Diagnostic and Therapeutic Considerations Towards Dientamoeba fragilis in Children: A Survey Amongst General Practitioners and Pediatricians in the Netherlands.

ABSTRACT: This survey was undertaken to obtain insight in the attitude of Dutch physicians towards pathogenicity, diagnostic- and therapeutic approach towards Dientamoeba fragilis in children. Physicians were invited by e-mail for a questionnaire. A total of 211 of 450 physicians (46.9%) completed the questionnaire, including 67 general practitioners (GPs) and 144 pediatricians. Of all respondents, 175 of 211 (82.9%) considered D fragilis a "potential pathogen", when other causes of gastro-intestinal complaints are ruled out. Only 16 of 211 (7.6%) performed diagnostic tests regularly. Diagnostic tests were performed by 162 of 211 (77%) of respondents in children with diarrhea and abdominal pain in consideration of duration of symptoms. Fecal polymerase chain reaction (PCR) was diagnostic modality of preference. Eighty-nine of 142 (62.7%) prescribed metronidazole as antibiotic of first choice. This study shows heterogeneity in clinical practice amongst Dutch physicians regarding diagnostic- and therapeutic approach of D fragilis in children. Different attitude towards pathogenicity and inconsistent guidelines could be causative factors.

Guideline adherence and clinical relevance of laboratory investigations during follow-up in paediatric coeliac disease: A Dutch single-centre cohort study.

AIM: Dutch national guidelines on follow-up of paediatric celiac disease (CD) are available. The primary aim was to evaluate guideline adherence by paediatricians during follow-up. The secondary aim was to determine the clinical relevance and diagnostic yield of routine laboratory tests suggested by these guidelines. METHODS: A retrospective, single-centre, cohort study was performed in paediatric CD patients who visited Tergooi Hospital, the Netherlands, between January 2017 and December 2019, with follow-up of at least twelve months after diagnosis. We analysed guideline adherence, number of outpatient visits and all laboratory data. RESULTS: We included 91 CD children with a median follow-up of 4.0 years (range 1-16 years) and 162 follow-up visits. Strict adherence amongst paediatricians during follow-up was 8.0% (13/162 cases). A total of 1570 laboratory tests were performed of which 45.4% (713/1570) was in strict compliance with the Dutch national guidelines. Clinically relevant deviations were observed in 5.3% of requested laboratory tests. CONCLUSION: Strict guideless adherence amongst paediatricians in follow-up of paediatric CD was low and the clinical relevance of the suggested routine laboratory tests is limited. This underlines the increasing notion that evidence-based guidelines on follow-up of CD are warranted.

Intestinal Microbiota in Children With Symptomatic Dientamoeba fragilis Infection: A Case-control Study.

BACKGROUND: Dientamoeba fragilis in children has been associated with gastrointestinal symptoms, like abdominal pain and diarrhea. The mechanism underlying these symptoms in children with D. fragilis remains unclear. We hypothesized that concomitant microbial alterations, which have been described in other parasitic infections, may be associated with gastrointestinal symptoms in D. fragilis. METHODS: In this case-control study performed in 2 centers, 19 children referred to a pediatrician because of gastrointestinal symptoms and with a positive fecal PCR for D. fragilis were included as cases. We included 19 healthy children as controls and matched for age and gender, selected from an existing cohort of 63 children. A PCR for D. fragilis was performed on fecal samples of the 19 controls to assess D. fragilis carriership in this asymptomatic group. Microbiota was analyzed with the IS-pro technique, and the intestinal microbiota composition and diversity were compared between the 2 groups. RESULTS: Microbiota of children with D. fragilis and gastrointestinal symptoms did not significantly differ in terms of composition and diversity compared with controls, both on phylum and species level. In the asymptomatic controls, a positive fecal PCR for D. fragilis was found in 16 of 19 (84.2%). CONCLUSION: Intestinal microbiota does not seem to play a key role in the presence of clinical symptoms in children with D. fragilis. The pathogenicity of D. fragilis and pathophysiologic pathways underlying the development of gastrointestinal symptoms remains yet to be clarified.

Dientamoeba fragilis in children: a systematic review on diagnostic considerations and efficacy of treatment.

Introduction: The presence of D. fragilis in feces is characterized by an asymptomatic carrier ship to a spectrum of gastrointestinal symptoms. However, a causal relationship remains to be elucidated. In this systematic review, we aimed to evaluate the relationship between the eradication of D. fragilis and symptoms to establish the strength of evidence that D. fragilis in symptomatic children warrants antibiotic treatment.Areas covered: This systematic review covers a challenge in daily clinical practice. Is it necessary to test for D. fragilis in children with gastrointestinal symptoms and does a positive fecal PCR test warrant treatment?Expert opinion: Testing for D. fragilis seems justified in a selection of children with persistent unexplained chronic abdominal pain and diarrhea. Treatment of D. fragilis should be withhold until other causes like celiac disease have been excluded. Both microscopic and Real Time-PCR methods (or a combination of the two) can be used for diagnosis. Paromomycin or clioquinol are antibiotics of choice based on their small spectrum of activity, fewer side effects, and better eradication rates than metronidazole. Future randomized studies, with strict inclusion criteria, appropriate diagnostic testing, and doses of antibiotics based on bodyweight are warranted.

Large Variation in Clinical Practice amongst Pediatricians in Treating Children with Recurrent Abdominal Pain.

