Early Serum Infliximab Levels in Pediatric Ulcerative Colitis.

Background: Data on serum infliximab concentrations during induction in pediatric ulcerative colitis are limited. The study aim is to evaluate the relationship between serum infliximab concentrations during induction and short-term clinical remission in children with ulcerative colitis. Methods: We carried out a prospective, multi-center cohort study in pediatric patients with ulcerative colitis. Serum infliximab concentrations were collected at peak dose #1, week 1, trough pre-dose #2, and trough pre-dose #3. Infliximab dosing was left to investigator discretion. Clinical remission was defined by pediatric ulcerative colitis activity index <10 at week 8. Results: Twenty-four of thirty-four subjects (71%) achieved clinical remission at week 8. The median infliximab concentrations were 33.0 µg/mL (interquartile range: 26.5-52.1 µg/mL) pre-dose #2 and 22.5 µg/mL (interquartile range:15.9-32.3 µg/mL) pre-dose #3. Trough pre-dose #2 infliximab concentration yielded area under receiver operator characteristic curve 0.7, 95% CI: 0.5-0.9 in predicting week 8 clinical remission; a cut-off of 33.0 µg/mL yielded 62.5% sensitivity, 66.7% specificity. Trough pre-dose #3 infliximab concentrations were lower for subjects <10 years compared to ≥ 10 years [median 15.9 µg/mL, interquartile range (IQR) 8.5-21.8 µg/mL vs. 27.7 µg/mL, IQR 17.2-46.7 µg/mL, p = 0.01] and correlated with baseline weight (Spearman's rank correlation coefficient 0.45, p = 0.01). The median half-life following first IFX dose was 6.04 days (IQR 5.3-7.9 days). Conclusions: Infliximab concentrations ≥33 µg/mL prior to the second dose were associated with week 8 clinical remission. As young age and low body weight impact infliximab concentration, prospective studies with proactive adjustment in pediatric patients with ulcerative colitis should be carried out. Clinicians caring for children with UC should diligently adjust and monitor infliximab to optimize response.

Transient Elastography in the Evaluation of Cystic Fibrosis-Associated Liver Disease: Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: Complications of cystic fibrosis-associated liver disease (CFLD) are a leading nonpulmonary cause of death. Transient elastography (TE) has recently been investigated to detect CFLD. This study reviews the current literature for TE in the detection CFLD. A meta-analysis was performed to determine the ideal liver stiffness measurement (LSM) cutoff. METHODS: PubMed, Medline, EMBASE and Web of Science were searched from inception until April 2016 for publications involving the detection of CFLD with TE. Data were extracted using a fixed protocol (a priori design) including study design, population characteristics, probe size and AST Platelet Ratio Index (APRI). RESULTS: Diagnostic properties were summarized from six studies of 605 patients. Cutoff for LSM was determined using pooled data submitted by authors. The cutoff for LSM and APRI were ≥5.95 kPa and ≥0.329 respectively, yielding a sensitivity, specificity and area under receiver operator characteristic of 55%, 87%, 0.76, 52%, 93% and 0.84 for LSM and APRI, respectively. When LSM ≥5.95 kPa and APRI ≥0.329, the sensitivity, specificity, positive predictive value and negative predictive value were 43%, 99%, 92% and 87% with a diagnostic odds ratio of 74.9. A bivariate metaregression model showed that pediatric specific cutoffs for liver stiffness and APRI may not be necessary. CONCLUSION: Individually, LSM and APRI have poor sensitivity but good specificity for detecting CFLD. They are most useful when combined. We propose that patients with LSM ≥5.95 kPa and APRI ≥0.329 be investigated thoroughly for the presence of cystic fibrosis-associated liver disease.

Serologic Status of Routine Childhood Vaccines, Cytomegalovirus, and Epstein-Barr Virus in Children With Inflammatory Bowel Disease.

