis","volume":"99","author":"Chabok","year":"2012","journal-title":"Br J Surg"},{"key":"2023063011091710200_znac086-B13","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1002\/bjs.10309","article-title":"Randomized clinical trial of observational versus antibiotic treatment for a first episode of CT-proven uncomplicated acute diverticulitis","volume":"104","author":"Daniels","year":"2017","journal-title":"Br J Surg"},{"key":"2023063011091710200_znac086-B14","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1002\/bjs.10660","article-title":"Randomized clinical trial of antibiotic therapy for uncomplicated appendicitis","volume":"104","author":"Park","year":"2017","journal-title":"Br J Surg"},{"key":"2023063011091710200_znac086-B15","doi-asserted-by":"crossref","first-page":"e023623","DOI":"10.1136\/bmjopen-2018-023623","article-title":"A randomised placebo-controlled double-blind multicentre trial comparing antibiotic therapy with placebo in the treatment of uncomplicated acute appendicitis: APPAC III trial study protocol","volume":"8","author":"Sippola","year":"2018","journal-title":"BMJ Open"},{"key":"2023063011091710200_znac086-B16","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1097\/01.sla.0000133083.54934.ae","article-title":"Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey","volume":"240","author":"Dindo","year":"2004","journal-title":"Ann Surg"},{"key":"2023063011091710200_znac086-B17","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1007\/s00464-013-3257-0","article-title":"Risk of colon cancer after computed tomography-diagnosed acute diverticulitis: is routine colonoscopy necessary?","volume":"28","author":"Sallinen","year":"2014","journal-title":"Surg Endosc"},{"key":"2023063011091710200_znac086-B18","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1001\/archsurg.2011.2","article-title":"Epidemiological similarities between appendicitis and diverticulitis suggesting a common underlying pathogenesis","volume":"146","author":"Livingston","year":"2011","journal-title":"Arch Surg"},{"key":"2023063011091710200_znac086-B19","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1097\/DCR.0000000000000579","article-title":"Symptomatic treatment for uncomplicated acute diverticulitis: a prospective cohort study","volume":"59","author":"Mali","year":"2016","journal-title":"Dis Colon Rectum"},{"key":"2023063011091710200_znac086-B20","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1002\/bjs.11465","article-title":"Observational versus antibiotic treatment for uncomplicated diverticulitis: an individual-patient data meta-analysis","volume":"107","author":"van Dijk","year":"2020","journal-title":"Br J Surg"},{"key":"2023063011091710200_znac086-B21","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1177\/14574969211011032","article-title":"Changing paradigms in the management of acute uncomplicated diverticulitis","volume":"110","author":"Chabok","year":"2021","journal-title":"Scand J Surg"},{"key":"2023063011091710200_znac086-B22","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1056\/NEJMra1907805","article-title":"Placebo and nocebo effects","volume":"382","author":"Colloca","year":"2020","journal-title":"N Engl J Med"},{"key":"2023063011091710200_znac086-B23","doi-asserted-by":"crossref","first-page":"2182","DOI":"10.1056\/NEJMc2031173","article-title":"N-of-1 trial of a statin, placebo, or no treatment to assess side effects","volume":"383","author":"Wood","year":"2020","journal-title":"N Engl J Med"},{"key":"2023063011091710200_znac086-B24","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1001\/jama.2020.23607","article-title":"Evolving issues in the use of antibiotics for the treatment of uncomplicated appendicitis","volume":"325","author":"Minneci","year":"2021","journal-title":"JAMA"},{"key":"2023063011091710200_znac086-B25","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1097\/SLA.0000000000004785","article-title":"A randomised clinical trial evaluating the efficacy and quality of life of antibiotic only treatment of acute uncomplicated appendicitis: results of the COMMA trial","volume":"274","author":"O\u2019Leary","year":"2021","journal-title":"Ann Surg"},{"key":"2023063011091710200_znac086-B26","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1097\/SLA.0000000000003225","article-title":"Antibiotic treatment and appendectomy for uncomplicated acute appendicitis in adults and children: a systematic review and meta-analysis","volume":"270","author":"Podda","year":"2019","journal-title":"Ann Surg"},{"key":"2023063011091710200_znac086-B27","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1001\/jamasurg.2021.5003","article-title":"Factors associated with primary nonresponsiveness to antibiotics in adults with uncomplicated acute appendicitis: a prespecified secondary analysis of a randomized clinical trial","volume":"156","author":"Haijanen","year":"2021","journal-title":"JAMA Surg"},{"key":"2023063011091710200_znac086-B28","doi-asserted-by":"crossref","first-page":"e216900","DOI":"10.1001\/jamasurg.2021.6900","article-title":"Patient factors associated with appendectomy within 30 days of initiating antibiotic treatment for appendicitis","volume":"157","author":"Writing Group for the CODA Collaborative","year":"2022","journal-title":"JAMA Surg"}],"container-title":["British Journal of Surgery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bjs\/article-pdf\/109\/6\/503\/50748056\/znac086.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bjs\/article-pdf\/109\/6\/503\/50748056\/znac086.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T11:09:48Z","timestamp":1688123388000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bjs\/article\/109\/6\/503\/6563438"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,6]]},"references-count":28,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,4,6]]},"published-print":{"date-parts":[[2022,5,16]]}},"URL":"https:\/\/doi.org\/10.1093\/bjs\/znac086","relation":{},"ISSN":["0007-1323","1365-2168"],"issn-type":[{"value":"0007-1323","type":"print"},{"value":"1365-2168","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,5,16]]},"published":{"date-parts":[[2022,4,6]]}}}