Assessing micro- vs macro-costing approaches for treating appendicitis in children with appendicectomy or non-operatively.

OBJECTIVES: We conducted a health economic sub-study within a feasibility RCT comparing a non-operative treatment pathway as an alternative to appendicectomy for the treatment of uncomplicated acute appendicitis in children. The objectives were to understand and assess data collection tools and methods and to determine indicative costs and benefits assessing the feasibility of conducting a full economic evaluation within the definitive trial. METHODS: We compared different methods of estimating treatment costs including micro-costing, hospital administrative data (PLICS) and health system (NHS) reference costs. We compared two different HRQoL instruments (CHU-9D and EQ-5D-5L) in terms of data completeness and sensitivity to change over time, including potential ceiling effects. We also explored how the timing of data collection and duration of the analysis could affect QALYs (Quality Adjusted Life Years) and the results of the cost-utility analysis (CUA) within the future RCT. RESULTS: Using a micro-costing approach, the total per treatment costs were in alignment with hospital administrative data (PLICS). Average health system reference cost data (macro-costing using NHS costs) could potentially underestimate these treatment costs, particularly for non-operative treatment. Costs incurred following hospital discharge in the primary care setting were minimal, and limited family borne costs were reported by parents/carers. While both HRQoL instruments performed relatively well, our results highlight the problem of ceiling effect and the importance of the timing of data collection and the duration of the analysis in any future assessment using QALYs and CUA. CONCLUSIONS: We highlighted the importance of obtaining accurate individual-patient cost data when conducting economic evaluations. Our results suggest that timing of data collection and duration of the assessment are important considerations when evaluating cost-effectiveness and reporting cost per QALY. CLINICAL TRIAL REGISTRATION: Current Controlled Trials ISRCTN15830435.

Cost-Effectiveness of Laparoscopic and Open Pediatric Inguinal Hernia Repair.

Aim: Laparoscopic inguinal hernia (IH) repair is an alternative to open surgery. A potential advantage of laparoscopic repair is prevention of contralateral metachronous hernia although some studies report higher recurrence rate. We aim to determine the cost-effectiveness of open versus laparoscopic IH repair taking into account metachronous and recurrence rates. Methods: Retrospective single-center study of children (<5 years) undergoing elective open or laparoscopic repair for a unilateral IH between February 2018 and October 2019. Ten cases in each of four groups were included (open day case, open overnight, laparoscopic day case, and laparoscopic overnight). Cases incurring a higher cost due to comorbidities or additional procedure were excluded. Patient-level information and costing system data were obtained from the hospital finance. Mean (standard deviation [SD]) procedural cost was compared for open and laparoscopic procedures. A financial model was created factoring metachronous and recurrent rates. Results: Cost of open day case repair was £1866.24 (SD: 311.15) compared with £2210.13 (SD: 391.36) for day case laparoscopic repair. For overnight repair, cost of open was £2442.82 (SD: 497.05) compared with £2585.35 (SD: 384.66) for laparoscopic. On calculating the cost-effectiveness point using the difference in metachronous and recurrence rate between the two procedures, laparoscopic is more cost-effective than open day case repair at 18.43%. For overnight repair, the difference rate is 5.84%. Conclusion: Our data suggest that based on metachronous and recurrence rates in the current literature, laparoscopic IH repair is more cost-effective than open repair for cases requiring overnight stay, whereas for day case procedures open IH repair is more cost-effective.

Conservative treatment for uncomplicated appendicitis in children: the CONTRACT feasibility study, including feasibility RCT.