BACKGROUND: Data on the serologic status of childhood vaccines, cytomegalovirus (CMV) and Epstein-Barr virus (EBV), are limited in inflammatory bowel disease (IBD). Therefore, we evaluated vaccine coverage and seroprotection, along with CMV and EBV seropositivity, in pediatric IBD. METHODS: In a cross-sectional study, demographic data, IBD history, vaccine records, and serum for antibodies against measles, mumps, rubella, diphtheria, tetanus, varicella, hepatitis B (HBV), CMV, and EBV were collected from children with IBD. We evaluated potential factors associated with serologic status. RESULTS: Of 156 subjects, vaccine coverage was up to date for age in 93.5% for measles, mumps, rubella, 95.6% for diphtheria, tetanus, pertussis, polio, hemophilus influenza B, 75.8% for HBV, and 93.5% for varicella, including past infection and vaccination. Seroprotection was present in 65.8% for measles, 60.5% for mumps, 79.1% for rubella, 79.5% for diphtheria, 80.8% for tetanus, 70.5% for varicella, and 62.8% for HBV of subjects. Older age at diagnosis was associated with seroprotection among subjects with complete HBV (odds ratio [OR], 1.20; 95% confidence interval [CI], 1.03-1.39) and rubella series (OR, 1.18; 95% CI, 1.02-1.37). Older age at serum collection was associated with seroprotection among subjects with prior varicella vaccination or infection (OR, 1.69; 95% CI, 1.33-2.15). Only 25.2% and 37.8% demonstrated seropositivity to CMV and EBV, respectively. Among subjects on immunosuppressive medications, 75.3% and 62.4% were seronegative for CMV and EBV, respectively. CONCLUSIONS: Children with IBD have low serologic protection to childhood vaccines in spite of high vaccine coverage and universal vaccinations. Children with IBD, including a large proportion on immunosuppressive medications, have low seropositivity to CMV and EBV.

Rising post-colectomy complications in children with ulcerative colitis despite stable colectomy rates in United States.

BACKGROUND AND AIMS: In children with ulcerative colitis, data on temporal colectomy trends and in-hospital post-colectomy complications are limited. Thus, we evaluated time trends in colectomy rates and post-colectomy complications in children with ulcerative colitis. METHODS: We identified all children (≤18years) with a diagnosis code of ulcerative colitis (ICD-9: 556.X) and a procedure code of colectomy (ICD-9: 45.8 and 45.7) in the Kids' Inpatient Database for 1997, 2000, 2003, 2006 and 2009. The incidence of colectomies for pediatric ulcerative colitis was calculated and Poisson regression analysis was performed to evaluate the change in colectomy rates. In-hospital postoperative complication rates were assessed and predictors for postoperative complications were evaluated using multivariate logistic regression. RESULTS: The annual colectomy rate in pediatric ulcerative colitis was 0.43 per 100,000person-years, which was stable throughout the study period (P>.05). Postoperative complications were experienced in 25%, with gastrointestinal (13%) and infectious (9.3%) being the most common. Postoperative complication rates increased significantly by an annual rate of 1.1% from 1997 to 2009 (P=.01). However, other independent predictors of postoperative complications were not identified. Patients with postoperative complications had significantly longer median length of stay (14.3days vs 8.2days; P<.001) and higher median hospital charges per patient (US $81,567 vs US $55,461; P<.001) compared to those without complications. CONCLUSION: Colectomy rates across the United States in children with ulcerative colitis have remained stable between 1997 and 2009; however, in-hospital postoperative complication rates have increased.

Nationwide temporal trends in incidence of hospitalization and surgical intestinal resection in pediatric inflammatory bowel diseases in the United States from 1997 to 2009.

