Core Outcome Set for Necrotizing Enterocolitis Treatment Trials.

BACKGROUND AND OBJECTIVES: Variability in outcome reporting in necrotizing enterocolitis (NEC) treatment trials hinders conducting meta-analyses and implementing novel treatments. We aimed to develop a core outcome set (COS) for NEC treatment trials including outcome measures most relevant to patients and physicians, from NEC diagnosis to adulthood. METHODS: Clinicians and/or researchers from low-middle- and high-income countries were approached based on their scientific contributions to NEC literature, and patients and parents through local organizations. We presented participants with 45 outcomes used in NEC research, identified through a systematic review. To achieve consensus, outcomes were rated on a scale of 1 to 9 in 3 online Delphi rounds, and discussed at a final consensus meeting. RESULTS: Seventy-one participants from 25 countries completed all Delphi rounds, including 15 patients and family representatives. Thirteen outcomes reached consensus in one of the stakeholder groups and were included in the consensus meeting, 6 outcomes reached consensus in both groups. Twenty-seven participants from both high- and low-middle-income countries attended the online consensus meeting, including family representatives and NEC patients. After discussion and a final vote, 5 outcomes reached consensus to be included: mortality, NEC-related mortality, short bowel syndrome, quality of life, and neurodevelopmental impairment. CONCLUSIONS: This NEC COS includes 5 predominantly long-term outcomes agreed upon by clinicians, patients, and family representatives. Use of this international COS will help standardize outcome selection in clinical trials, ensure these are relevant to those most affected by NEC care, and, ultimately, improve the care of infants with NEC.

The Role of Nitrous Oxide in Minor Pediatric Procedures in the Emergency Department: A Systematic Review.

BACKGROUND: Pediatric patients undergoing minor, but painful procedures in an Emergency Department (ED) need adequate relief of pain and distress to prevent long term negative effects and adversely impact procedures. Inhaled nitrous oxide (N2O) is a needle-free pain management option. We conducted a systematic review to determine whether N2O is as effective as local anesthesia in minor procedures. The purpose of this study was to evaluate available evidence regarding analgesic effectiveness of N2O in pediatric patients. METHODS: We searched MEDLINE, Embase, Cochrane and Cinahl databases for controlled trials published in English with pediatric patients in an ED treated with N2O compared to local anesthesia and with pain as primary outcome. Adverse events was one of the secondary outcomes. The GRADE system was used to rate the overall quality of evidence. RESULTS: We included seven studies with a total of 371 patients. Two studies showed N2O was equally effective in pain treatment as local anesthesia. Five studies showed N2O combined with local anesthesia is more effective in reducing pain than local anesthesia alone. None of the included studies reported major adverse effects. The quality of evidence is low. CONCLUSIONS: N2O can have an important contribution in pain management, but should be combined with local anesthesia for optimal pain management in pediatric patients undergoing minor, but painful procedures in an ED. LEVEL OF EVIDENCE: IV.

Trends in Simple and Complex Appendicitis in Children and the Potential Correlation to Common Viral Pathogens-A Retrospective Cohort Study between 2010 and 2019 in The Netherlands.

The aim of this study was to evaluate the annual, seasonal and monthly trends in children with simple and complex appendicitis and their correlation to common viral pathogens in the Netherlands. A consecutive multicenter retrospective cohort study was performed between 2010 and 2019 including children (<18 years) surgically treated for appendicitis. The primary outcome was the distribution of children with simple and complex appendicitis per year, season and month. Relevant seasonal variation was defined as ≥5%. The secondary outcome was a positive correlation of the number of patients with simple and complex appendicitis to common viral pathogens (data anonymously provided by the Dutch Working Group on Clinical Virology from the Dutch Society for Clinical Microbiology (NVMM)). In total, 896 patients were included: N = 524 (58%) patients with simple and N = 372 (42%) with complex appendicitis. Of the children aged 0-5 years, 81% had complex appendicitis, versus 38% in 6-18 years (p < 0.001). An overall decline was demonstrated for both simple and complex appendicitis between 2010 and 2019. No seasonal variation was found for simple appendicitis. For complex appendicitis, the highest number of patients was found in spring, and lowest in summer (N = 372, spring 28.2 ± 5.1% versus summer 21.0 ± 5.8%, p = 0.011), but the variance was regarded as not relevant (<5% from baseline). A positive correlation was found between complex appendicitis with Adenovirus 40.41 (R = 0.356, 95%CI 0.045-0.604, p = 0.026) and simple appendicitis with Adenovirus NON 40.41 (R = 0.332, 95%CI 0.019-0.586, p = 0.039), but these correlations did not remain significant after a Bonferroni correction (p < 0.003). In conclusion, we found no relevant seasonal variation for simple or complex appendicitis, nor positive correlation with common viral pathogens.

