Virtual reality hypnosis for needle-related procedural pain and fear management in children: a non-inferiority randomized trial.

Needle-related procedures can cause pain and fear in children and may lead to avoidance of future medical care. The aim of this study is to investigate whether virtual reality hypnosis (VRH) is non-inferior to medical hypnosis (MH) by a trained healthcare provider in reducing pain in children. This non-inferiority randomized trial was conducted at a teaching hospital in the Netherlands. Children aged 6 to 18 years were randomized to treatment with VRH or MH. The primary outcome was self-reported pain, using the Wong-Baker FACES Scale (WBFS) with the non-inferiority margin defined as a difference of 1.5 points. Secondary outcomes included observer-reported pain (Numeric Rating Scale), fear (scored by children and observers with the Children's Fear Scale), blood pressure, heart rate, treatment satisfaction, and adverse effects. We randomized 138 children to VRH or MH treatment and included 114 children in the analyses (VRH n = 60, MH n = 54). We found non-inferiority for VRH compared to MH on patient-reported pain (mean difference = - 0.17, 95%CI - 1.01;0.66). Secondary outcomes were comparable between VRH and MH groups. Both treatments scored high on patient satisfaction (VRH median = 9.0, MH median = 10.0, p = 0.512). CONCLUSION: VRH may be an effective and safe treatment option besides MH for reducing patient-reported pain in children during a needle-related procedure. VRH was non-inferior to MH in patient-reported fear and both treatments were comparable in terms of patient-reported fear, observer-reported pain and fear, physical distress, and patient satisfaction. TRIAL REGISTRATION: ICTRP https://trialsearch.who.int/ , trial ID NL9385; date registered: 03/04/2021. WHAT IS KNOWN: • Medical hypnosis is effective in reducing procedural distress in children during needle-related procedures. • Virtual reality (VR) is an audiovisual electronic device that guides users into an immersive three-dimensional environment. WHAT IS NEW: • This study shows that VR hypnosis is non-inferior to medical hypnosis in reducing pain and fear in children undergoing a needle-related procedure. • Both VR hypnosis and medical hypnosis were appreciated highly by children to distract them during needle-related procedures.

Diagnostic accuracy of fibrosis tests in children with non-alcoholic fatty liver disease: A systematic review.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in children. Even at young age, it can progress to liver fibrosis. Given the drawbacks of liver biopsy, there is a need for non-invasive methods to accurately stage liver fibrosis in this age group. In this systematic review, we evaluate the diagnostic accuracy of non-invasive methods for staging liver fibrosis in children with NAFLD. METHODS: We searched MEDLINE, Embase, Web of Science and the Cochrane Library, for studies that evaluated the performance of a blood-based biomarker, prediction score or imaging technique in staging liver fibrosis in children with NAFLD, using liver biopsy as the reference standard. RESULTS: Twenty studies with a total of 1787 NAFLD subjects were included, which evaluated three prediction scores, five simple biomarkers, two combined biomarkers and six imaging techniques. Most studies lacked validation. Substantial heterogeneity of studies and limited available study data precluded a meta-analysis of the few fibrosis tests evaluated in more than one study. The most consistent accuracy data were found for transient elastography by FibroScan®, ELF test and ultrasound elastography, with an area under the receiver operating characteristics curve varying between 0.92 and 1.00 for detecting significant fibrosis. CONCLUSION: Due to the lack of validation, the accuracy and clinical utility of non-invasive fibrosis tests in children with NAFLD remains uncertain. As studies have solely been performed in tertiary care settings, accuracy data cannot directly be translated to screening populations.

Survey on screening for paediatric non-alcoholic fatty liver disease in clinical practice in Dutch hospitals.

AIM: Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent liver disease that affects 34% of children with obesity. Besides the liver-related morbidity, NAFLD also increases the risk of cardiometabolic diseases at adult age. Diverse screening recommendations exist on paediatric NAFLD. The aim of this study was to assess screening practices among paediatricians managing children with obesity in the Netherlands. METHODS: Between 2016 and 2017, an Internet-based survey was sent to all 167 members of the endocrinology section of the Dutch Paediatricians Society, that includes all paediatricians involved in obesity care. Descriptive statistics (frequencies) were used to analyse responses. RESULTS: In total, 42/167 (25%) of the invited paediatricians responded. Thirty-six of 42 respondents (86%) screen for NAFLD. One-third of those do not follow any guideline. Most respondents use ALT as screening tool, with thresholds varying between 21-80 IU/L. The majority (29/36) indicate they lack guidance on screening and follow-up. CONCLUSION: In this study sample of Dutch paediatricians, screening for paediatric NAFLD is widely, albeit not universally, performed and in a highly variable way. This underlines the need come to a uniform and comprehensive screening strategy and raise awareness about NAFLD among physicians treating children with obesity.