BACKGROUND: Although non-operative treatment is known to be effective for the treatment of uncomplicated acute appendicitis in children, randomised trial data comparing important outcomes of non-operative treatment with those of appendicectomy are lacking. OBJECTIVES: The objectives were to ascertain the feasibility of conducting a multicentre randomised controlled trial comparing the clinical effectiveness and cost-effectiveness of a non-operative treatment pathway with appendicectomy for the treatment of uncomplicated acute appendicitis in children. DESIGN: This was a mixed-methods study, which included a feasibility randomised controlled trial, embedded and parallel qualitative and survey studies, a parallel health economic feasibility study and the development of a core outcome set. SETTING: This study was set in three specialist NHS paediatric surgical units in England. PARTICIPANTS: Children (aged 4-15 years) clinically diagnosed with uncomplicated acute appendicitis participated in the feasibility randomised controlled trial. Children, their families, recruiting clinicians and other health-care professionals involved in caring for children with appendicitis took part in the qualitative study. UK specialist paediatric surgeons took part in the survey. Specialist paediatric surgeons, adult general surgeons who treat children, and children and young people who previously had appendicitis, along with their families, took part in the development of the core outcome set. INTERVENTIONS: Participants in the feasibility randomised controlled trial were randomised to a non-operative treatment pathway (broad-spectrum antibiotics and active observation) or appendicectomy. MAIN OUTCOME MEASURES: The primary outcome measure was the proportion of eligible patients recruited to the feasibility trial. DATA SOURCES: Data were sourced from NHS case notes, questionnaire responses, transcribed audio-recordings of recruitment discussions and qualitative interviews. RESULTS: Overall, 50% (95% confidence interval 40% to 59%) of 115 eligible patients approached about the trial agreed to participate and were randomised. There was high acceptance of randomisation and good adherence to trial procedures and follow-up (follow-up rates of 89%, 85% and 85% at 6 weeks, 3 months and 6 months, respectively). More participants had perforated appendicitis than had been anticipated. Qualitative work enabled us to communicate about the trial effectively with patients and families, to design and deliver bespoke training to optimise recruitment and to understand how to optimise the design and delivery of a future trial. The health economic study indicated that the main cost drivers are the ward stay cost and the cost of the operation; it has also informed quality-of-life assessment methods for future work. A core outcome set for the treatment of uncomplicated acute appendicitis in children and young people was developed, containing 14 outcomes. There is adequate surgeon interest to justify proceeding to an effectiveness trial, with 51% of those surveyed expressing a willingness to recruit with an unchanged trial protocol. LIMITATIONS: Because the feasibility randomised controlled trial was performed in only three centres, successful recruitment across a larger number of sites cannot be guaranteed. However, the qualitative work has informed a bespoke training package to facilitate this. Although survey results suggest adequate clinician interest to make a larger trial possible, actual participation may differ, and equipoise may have changed over time. CONCLUSIONS: A future effectiveness trial is feasible, following limited additional preparation, to establish appropriate outcome measures and case identification. It is recommended to include a limited package of qualitative work to optimise recruitment, in particular at new centres. FUTURE WORK: Prior to proceeding to an effectiveness trial, there is a need to develop a robust method for distinguishing children with uncomplicated acute appendicitis from those with more advanced appendicitis, and to reach agreement on a primary outcome measure and effect size that is acceptable to all stakeholder groups involved. TRIAL REGISTRATION: Current Controlled Trials ISRCTN15830435. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 10. See the NIHR Journals Library website for further project information.

Appendicitis is usually treated with an operation to remove the appendix. But we have learned, from other research, that some children with appendicitis may not need an operation, and could be treated with antibiotics instead. To find out how these two different treatments compare with one another, we need to do a big study. First, though, we need to see if doing that kind of study would even be possible (or 'feasible'). We carried out a feasibility study that had several parts. First, we did a small study with children who had appendicitis, whereby children were randomly allocated to have either antibiotics or an operation, with an equal chance of having either treatment. Second, we asked parents and health-care staff about why they wanted, or did not want, to take part in that small study. This helped us to understand how to make a bigger future study as acceptable as possible to children, families and surgeons. Third, we asked parents, patients and surgeons what they think are the most important things ­ or 'outcomes' ­ we should look at in future research on children who have appendicitis. From that, we developed a list of outcomes that should be included in our future big study, so we can be certain that the research we do is likely to help parents and surgeons. Overall, we established that a future big study is feasible and we have plenty of information to help us with how to plan it best, so that it has the greatest possible chance of success. We were also guided in all of these steps of the research by a group of parents, children and young people, some of whom had appendicitis and some of whom did not.

The impact of trisomy 21 on epidemiology, management, and outcomes of congenital duodenal obstruction: a population-based study.

