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      Cost analysis of antibiotic therapy versus appendectomy for treatment of uncomplicated acute appendicitis: 5-year results of the APPAC randomized clinical trial

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          Abstract

          Background

          The efficacy and safety of antibiotic treatment for uncomplicated acute appendicitis has been established at long-term follow-up with the majority of recurrences shown to occur within the first year. Overall costs of antibiotics are significantly lower compared with appendectomy at short-term follow-up, but long-term durability of these cost savings is unclear. The study objective was to compare the long-term overall costs of antibiotic therapy versus appendectomy in the treatment of uncomplicated acute appendicitis in the APPAC (APPendicitis ACuta) trial at 5 years.

          Methods and findings

          This multicentre, non-inferiority randomized clinical trial randomly assigned 530 adult patients with CT-confirmed uncomplicated acute appendicitis to appendectomy or antibiotic treatment at six Finnish hospitals. All major costs during the 5-year follow-up were recorded, whether generated by the initial visit and subsequent treatment or possible recurrent appendicitis. Between November 2009 and June 2012, 273 patients were randomized to appendectomy and 257 to antibiotics. The overall costs of appendectomy were 1.4 times higher (p<0.001) (€5716; 95% CI: €5510 to €5925) compared with antibiotic therapy (€4171; 95% CI: €3879 to €4463) resulting in cost savings of €1545 per patient (95% CI: €1193 to €1899; p<0.001) in the antibiotic group. At 5 years, the majority (61%, n = 156) of antibiotic group patients did not undergo appendectomy.

          Conclusions

          At 5-year follow-up antibiotic treatment resulted in significantly lower overall costs compared with appendectomy. As the majority of appendicitis recurrences occur within the first year after the initial antibiotic treatment, these results suggest that treating uncomplicated acute appendicitis with antibiotics instead of appendectomy results in lower overall costs even at longer-term follow-up.

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          Most cited references22

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          Acute appendicitis: modern understanding of pathogenesis, diagnosis, and management.

          Acute appendicitis is one of the most common abdominal emergencies worldwide. The cause remains poorly understood, with few advances in the past few decades. To obtain a confident preoperative diagnosis is still a challenge, since the possibility of appendicitis must be entertained in any patient presenting with an acute abdomen. Although biomarkers and imaging are valuable adjuncts to history and examination, their limitations mean that clinical assessment is still the mainstay of diagnosis. A clinical classification is used to stratify management based on simple (non-perforated) and complex (gangrenous or perforated) inflammation, although many patients remain with an equivocal diagnosis, which is one of the most challenging dilemmas. An observed divide in disease course suggests that some cases of simple appendicitis might be self-limiting or respond to antibiotics alone, whereas another type often seems to perforate before the patient reaches hospital. Although the mortality rate is low, postoperative complications are common in complex disease. We discuss existing knowledge in pathogenesis, modern diagnosis, and evolving strategies in management that are leading to stratified care for patients.
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            Global disease burden of conditions requiring emergency surgery.

            Surgical disease is inadequately addressed globally, and emergency conditions requiring surgery contribute substantially to the global disease burden. This was a review of studies that contributed to define the population-based health burden of emergency surgical conditions (excluding trauma and obstetrics) and the status of available capacity to address this burden. Further data were retrieved from the Global Burden of Disease Study 2010 and the University of Washington's Institute for Health Metrics and Evaluation online data. In the index year of 2010, there were 896,000 deaths, 20 million years of life lost and 25 million disability-adjusted life-years from 11 emergency general surgical conditions reported individually in the Global Burden of Disease Study. The most common cause of death was complicated peptic ulcer disease, followed by aortic aneurysm, bowel obstruction, biliary disease, mesenteric ischaemia, peripheral vascular disease, abscess and soft tissue infections, and appendicitis. The mortality rate was higher in high-income countries (HICs) than in low- and middle-income countries (LMICs) (24.3 versus 10.6 deaths per 100,000 inhabitants respectively), primarily owing to a higher rate of vascular disease in HICs. However, because of the much larger population, 70 per cent of deaths occurred in LMICs. Deaths from vascular disease rose from 15 to 25 per cent of surgical emergency-related deaths in LMICs (from 1990 to 2010). Surgical capacity to address this burden is suboptimal in LMICs, with fewer than one operating theatre per 100,000 inhabitants in many LMICs, whereas some HICs have more than 14 per 100,000 inhabitants. The global burden of surgical emergencies is described insufficiently. The bare estimates indicate a tremendous health burden. LMICs carry the majority of emergency conditions; in these countries the pattern of surgical disease is changing and capacity to deal with the problem is inadequate. The data presented in this study will be useful for both the surgical and public health communities to plan a more adequate response. © 2013 BJS Society Ltd. Published by John Wiley & Sons Ltd.
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              Five-Year Follow-up of Antibiotic Therapy for Uncomplicated Acute Appendicitis in the APPAC Randomized Clinical Trial