Appendicitis and its associated mortality and morbidity in infants up to 3 months of age: A systematic review.

Background and Aims: Although appendicitis is rare in young infants, the reported mortality is high. Primary aim of this systematic review was to provide updated insights in the mortality and morbidity (postoperative complications, Clavien-Dindo grades I-IV) of appendicitis in infants ≤3 months of age. Secondary aims comprised the evaluation of patient characteristics, diagnostic work-up, treatment strategies, comorbidity, and factors associated with poor outcome. Methods: This systematic review was reported according to the PRISMA statement with a search performed in Pubmed, Embase and Web of Science (up to September 5th 2022). Original articles (published in English ≥1980) reporting on infants ≤3 months of age with appendicitis were included. Both patients with abdominal appendicitis and herniated appendicitis (such as Amyand's hernia) were considered. Data were provided descriptively. Results: In total, 131 articles were included encompassing 242 cases after identification of 4294 records. Overall, 184 (76%) of the 242 patients had abdominal and 58 (24%) had herniated appendicitis. Two-hundred (83%) of the patients were newborns (≤28 days) and 42 (17%) were infants between 29 days and ≤3 months of age. Either immediate, or after initial conservative treatment, 236 (98%) patients underwent surgical treatment. Some 168 (69%) patients had perforated appendicitis. Mortality was reported in 20 (8%) patients and morbidity in an additional 18 (8%). All fatal cases had abdominal appendicitis and fatal outcome was relatively more often reported in newborns, term patients, patients with relevant comorbidity, nonperforated appendicitis and those presented from home. Conclusion: Mortality was reported in 20 (8%) infants ≤3 months of age and additional morbidity in 18 (8%). All patients with fatal outcome had abdominal appendicitis. Several patient characteristics were relatively more often reported in infants with poor outcome and adequate monitoring, early recognition and prompt treatment may favour the outcome.

Development of an international core outcome set for treatment trials in necrotizing enterocolitis-a study protocol.

AIM: Necrotizing enterocolitis (NEC) is the most lethal disease of the gastrointestinal tract of preterm infants. New and existing management strategies need clinical evaluation. Large heterogeneity exists in the selection, measurement, and reporting of outcome measures in NEC intervention studies. This hampers meta-analyses and the development of evidence-based management guidelines. We aim to develop a Core Outcome Set (COS) for NEC that includes the most relevant outcomes for patients and physicians, from moment of diagnosis into adulthood. This COS is designed for use in NEC treatment trials, in infants with confirmed NEC. METHODS: This study is designed according to COS-STAD (Core Outcome Set-STAndards for Development) recommendations and the COMET (Core Outcome Measures in Effectiveness Trials) Initiative Handbook. We obtained a waiver from the Ethics Review Board and prospectively registered this study with COMET (Study 1920). We will approach 125 clinicians and/or researchers from low-middle and high-income countries based on their scientific output (using SCIVAL, a bibliometric tool). Patients and parents will be approached through local patient organisations. Participants will be separated into three panels, to assess differences in priorities between former patients and parents (1. lay panel), clinicians and researchers involved in the neonatal period (2. neonatal panel) and after the neonatal period (3. post-neonatal panel). They will be presented with outcomes currently used in NEC research, identified through a systematic review, in a Delphi process. Eligible outcome domains are also identified from the patients and parents' perspectives. Using a consensus process, including three online Delphi rounds and a final face-to-face consensus meeting, the COS will be finalised and include outcomes deemed essential to all stakeholders: health care professionals, parents and patients' representatives. The final COS will be reported in accordance with the COS-Standards for reporting (COS-STAR) statement. CONCLUSIONS: Development of an international COS will help to improve homogeneity of outcome measure reporting in NEC, will enable adequate and efficient comparison of treatment strategies, and will help the interpretation and implementation of clinical trial results. This will contribute to high-quality evidence regarding the best treatment strategy for NEC in preterm infants.