PURPOSE: Congenital duodenal obstruction (CDO) is associated with trisomy 21 (T21), or Down's syndrome, in around a third of infants. The aim of this study was to explore the impact of T21 on the epidemiology, management, and outcomes of infants with CDO. METHODS: Data were prospectively collected from specialist neonatal surgical centres in the United Kingdom over a 12 month period from March 2016 using established population-based methodology for all babies with CDO. Infants with T21 were compared to those without any chromosomal anomaly. RESULTS: Of 102 infants with CDO that underwent operative repair, T21 was present in 33 [32% (95% CI 23-41%)] babies. Cardiac anomalies were more common in those with T21 compared to those without a chromosomal anomaly (91 vs 17%, p < 0.001), whereas associated gastrointestinal anomalies were less common in infants with T21 (3 vs 12%, p = 0.03). Surgical management was not influenced by T21. Time to achieve full enteral feed, need for repeat related surgery, and mortality were similar between groups. Infants with T21 had a longer median initial inpatient stay (23 vs 16.5 days, p = 0.02). CONCLUSIONS: Infants with T21 have a higher incidence of cardiac anomalies and a longer initial inpatient stay; however, it does not change CDO management or outcomes. This information is important for prenatal and postnatal counselling of parents of infants with CDO and T21.

Health economics and quality of life in a feasibility RCT of paediatric acute appendicitis: a protocol study.

BACKGROUND: Acute appendicitis is one of the most common acute surgical emergencies in children and accounts for an annual cost of approximately £50 million to the National Health Service. Investigating alternative treatment options offers the best prospect of enhancing the quality of care for patients and potential opportunities for cost savings through better allocative efficiency. A feasibility randomised controlled trial (RCT) comparing a non-operative treatment pathway with appendicectomy for children with acute uncomplicated appendicitis is underway (CONTRACT feasibility RCT). AIMS: The prime objective of this economic substudy conducted alongside the CONTRACT feasibility RCT is to better understand and assess: (1) cost data collection tools and cost drivers by identifying patients' pathways and (2) patient quality of life by assessing alternative paediatric health-related quality of life (HRQoL) instruments. Outcomes from this study will inform a future efficacy RCT assessing the effectiveness and cost-effectiveness of non-operative treatment pathway for the treatment of acute uncomplicated appendicitis in children. METHODS: The economic substudy will use individual-level data and will be conducted from the health system perspective over the study's 6-month follow-up period. Microcosting will include health resource and service use, while potential benefits acquired will be measured using the HRQoL measures, Child Health Utility 9D (CHU-9D) and Euroqol-5 dimensions and 5 levels (EQ-5D-5L). We will assess the appropriateness of using the cost per quality-adjusted life year framework in the future RCT, as well as testing and identifying the most suitable HRQoL instrument. CONCLUSIONS: The outcomes of the investigational economic substudy will be used to inform the design of our future definitive RCT. However, the result from this economic study will also provide a detailed description and account of the issues inherent in paediatric Economic Evaluations Alongside Clinical Trials with an emphasis on costing methods of interventions taking place in secondary care settings. TRIAL REGISTRATION NUMBER: ISRCTN1583043.

CONTRACT Study - CONservative TReatment of Appendicitis in Children (feasibility): study protocol for a randomised controlled Trial.

BACKGROUND: Currently, the routine treatment for acute appendicitis in the United Kingdom is an appendicectomy. However, there is increasing scientific interest and research into non-operative treatment of appendicitis in adults and children. While a number of studies have investigated non-operative treatment of appendicitis in adults, this research cannot be applied to the paediatric population. Ultimately, we aim to perform a UK-based multicentre randomised controlled trial (RCT) to test the clinical and cost effectiveness of non-operative treatment of acute uncomplicated appendicitis in children, as compared with appendicectomy. First, we will undertake a feasibility study to assess the feasibility of performing such a trial. METHODS/DESIGN: The study involves a feasibility RCT with a nested qualitative research to optimise recruitment as well as a health economic substudy. Children (aged 4-15 years inclusive) diagnosed with acute uncomplicated appendicitis that would normally be treated with an appendicectomy are eligible for the RCT. Exclusion criteria include clinical/radiological suspicion of perforated appendicitis, appendix mass or previous non-operative treatment of appendicitis. Participants will be randomised into one of two arms. Participants in the intervention arm are treated with antibiotics and regular clinical assessment to ensure clinical improvement. Participants in the control arm will receive appendicectomy. Randomisation will be minimised by age, sex, duration of symptoms and centre. Children and families who are approached for the RCT will be invited to participate in the embedded qualitative substudy, which includes recording of recruitment consultants and subsequent interviews with participants and non-participants and their families and recruiters. Analyses of these will inform interventions to optimise recruitment. The main study outcomes include recruitment rate (primary outcome), identification of strategies to optimise recruitment, performance of trial treatment pathways, clinical outcomes and safety of non-operative treatment. We have involved children, young people and parents in study design and delivery. DISCUSSION: In this study we will explore the feasibility of performing a full efficacy RCT comparing non-operative treatment with appendicectomy in children with acute uncomplicated appendicitis. Factors determining success of the present study include recruitment rate, safety of non-operative treatment and adequate interest in the future RCT. Ultimately this feasibility study will form the foundation of the main RCT and reinforce its design. TRIAL REGISTRATION: ISRCTN15830435 . Registered on 8 February 2017.