              Short-term results support antibiotics as an alternative to surgery for treating uncomplicated acute appendicitis, but long-term outcomes are not known.
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                Author and article information

                Contributors
                Role: MethodologyRole: Project administrationRole: SoftwareRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Project administrationRole: ValidationRole: VisualizationRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: Validation
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: Supervision
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: SoftwareRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                25 July 2019
                2019
                : 14
                : 7
                : e0220202
                Affiliations
                [1 ] Division of Digestive Surgery and Urology, Turku University Hospital, Turku, Finland
                [2 ] Department of Surgery, University of Turku, Turku, Finland
                [3 ] Department of Public Health, University of Turku, Turku, Finland
                [4 ] University of Namibia, Windhoek, Namibia
                [5 ] Department of Surgery, Mikkeli Central Hospital, Mikkeli, Finland
                [6 ] Department of Surgery, Oulu University Hospital, Oulu, Finland
                [7 ] Division of Surgery, Gastroenterology and Oncology, Tampere University Hospital, Tampere, Finland
                [8 ] Department of Surgery, Jyväskylä Central Hospital, Jyväskylä, Finland
                [9 ] Department of Surgery, Kuopio University Hospital, Kuopio, Finland
                [10 ] Department of Biostatistics, University of Turku, Turku, Finland
                Vita Salute University of Milan, ITALY
                Author notes

                Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: P.S. has received personal fees for lectures from Merck, Lilly, and Orion Pharma. All other authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0002-6295-557X
                http://orcid.org/0000-0001-8821-8925
                Article
                PONE-D-19-11514
                10.1371/journal.pone.0220202
                6657874
                31344073
                d19f29c5-b29a-40c0-8dfb-109aba7a5e06
                © 2019 Haijanen et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 25 April 2019
                : 10 July 2019
                Page count
                Figures: 1, Tables: 2, Pages: 12
                Funding
                Funded by: Mary and Georg C. Ehrnrooth Foundation
                Award Recipient :
                Funded by: EVO foundation (government research grant)
                Award Recipient :
                The primary investigator P.S. has received funding for this study from Mary and Georg C. Ehrnrooth Foundation and EVO foundation (government research grant). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Pharmacology
                Drugs
                Antimicrobials
                Antibiotics
                Biology and Life Sciences
                Microbiology
                Microbial Control
                Antimicrobials
                Antibiotics
                Medicine and Health Sciences
                Gastroenterology and Hepatology
                Appendicitis
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Digestive System Procedures
                Appendectomy
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Medicine and Health Sciences
                Health Care
                Health Care Facilities
                Hospitals
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Laparoscopy
                Social Sciences
                Economics
                Labor Economics
                Salaries
                Social Sciences
                Economics
                Economic Analysis
                Custom metadata
                Data cannot be shared publicly as data contain potentially sensitive patient information, and written permission to publicly share data was not received from each patient. Data can be made available to qualified researchers upon request; data request may be sent to Eliisa Löyttyniemi, University of Turku ( eliisa.loyttyniemi@ 123456utu.fi ) or the corresponding author.

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                Uncategorized

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