International Core Outcome Set for Acute Simple Appendicitis in Children: Results of a Systematic Review, Delphi Study, and Focus Croups With Young People.

OBJECTIVE: To develop an international core outcome set (COS), a minimal collection of outcomes that should be measured and reported in all future clinical trials evaluating treatments of acute simple appendicitis in children. SUMMARY OF BACKGROUND DATA: A previous systematic review identified 115 outcomes in 60 trials and systematic reviews evaluating treatments for children with appendicitis, suggesting the need for a COS. METHODS: The development process consisted of 4 phases: (1) an updated systematic review identifying all previously reported outcomes, (2) a 2-stage international Delphi study in which parents with their children and surgeons rated these outcomes for inclusion in the COS, (3) focus groups with young people to identify missing outcomes, and (4) international expert meetings to ratify the final COS. RESULTS: The systematic review identified 129 outcomes which were mapped to 43 unique outcome terms for the Delphi survey. The first-round included 137 parents (8 countries) and 245 surgeons (10 countries), the second-round response rates were 61% and 85% respectively, with 10 outcomes emerging with consensus. After 2 young peoples' focus groups, 2 additional outcomes were added to the final COS (12): mortality, bowel obstruction, intraabdominal abscess, recurrent appendicitis, complicated appendicitis, return to baseline health, readmission, reoperation, unplanned appendectomy, adverse events related to treatment, major and minor complications. CONCLUSION: An evidence-informed COS based on international consensus, including patients and parents has been developed. This COS is recommended for all future studies evaluating treatment ofsimple appendicitis in children, to reduce heterogeneity between studies and facilitate data synthesis and evidence-based decision-making.

Hypothermic Machine Perfusion as a National Standard Preservation Method for Deceased Donor Kidneys.

BACKGROUND: Recently, continuous nonoxygenated hypothermic machine perfusion (HMP) has been implemented as standard preservation method for deceased donor kidneys in the Netherlands. This study was designed to assess the effect of the implementation of HMP on early outcomes after transplantation. METHODS: Kidneys donated in the Netherlands in 2016 and 2017 were intended to be preserved by HMP. A historical cohort (2010-2014) preserved by static cold storage was chosen as the control group. Primary outcome was delayed graft function (DGF). Additional analyses were performed on safety, graft function, and survival up until 2 y after transplantation. RESULTS: Data were collected on 2493 kidneys. Analyses showed significantly more donation after circulatory death, preemptive transplantation, and retransplants in the project cohort. Of the 681 kidneys that were transplanted during the project, 81% were preserved by HMP. No kidneys were discarded due to HMP-related complications. DGF occurred in 38.2% of the project cohort versus 43.7% of the historical cohort (P < 0.001), with a significantly shorter duration within the project cohort (7 versus 9 d, P = 0.003). Multivariate regression analysis showed an odds ratio of 0.69 (95% confidence interval, 0.553-0.855) for the risk of DGF when using HMP compared with cold storage (P = 0.001). There was no significant difference in kidney function, graft survival, and recipient survival up until 2 y posttransplantation. CONCLUSIONS: This study showed that HMP as a standard preservation method for deceased donor kidneys is safe and feasible. HMP was associated with a significant reduction of DGF.

Establishing a core outcome set for treatment of uncomplicated appendicitis in children: study protocol for an international Delphi survey.

INTRODUCTION: Appendicitis is a global disease affecting roughly 1 in every 12 people in the world, with the highest incidence between ages 10 and 19 years. To date, a wide variety of health outcomes have been reported in randomised controlled trials and meta-analyses evaluating treatments for appendicitis. This is especially the case in studies comparing non-operative treatment with operative treatment. A set of standard outcomes, to be reported in all future trials, is needed to allow for adequate comparison and interpretation of clinical trial results and to make data pooling possible. This protocol describes the development of such a global core outcome set (COS) to allow unified reporting of treatment interventions in children with acute uncomplicated appendicitis. METHODS AND ANALYSIS: We use current international standard methodology for the development and reporting of this COS. Its development consists of three phases: (1) an update of the most recent systematic review on outcomes reported in uncomplicated paediatric appendicitis research to identify additional outcomes, (2) a three-step global Delphi study to identify a set of core outcomes for which there is consensus between parents and (paediatric) surgeons and (3) an expert meeting to finalise the COS and its definitions. Children and young people will be involved through their parents during phase 2 and will be engaged directly using a customised face-to-face approach. ETHICS AND DISSEMINATION: The medical research ethics committee of the Academic Medical Center Amsterdam has approved the study. Each participating country/research group will ascertain ethics board approval. Electronic informed consent will be obtained from all participants. Results will be presented in peer-reviewed academic journals and at (international) conferences. TRIAL REGISTRATION NUMBER: COMET registration: 1119.

Initial non-operative management of uncomplicated appendicitis in children: a protocol for a multicentre randomised controlled trial (APAC trial).

INTRODUCTION: Based on epidemiological, immunological and pathology data, the idea that appendicitis is not necessarily a progressive disease is gaining ground. Two types are distinguished: simple and complicated appendicitis. Non-operative treatment (NOT) of children with simple appendicitis has been investigated in several small studies. So far, it is deemed safe. However, its effectiveness and effect on quality of life (QoL) have yet to be established in an adequately powered randomised trial. In this article, we provide the study protocol for the APAC (Antibiotics versus Primary Appendectomy in Children) trial. METHODS AND ANALYSIS: This multicentre, non-inferiority, randomised controlled trial randomises children aged 7-17 years with imaging-confirmed simple appendicitis between appendectomy and NOT. Patients are recruited in 15 hospitals. The intended sample size, based on the primary outcome, rate of complications and a non-inferiority margin of 5%, is 334 patients.NOT consists of intravenous antibiotics for 48-72 hours, daily blood tests and ultrasound follow-up. If the patient meets the predefined discharge criteria, antibiotic treatment is continued orally at home. Primary outcome is the rate of complications at 1-year follow-up. An independent adjudication committee will assess all complications and their relation to the allocated treatment. Secondary outcomes include, but are not limited to, delayed appendectomies, QoL, pain and (in)direct costs.The primary outcome will be analysed both according to the intention-to-treat principle and the per-protocol principle, and is presented with a one-sided 97.5% CI. We will use multiple logistic and linear regression for binary and continuous outcomes, respectively, to adjust for stratification factors. ETHICS AND DISSEMINATION: The protocol has been approved by the Medical Ethics Review Committee of the Academic Medical Center, Amsterdam. Data monitoring is performed by an independent institute and a Data Safety Monitoring Board has been assigned. Results will be presented in peer-reviewed academic journals and at (international) conferences. TRIAL REGISTRATION NUMBER: NCT02848820; NTR5977; Pre-results.

Midget submarine for diagnosing midgut lesions in children.

Anaemia due to obscure gastrointestinal blood loss remains a challenge to the clinician, especially when blood loss is severe enough to result in profound anaemia while further investigations fail to identify the cause of bleeding. A description of how wireless capsule endoscopy revealed a bleeding jejunal haemangioma in a 2.5-year-old boy with recurrent anaemia is given. New techniques such as wireless capsule endoscopy and double balloon enteroscopy are feasible and provide a valuable adjunct to the diagnostic investigation of children with obscure enteral blood loss.