Management and outcome of high-risk neuroendocrine tumors of the appendix in children; A systematic review.

This study systematically reviewed the literature to investigate the value of secondary surgery for children with a high-risk neuroendocrine tumor (NET) of appendix. A systematic search was performed in PubMed, Embase and Web of Science. All randomized controlled trials, cohort studies, and case series reporting on the management and outcomes of patients (<20 years) with a histopathologically proven NET of the appendix were eligible for inclusion. Two authors independently selected eligible articles, assessed risk of bias, and extracted data. The outcomes of patients with a high-risk NET treated with secondary surgery were compared to those treated without secondary surgery. Primary outcomes were recurrence rate and disease-free survival. The literature search yielded 667 articles, of which 29 were included. These studies reported on 1112 patients, of whom 145 (13%) had high-risk NET. Heterogeneity between studies was large and risk of bias was serious in 26 and moderate in three studies. Secondary surgery after primary appendectomy was performed in 64 of 145 patients (44%). Length of follow-up ranged between 0 and 612 months. In both treatment groups no recurrences were reported, and thus disease-free survival was 100%. Based on current literature, the value of secondary surgery for pediatric high-risk NET of the appendix may be questioned. However, evidence is scarce, of low-quality, and heterogeneity between studies is large. Large international studies with adequate follow-up are needed to generate high-quality evidence on this topic.

Enhanced Th17 responses in the appendix of children with complex compared to simple appendicitis are associated with microbial dysbiosis.

Introduction: Appendicitis is one of the most common causes of acute abdominal surgery in children. The clinical course of appendicitis ranges from simple to complex appendicitis. The mechanisms underlying the heterogeneity of appendicitis in children remain largely unclear. Dysregulated T cell responses play an important role in several inflammatory diseases of the intestine, but the extend of T cell dysregulation in appendicitis in children is less well known. Methods: To characterize appendiceal T cells in simple and complex appendicitis we performed in-depth immunophenotyping of appendiceal-derived T cells by flow cytometry and correlated this to appendiceal-derived microbiota analyses of the same patient. Results: Appendix samples of twenty children with appendicitis (n = 8 simple, n = 12 complex) were collected. T cells in complex appendicitis displayed an increased differentiated phenotype compared to simple appendicitis, including a loss of both CD27 and CD28 by CD4+ T cells and to a lesser extent by CD8+ T cells. Frequencies of phenotypic tissue-resident memory CD69+CD4+ T cells and CD69+CD8+ T cells were decreased in children with complex compared to simple appendicitis, indicating disruption of local tissue-resident immune responses. In line with the increased differentiated phenotype, cytokine production of in particular IL-17A by CD4+ T cells was increased in children with complex compared to simple appendicitis. Furthermore, frequencies of IL-17A+ CD4+ T cells correlated with a dysregulation of the appendiceal microbiota in children with complex appendicitis. Conclusion: In conclusion, disruption of local T cell responses, and enhanced pro-inflammatory Th17 responses correlating to changes in the appendiceal microbiota were observed in children with complex compared to simple appendicitis. Further studies are needed to decipher the role of a dysregulated network of microbiota and Th17 cells in the development of complex appendicitis in children.

The potential of rectal swabs to differentiate simple and complex appendicitis in children with a microbiota-based test.