Current Research on the Epidemiology, Pathogenesis, and Management of Necrotizing Enterocolitis.

Despite decades of research on necrotizing enterocolitis, we still do not fully understand the pathogenesis of the disease, or how to prevent or how to treat it. However, as a result of recent significant advances in the microbiology, molecular biology, and cell biology of the intestine of preterm infants and infants with necrotizing enterocolitis, there is some hope that research into this devastating disease will yield some important translation into effective prevention, more rapid diagnosis, and novel therapies.

Active observation versus interval appendicectomy after successful non-operative treatment of an appendix mass in children (CHINA study): an open-label, randomised controlled trial.

BACKGROUND: Despite a scarcity of supporting evidence, most surgeons recommend routine interval appendicectomy after successful non-operative treatment of an appendix mass in children. We aimed to compare routine interval appendicectomy with active observation. METHODS: We enrolled participants in the CHildren's INterval Appendicectomy (CHINA) study, a multicentre, open-label, randomised controlled study at 19 specialist paediatric surgery centres, 17 of which were in the UK, one in Sweden, and one in New Zealand. 106 children aged 3-15 years were assigned (1:1) by weighted minimisation to interval appendicectomy or active observation with minimisation for age, trial centre, sex, and presence of a faecolith on imaging. Eligible children had acute appendicitis with an appendix mass and were successfully treated without appendicectomy or other surgical intervention. Children were excluded from the study if they had coexisting gastrointestinal disease or had a substantial coexisting medical condition or immune defect. Because of the nature of the interventions, blinding was not possible. The primary outcome was the proportion of children developing histologically proven recurrent acute appendicitis or a clinical diagnosis of recurrent appendix mass within 1 year of enrolment after successful non-operative treatment of appendix mass (active observation group) and incidence of severe complications related to interval appendicectomy. Data were analysed on an intention-to-treat basis. This study is registered with ISRCTN, number 93815412. FINDINGS: Between Aug 8, 2011, and Dec 31, 2014, we randomly assigned 106 patients, 52 patients to interval appendicectomy and 54 to active observation. Two children in the interval appendicectomy group were withdrawn due to withdrawal of consent; two in the active observation group were withdrawn because they became ineligible after allocation. Six children under active observation had histologically proven recurrent acute appendicitis. Three children in the interval appendicectomy group had severe complications. Thus, the proportion of children with histologically proven recurrent acute appendicitis under active observation was 12% (95% CI 5-23) and the proportion of children with severe complications related to interval appendicectomy was 6% (95% CI 1-17). INTERPRETATION: More than three-quarters of children could avoid appendicectomy during early follow-up after successful non-operative treatment of an appendix mass. Although the risk of complications after interval appendicectomy is low, complications can be severe. Adoption of a wait-and-see approach, reserving appendicectomy for those who develop recurrence or recurrent symptoms, results in fewer days in hospital, fewer days away from normal daily activity, and is cheaper than routine interval appendicectomy. These high-quality data will allow clinicians, parents, and children to make an evidence-based decision regarding the justification for interval appendicectomy. FUNDING: BUPA Foundation.

A standardised investigative strategy prior to revisional oesophageal surgery in children: High incidence of unexpected findings.

