Missed Opportunities in Guideline-Based Fatty Liver Screening Among 3.5 Million Children.

OBJECTIVE: Determine screening rates and examine socio-demographic characteristics of metabolic dysfunction-associated steatotic liver disease (MAFLD) screening in a large population of obese children. METHODS: We used Explorys (IBM) which contains aggregated population-level electronic health record data from approximately 360 hospitals and 317,000 providers across the United States to determine MAFLD screening rates. In children 10 to 14 years, obesity was determined based on body mass index ≥ 95%, or encounter with an international classification of disease obesity code. We determined screening rates by calculating the percentage of children with obesity who had an alanine aminotransferase tested, further analyzed by gender, race, and insurance. RESULTS: Of 3,558,420 children, 513,170 (14.4%) were obese. Of obese children, only 9.3% were screened for MAFLD. Females were more likely screened than males (odds ratio (OR) 1.09 (95% confidence intervals (CI): 1.07-1.12)); White children were more likely screened than non-White children (OR 1.21 (95% CI: 1.18-1.23)), and children with Medicaid more likely screened than children with non-Medicaid insurance (OR 1.34 (95% CI: 1.32-1.37)). CONCLUSIONS: The percentage of obese children receiving screening for MAFLD was low. Female gender, White race, and Medicaid insurance were associated with increased screening rates. These findings highlight the need to increase adherence to MAFLD screening. Reporting screening as a health quality measure may reduce implementation gaps in MAFLD screening.

Adolescent Hepatitis C: Prevalence, Impact, and Management Challenges.

The prevalence of Hepatitis C virus infection (HCV), a leading cause of chronic liver disease worldwide, is rising in the United States (US) and other high-income countries, especially among youth and young adults. This surge in cases is closely associated with the opioid crisis and intravenous drug use (IVDU). However, its prevalence and impact on the adolescent population have not been thoroughly studied and therefore is poorly understood. The pediatric population tends to have milder liver disease and progression when compared to adults; however, there is a risk of developing liver cirrhosis, in addition to facing decreased quality of life and stigmatization from the disease. The recent approval of direct-acting antiviral (DAA) regimens for all HCV genotypes and age greater than 3 years has revolutionized its management. Therapy has shifted from the prolonged interferon-based regimens, to shorter duration, once daily oral pills that are highly effective, curative and with fewer side effects. Therapy is now indicated for all adolescents with hepatitis C virus infection, regardless of stage of liver disease, recent IVDU, or coinfection with HIV, therefore eliminating a lifetime risk of chronic liver disease, cirrhosis and hepatocarcinoma. Nonetheless, adolescents are rarely tested or treated for hepatitis C infection, and very few adolescents complete therapy. Implementation of point of care (POC) testing of high-risk youth at drug treatment centers or other juvenile facilities may be a good strategy to increase testing, diagnosis and therapy. This review article aims to educate pediatricians and other primary care providers to help decrease the existing knowledge gap on the subject.

Burden of Psychiatric Disorders among Pediatric and Young Adults with Inflammatory Bowel Disease: A Population-Based Analysis.

PURPOSE: There is increasing prevalence of psychiatric disorders among inflammatory bowel Disease (IBD) population. Further, presence of psychiatric disorders has been shown as an independent predictor of quality of life among patients with IBD. We intended to explore the prevalence of various psychiatric disorders among pediatric and young adult population with IBD as a population-based analysis. METHODS: We did a retrospective case control analysis using a deidentified cloud-based database including health care data across 26 health care networks comprising of more than 360 hospitals across USA. Data collected across different hospitals were classified and stored according to Systematized Nomenclature of Medicine-Clinical Terms. We preidentified 10 psychiatric disorders and the queried the database for the presence of at least one of the ten psychiatric disorders among IBD patients between 5 and 24 years of age and compared with controls. RESULTS: Total of 11,316,450 patients in the age group between 5 and 24 years and the number of patients with a diagnosis of IBD, Crohn's disease or ulcerative colitis were 58,020. The prevalence of psychiatric disorders was 21.6% among IBD mainly comprising of depression and anxiety disorder. Multiple logistic regression analysis showed, IBD is 5 times more likely associated with psychiatric disorders than controls, p<0.001). We showed a steady increasing trend in the incidence of psychiatric disorders among IBD patients (2% in 2006 to 15% in 2017). CONCLUSION: Largest population-based analysis demonstrated an increased prevalence of psychiatric disorders among IBD patients. Our study emphasizes the need for psychological and mental health services to be incorporated as a part of the routine IBD clinic.