Currently, accurate biomarkers differentiating simple (phlegmonous) from complex (gangrenous and/or perforated) appendicitis in children are lacking. However, both types may potentially require different treatment strategies, and the search for diagnostic modalities remains warranted. Previously, we demonstrated a distinct microbiota (both an increased bacterial diversity and abundance) in the appendix of children with complex compared to simple appendicitis. From the same cohort of patients we have collected 35 rectal swabs under general anesthesia prior to appendectomy and microbiota analysis was performed by IS-pro, a 16S-23S rDNA-based clinical microbiota profiling technique. Using the obtained IS-profiles, we performed cluster analyses (UPGMA), comparison of diversity (Shannon Diversity Index) and intensity (abundance in relative fluorescence units) on phylum level, and comparison on species level of bacteria between simple and complex appendicitis. Regarding these analyses, we observed no clear differences between simple and complex appendicitis. However, increased similarity of the microbial composition of the appendix and rectal swab was found within children with complex compared to simple appendicitis. Furthermore, PLS-DA regression analysis provided clear visual differentiation between simple and complex appendicitis, but the diagnostic power was low (highest AUC 0.65).   Conclusion: Microbiota analysis of rectal swabs may be viable to differentiate between simple and complex appendicitis prior to surgery as a supervised classification model allowed for discrimination of both types. However, the current diagnostic power was low and further validation studies are needed to assess the value of this method. What is Known: • Simple and complex appendicitis in children may require different treatment strategies, but accurate preoperative biomarkers are lacking. • Clear differentiation can be made between both types in children based upon the microbial composition in the appendix. What is New: • Increased similarity was found between the microbial composition of the appendix and rectal swab within children with complex compared to simple appendicitis. • Using a supervised classification model rectal swabs may be viable to discriminate between simple and complex appendicitis, but the diagnostic power was low.

The Management of Post-appendectomy Abscess in Children; A Historical Cohort Study and Update of the Literature.

Introduction: Recent studies have shown that specific cases of post-appendectomy abscess (PAA) in children could be treated conservatively. However, due to the lack of high-quality evidence, choice of treatment still depends on preferences of the treating surgeon, leading to heterogeneity in clinical practice. Therefore, we aimed to provide an update of recent literature on the management of PAA in children and subsequently evaluate the outcomes of a large multicenter cohort of children treated for PAA. Methods: A literature search was performed in Pubmed and Embase, selecting all randomized controlled trials, prospective and retrospective cohort studies, and case series published from 2014 and onward and reporting on children (<18 years) treated for a PAA. Subsequently, a historical cohort study was performed, including all children (<18 years) treated for a radiologically confirmed PAA between 2014 and 2021 in a tertiary referral center and two large peripheral centers. Medical charts were reviewed to compare non-invasive (i.e., antibiotics) and invasive (i.e., drainage procedures) treatment strategies. Primary outcome was the success rate of treatment, defined as no need for further interventions related to PAA or its complications. Results: The search yielded 1,991 articles, of which three were included. Treatment success ranged between 69-88% and 56-100% for non-invasive and invasive strategies, respectively. Our multicenter cohort study included 70 children with a PAA, of which 29 (41%) were treated non-invasively and 41 (59%) invasively. In the non-invasive group, treatment was effective in 21 patients (72%) compared to 25 patients (61%) in the invasive group. Non-invasive treatment was effective in 100% of unifocal small (<3 cm) and 80% of unifocal medium size PAA (3-6 cm), but not effective for multiple abscesses. Conclusion: Non-invasive treatment of especially unifocal small and medium size (<6 cm) PAA in children seems to be safe and effective. Based on these results, a standardized treatment protocol was developed. Prospective validation of this step-up approach-based treatment protocol is recommended.

Implementing Nonoperative Treatment Strategy for Simple Pediatric Appendicitis: A Qualitative Study.

