Non-radiologist-performed abdominal point-of-care ultrasonography in paediatrics — a scoping review

Background - Historically, US in the paediatric setting has mostly been the domain of radiologists. However, in the last decade, there has been an uptake of non-radiologist point-of-care US. Objective - To gain an overview of abdominal non-radiologist point-of-care US in paediatrics. Materials and methods - We conducted a scoping review regarding the uses of abdominal non-radiologist point-of-care US, quality of examinations and training, patient perspective, financial costs and legal consequences following the use of non-radiologist point-of-care US. We conducted an advanced search of the following databases: Medline, Embase and Web of Science Conference Proceedings. We included published original research studies describing abdominal non-radiologist point-of-care US in children. We limited studies to English-language articles from Western countries. Results - We found a total of 5,092 publications and selected 106 publications for inclusion: 39 studies and 51 case reports or case series on the state-of-art of abdominal non-radiologist point-of-care US, 14 on training of non-radiologists, and 1 each on possible harms following non-radiologist point-of-care US and patient satisfaction. According to included studies, non-radiologist point-of-care US is increasingly used, but no standardised training guidelines exist. We found no studies regarding the financial consequences of non-radiologist point-of-care US. Conclusion - This scoping review supports the further development of non-radiologist point-of-care US and underlines the need for consensus on who can do which examination after which level of training among US performers. More research is needed on training non-radiologists and on the costs-to-benefits of non-radiologist point-of-care US

Polyethylene glycol 3350 with electrolytes versus polyethylene glycol 4000 for constipation: A randomized, controlled trial

Objective: The long-term efficacy and safety of polyethylene glycol (PEG) in constipated children are unknown, and a head-to-head comparison of the different PEG formulations is lacking. We aimed to investigate noninferiority of PEG3350 with electrolytes (PEG3350+E) compared to PEG4000 without electrolytes (PEG4000). Methods: In this double-blind trial, children aged 0.5 to 16 years with constipation, defined as a defecation frequency of <3 times per week, were randomized to receive either PEG3350+E or PEG4000. Primary outcomes were change in total sum score (TSS) at week 52 compared to baseline, and dose range determination. TSS was the sum of the severity of 5 constipation symptoms rated on a 4-point scale (0-3). Noninferiority margin was a difference in TSS of ≤1.5 based on a 95%-confidence interval [CI]. Treatment success was defined as a defecation frequency of ≥3 per week with <1 episode of fecal incontinence. Results: Ninety-seven subjects were included, of whom 82 completed the study.Mean reduction inTSSwas-3.81 (95%CI:-4.96 to-2.65) and-3.74 (95%CI: -5.08 to -2.40), for PEG3350+E and PEG4000, respectively. Noninferiority criteria were not met (maximum difference between groups: -1.81 to 1.68).Daily sachet usewas: 0 to 2 years: 0.4 to 2.3 and 0.9 to 2.1; 2 to 4 years: 0.1 to 3.5 and 1.2 to 3.2; 4 to 8 years: 1.1 to 2.8 and 0.7 to 3.8; 8 to 16 years 0.6 to 3.7 and 1.0 to 3.7, in PEG3350+E and PEG4000, respectively. Treatment success after 52 weeks was achieved in 50% and 45% of children, respectively (P=0.69). Rates of adverse events were similar between groups, and no drug-related serious adverse events occurred. Conclusions: Noninferiority regarding long-term constipation-related symptoms of PEG3350+E compared to PEG4000 was not demonstrated. However, analysis of secondary outcomes suggests similar efficacy and safety of these agents

Disease progression in paediatric- and adult-onset sclerosing cholangitis : Results from two independent Dutch registries

Background & Aims: Sclerosing cholangitis (SC) is a severe liver disease leading to destruction of bile ducts. It is believed to run a milder course in children than in adults. To test this assumption, we evaluated time-to-complication curves in two independent paediatric-onset cohorts from the same geographical area. Methods: Short-term disease outcomes were evaluated with an online clinical registry that was filled with data on children with SC diagnosed between 2000 and 2017 and who were followed bi-annually thereafter. Long-term disease outcomes were evaluated in a paediatric-onset subcohort derived from a previously published population-based study from the Netherlands. Time-to-complication in the first cohort was defined as the time from diagnosis until portal hypertension, biliary obstructions and infections, development of malignancy, or liver transplantation, whichever came first. In the second cohort time-to-complication was defined as the time until liver transplantation or PSC-related death. Results: Median age at diagnosis in the first cohort (n = 86) was 12.3 years. In the first 5 years post-diagnosis 23% of patients developed complications. The patients in the population-based study (n = 683) were stratified into those diagnosed before the age of 18 years (‘paediatric-onset’ subcohort, n = 43) and those diagnosed after the age of 18 years (‘adult-onset’ subcohort, n = 640). Median age at diagnosis was 14.6 and 40.2 years, respectively. Median time-to-complication in the paediatric-onset and adult-onset subcohorts was not statistically different. Conclusion: Paediatric and adult-onset SC run a similar long-term disease course. Paediatricians who treat children with SC should monitor them closely to recognize early complications and control long-term sequelae