Clinical Characteristics of Children Needing Inpatient Treatment after Failed Outpatient Treatment for Fecal Impaction.

PURPOSE: Treatment of chronic constipation and fecal impaction is usually outpatient and requires high or frequent doses of laxatives. However, there are children who fail outpatient treatments, sometimes repeatedly, and are ultimately hospitalized. We sought to compare the characteristics of the children who failed outpatient treatment and needed inpatient treatment vs those who achieved success with outpatient treatment, in an effort to identify attributes that might be associated with a higher likelihood towards hospitalization. METHODS: In this retrospective cohort study, we reviewed the medical records of all patients aged 0 to 21 years, with chronic functional constipation and fecal impaction seen in the pediatric gastroenterology clinic over a period of 2 years. RESULTS: Total of 188 patients met inclusion criteria. While 69.2% were successfully treated outpatient (referred to as the outpatient group), 30.9% failed outpatient treatment and were hospitalized (referred to as the inpatient group). The characteristics of the inpatient group including age at onset of 3.6±3.6 years (p=0.02); black ethnicity (odds ratio [OR] 4.31, 95% confidence interval [95% CI] 2.04-9.09); p<0.001); prematurity (OR 2.39, 95% CI 1.09-5.26; p=0.02]; developmental delay (OR 2.20, 95% CI 1.12-4.33; p=0.02); overflow incontinence (OR 2.26, 95% CI 1.12-4.53, p=0.02); picky eating habits (OR 2.02, 95% CI 1.00-4.08; p=0.04); number of ROME III criteria met: median 4, interquartile range 3-5 (p=0.04) and 13±13.7 constipation related prior encounters (p=0.001), were significantly different from the outpatient group. CONCLUSION: Identification of these characteristics may be helpful in anticipating challenges and potential barriers to effective outpatient treatment.

Usefulness of Assessment of Stool Form by the Modified Bristol Stool Form Scale in Primary Care Pediatrics.

PURPOSE: Rome criteria are considered the gold standard for diagnosing functional constipation. The modified Bristol stool form scale (m-BSFS) was validated to measure stool form in children. However, neither the potential use of the m-BSFS as a tool to facilitate the diagnosis of potential constipation, nor the agreement between m-BSFS and stool consistency by Rome has been studied. Our objective is to determine if m-BSFS is a reliable tool to facilitat detection of constipation; and the agreement between stool form by m-BSFS and hard stool criteria in Rome. METHODS: A survey tool with the Rome III criteria and the m-BSFS was developed. A Likert-scale addressed frequency of each stool form on the m-BSFS. Responses to Rome III and m-BSFS were compared. RESULTS: The sensitivity and specificity of the m-BSFS was 79.2% and 66.0% respectively; and in children <4 years. improved to 81.2% and 75.0% respectively. There was poor agreement between hard stools by m-BSFS and the painful or hard bowel movement question of Rome Criteria. CONCLUSION: The potential utility of m-BSFS as a reasonably good tool to facilitate the diagnosis of potential constipation in children is shown. The poor agreement between painful or hard stool question in Rome III, and ratings for hard stool on the m-BSFS illustrates that one's perception may differ between a question and a picture. A useful pictorial tool to appraise stool form may, thus, be a favorable complement in the process of enquiry about bowel habits in well-child care.

Health-related quality of life in children with autoimmune liver disease.