INTRODUCTION: A nonoperative treatment strategy (NOT) with antibiotics for children with simple appendicitis could reduce anesthesia and surgery-related complications. As the implementation of a new treatment in routine clinical practice may take years, this study aims to identify barriers and facilitators for implementation of NOT for children with simple appendicitis. MATERIALS AND METHODS: To identify barriers and facilitators for its implementation, we conducted 14 semistructured interviews and a focus group with health insurance/hospital policymakers, surgical clinicians, and young people-together with their parents-who have been treated surgically or with antibiotics. Transcripts were open coded and categorized as per the framework for healthcare innovations by Fleuren et al. RESULTS: We identified four main themes: (1) Appendicitis is a well-known disease. Children, parents, and clinicians regard appendectomy as routine and safe, making them reluctant toward other treatment options. (2) Clinicians regard uptake of NOT in the national appendicitis guideline necessary for its implementation. (3) For identification of patients best suited for NOT more experience and scientific evidence is needed. (4) Appendectomy and NOT have different risk and benefits making the treatment choice depended on individual patient preferences. CONCLUSIONS: By addressing how NOT and operative treatment are regarded by patients and surgeons could have a substantial impact on the implementation of NOT for children with simple appendicitis. Furthermore, the individual preferences of patients need to be taken into account when choosing between operative and NOT. In other words, offering NOT in a shared decision-making model seems the first appropriate step in its implementation.

The prevalence of non-accidental trauma among children with polytrauma: A nationwide level-I trauma centre study.

OBJECTIVE: We aimed to investigate the prevalence and characteristics of non-accidental trauma (NAT) in children with polytrauma treated at level-I trauma centres (TC). SUMMARY OF BACKGROUND: Data 6-10% Of children who present at the emergency department with injuries, sustain polytrauma. Polytrauma may result from either accidental (AT) or NAT, i.e. inflicted or neglect. The prevalence of NAT among children with polytrauma is currently unclear. METHODS: This is a retrospective study that included children (0-18 years) with an Injury Severity Score >15, who presented at one of the 11 Level-I trauma centers (TC) in the Netherlands between January 1, 2010 and January 1, 2016. Outcomes were classified based on the conclusions of the Child Abuse and Neglect-team. Cases in which conclusions were unavailable and there was no clear accidental cause of injuries were reviewed by an expert panel. RESULTS: The study included 1623 children, 1452 (89%) were classified as AT, 171 (11%) as NAT; 39 (2,4%) inflicted and 132 (8,1%) neglect. Of pre-school aged children (<5 years) 41% sustained NAT (OR26.73, 95%CI 17.70-40.35), 35/342 (10%) inflicted and 104/342 (31%) neglect. Admission due to 'cardiopulmonary arrest' was the result of inflicted trauma (30% vs 0%,p < 0.001). NAT had a higher mortality rate (16% vs 10%, p = 0.006). Indicators of NAT were: (near-)drowning (OR10.74, 95%CI 5.94-19.41), burn (OR8.62, 95%CI 4.08-18.19) and fall from height (OR2.18, 95%CI 1.56-3.02). CONCLUSIONS: NAT was the cause of polytrauma in 11% of children in our nationwide level-I TC study; 41% of these polytrauma were the result of NAT experienced by preschool-aged children. Our data show the importance of awareness for NAT.

Prevalence of inflicted and neglectful femur shaft fractures in young children in national level I trauma centers.

BACKGROUND: The prevalence of inflicted femur fractures in young children varies (1.5-35.2%), but these data are based on small retrospective studies with high heterogeneity. Age and mobility of the child seem to be indicators of inflicted trauma. OBJECTIVE: This study describes other factors associated with inflicted and neglectful trauma that can be used to distinguish inflicted and neglectful from accidental femur fractures. MATERIALS AND METHODS: This retrospective study included children (0-6 years) who presented with an isolated femur fracture at 1 of the 11 level I trauma centers in the Netherlands between January 2010 and January 2016. Outcomes were classified based on the conclusions of the Child Abuse and Neglect teams or the court. Cases in which conclusions were unavailable and there was no clear accidental cause were reviewed by an expert panel. RESULTS: The study included 328 children; 295 (89.9%) cases were classified as accidental trauma. Inflicted trauma was found in 14 (4.3%), while 19 (5.8%) were cases of neglect. Indicators of inflicted trauma were age 0-5 months (29%, positive likelihood ratio [LR +] 8.35), 6-12 months (18%, LR + 5.98) and 18-23 months (14%, LR + 3.74). Indicators of neglect were age 6-11 months (18%, LR + 4.41) and age 18-23 months (8%, LR + 1.65). There was no difference in fracture morphology among groups. CONCLUSION: It is unlikely that an isolated femur fracture in ambulatory children age > 24 months is caused by inflicted trauma/neglect. Caution is advised in children younger than 24 months because that age is the main factor associated with inflicted trauma/neglect and inflicted femur fractures.