BACKGROUND/PURPOSE: Revisional oesophageal reconstructive surgery carries uncommon and unusual risks related to previous surgery. To provide maximum anatomical detail and facilitate successful outcome, we report a standardised pre-operative investigative strategy for all such patients. METHODS: Prospective 8-month cohort study following the introduction of this strategy. All patients underwent high resolution thoracic contrast CT scan and micro-laryngo-bronchoscopy by a paediatric ENT surgeon in addition to upper gastrointestinal contrast study, oesophagoscopy, and echocardiogram. RESULTS: Seven children (median age 5.6 months [range 2.2-60]) completed the pathway. Four were referred with recurrence of a previously divided tracheo-oesophageal fistula (3 congenital, 1 acquired) and 3 (all with oesophagostomy) for oesophageal replacement for congenital isolated oesophageal atresia (OA, n=1) and failed repair of OA with distal TOF with wide gap (n=2). Overall, unanticipated findings were demonstrated in 6/7 children and comprised severe tracheomalacia and right main bronchus stenosis requiring aortopexy (n=1), vocal cord palsy (n=2), extensive mediastinal rotation (n=1), proximal tracheal diverticulum (n=1), severe subglottic stenosis requiring airway reconstruction (n=1), proximal tracheal diverticulum (n=1), right sided aortic arch (n=1) and left sided aortic arch (previously reported to be right sided, n=1). CONCLUSIONS: This standardised approach for this complex group of patients reveals a high incidence of unexpected anatomical and functional anomalies with significant surgical and possible medico-legal implications. We recommend these investigations during the pre-operative work-up prior to all revisional oesophageal surgery.

Cost-effectiveness of laparoscopic versus open pyloromyotomy.

BACKGROUND: Infantile hypertrophic pyloric stenosis can be corrected by either open (OP) or laparoscopic pyloromyotomy (LP). LP may provide clinical benefits of reduced time to postoperative full feeds and reduced postoperative inpatient stay, but the cost effectiveness is not known. Our aim was to compare the cost effectiveness of laparoscopic and open pyloromyotomy. METHODS: OP and LP were compared in a multicenter randomized double-blind controlled trial, for which the primary outcomes were time to full feeds and time to discharge. In order to undertake a detailed cost analysis, we assigned costs, calculated on an individual patient basis, to laboratory costs, imaging, medical staff, medication, ward, operative, and outpatient appointments for 74 patients recruited from one of the participating centers. Data (mean ± SEM) were compared using linear regression analysis, adjusting for the minimization criteria used in the trial. RESULTS: Operation costs were similar between the two groups ($3,276 ± $244 LP versus $3,535 ± $152 OP). A shorter time to full feeds and shorter hospital stay in LP versus OP patients resulted in a highly significant difference in ward costs ($2,650 ± $126 LP versus $3,398 ± $126 OP; P = .001) and a small difference in other costs. Overall, LP patients were $1,263 (95% confidence interval $395-$2,130; P = .005) less expensive to treat than OP patients. Sensitivity analyses of laparoscopic hardware usage and of incomplete pyloromyotomy indicated that LP was consistently less expensive than OP. CONCLUSIONS: LP is a cost-effective alternative to OP as it delivers improved clinical outcome at a lower price.

Surgery for hydrocele in children-an avoidable excess?

BACKGROUND: There is little consensus over the optimal timing of ligation of a patent processus vaginalis (PPV) in boys with hydrocele. We hypothesized that a proportion of procedures may be unnecessary because they are performed at an age before which the PPV may be expected to close spontaneously. Such excess may expose the child to unnecessary surgery and have significant cost implications. METHODS: A systematic literature review relating to timing of PPV ligation and a population-based study to define number of PPV ligations performed annually in England and age at surgery were conducted. RESULTS: Most hydroceles resolve before 2 years of age, but their natural history beyond this age is poorly documented. Current guidelines recommend PPV ligation at 2 years of age. An average of 2878 operations for hydrocele is performed per year in children in England. Commonest age at repair is 2 years. There are no randomized controlled trials comparing PPV ligation with an observational nonoperative approach. CONCLUSIONS: The natural history of hydrocele is poorly documented beyond the age of 2 years. There is no good evidence to support current practice. Delaying surgery may reduce the number of procedures necessary without increasing morbidity. A prospective study to investigate this is warranted.