Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir Mini-Tabs Plus Ribavirin for Children Aged 3-11 Years with Hepatitis C Genotype 1a.

INTRODUCTION: To assess the safety, efficacy, and pharmacokinetics of mini-tablet formulations of ombitasvir (OBV), paritaprevir (PTV), ritonavir, and dasabuvir (DSV) with or without ribavirin for 12 weeks in children infected with chronic hepatitis C virus (HCV) genotype (GT) 1. METHODS: This is an ongoing, open-label, Phase 2/3 study in children 3-11 years old infected with HCV GT1 who were HCV treatment-naïve and non-cirrhotic. Pediatric mini-tablet formulations of OBV, PTV, ritonavir, and DSV plus ribavirin oral solution were administered for 12 weeks based on body weight. Endpoints included SVR12, adverse events (AEs), and pharmacokinetic parameters. RESULTS: Overall, 26 children received OBV, PTV, ritonavir, and DSV plus ribavirin; 14 were 3-8 years old and 12 were 9-11 years old; 35% were male; and all had chronic HCV GT1a infection. The SVR12 rate was 96% (25/26; 95% CI 81.1-99.3), with 1 child failing to achieve SVR12 due to non-adherence and treatment discontinuation. Treatment-emergent AEs of Grade ≥ 3 occurred in 3 children; 2 events in 1 child were considered serious; and none were considered treatment-related. No AEs led to discontinuation of study treatment. The most common AEs were headache (27%), fatigue (23%), pyrexia (19%), and vomiting (19%). Pharmacokinetic results showed mini-tablet formulations of OBV, PTV, DSV, and ritonavir drug exposures were comparable to the adult formulation. CONCLUSION: The mini-tablet combination of OBV, PTV, ritonavir, and DSV plus ribavirin to treat HCV GT1a infection for 12 weeks was highly effective and suitable in children 3-11 years of age. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02486406.

Health-related quality of life in youth with Crohn disease: role of disease activity and parenting stress.

OBJECTIVES: Health-related quality of life (HRQOL) is an important, but understudied construct in pediatric inflammatory bowel disease. Family level predictors of HRQOL have been understudied as are the mechanisms through which disease activity affects HRQOL. The present study examines the relation between a family level factor (parenting stress) and HRQOL in youth with Crohn disease. Parenting stress is examined as a mechanism through which disease activity affects HRQOL. METHODS: A total of 99 adolescents with Crohn disease and their parents were recruited across 3 sites. Adolescents completed the IMPACT-III (inflammatory bowel disease-specific HRQOL). Parents completed the Pediatric Inventory for Parents, a measure of medically related parenting stress that assesses stress because of the occurrence of medical stressors and stress because of the perceived difficulty of stressors. Disease activity was obtained from medical records. RESULTS: Parenting stress because of the occurrence of medical stressors partially mediated the disease severity-HRQOL relation, reducing the relation between these variables from 49.67% to 31.58% (B= -0.56, P < 0.0001). Bootstrapping analysis confirmed that the indirect effect of disease severity on HRQOL via parenting stress significantly differed from zero. Parenting stress because of the perceived difficulty of medical stressors partially mediated the disease severity-HRQOL relation, reducing the relation from 49.67% to 30.29% (B= -0.55, P < 0.0001). The indirect effect was confirmed via bootstrapping procedures. CONCLUSIONS: As disease severity increased, parenting stress also increased, and adolescent HRQOL decreased. Parenting stress should be considered and assessed for along with medical factors as part of a comprehensive approach to improve HRQOL in adolescents with Crohn disease.

Elevated Alkaline Phosphatase in Children: An Algorithm to Determine When a "Wait and See" Approach is Optimal.

Due to the possibility of underlying hepatobiliaryor bone diseases, the diagnostic work up of a child with elevated alkaline phosphatase (AP) levels can be quite costly. In a significant proportion of these patients, elevated AP is benign, requiring no intervention: hence, known as transient hyperphosphatasemia (THP) of infants and children. A 27-month old previously healthy Caucasian female was found to have isolated elevation of AP four weeks after the initial symptoms of acute gastroenteritis. One month later, when seen in hepatobiliary clinic, signs and symptoms of gastrointestinal, hepatobiliary, or bone disease were absent and physical examination was normal. The diagnosis of THP was made, and, as anticipated, AP levels normalized after four months. Using this case as an example, we suggest an algorithm that can be utilized as a guide in a primary care setting to arrive at the diagnosis of THP and avoid further tests or referrals.

Pancreatic disease in children and adolescents.