Identification of the optimal treatment strategy for complex appendicitis in the paediatric population: a protocol for a multicentre prospective cohort study (CAPP study).

INTRODUCTION: In daily practice large heterogeneity in the treatment of children with complex appendicitis exists. Complex appendicitis can be divided into two subtypes; complex appendicitis with and without appendiceal mass and/or abscess. As complex appendicitis is associated with high morbidity and costs, identification of the optimal treatment strategy is essential. In this article, we present the study protocol for the CAPP (Complex Appendicitis in the Pediatric Population) study. METHODS AND ANALYSIS: This nation-wide, multi-centre, comparative, non-randomised prospective cohort study includes all children <18 years old with a preoperative suspicion of complex appendicitis, which is based on imaging confirmed acute appendicitis and predefined criteria regarding the severity of appendicitis. Eligible patients are recruited in more than 30 hospitals. Open appendectomy will be compared with laparoscopic appendectomy for children without appendiceal mass and/or abscess and initial non-operative treatment (ie, intravenous antibiotics with or without percutaneous drainage) to direct appendectomy for children with appendiceal mass and/or abscess. Based on historical data supplied by the participating hospitals and an inclusion period of 2 years and 9 months, a sample size of 1308 patients is aimed. Primary outcome is the proportion of patients experiencing any complication at 3 months follow-up. Reported complications will be assessed by an independent adjudication committee. Secondary outcomes include, but are not limited to, quality of life, and (in)direct costs. To adjust for baseline differences and selection bias, outcomes will be compared after propensity score analysis (inverse probability weighting and stratification). ETHICS AND DISSEMINATION: The Medical Ethics Review Committee of the Amsterdam UMC, location AMC, declared that the Medical Research involving Human Subjects Act (WMO) did not apply to this study. Therefore, no official approval was required by national law. Study results will be presented in peer-reviewed scientific journals and at (inter)national conferences. TRIAL REGISTRATION NUMBERS: NCT04755179; NL9371.

Predictive scoring systems to differentiate between simple and complex appendicitis in children (PRE-APP study).

BACKGROUND: Several clinical prediction rules have been developed for preoperative differentiation between simple and complex appendicitis in children, as potential treatment strategies differ. This study aimed to externally validate applicable clinical prediction rules that could be used to differentiate between simple and complex appendicitis in children. METHODS: Potential clinical prediction rules were identified by a scoping review of the literature. Clinical prediction rules applicable in our daily practice were subsequently externally validated in a multicenter historical cohort consisting of 1 tertiary center and 1 large teaching hospital. All children (<18 years old) with histopathologically confirmed acute appendicitis between 2013 and 2020 were included. Test results of clinical prediction rules were compared to the gold standard of either simple or complex appendicitis consisting of predefined perioperative and histopathological criteria. Areas under the receiver operating characteristic curves were determined for the selected clinical prediction rules. Areas under the receiver operating characteristic curve >0.7 were considered acceptable and potentially useful. RESULTS: In total, 31 clinical prediction rules were identified, of which 12 could be evaluated in our cohort consisting of 550 children. The main reason to exclude clinical prediction rules was the use of variables that were not routinely measured in our cohort. In our cohort, 208/550 (38%) were diagnosed with complex appendicitis according to the gold standard. Clinical prediction rules with areas under the receiver operating characteristic curve >0.7 were: Gorter (0.81), Bogaard (0.79), Bröker (0.79), Graham (0.77), Hansson (0.76), BADCF (0.76), and Eddama (0.75). CONCLUSION: In this study, clinical prediction rules consisting of a combination of clinical and objective variables had the highest discriminative ability. External validation showed that 7 clinical prediction rules were potentially useful. Integration of these clinical prediction rules in daily practice is proposed to guide decision making regarding treatment strategies.

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.

Child abuse and neglect in paediatric burns: The majority is caused by neglect and thus preventable.

