RÉSUMÉ
BACKGROUND AND OBJECTIVE: Mast cells have been implicated in abdominal pain-associated disorders of gut-brain interaction, such as functional dyspepsia. As such, ketotifen, a second-generation antihistamine and mast cell stabilizer, could represent a viable treatment option in these conditions. The primary aim of the current pilot study was to assess clinical response to ketotifen and assess pharmacokinetics in youth with functional dyspepsia. METHODS: We conducted a pilot randomized, double-blind, placebo-controlled, cross-over trial of ketotifen in 11 youth with functional dyspepsia and duodenal mucosal eosinophilia with 4 weeks of active treatment at a dose of 1 mg twice daily. Global clinical response was graded on a 5-point Likert Scale. A single plasma sample was obtained at steady state for pharmacokinetic analysis. RESULTS: Ketotifen was not superior to placebo with regard to global clinical response. Only 18% of patients demonstrated a complete or near-complete clinical response. The estimated half-life was 3.3 h. CONCLUSIONS: While ketotifen was not superior to placebo, this study highlights several important challenges for developing drug trials for youth with chronic abdominal pain. Recommendations are made for designing a larger treatment trial for ketotifen in this patient group. CLINICAL TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov: NCT02484248.
Sujet(s)
Études croisées , Dyspepsie , Éosinophilie , Kétotifène , Humains , Kétotifène/pharmacocinétique , Kétotifène/usage thérapeutique , Kétotifène/administration et posologie , Kétotifène/pharmacologie , Projets pilotes , Enfant , Adolescent , Dyspepsie/traitement médicamenteux , Méthode en double aveugle , Femelle , Mâle , Éosinophilie/traitement médicamenteux , Antihistaminiques des récepteurs H1/pharmacocinétique , Antihistaminiques des récepteurs H1/usage thérapeutique , Antihistaminiques des récepteurs H1/administration et posologie , Muqueuse intestinale/métabolisme , Douleur abdominale/traitement médicamenteux , Douleur abdominale/étiologie , Résultat thérapeutiqueRÉSUMÉ
The liver is the primary organ responsible for clearing most drugs from the body and thus determines systemic drug concentrations over time. Drug clearance by the liver appears to be directly related to organ size. In children, organ size changes as children age and grow. Liver volume has been correlated with body surface area (BSA) in healthy children and adults and has been estimated by functions of BSA. However, these relationships were derived from "typical" populations and it is unknown whether they extend to estimations of liver volumes for population "outliers," such as children with overweight or obesity, who today represent one-third of the pediatric population. Using computerized tomography or magnetic resonance imaging, this study measured liver volumes in 99 children (2-21 years) with normal weight, overweight, or obesity and compared organ measurements with estimates calculated using an established liver volume equation. A previously developed equation relating BSA to liver volume adequately estimates liver volumes in children, regardless of weight status.
Sujet(s)
Surface corporelle , Foie/anatomie et histologie , Obésité/physiopathologie , Surpoids/physiopathologie , Adolescent , Enfant , Enfant d'âge préscolaire , Jeux de données comme sujet , Femelle , Élimination hépatobiliaire , Humains , Foie/imagerie diagnostique , Foie/métabolisme , Imagerie par résonance magnétique/statistiques et données numériques , Mâle , Taux de clairance métabolique , Taille d'organe/physiologie , Études rétrospectives , Tomodensitométrie/statistiques et données numériques , Jeune adulteRÉSUMÉ
Obesity is the single greatest risk factor for nonalcoholic fatty liver disease (NAFLD). Without intervention, most pediatric patients with NAFLD continue to gain excessive weight, making early, effective weight loss intervention key for disease treatment and prevention of NAFLD progression. Unfortunately, outside of a closely monitored research setting, which is not representative of the real world, lifestyle modification success for weight loss in children is low. Bariatric surgery, though effective, is invasive and can worsen NAFLD postoperatively. Thus, there is an evolving and underutilized role for pharmacotherapy in children, both for weight reduction and NAFLD management. In this perspective article, we provide an overview of the efficacy of weight reduction on pediatric NAFLD treatment, discuss the pros and cons of currently approved pharmacotherapy options, as well as drugs commonly used off-label for weight reduction in children and adolescents. We also highlight gaps in, and opportunities for, streamlining obesity trials to include NAFLD assessment as a valuable, secondary, therapeutic outcome measure, which may aid drug repurposing. Finally, we describe the already available, and emerging, minimally-invasive biomarkers of NAFLD that could offer a safe and convenient alternative to liver biopsy in pediatric obesity and NAFLD trials.
