Publications (59) View all
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Article: Relationship Between Azathioprine Dosage and Thiopurine Metabolites in Pediatric IBD Patients: Identification of Covariables Using Multilevel Analysis.
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ABSTRACT: : Previous studies have reported no or only a very poor correlation between 6-methylmercaptopurine/6-thioguanine nucleotide (6-MeMPN/6-TGN) and azathioprine (AZA) dose in the treatment of inflammatory bowel disease (IBD). However, metabolite levels are often repeatedly measured yielding a hierarchical data structure that requires more appropriate data analysis. : This study explored the relationship between the weight-based dosage of AZA and metabolites levels in 86 pediatric IBD patients using multilevel analysis. Other covariates related to patient characteristics and treatment were evaluated. : This is the first study to demonstrate positive correlations between AZA dose and 6-TGN and 6-MeMPN levels and 6-MeMPN/6-TGN ratio (P < 0.001) in IBD children. Other novel predictors of metabolites were reported. Younger children exhibited lower 6-TGN and 6-MeMPN levels, probably suggesting age-related differences in metabolism and/or absorption of thiopurines. Coadministration of infliximab resulted in a significant increase in 6-TGN levels (P = 0.023). Moreover, alanine aminotransferase values positively correlated with 6-MeMPN levels (P = 0.032). The duration of AZA therapy, gender, and thiopurine methyltransferase activity were associated with metabolite levels. The wide interindividual variability in metabolite levels that accounted for 67.7%, 48.6%, and 49.4% of variance in the 6-TGN and 6-MeMPN levels and the ratio, respectively, were confirmed. : The reliable AZA dose-metabolites relationship is useful for clinicians to guide the dosing regimen to maximize clinical response and minimize side effects or to consider alternative therapies when patients have preferential production of the toxic 6-MeMPN. These results may be of potential interest for optimizing thiopurine therapy to achieve safe and efficacious AZA use in pediatric IBD patients.Therapeutic drug monitoring 04/2013; 35(2):251-7. · 2.43 Impact Factor -
Article: Multifaceted intervention to enhance the screening and care of hospitalised malnourished children: study protocol for the PREDIRE cluster randomized controlled trial.
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ABSTRACT: BACKGROUND: Hospital malnutrition is an underestimated problem and as many as half of malnourished patients do not receive appropriate treatment. In order to extend the management of malnutrition in health care facilities, multidisciplinary teams focusing on clinical nutrition were established in France. The establishment of such teams within hospital facilities remains nonetheless difficult. We have consequently developed a multifaceted intervention coordinated by a Nutritional Support Team (NST). Our study aims to evaluate the impact of this multifaceted intervention coordinated by a NST, in adherence to recommended practices for the care of malnourished children, among health care workers of a paediatric university hospital.Methods/design: We carried out 1) a six-month observational phase focusing on the medical care procedures relative to malnourished children followed by 2) a cluster randomised controlled trial phase to evaluate the impact of a multidisciplinary nutrition team over an 18 month time frame.Based on power analyses and assuming a conservative intracluster correlation coefficient, 1289 children were needed to detect a 25% difference in rates between the two groups of the cluster trial.The implementation of our intervention was coordinated by the NST and had three major components: a) access to a computerised malnutrition screening system associated with an automatic alert system, b) an awareness campaign directed toward the health care workers and c) a leadership based strategy.Main outcomes included the number of daily weighings during hospitalisation, the investigation of malnutrition etiology and the management of malnutrition by a dietician and/or the NST.Due to the clustered nature of the data with children nested in departments, a generalized estimated equations approach will be used to analyse the impact of the multifaceted intervention on primary and secondary outcomes. DISCUSSION: Our results will provide an overall response regarding the effectiveness of our multifaceted intervention and we should be able to suggest an organization and mode of operation of NST.Trial registration: ClinicalTrials.gov: NCT01081587.BMC Health Services Research 03/2013; 13(1):107. · 1.66 Impact Factor -
Article: Improving outcomes of biliary atresia: French national series 1986-2009.