Many childhood pancreatic disorders are rare, although they can represent significant and potentially severe disease. The spectrum of disease is very broad, ranging from the complex and bizarre congenital anomalies to the more typical acquired causes (e.g., drug-induced pancreatitis or trauma injury). Genetics appears to play a major role in many childhood pancreas diseases, unlike adults where alcohol is a major factor. Nevertheless, there are similarities, and most of the disorders discussed here can be found in both the pediatric and adult age groups. Some of these disorders may be evolving and may be seen in both young and older patients. Newer imaging modalities and therapeutic endoscopy continue to be studied, although their ultimate role and utility in children has yet to be fully elucidated.

Brief report: the association between peer victimization, prosocial support, and treatment adherence in children and adolescents with Inflammatory Bowel Disease.

OBJECTIVE: To examine the relationship between peer victimization, prosocial support, and treatment adherence in children and adolescents with Inflammatory Bowel Disease (IBD). METHOD: Thirty-eight children diagnosed with IBD, between the ages of 7-19 years, and their parents were recruited from an outpatient Gastroenterology Clinic. Each child completed the Social Experience Questionnaire. The child, parent, and treating physician completed a one-item measure of child medication adherence. RESULTS: Child reported positive social interactions moderated the relationship between child reported peer victimization and self-reported medication adherence (t = -2.09; p = .045). These relationships held when parent report of child adherence was substituted for child reported adherence in this model (t = -2.37; p = .024). CONCLUSIONS: The findings from this pilot study suggest that prosocial support may buffer children with IBD from experiencing the more negative effects of peer victimization on treatment adherence and highlight the importance of social interactions in youth with IBD. Implications for treatment are discussed.

Antibodies to Escherichia coli outer membrane porin C in the absence of anti-Saccharomyces cerevisiae antibodies and anti-neutrophil cytoplasmic antibodies are an unreliable marker of Crohn disease and ulcerative colitis.

OBJECTIVES: Antibodies to Escherichia coli outer membrane porin C (anti-OmpC), Saccharomyces cerevisiae, and neutrophil-specific nuclear antigens are associated with inflammatory bowel disease (IBD) in children and young adults. We hypothesized that anti-OmpC, in the absence of anti-S cerevisiae antibodies (ASCA) and antineutrophil cytoplasmic antibodies (ANCA), is an assay that overestimates the presence of Crohn disease (CD) and ulcerative colitis (UC). PATIENTS AND METHODS: A retrospective review of patients evaluated at our institution between January 2002 and June 2006 revealed that 170 had serodiagnostic immunological assays performed as part of an evaluation for possible IBD. The assays were screened for a pattern in which anti-OmpC was present in the absence of ASCA and ANCA. RESULTS: Seven patients between 3 and 20 years of age were discovered to be positive for anti-OmpC but negative for ASCA and ANCA. These patients were determined to have significant medical conditions without combined radiographic, endoscopic, or histological evidence of IBD. Despite the reported 85% positive predictive value of anti-OmpC for IBD, none of the 7 patients with isolated anti-OmpC had a diagnosis of CD or UC. CONCLUSIONS: Anti-OmpC, in the absence of ASCA and ANCA, is a serological pattern noted in a subset of medically complex cases in children and young adults without CD or UC.

Comparison of the 13C-urea blood test to histology and rapid urease testing in the diagnosis of Helicobacter pylori infection in children.

OBJECTIVE: Helicobacter pylori infection is commonly investigated in children with abdominal pain. The definitive means of diagnosing infection, histology, requires endoscopy and sedation, making it invasive and expensive. Our objective was to compare histology against a less invasive and safer method, the 13C-urea blood test. PATIENTS AND METHODS: Forty children with abdominal pain undergoing upper endoscopy were randomized into either of 2 dosages of 13C-urea. Several biopsies were taken for histology and rapid urease testing. After endoscopy, each child ingested a randomly assigned dosage of either 75 mg or 125 mg 13C-urea, and blood was withdrawn 30 min later. RESULTS: Irrespective of the dosage of 13C-urea, the 13C-urea blood test performed with high accuracy (89%) when compared against either histology or rapid urease testing. The sensitivity and specificity of the blood test was 83% and 91%, respectively. When the smaller dosage of 13C-urea was used, the accuracy of the blood test was 100% compared with histology. There were no adverse events related to using either dosage of 13C-urea. CONCLUSIONS: The 13C-urea blood test may be comparable with histology in diagnosing H. pylori infection in children, and the smaller dosage of 13C-urea does not adversely affect blood test performance. The 13C-urea blood test is well tolerated in children.