BACKGROUND: Data are limited on temporal trends in outcomes of hospitalization and surgery in pediatric Crohn's disease (CD) and ulcerative colitis (UC). Thus, we evaluated the U.S. nationwide temporal trends for incidence of hospitalization and intestinal resection along with associated resource utilization. METHODS: We used the Kids' Inpatient Database (1997, 2000, 2003, 2006, and 2009) to identify all admissions for children aged 18 years or younger with a primary CD (International Classification of Diseases, Ninth Revision [ICD-9]: 555.X) or UC (ICD-9: 556.X) diagnosis or a secondary CD or UC diagnosis and procedural code of intestinal resection. Poisson regression analysis was performed to evaluate time trends in the incidence of hospitalization, intestinal resection, and hospital resource utilization. RESULTS: The annual incidence of hospitalization was 5.7 and 3.5 per 100,000 children for CD and UC, respectively, with significant increases over time for CD (annual percent increase [API], 3.8%; 95% confidence interval [CI], 3.0%-4.5%) and UC (API, 4.5%; 95% CI, 4.3%-4.7%). Median hospital days per hospitalization for CD and UC remained stable, whereas median charge per hospitalization increased for CD (API, 4.1%; 95% CI, 2.6%-5.6%) and UC (API, 4.7%; 95% CI, 3.5%-5.9%). The annual incidence of intestinal resection remained stable for UC at 0.6 per 100,000 children but climbed for CD (API, 2.1%; 95% CI, 0.1-4.2). CONCLUSIONS: The annual incidence of hospitalization is climbing in pediatric inflammatory bowel diseases, accompanied by rising intestinal resection rates for CD and stable colectomy rates for UC. With escalating resource utilization, the economic and health burden of pediatric inflammatory bowel diseases is substantial.

Immunization history of children with inflammatory bowel disease.

BACKGROUND: Protection against vaccine-preventable diseases is important in children with inflammatory bowel disease (IBD) due to frequent immunosuppressive therapy use. The chronic relapsing nature and treatment regimen of IBD may necessitate modified timing of immunizations. OBJECTIVE: To evaluate the completeness of immunizations in children with IBD. METHODS: Immunization records of all children with IBD followed at the Alberta Children's Hospital (Calgary, Alberta) were reviewed. For children with incomplete immunization according to the province of Alberta schedule, the reasons for such were clarified. Demographic data and age at diagnosis were also collected. RESULTS: Immunization records were obtained from 145 (79%) children with IBD. Fifteen children had incomplete routine childhood immunizations, including two with no previous immunizations. The most common incomplete immunizations included hepatitis B (n=9), diphtheria, tetanus, acellular pertussis at 14 to 16 years of age (n=7), and diphtheria, tetanus, acellular pertussis, inactivated polio at four to six years of age (n=6). The reasons for incomplete immunization included use of immunosuppressive therapy at time of scheduled immunization; IBD-related symptoms at time of scheduled immunization; parental refusal; recent move from elsewhere with different immunization schedule; unawareness of routine immunization; and needle phobia. CONCLUSIONS: Although the majority of children with IBD had complete childhood immunizations, suboptimal immunizations were present in 10%. With increasing use of immunosuppressive therapy in IBD, physicians caring for children with IBD must periodically evaluate immunization status and ensure the completeness of childhood immunizations.

Incidence and prevalence of eosinophilic esophagitis in children.

OBJECTIVES: The aim of the present study was to conduct a systematic review with meta-analysis on the epidemiology of eosinophilic esophagitis (EoE) in children. METHODS: Studies investigating incidence and prevalence of EoE in children (≤ 18 years) were identified in a systematic review of MEDLINE (1950-2011) and Embase (1980-2011). Meta-analyses were performed for incidence and subgroups with ≥ 5 studies: esophagogastroduodenoscopy (EGD) for any indication, histologic esophageal disease, and celiac disease, and EGD for abdominal pain. We used a random effects model, Q statistic to assess heterogeneity, and joinpoint analysis to assess time trends. RESULTS: We included 25 studies. The incidence of EoE varied from 0.7 to 10/100,000 per person-year and the prevalence ranged from 0.2 to 43/100,000. The incidence and prevalence increased over time. Prevalence was highest in children with food impaction or dysphagia (63%-88%). The pooled prevalence was 3.7% (95% confidence interval [CI] 2.4-5.1) in EGD for any indication, 24% (95% CI 19-28) in histologic esophageal disease, 2.3% (95% CI 1.0-3.6) in celiac disease, and 2.6% (95% CI 1.2-4.1) in EGD for abdominal pain. CONCLUSIONS: During the last 2 decades, the incidence and prevalence of EoE in children have increased significantly; however, the population-based incidence and prevalence of EoE vary widely across geographic variations, potentially because of variations in case of ascertainment between centers. Because EoE is common among children with food impaction and dysphagia, children with this presenting complaint should be rapidly identified at triage for timely endoscopic assessment.

Postoperative complications following colectomy for ulcerative colitis in children.