Development of a clinical pathway for bariatric surgery as an integral part of a comprehensive treatment for adolescents with severe obesity in the Netherlands.

Introduction In the Netherlands, bariatric surgery in adolescents is currently only allowed in the context of scientific research. Besides this, there was no clinical pathway for bariatric surgery in adolescents. In this paper, the development of a comprehensive clinical pathway for bariatric surgery in adolescents with severe obesity in the is described. Methods The clinical pathway for bariatric surgery in adolescents consists of an eligibility assessment as well as comprehensive peri- and postoperative care. Regarding the eligibility assessment, the adolescents need to be identified by their attending pediatricians and afterwards be evaluated by specialized pediatric obesity units. If the provided treatment is considered to be insufficiently effective, the adolescent will anonymously be evaluated by a national board. This is an additional diligence procedure specifically established for bariatric surgery in adolescents. The national board consists of independent experts regarding adolescent bariatric surgery, and evaluates whether the adolescents meet the criteria defined by the national professional associations. The final step is an assessment by a multidisciplinary team for adolescent bariatric surgery. The various disciplines (pediatrician, bariatric surgeon, psychologist, dietician) evaluate whether an adolescent is eligible for bariatric surgery. In this decision-making process, it is crucial to assess whether the adolescent is expected to adhere to postoperative behavioral changes and follow-up. When an adolescent is deemed eligible for bariatric surgery, he or she will receive preoperative counselling by a bariatric surgeon to decide on the type of bariatric procedure (Roux-en-Y gastric bypass or sleeve gastrectomy). Postoperative care consists of intensive guidance by the multidisciplinary team for adolescent bariatric surgery. In this guidance, several regular appointments are included and additional care will be provided based on the needs of the adolescent and his or her family. Furthermore, the multidisciplinary lifestyle intervention, in which the adolescents participated before bariatric surgery, continues in coordination with the multidisciplinary team for adolescent bariatric surgery, and this ensures long-term counselling and follow-up. Conclusion The implementation of bariatric surgery as an integral part of a comprehensive treatment for adolescents with severe obesity requires the development of a clinical pathway with a variety of disciplines.

Ethnic diversity outpatient clinic in paediatrics.

BACKGROUND: The health status of chronic sick ethnic minority children in the Netherlands is unequal compared with indigenous Dutch children. In order to optimize the health care for these children a specific patient-oriented clinic in ethnic-cultural diversity: the Mosaic Outpatient Clinic (MOC) was integrated in the general Paediatric Outpatient Departments (POPD) of three hospitals in Amsterdam. METHODS: Feasibility of the MOC, factors influencing the health care process and encountered bottlenecks in health care were studied in ethnic minority children with asthma, diabetes type 1 or metabolic disease originating from Morocco, Turkey and Surinam. Feasibility was determined by the number of patients attended, support from the paediatric medical staff and willingness of the patients to participate. Influences on the health care process comprised parents' level of knowledge of disease, sense of disease severity, level of effort, linguistic skills, health literacy, adherence to treatment and encountered bottlenecks in the health care process. Moreover, the number of admissions and visits to the POPD in the years before, during and after the MOC were analysed. RESULTS: In 2006 a total of 189 ethnic minority children were seen. Integration of the MOC within the general POPD of the hospital is feasible. The ability of the parents to speak and understand Dutch was found to be 58%, functional health literacy was 88%; sufficient knowledge of disease and sense of disease severity were 59% and 67%, respectively. The main bottlenecks in the healthcare process: poor knowledge of disease, limited sense of disease severity and low health literacy in the parents proved to be the best predictors for decreased adherence. After attending the MOC there was a decrease in the number of admissions and visits to the POPD for asthma while the number of visits increased in patients with diabetes and the amount of no-shows decreased in patients with a metabolic disease. CONCLUSION: Integration of a MOC in the general POPD is feasible and appreciated by the parents, provides more insight in the problems ethnic minority children and their parents face and shows promising directions for optimizing adherence in these children.

