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Association of Nonoperative Management Using Antibiotic Therapy vs Laparoscopic Appendectomy With Treatment Success and Disability Days in Children With Uncomplicated Appendicitis

Educational Objective
To understand differences in outcomes of appendicitis when the treatment approach is chosen by patients and their families.
1 Credit CME
Key Points

Question  Among children with uncomplicated appendicitis, what is the success rate of an initial nonoperative management strategy with antibiotic therapy alone and is this approach associated with fewer disability days compared with an initial strategy of urgent laparoscopic surgery?

Findings  In this nonrandomized controlled intervention study that used propensity score weighting and included 1068 children, 67.1% of the children who received initial nonoperative management with antibiotics alone did not require appendectomy by 1 year. Compared with a strategy of urgent surgery (≤12 hours of admission), initial management with antibiotics alone was significantly associated with fewer patient disability days at 1 year (6.6 days vs 10.9 days).

Meaning  Among children with uncomplicated appendicitis, an initial nonoperative management strategy with antibiotics was successful for most children and, compared with urgent surgery, was associated with significantly fewer disability days at 1 year. However, the prespecified thresholds for success rate of nonoperative management and disability days were not met, and there were substantial missing data.

Abstract

Importance  Nonoperative management with antibiotics alone has the potential to treat uncomplicated pediatric appendicitis with fewer disability days than surgery.

Objective  To determine the success rate of nonoperative management and compare differences in treatment-related disability, satisfaction, health-related quality of life, and complications between nonoperative management and surgery in children with uncomplicated appendicitis.

Design, Setting, and Participants  Multi-institutional nonrandomized controlled intervention study of 1068 children aged 7 through 17 years with uncomplicated appendicitis treated at 10 tertiary children’s hospitals across 7 US states between May 2015 and October 2018 with 1-year follow-up through October 2019. Of the 1209 eligible patients approached, 1068 enrolled in the study.

Interventions  Patient and family selection of nonoperative management with antibiotics alone (nonoperative group, n = 370) or urgent (≤12 hours of admission) laparoscopic appendectomy (surgery group, n = 698).

Main Outcomes and Measures  The 2 primary outcomes assessed at 1 year were disability days, defined as the total number of days the child was not able to participate in all of his/her normal activities secondary to appendicitis-related care (expected difference, 5 days), and success rate of nonoperative management, defined as the proportion of patients initially managed nonoperatively who did not undergo appendectomy by 1 year (lowest acceptable success rate, ≥70%). Inverse probability of treatment weighting (IPTW) was used to adjust for differences between treatment groups for all outcome assessments.

Results  Among 1068 patients who were enrolled (median age, 12.4 years; 38% girls), 370 (35%) chose nonoperative management and 698 (65%) chose surgery. A total of 806 (75%) had complete follow-up: 284 (77%) in the nonoperative group; 522 (75%) in the surgery group. Patients in the nonoperative group were more often younger (median age, 12.3 years vs 12.5 years), Black (9.6% vs 4.9%) or other race (14.6% vs 8.7%), had caregivers with a bachelor’s degree (29.8% vs 23.5%), and underwent diagnostic ultrasound (79.7% vs 74.5%). After IPTW, the success rate of nonoperative management at 1 year was 67.1% (96% CI, 61.5%-72.31%; P = .86). Nonoperative management was associated with significantly fewer patient disability days at 1 year than did surgery (adjusted mean, 6.6 vs 10.9 days; mean difference, −4.3 days (99% CI, −6.17 to −2.43; P < .001). Of 16 other prespecified secondary end points, 10 showed no significant difference.

Conclusion and Relevance  Among children with uncomplicated appendicitis, an initial nonoperative management strategy with antibiotics alone had a success rate of 67.1% and, compared with urgent surgery, was associated with statistically significantly fewer disability days at 1 year. However, there was substantial loss to follow-up, the comparison with the prespecified threshold for an acceptable success rate of nonoperative management was not statistically significant, and the hypothesized difference in disability days was not met.

Trial Registration  ClinicalTrials.gov Identifier: NCT02271932

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Article Information

Corresponding Author: Peter C. Minneci, MD, MHSc, Center for Surgical Outcomes Research, Abigail Wexner Research Institute at Nationwide Children’s Hospital, 700 Children’s Dr, FB 3A.3, Columbus, OH 43205 (peter.minneci@nationwidechildrens.org).

Accepted for Publication: June 3, 2020.

Published Online: July 27, 2020. doi:10.1001/jama.2020.10888

Author Contributions: Dr Minneci had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Minneci, Hade, Saito, Gadepalli, Kohler, Sato, Lal, Kabre, Fallat, Cooper, Deans.

Acquisition, analysis, or interpretation of data: Minneci, Hade, Lawrence, Sebastião, Saito, Mak, Hirschl, Gadepalli, Helmrath, Kohler, Leys, Sato, Lal, Landman, Kabre, Fallat, Cooper.

Drafting of the manuscript: Minneci, Hade, Lal, Deans.

Critical revision of the manuscript for important intellectual content: Minneci, Hade, Lawrence, Sebastião, Saito, Mak, Hirschl, Gadepalli, Helmrath, Kohler, Leys, Sato, Lal, Landman, Kabre, Fallat, Cooper, Deans.

Statistical analysis: Hade, Sebastião, Gadepalli, Cooper.

Obtained funding: Minneci, Deans.