PURPOSE: To evaluate intra- and inter-observer variability and guideline adherence amongst pediatricians in treating children aged between 4 and 18 years referred with recurrent abdominal pain (RAP) without red flags. METHODS: The first part of the study is a retrospective single-center cohort study. The diagnostic work-ups of eight pediatricians were compared to the national guidelines. Intra- and inter-observer variability were examined by Cramer's V test. Intra-observer variability was defined as the amount of variation within a pediatrician and inter-observer variability as the amount of variation between pediatricians in the application of diagnostic work-up in children with RAP. Prospectively, the same pediatricians were requested to provide a report on their management strategy with a fictitious case to prove similarities in retrospective diagnostic work-up. RESULTS: A total of 10 patients per pediatrician were analyzed. Retrospectively, a (very) weak association between pediatricians' diagnostic work-ups was found (0.22), which implies high inter-observer variability. The association between intra-observer diagnostic was moderate (range, 0.35-0.46). The Cramer's V of 0.60 in diagnostic work-up between pediatricians in the fictitious case implied the presence of a moderately strong association and lower inter-observer variability than in the retrospective study. Adherence to the guideline was 66.8%. CONCLUSION: We found a high intra- and inter-observer variability and moderate guideline adherence in daily clinical practice amongst pediatricians in treating children with RAP in a teaching hospital.

[Coeliac disease in children: a changing clinical spectrum]. / Coeliakie op de kinderleeftijd.

Over the past decades the clinical spectrum of paediatric coeliac disease has profoundly changed, from a classical presentation with distended abdomen, diarrhoea and failure to thrive to more atypical symptoms. These days, children commonly present with symptoms such as recurrent abdominal pain, fatigue, iron deficiency anaemia and constipation. Age at diagnosis has also increased over the past few years. In the past 20 years the incidence of the disease in the Netherlands has increased from 12.3 to 21.1 per 100,000 inhabitants, reaching a stable level in the past 5 years. In approximately 10% of children, serological test results are negative on first examination but become positive after repeated testing in the years that follow, emphasising the need for alertness when first tests are negative and symptoms persist. We underscore the guidelines' advice to apply a low threshold in testing for coeliac disease in children with atypical symptoms.

Pazopanib-related tumor lysis syndrome in metastatic clear cell renal cell carcinoma: a case report.

Introduction Tumor lysis syndrome (TLS) is a life-threatening emergency caused by rapid cell death as a result of anti-tumor therapy. In the era of targeted therapy it has increasingly been observed in solid malignancies such as hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC). Case We describe the case of a 58-year old man with the medical history of a memorial sloan kettering cancer centre (MSKCC) poor prognosis metastasized clear cell renal cell carcinoma (mRCC) who developed TLS within six days after initiating therapy with the tyrosine kinase inhibitor (TKI) pazopanib. Discussion The pharmacokinetics and pharmacodynamics of pazopanib are complex and characterized by a non-linear and time-dependent bioavailability. Pazopanib is almost completely bound to serum albumin (>99.9%). In this presented case, a low serum albumin (26 g/L) might have led to a higher free fraction of pazopanib, which could have resulted in more toxicity. Also, pazopanib is metabolised by the CYP3A4 isoform of the cytochrome P450 group. Low quantities of this enzyme may lead to an impaired and prolonged breakdown of the drug. Conclusion As far as we know this is the first report on pazopanib induced TLS. We advise further research in order to identify the exact mechanism behind TKI-induced TLS and the patients at risk of developing TLS.

Clinical spectrum of paediatric coeliac disease: a 10-year single-centre experience.

This study was undertaken to gain insight in the clinical spectrum of paediatric coeliac disease (CD) in a Dutch teaching hospital. We retrospectively compared the frequency of CD in children with a wide spectrum of complaints with and without CD antibodies in serum and were interested if certain complaints are more pathognomonic for CD. Furthermore, we expected that over a period of 10-year incidence rates of CD would have increased and shifted towards an atypical presentation with more non-gastrointestinal symptoms with increasing age. A retrospective, single-centre, case-control study was performed. All patients who presented at the Department of Paediatrics, Tergooi Hospital, with symptoms suspected for CD were eligible for inclusion during the study period from 1 January 2007 till 31 December 2016. Children were diagnosed with CD according to the 2005 and 2012 ESPGHAN guideline between 2007 and 2016, respectively. Demographic data, presenting symptoms, prevalence of associated conditions and serology results were examined. A total of 105 new cases of paediatric CD were observed, with an average of 10 new cases each year. The calculated incidence was 21.09 (CI 17.49-25.22)/100,000 under 18 years of age. About 40% were infants and toddlers, predominantly presenting with gastrointestinal symptoms. Primary and high school children had more display of atypical symptoms (p = 0.001, p = 0.017) and non-gastrointestinal symptoms (p = 0.009, p = 0.009) than infants and toddlers. In 8.6% of the CD patients, mostly primary school aged female patients, the serology was repeated at least once in time to become positive. The median time for serology to become positive was 609 days (range 140-1054). CONCLUSION: As it is well known, our study supports the increasing notion of a shift in the clinical spectrum of presenting symptoms in paediatric CD towards an atypical presentation, with more non-gastrointestinal symptoms and a diagnosis at a later age in a Dutch population, whereas the number of new cases did not increase over the years. What is Known: • The clinical spectrum of paediatric coeliac disease is shifting towards a presentation with more atypical and non-GI symptoms. • The incidence of paediatric coeliac disease is still increasing as is the age at which it is diagnosed. What is New: • An average of 10 paediatric CD cases are diagnosed per year in our general teaching hospital. • The calculated (gender-specific) incidence rates are higher than previously reported.