Mitochondrial long chain fatty acid beta-oxidation in man and mouse.

Several mouse models for mitochondrial fatty acid beta-oxidation (FAO) defects have been developed. So far, these models have contributed little to our current understanding of the pathophysiology. The objective of this study was to explore differences between murine and human FAO. Using a combination of analytical, biochemical and molecular methods, we compared fibroblasts of long chain acyl-CoA dehydrogenase knockout (LCAD(-/-)), very long chain acyl-CoA dehydrogenase knockout (VLCAD(-/-)) and wild type mice with fibroblasts of VLCAD-deficient patients and human controls. We show that in mice, LCAD and VLCAD have overlapping and distinct roles in FAO. The absence of VLCAD is apparently fully compensated, whereas LCAD deficiency is not. LCAD plays an essential role in the oxidation of unsaturated fatty acids such as oleic acid, but seems redundant in the oxidation of saturated fatty acids. In strong contrast, LCAD is neither detectable at the mRNA level nor at the protein level in men, making VLCAD indispensable in FAO. Our findings open new avenues to employ the existing mouse models to study the pathophysiology of human FAO defects.

Successful Treatment of Hereditary Folate Malabsorption With Intramuscular Folinic Acid.

BACKGROUND: Hereditary folate malabsorption is a multisystem disease owing to biallelic variants in the gene encoding the proton-coupled folate transporter. Hereditary folate malabsorption is treated with folinic acid, aimed to restore blood and cerebrospinal fluid folate levels. Little is known as to whether oral or intramuscular supplementation of folinic acid is most effective. METHODS: Here we describe a one-year-old boy with hereditary folate malabsorption presenting with the typical features including failure to thrive, aphthous stomatitis, macrocytic anemia along with severe developmental impairment and epilepsy, as well as a magnetic resonance imaging of the brain showing bilateral occipital, cortical calcifications characteristic of hereditary folate malabsorption. We compared the effect of treatment with oral folinic acid versus intramuscular folinic acid supplementation by measuring plasma and cerebrospinal fluid folate levels. RESULTS: Compared with oral administration, intramuscular treatment resulted in higher folate levels in blood and, most importantly, normalization of folate levels in cerebrospinal fluid. Clinically, nearly all systemic and neurological symptoms resolved. CONCLUSION: Normal cerebrospinal fluid folate levels can be achieved in individuals with hereditary folate malabsorption with intramuscular (but not with oral) administration of folinic acid.

Characterization of L-aminocarnitine, an inhibitor of fatty acid oxidation.

The pathogenesis of hypoketotic hypoglycemia and cardiomyopathy in patients with fatty acid oxidation (FAO) disorders is still poorly understood. In vitro studies are hampered by the lack of natural mutants to asses the effect of FAO inhibition. In addition, only a few inhibitors of FAO are known. Furthermore, most inhibitors of FAO are activating ligands of peroxisome proliferator-activated receptors (PPARs). We show that l-aminocarnitine (L-AC), a carnitine analog, inhibits FAO efficiently, but does not activate PPAR. L-AC inhibits carnitine palmitoyltransferase (CPT) with different sensitivities towards CPT1 and CPT2, as well as carnitine acylcarnitine translocase (CACT). We further characterized L-AC using fibroblasts cell lines from controls and patients with different FAO defects. In these cell lines acylcarnitine profiles were determined in culture medium after loading with [U-(13)C]palmitic acid. In control fibroblasts, L-AC inhibits FAO leading to a reduction of C2-acylcarnitine and elevation of C16-acylcarnitine. In very long-chain acyl-CoA dehydrogenase (VLCAD)-deficient fibroblasts, L-AC decreased the elevated C14-acylcarnitine and increased C16-acylcarnitine. In CACT and CPT2-deficient cell lines, L-AC did not change the already elevated C16-acylcarnitine level, showing that CPT1 is not inhibited. Oxidation of pristanic acid was only partly inhibited at high L-AC concentrations, indicating minimal CACT inhibition. Therefore, we conclude that in intact cells L-AC inhibits CPT2. Combined with our observation that l-AC does not activate PPAR, we suggest that L-AC is useful to simulate a FAO defect in cells from different origin.