BACKGROUND AND AIM: Health-related quality of life (HRQOL), a pivotal outcome indicator of health care interventions, has not been evaluated in children with autoimmune liver disease (AILD). The aim of this study was to determine HRQOL in children with AILD and the factors affecting it. METHODS: The Pediatric Quality Of Life Inventory, generic core scale, was used to collect HRQOL data on children with AILD. Specific liver disease-related questions were added. RESULTS: Survey responses were received from 30 of 40 patients. Patients' mean age at diagnosis was 11.6 ± 4.5 years, with M:F ratio of 1:1.3, and AILD for average of 4.6 ± 4.3 years. Seventy-three percent of patients had advanced liver disease. Mean overall health summary scores for the group per child and parent reports were 71.6 ± 19.0 and 71.3 ± 17.1, respectively, which were lower than healthy controls: 83.9 ± 12.5 and 82.3 ± 15.6 (P = 0.002). Frequent liver-related symptoms were associated with impaired physical and school functioning by child (P = 0.034 and 0.047) and parent reports (P = 0.051 and P = 0.018). Abdominal pain, fatigue, and psychological symptoms were found to adversely affect the HRQOL. Although it was difficult to estimate the effect of individual features of advanced liver disease such as cirrhosis, history of upper gastrointestinal bleed, and portal hypertension on the HRQOL, because of a relatively small sample size, the presence of ascites revealed lower social functioning score per parent report (P = 0.036). In an analysis of patients with any of the above complications versus those without, however, children reported lower social functioning scores (P = 0.018). There were no differences in HRQOL scores in children with autoimmune hepatitis versus primary sclerosing cholangitis versus autoimmune hepatitis/primary sclerosing cholangitis overlap syndrome. CONCLUSIONS: First study to date shows that AILD in children significantly affects HRQOL, especially with frequent liver disease-related symptoms, even in early stages of disease. Findings need to be validated in larger, multicenter studies and will help practitioners understand their patients better and optimize care.

Enhancement of humoral and cellular immunity with an anti-glucocorticoid-induced tumour necrosis factor receptor monoclonal antibody.

Adjuvants, including antibodies to tumour necrosis factor receptor superfamily members, augment immune responses. One member of this family, glucocorticoid-induced tumour necrosis factor receptor (GITR), is expressed at low levels on naive/resting T cells, B cells and macrophages, but at higher levels on T regulatory cells. The aim of this study was to determine the ability of a rat anti-mouse GITR monoclonal antibody, 2F8, to stimulate murine humoral and cellular immunity in a prime boost model with particular attention to posology and antigen-specific effects. 2F8 enhanced the humoral immune response to ovalbumin and haemagglutinin (HA) compared with controls and this enhancement was equal to or greater than that obtained in mice dosed with standard adjuvants. 2F8 F(ab')(2) fragments were as effective as intact antibody in boosting humoral immunity, indicating that FcR-mediated cross-linking of 2F8 is not required for efficacy. Moreover, the enhanced response was durable and antigen specific. Administration of 2F8 shifted the immune response towards a T helper type 1 response with significant enhancement of immunoglobulin G2a- and G2b-specific anti-HA antibodies, as well as enhanced cellular immunity as measured by ELISPOT. 2F8-treated mice also generated significantly more neutralizing antibodies to HA than control mice. Our findings show that anti-GITR is a robust, versatile adjuvant that, unlike commonly used adjuvants that primarily enhance humoral immunity, enhances both humoral and cellular immunity. These results support the continued development of anti-GITR for such indications as haematological and solid tumours, chronic viral infections, and as a vaccine adjuvant.

Use and safety of rifaximin in children with inflammatory bowel disease.

BACKGROUND: Rifaximin, Food and Drug Administration approved for traveler's diarrhea, has been used in adult patients with active inflammatory bowel disease (IBD). This retrospective review was undertaken to determine its role in the treatment of pediatric IBD. METHODS: A review of children with IBD, who were treated with rifaximin from 2005 to 2007 at our institution, was performed. Collected data included diagnosis, age, medication history, recent therapy, symptom, and interval to improvement. Response was rated as none, moderate, or optimum relief for each symptom. RESULTS: Twenty-three patients were identified, 12 with Crohn disease and 11 with ulcerative colitis (UC) with a median age of 13 years. The most common complaints were diarrhea in 20 patients (87%), abdominal pain in 17 (74%), and bloody stools in 15 (65%). Rifaximin was given at doses ranging between 10 and 30 mg/kg (Table 1). Of the 20 patients who presented with diarrhea 5 (25%) had relief of diarrhea within 1 week of starting rifaximin and total of 12 patients (60%) experienced relief within 4 weeks. Abdominal pain resolved in 3 of 17 patients (17.6%) within 1 week and in 12 of 17 (70.6%) within 4 weeks. Visible bleeding resolved in 10 of 15 patients (66.7%) within 4 weeks of therapy (Table 2). Analysis of concurrent medications showed 61% experienced relief of symptoms when addition of rifaximin was the only meaningful treatment change. CONCLUSIONS: Rifaximin was well-tolerated and showed favorable results. Larger doses of rifaximin were statistically better for abdominal pain. Further studies are needed to evaluate efficacy and optimal dosing of rifaximin in this population.