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ABSTRACT: This study analyses the prognosis of biliary atresia (BA) in France since liver transplantation (LT) became widely available. METHODS: The charts of all BA patients living in France and born between 1986 and 2009 were reviewed. Patients were divided into 3 cohorts according to their years of birth: 1986-96, 1997-2002 and 2003-2009. RESULTS: 1107 BA children were identified, 990 born in metropolitan France (incidence 1/18400 live births). Kasai operation was performed in 1044 (94%), leading to complete clearance of jaundice (total serum bilirubin ⩽ 20 μmol/l) in 38% of patients. Survival with native liver (SNL) after Kasai operation was 40%, 36% and 30% at 5, 10 and 20 years, stable in the 3 cohorts. Median age at Kasai operation was 59 days, unchanged over time. Twenty-year SNL was 39%, 32%, 28% and 19% after Kasai operation performed in the first, second, third months of life or thereafter (p=0.0002). 588 children underwent 692 LTs. Mortality without transplantation decreased over time: 16%, 7% and 4% in the 3 cohorts (p<0.0001). Survival after transplantation was 83%, 82% and 77% at 5, 10 and 20 years in the whole series. Five-year post transplant survival was 75%, 90% and 89% in the 3 cohorts (p<0.0001). In the whole series, overall BA patient survival was 81%, 80% and 77% at 5, 10 and 20 years. Five-year BA patient overall survival increased over time: 72%, 88% and 89% in the 3 cohorts (p<0.0001). CONCLUSION: BA patients currently have a 89% live expectancy, and a 30% chance to reach adulthood without transplantation. Early Kasai operation, without age threshold, reduces the need for liver transplantation till adulthood.Journal of Hepatology 02/2013; · 9.26 Impact Factor -
Article: Mosaic 18q21.2 deletions including the TCF4 gene: A clinical report.
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ABSTRACT: Pitt-Hopkins syndrome (PTHS) is characterized by distinctive facial dysmorphism, profound intellectual disability, and the possible occurrence of epilepsy and breathing anomalies. It is caused by haploinsufficiency of the TCF4 gene. No significant difference in clinical severity has been reported to date between PTHS patients carrying 18q21 deletions including the TCF4 gene, and those harboring TCF4 point mutations, suggesting a lack of genotype/phenotype correlation. Moreover, the size of 18q21 deletions including the TCF4 gene does not appear to have a significant effect on the phenotypic severity, suggesting that TCF4 haploinsufficiency is the most important prognostic factor in 18q deletions. We describe two unrelated patients presenting with clinical features reminiscent of PTHS and carrying mosaic interstitial 18q21 deletions characterized by array comparative genomic hybridization. One of the patients presented the lowest level of mosaic 18q21 deletion reported to date (5-10%). Our report and a review of the literature show that the mosaic status does not appear to have a significant effect on the clinical severity of 18q21 deletions, which are associated with a poor neurological outcome, whereas a mosaic TCF4 point mutation can result in a significantly milder phenotype. Malformations of internal organs are currently considered to be rare in PTHS. The patients described here had visceral anomalies, suggesting that a full morphological assessment, including heart and abdominal ultrasound scans, should be performed systematically in PTHS patients. © 2012 Wiley Periodicals, Inc.American Journal of Medical Genetics Part A 11/2012; · 2.39 Impact Factor -
Article: Evaluation of a point-of-care test based on deamidated gliadin peptides for celiac disease screening in a large pediatric population.
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ABSTRACT: OBJECTIVES: Celiac disease (CD) is nowadays known to be a common chronic enteropathy that is becoming a growing public health concern. Yet, it is estimated that more than 90% of patients remain undiagnosed. A point-of-care diagnostic test can be a rapid and cost-effective solution in the first-line screening of CD. The aim of this study is to evaluate the performance of a novel point-of-care screening test in a large pediatric population. MATERIALS AND METHODS: Serum samples were collected from a cohort of 250 children presenting either an increased risk or a clinical suspicion of CD. All sera were tested using the point-of-care test detecting IgA and IgG antibodies against a combination of three different deamidated gliadin peptides as well as total IgA. The results of the screening test were compared with an enzyme-linked tissue transglutaminase immunosorbent assay and with histology resulting from intestinal biopsies performed in patients with elevated titers of antitissue transglutaminase antibodies. RESULTS: The point-of-care test showed highly concordant results with the laboratory immunoassay, yielding a sensitivity of 93.1 (78-98.1%) and a specificity of 95% (91.2-97.2%), with a diagnostic accuracy of 94.8% (91.3-96.9%) and a negative predictive value of 99.1% (96.6-99.7%). The screening test identified all patients with celiac-type histology findings on biopsy, as well as all patients with concomitant IgA deficiency. CONCLUSION: With a high diagnostic accuracy, this novel point-of-care approach is an efficient tool for CD case finding in pediatric populations. It has the potential to improve the management of celiac patients in primary care by providing faster counseling and treatment.European journal of gastroenterology & hepatology 09/2012; · 1.66 Impact Factor