Sujet(s)
Mode de vie , Stéatose hépatique non alcoolique/traitement médicamenteux , Obésité/physiopathologie , Perte de poids , Enfant , Humains , Stéatose hépatique non alcoolique/anatomopathologie , Pronostic , Facteurs de risqueRÉSUMÉ
Abdominal pain has been associated with disaccharidase deficiencies. While relationships with individual symptoms have been assessed, relationships between disaccharidase deficiencies and symptom complexes or inflammation have not been evaluated in this group. The primary aims of the current study were to assess relationships between disaccharidase deficiency and symptoms or symptom complexes and duodenal inflammation, respectively. Patients with abdominal pain who underwent endoscopy with evaluation of disaccharidase activity levels were identified. After excluding all patients with inflammatory bowel disease, celiac disease, H. pylori, or gross endoscopic lesions, patients were evaluated for disaccharidase deficiency frequency. Disaccharidase were compared between patients with and without histologic duodenitis. Lastly, relationships between individual gastrointestinal symptoms or symptom complexes were evaluated. Lactase deficiency was found in 34.3% of patients and disaccharidase pan-deficiency in 7.6%. No individual symptoms or symptom complexes predicted disaccharidase deficiency. While duodenitis was not associated with disaccharidase deficiency, it was only present in 5.9% of patients. Disaccharidase deficiency, particularly lactase deficiency, is common in youth with abdominal pain and multiple deficiencies are not uncommon. Disaccharidase deficiency cannot be predicted by symptoms in this population. Further studies are needed to assess the clinical significance of disaccharidase deficiency.
Sujet(s)
Douleur abdominale/métabolisme , Disaccharidases/déficit , Duodénite/métabolisme , Inflammation/métabolisme , Adolescent , Enfant , Femelle , Humains , Mâle , Études rétrospectivesRÉSUMÉ
Meckel's diverticulum (MD) is a well-defined diagnosis in children presenting with either bleeding or obstruction. Although anecdotally adult patients may present with complications from MD, their presentation seems to be different, with a reported predominance of non-bleed-related presentations. Reports in this population, however, are limited, and little is known of the epidemiology of MD in older patients. We performed a retrospective analysis of the Agency of Healthcare Research and Quality National Inpatient Sample of all US hospital discharges from 2012 to 2016. We identified patients with a primary discharge diagnosis of MD. Data were abstracted as raw numbers and population weighted rates of discharge with age group, income level, length of stay (LOS) and hospital charges as additional information. On average, 2030 individuals were discharged annually; most (71.1%) were adults (>18 years). Although MD was predominant in males in all age groups, the gender ratio decreased with older age categories from 3.5:1.0 (1-17 years) to 1.6:1.0 (65-84 years). LOS averaged 5.3 days with no clear relationship to other parameters. Median income category, however, closely correlated (R2=0.9996) with diagnosis in older age categories. MD may be significantly more prevalent in adult patients than was previously understood. Differences in gender preponderance suggest that gender may influence the pattern of presentation. Diagnosis in older individuals is closely associated with income or socioeconomic status but not hospital charges or LOS.
Sujet(s)
Laparoscopie , Diverticule de Meckel , Adolescent , Sujet âgé , Sujet âgé de 80 ans ou plus , Enfant , Enfant d'âge préscolaire , Hémorragie gastro-intestinale , Humains , Nourrisson , Durée du séjour , Mâle , Diverticule de Meckel/diagnostic , Diverticule de Meckel/épidémiologie , Diverticule de Meckel/chirurgie , Études rétrospectivesRÉSUMÉ
Nonalcoholic fatty liver disease (NAFLD) affects up to 70% of children with obesity and has become the number one etiology for liver transplant in the United States. Early, effective intervention is critical to prevent disease progression into adulthood. Yet, it is seldom achieved through lifestyle modification alone. Thus, children must be included in NAFLD pharmacology trials, which, to date, continue to focus primarily on adult populations. This commentary serves as a call to action.