INTRODUCTION: It is complex to distinguish negligent burns from inflicted and non-intentional burns, especially since no deliberate action caused the burn. Its recognition is important to create a safe life without (future) burns for our loved-ones who cannot take care of themselves (yet). Our aim was to investigate the incidence and associated characteristics of negligent burns are among children treated at a burn center. METHODS: We retrospectively reviewed medical files of all children attending a Dutch burn center with an acute burn between January 2013-December 2015. The conclusion of the Child Abuse and Neglect team (CAN) was used to define inflicted, negligent or non-intentional burns. The remaining cases were reviewed by an expert panel using a standardized protocol. Demographic and social data as well as clinical information about the burn were collected. RESULTS: In total 330 children were included. Negligent burns accounted for 56%, non-intentional for 42% and inflicted for 2% of the burns. Negligent burns were associated with: hot beverages (OR 4.40, 95%CI 2.75-7.05), a younger age (p < 0.001), occurrence at home (OR 4.87 95%CI 2.80-8.45) and were located at the anterior trunk (OR 2.75, 95%CI 1.73-4.35) and neck (OR 1.98, 95%CI 1.12-3.50). CONCLUSION: This study shows that neglect is a major factor in the occurrence of burns in young children, therefore we conclude that the majority of paediatric burns are preventable. Educational programs creating awareness and focussing on prevention of these burns should be aimed at households, since the majority of negligent as cause of preventable burns occur at home.

High prevalence of non-accidental trauma among deceased children presenting at Level I trauma centers in the Netherlands.

PURPOSE: Between 0.1-3% of injured children who present at a hospital emergency department ultimately die as a result of their injuries. These events are typically reported as unnatural causes of death and may result from either accidental or non-accidental trauma (NAT). Examples of the latter include trauma that is inflicted directly or resulting from neglect. Although consultation with a forensic physician is mandatory for all deceased children, the prevalence of fatal inflicted trauma or neglect among children is currently unclear. METHODS: This is a retrospective study that included children (0-18 years) who presented and died at one of the 11 Level I trauma centers in the Netherlands between January 1, 2014, and January 1, 2019. Outcomes were classified based on the conclusions of the Child Abuse and Neglect team or those of forensic pathologists and/or the court in cases referred for legally mandated autopsies. Cases in which conclusions were unavailable and there was no clear accidental cause of death were reviewed by an expert panel. RESULTS: The study included 175 cases of childhood death. Seventeen (9.7%) of these children died due to inflicted trauma (9.7%), 18 (10.3%) due to neglect, and 140 (80%) due to accidents. Preschool children (< 5 years old) were significantly more likely to present with injuries due to inflicted trauma and neglect compared to older children (44% versus 6%, p < 0.001, odds ratio [OR] 5.80, 95% confidence interval [CI] 2.66-12.65). Drowning accounted for 14 of the 18 (78%) pediatric deaths due to neglect, representing 8% of the total cases. Postmortem radiological studies and autopsies were performed on 37 (21%) of all cases of childhood death. CONCLUSION: One of every five pediatric deaths in our nationwide Level I trauma center study was attributed to NAT; 44% of these deaths were the result of trauma experienced by preschool-aged children. A remarkable number of fatal drownings were due to neglect. Postmortem radiological studies and autopsies were performed in only one-fifth of all deceased children. The limited use of postmortem investigations may have resulted in missed cases of NAT, which will result in an overall underestimation of fatal NAT experienced by children.

Accuracy of ultrasonography for differentiating between simple and complex appendicitis in children.

PURPOSE: Accurate differentiation between simple and complex appendicitis is important since differences in treatment exist. This study aimed to assess the accuracy of ultrasonography in differentiating between simple and complex appendicitis. METHODS: Data from children aged < 18 years who underwent appendectomy between the 1st of January 2013 and the 1st of January 2018 were analyzed retrospectively. Ultrasonography reports of eligible children were divided into simple (test negative) and complex appendicitis (test positive) based on predefined criteria and compared to a gold standard (a combination of predefined perioperative and histopathological criteria). Sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) were calculated to measure ultrasonographic accuracy in differentiating between simple and complex appendicitis. RESULTS: 176 children were eligible for inclusion. The mean age at the time of operation was 10.1 ± SD 4.6 years. 84 (47.7%) children had simple appendicitis and 92 (52.3%) had complex appendicitis. The use of ultrasonography yielded a sensitivity: 46%, specificity: 90%, PPV: 84%, and NPV: 60%. CONCLUSION: Ultrasonography as standalone modality is not suitable for differentiating between simple and complex appendicitis in children. To improve preoperative differentiation, other variables such as clinical signs and laboratory data are necessary in conjunction with ultrasonography findings.