Administrative, technical, or material support: Minneci, Hade, Lawrence, Sebastião, Hirschl, Gadepalli, Helmrath, Kohler, Sato, Lal, Kabre.

Supervision: Minneci, Hade, Hirschl, Helmrath, Sato, Lal, Landman, Kabre, Cooper, Deans.

Other - site principal investigator: Saito.

Conflict of Interest Disclosures: Dr Minneci reported grants from PCORI during the conduct of the study. Dr Hade reported grants from PCORI during the conduct of the study; grants from NIH, grants from Smart Columbus, and grants from PCORI/PCORnet outside the submitted work. Dr Saito reported grants from PCORI during the conduct of the study; grants from AHRQ outside the submitted work. Dr Mak reported grants from PCORI during the conduct of the study; grants from Thrasher outside the submitted work. Dr Gadepalli reported grants from PCORI during the conduct of the study. Dr Sato reported grants from PCORI during the conduct of the study. Dr Cooper reported grants from PCORI during the conduct of the study. Dr Deans reported grants from PCORI during the conduct of the study. No other disclosures were reported.

Funding/Support: This study is funded by award CER-1507-31325 from PCORI, an independent, nonprofit organization authorized by the US Congress in 2010. This project is also supported by grant UL1TR001070 from the National Center for Advancing Translational Sciences.

Role of the Funder/Sponsor: Funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Group Information: Gail Besner, MD, Nationwide Children’s Hospital; Jessica Kandel, MD, University of Chicago Medicine–Comer Children’s Hospital; Frederick Rescorla, MD, Riley Children’s Hospital; Marleta Reynolds, MD; Ann & Robert Lurie Children’s Hospital of Chicago; Daniel von Allmen, MD, Cincinnati Children’s Hospital and Medical Center; and Brad Warner, MD, St Louis Children’s Hospital; Cynthia Downard, MD, University of Louisville School of Medicine; Beth Rymeski, MD, Cincinnati Children’s Hospital and Medical Center; Julia Grabowksi, MD, Ann & Robert Lurie Children’s Hospital of Chicago; Peter C. Minneci, MD, MHSc, Nationwide Children’s Hospital, Columbus, Ohio; Jacqueline M. Saito, MD, Washington University School of Medicine, St Louis, Missouri; Grace Z. Mak, MD, University of Chicago; Ronald B. Hirschl, MD, University of Michigan, Ann Arbor; Samir Gadepalli, MD, MBA, University of Michigan, Ann Arbor; Michael A. Helmrath, MD, University of Cincinnati College of Medicine; Jonathan E. Kohler, MD, University of Wisconsin, Madison; Charles M. Leys, MD, University of Wisconsin, Madison; Thomas T. Sato, MD, Medical College of Wisconsin, Milwaukee; Dave R. Lal, MD, Medical College of Wisconsin, Milwaukee; Matthew P. Landman, MD, Indiana University School of Medicine, Indianapolis; Rashmi Kabre, MD, Northwestern University Feinberg School of Medicine, Chicago; Mary E. Fallat, MD, University of Louisville School of Medicine, Louisville, Kentucky; and Katherine J. Deans, MD, MHSc, Nationwide Children’s Hospital, Columbus. None were compensated for their role in the study.

Disclaimer: The content of this work is solely the responsibility of the authors and does not necessarily represent the official views of PCORI, its Board of Governors or Methodology Committee, the National Center for Advancing Translational Sciences or the National Institutes of Health.

Data Sharing Statement: See Supplement 3.

Additional Contributions: We thank our multidisciplinary stakeholder members for all of their input and dedication to this study: Patient or caregivers: Alyssa Gilman, Amanda Forystek, Endia McHenry, Sonya Sigers, Kaleb Boyd, Liz Sullivan, Maxwell Blom, Melissa R. Blom, Lorelei Moulin, Darcy Moulin, Nicholas Hawke, Kimberly Hawke, William Hawke, Nicolas Valdes, Lisa Valdes, Maurilio Valdes, Nolan Chehak, LuAnne Farr, Joshua Montalvo, Illuminado Castellano, Rheya Wheeler, Cherie Caldwell, Robert Rohloff, Samantha Schlaeppi, Tanner Goodman, Lisa Shrader, William Blake Godwin, Diana Godwin, Trinity Patten, Rebeccah Abanukam, Aubrey K. Gibson, Aria K. Gibson, Jason Gibson, Christy L. McDonald, and Bobby J. McDonald Jr; Nationwide Children’s Hospital: R. Lawrence Moss, MD, Courtney Porter, RN, Kathryn Nuss, MD, Paul Seese, RN; Sean Gleeson, MD, MBA; University of Chicago Medicine: Alisa McQueen, MD; University of Louisville School of Medicine: Stephan Baum, MD; Ann & Robert Lurie Children’s Hospital of Chicago: Dana Aronson Schinasi, MD; Washington University: Gian Musarra, MD, Medical College of Wisconsin: Michael Levas, MD; and Darryl Robbins, DO, community physician, all of whom received a stipend for their participation. We also thank the following staff members on this project: Beth Fischer, PhD, and Karen Leonhart, BS, Nationwide Children’s Hospital; Jana Creps, University of Michigan–C.S. Mott Children’s Hospital; Michelle Knezevich, MS, Children’s Hospital of Milwaukee, who received no remuneration beyond their salaries.

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