BACKGROUND AND AIMS: Colectomy rates for ulcerative colitis (UC) and data on postcolectomy complications in children are limited. Thus, we assessed colectomy rates, early postcolectomy complications, and clinical predictors in children with UC undergoing a colectomy. METHODS: Children (18 years old or older) with UC who underwent colectomy from 1983 to 2009 were identified (n=30). All of the medical charts were reviewed. The diagnostic accuracy of International Classification of Diseases codes for UC and colectomy were validated. The primary outcome was postoperative complications defined as Clavien-Dindo classification grade II or higher. The yearly incidence of colectomies for pediatric UC was calculated and temporal trends were evaluated. RESULTS: The sensitivity and positive predictive value of UC and colectomy International Classification of Diseases codes were 96% and 100%, respectively. The median ages at UC diagnosis and colectomy were 10.9 and 12.1 years, respectively. All of the children had pancolitis and 63% underwent emergent colectomy. Postoperatively, 33% experienced at least 1 complication. Patients with emergent colectomy were more likely to have a postoperative complication compared with patients with elective colectomy (90% vs 50%; P=0.03). For emergent colectomy, postoperative complications were associated with a disease flare of ≥2 weeks before admission (60% vs 0%; P=0.03) and >2 weeks from admission to colectomy (78% vs 22%; P=0.04). The average annual rate of pediatric colectomy was 0.059/100,000 person-years and stable from 1983 to 2009 (P>0.05). CONCLUSIONS: Colectomy UC was uncommon and rates have remained stable. Postcolectomy complications were common, especially in patients undergoing emergent colectomy. Optimizing timing of colectomy may reduce postoperative complications.

Immunogenicity and safety of influenza vaccination in children with inflammatory bowel disease.

BACKGROUND: Protection against vaccine-preventable diseases is important in inflammatory bowel disease (IBD) because of increased susceptibility and severity of infection with immunosuppressive therapy. However, immunosuppressive therapy may affect vaccine response. This study aimed to evaluate immunogenicity and safety of influenza vaccination in children with IBD. METHODS: In this prospective cohort study, 60 children with IBD and 53 healthy controls had serum collected for preimmunization hemagglutination-inhibition antibody titers to the 2008 inactivated influenza vaccine components. Three to 5 weeks following vaccine [A/Brisbane/10/2007(H3N2), A/Brisbane/59/2007(H1N1), B/Florida/4/2006] administration, all participants had serum collected for postimmunization titers. A 4-fold or greater increase between pre- and postimmunization titers indicated an immunogenic response; a postimmunization titer ≥1:40 indicated serologic protection. Children with IBD were classified into immunosuppression status by therapy. RESULTS: Seventy percent, 72%, and 53% of children with IBD mounted an immunogenic response to H3N2, H1N1, and influenza B components, respectively. Among children with IBD, serologic protection was achieved in 95%, 98%, and 85% to H3N2, H1N1, and influenza B components, respectively. For influenza B, children with IBD were less likely to mount an immunogenic response compared to controls (53% versus 81%, P = 0.0009), and immunosuppressed children with IBD were less likely to achieve serologic protection compared to nonimmunosuppressed children with IBD (79% versus 100%, P = 0.02). The majority (98%) tolerated the vaccine. CONCLUSIONS: Although children with IBD achieve appropriate immunogenicity to influenza A, immunogenicity to influenza B appears to be diminished, especially with immunosuppressive therapy.

Use of complementary and alternative medicine by patients with inflammatory bowel disease.

In this review article we provide a broad overview of complementary and alternative medicine (CAM) use in inflammatory bowel diseases (IBDs), including prevalence of use, common therapies used, and reasons for and factors associated with CAM use. CAM is commonly used by those suffering from IBD. Multiple forms of CAM are used to treat IBD, and often patients use multiple CAM therapies and continue to use conventional medical therapies. Patients using CAM report benefits that extend beyond simply improved disease control. Using CAM allows patients to exert a greater degree of control over their disease and its management than they are afforded by conventional medicine. There is limited evidence on the efficacy of CAM therapies in IBD. It is important for physicians caring for those with IBD to be familiar with common forms of CAM and to be able to provide general counseling to their patients about CAM use.