Disease progression in paediatric- and adult-onset sclerosing cholangitis : Results from two independent Dutch registries

Background & Aims: Sclerosing cholangitis (SC) is a severe liver disease leading to destruction of bile ducts. It is believed to run a milder course in children than in adults. To test this assumption, we evaluated time-to-complication curves in two independent paediatric-onset cohorts from the same geographical area. Methods: Short-term disease outcomes were evaluated with an online clinical registry that was filled with data on children with SC diagnosed between 2000 and 2017 and who were followed bi-annually thereafter. Long-term disease outcomes were evaluated in a paediatric-onset subcohort derived from a previously published population-based study from the Netherlands. Time-to-complication in the first cohort was defined as the time from diagnosis until portal hypertension, biliary obstructions and infections, development of malignancy, or liver transplantation, whichever came first. In the second cohort time-to-complication was defined as the time until liver transplantation or PSC-related death. Results: Median age at diagnosis in the first cohort (n = 86) was 12.3 years. In the first 5 years post-diagnosis 23% of patients developed complications. The patients in the population-based study (n = 683) were stratified into those diagnosed before the age of 18 years (‘paediatric-onset’ subcohort, n = 43) and those diagnosed after the age of 18 years (‘adult-onset’ subcohort, n = 640). Median age at diagnosis was 14.6 and 40.2 years, respectively. Median time-to-complication in the paediatric-onset and adult-onset subcohorts was not statistically different. Conclusion: Paediatric and adult-onset SC run a similar long-term disease course. Paediatricians who treat children with SC should monitor them closely to recognize early complications and control long-term sequelae

Exome sequencing in patient-parent trios suggests new candidate genes for early-onset primary sclerosing cholangitis

BACKGROUND & AIMS: Primary sclerosing cholangitis (PSC) is a rare bile duct disease strongly associated with inflammatory bowel disease (IBD). Whole-exome sequencing (WES) has contributed to understanding the molecular basis of very early-onset IBD, but rare protein-altering genetic variants have not been identified for early-onset PSC. We performed WES in patients diagnosed with PSC ≤ 12 years to investigate the contribution of rare genetic variants to early-onset PSC. METHODS: In this multicentre study, WES was performed on 87 DNA samples from 29 patient-parent trios with early-onset PSC. We selected rare (minor allele frequency < 2%) coding and splice-site variants that matched recessive (homozygous and compound heterozygous variants) and dominant (de novo) inheritance in the index patients. Variant pathogenicity was predicted by an in-house developed algorithm (GAVIN), and PSC-relevant variants were selected using gene expression data and gene function. RESULTS: In 22 of 29 trios we identified at least 1 possibly pathogenic variant. We prioritized 36 genes, harbouring a total of 54 variants with predicted pathogenic effects. In 18 genes, we identified 36 compound heterozygous variants, whereas in the other 18 genes we identified 18 de novo variants. Twelve of 36 candidate risk genes are known to play a role in transmembrane transport, adaptive and innate immunity, and epithelial barrier function. CONCLUSIONS: The 36 candidate genes for early-onset PSC need further verification in other patient cohorts and evaluation of gene function before a causal role can be attributed to its variants

Late hepatic toxicity surveillance for survivors of childhood, adolescent and young adult cancer: Recommendations from the international late effects of childhood cancer guideline harmonization group

Background: Survivors of childhood, adolescent and young adult (CAYA) cancer may develop treatment-induced chronic liver disease. Surveillance guidelines can improve survivors’ health outcomes. However, current recommendations vary, leading to uncertainty about optimal screening. The International Late Effects of Childhood Cancer Guideline Harmonization Group has developed recommendations for the surveillance of late hepatotoxicity after CAYA cancer. Methods: Evidence-based methods based on the GRADE framework were used in guideline development. A multidisciplinary guideline panel performed systematic literature reviews, developed evidence summaries, appraised the evidence, and formulated recommendations on the basis of evidence, clinical judgement, and consideration of benefits versus the harms of the surveillance while allowing for flexibility in implementation across different health care systems. Results: The guideline strongly recommends a physical examination and measurement of serum liver enzyme concentrations (ALT, AST, gGT, ALP) once at entry into long-term follow-up for survivors treated with radiotherapy potentially exposing the liver (moderate- to high-quality evidence). For survivors treated with busulfan, thioguanine, mercaptopurine, methotrexate, dactinomycin, hematopoietic stem cell transplantation (HSCT), or hepatic surgery, or with a history of chronic viral hepatitis or sinusoidal obstruction syndrome, similar surveillance for late hepatotoxicity once at entry into LTFU is reasonable (low-quality evidence/expert opinion, moderate recommendation). For survivors who have undergone HSCT and/or received multiple red blood cell transfusions, surveillance for iron overload with serum ferritin is strongly recommended once at long-term follow-up entry. Conclusions: These evidence-based, internationally-harmonized recommendations for the surveillance of late hepatic toxicity in cancer survivors can inform clinical care and guide future research of health outcomes for CAYA cancer survivors