Paediatric femur fractures-the value of contextual information on judgement in possible child abuse cases: are we bias?

The majority of paediatric femur fractures result from accidental trauma; however, it is important to consider non-accidental trauma, especially in pre-ambulatory children. We study whether irrelevant contextual information subconsciously influences conclusions of healthcare professionals with respect to whether observations provide evidence for non-accidental trauma. A survey with nine radiographs of femur shaft fractures was designed. Two different clinical histories (vignettes) with contextual information were designed, non-abuse versus abuse context. One of both vignettes was randomly assigned to the radiograph shown to the participant, followed by a question with a 5-point answer scale, which represents a verbal expression of the likelihood ratio of the fracture regarding a non-accidental versus accidental cause. Participants were medical residents and staff members of different specialties from several Dutch hospitals. A total of 172 participants responded. The reported evidential strength of the vignettes with a non-abuse context was 0.19 (n = 784; 95%CI 0.10-0.28) and for the abuse context 0.94 (n = 764; 95%CI 0.86-1.02; p < 0.001). Women reported a stronger evidential strength than men, but both were influenced by context. Emergency department and paediatric doctors were more likely to decide that non-accidental trauma was the cause; paediatric radiologists were the least likely. Experience in years of practice and current function did not prevent participants from being bias.Conclusion: This study shows that the interpretation of medical results by healthcare professionals can be influenced by contextual information, such as low income and marital status, which are irrelevant to the decision as to whether abuse might have occurred. Given the same information about an injury, women, emergency department and paediatric doctors were more likely to decide that non-accidental trauma was the cause, while paediatric radiologists were least likely to decide this outcome. It is important to prevent contextual influence as much as possible, by recognizing it and implementing a management contextual information procedure. What is Known: • Contextual information is of possible influence on healthcare professionals in identifying non-accidental trauma. • Increased working experience is thought to be protective against this influence. What is New: • Contextual information influenced the interpretation of medical results by healthcare professionals regardless of work experience. • The interpretation of medical results by healthcare professionals is influenced by both affirmative and negative contextual information.

Outcomes after appendectomy in children with acute appendicitis treated at a tertiary paediatric centre: results from a retrospective cohort study.

PURPOSE: In general, an appendectomy is presumed to have a limited burden of disease. However, in current literature, reported complication rates vary. This study aims to provide additional insights in the incidence of post-appendectomy complications in children with acute appendicitis. METHODS: This retrospective cohort study included children (0-17 years old) that underwent appendectomy at our tertiary referral centre for suspected acute appendicitis (January 2011-December 2018). Children referred to our centre, and those that underwent non-operative treatment were excluded. Post-appendectomy complications were recorded from electronic medical charts using predefined definitions and classified as severe (Clavien-Dindo III-IV) or less severe (Clavien-Dindo I-II). RESULTS: A total of 131 children were included. Simple and complex appendicitis was diagnosed in 66 (50%) and 60 (46%) children, respectively. A non-inflamed appendix was seen in five (4%) children. One or more complications were identified in 33 (25%) patients. Eight (12%) children with simple appendicitis developed a complication, three of these were severe. In children with complex appendicitis, 23 (38%) children developed a complication, 14 of these were severe. CONCLUSION: This study shows a high rate of complications compared with current literature, both in children with simple and complex appendicitis. This is probably the result of our definition of complications and being a tertiary referral centre receiving more severe appendicitis cases. However, these results still show that appendectomy is not always a routine procedure with only few complications. Substantiating the need to keep optimizing treatment for children with appendicitis.