Comparative Effectiveness of Anti-TNF in Combination With Low-Dose Methotrexate vs Anti-TNF Monotherapy in Pediatric Crohn's Disease: A Pragmatic Randomized Trial.

BACKGROUND & AIMS: Tumor necrosis factor inhibitors, including infliximab and adalimumab, are a mainstay of pediatric Crohn's disease therapy; however, nonresponse and loss of response are common. As combination therapy with methotrexate may improve response, we performed a multicenter, randomized, double-blind, placebo-controlled pragmatic trial to compare tumor necrosis factor inhibitors with oral methotrexate to tumor necrosis factor inhibitor monotherapy. METHODS: Patients with pediatric Crohn's disease initiating infliximab or adalimumab were randomized in 1:1 allocation to methotrexate or placebo and followed for 12-36 months. The primary outcome was a composite indicator of treatment failure. Secondary outcomes included anti-drug antibodies and patient-reported outcomes of pain interference and fatigue. Adverse events (AEs) and serious AEs (SAEs) were collected. RESULTS: Of 297 participants (mean age, 13.9 years, 35% were female), 156 were assigned to methotrexate (110 infliximab initiators and 46 adalimumab initiators) and 141 to placebo (102 infliximab initiators and 39 adalimumab initiators). In the overall population, time to treatment failure did not differ by study arm (hazard ratio, 0.69; 95% CI, 0.45-1.05). Among infliximab initiators, there were no differences between combination and monotherapy (hazard ratio, 0.93; 95% CI, 0.55-1.56). Among adalimumab initiators, combination therapy was associated with longer time to treatment failure (hazard ratio, 0.40; 95% CI, 0.19-0.81). A trend toward lower anti-drug antibody development in the combination therapy arm was not significant (infliximab: odds ratio, 0.72; 95% CI, 0.49-1.07; adalimumab: odds ratio, 0.71; 95% CI, 0.24-2.07). No differences in patient-reported outcomes were observed. Combination therapy resulted in more AEs but fewer SAEs. CONCLUSIONS: Among adalimumab but not infliximab initiators, patients with pediatric Crohn's disease treated with methotrexate combination therapy experienced a 2-fold reduction in treatment failure with a tolerable safety profile. CLINICALTRIALS: gov, Number: NCT02772965.

Isolated Terminal Ileitis in Children.

Isolated terminal ileitis in adults is a well described entity that rarely progresses to Crohn disease (CD), and pediatric literature on this topic is very limited. We describe the prevalence, clinical, endoscopic, histologic, and radiological features, along with long-term outcome of isolated terminal ileitis in our institution. We reviewed charts of 956 children who underwent colonoscopy from 2013 to 2017. Thirty-three children had isolated histologically-defined terminal ileitis. Seventeen children were diagnosed with CD and 16 children had idiopathic terminal ileitis. Children with CD had higher prevalence of abnormal C-reactive protein levels, severe inflammation, and radiological evidence of bowel wall thickening compared with children with idiopathic ileitis. Children with idiopathic ileitis did not develop CD over a follow-up period of 83 months. In contrast to adults, CD is common in children with isolated terminal ileitis and those with idiopathic ileitis do well over long-term.

Analysis of Failure Rates for COVID-19 Entrance Screening at a US Academic Medical Center.

This quality improvement study analyzes the rate of failures in entrance screening for COVID-19 among individuals entering a large academic medical center.

Sustained Improvement in Patient Experience by Optimizing Patient Flow in Ambulatory Settings.

Patient experience has become a priority for healthcare institutions as it affects clinical quality of care, financial reimbursement, provider, and patient satisfaction. We report our experience of improving patient experience measured by Press Ganey surveys in a busy multidisciplinary clinic over 65 months. We optimized patient flow in the clinic by technology-facilitated communication among the clinic staff and by a modest space redesign. We noted a significant improvement in "clinic visit" scores from baseline of 82.1 to 84.6 at year 1, 86.1 at year 2, 88.7 at year 3, and 88.9 at year 4 (P < .001). In comparison with previous short-term studies, we were able to sustain improvement in patient experience scores over 4 years due to optimized patient flow and monitoring of clinic operations. A similar approach can be implemented in other ambulatory settings and is likely to cause a long-term positive impact on patient experience.

A Quality Improvement Project to Improve First Case On-time Starts in the Pediatric Operating Room.

BACKGROUND: Delays in the operating room (OR) can lead to increased hospital costs as well as patient and provider dissatisfaction. Starting the first case on time in the OR can potentially prevent subsequent delays. We designed a quality improvement project to improve the first case on-time starts in the pediatric OR at a tertiary care children's hospital. METHODS: Following the collection of baseline data, we formed an interdisciplinary team. We analyzed the causes of delay and used the Six Sigma methodology of Define, Measure, Analyze, Improve, and Control. We identified key drivers and implemented several low-cost interventions using Plan-Do-Study-Act cycles. Major interventions included preoperative care coordination, strategic staggering of OR cases, and introduction of "Wow Bucks" incentives. We monitored start times and the delay in minutes for all first cases weekly. The OR minutes saved per week were calculated and used to estimate cost savings. RESULTS: We studied a total of 1981 first-start cases from May 2018 to October 2019. The first case on-time starts improved from 62% to 77% over the study period. There was a significant improvement in total minutes delayed for all the first cases from 197.9 minutes per week down to 133 minutes per week (P < 0.05). Estimated cost savings were $4,023 per week due to improved OR utilization. CONCLUSIONS: A multidisciplinary collaborative team approach using quality improvement tools can improve on-time starts in the pediatric OR.

Implementing a Novel Quality Improvement-Based Approach to Data Quality Monitoring and Enhancement in a Multipurpose Clinical Registry.

OBJECTIVE: To implement a quality improvement based system to measure and improve data quality in an observational clinical registry to support a Learning Healthcare System. DATA SOURCE: ImproveCareNow Network registry, which as of September 2019 contained data from 314,250 visits of 43,305 pediatric Inflammatory Bowel Disease (IBD) patients at 109 participating care centers. STUDY DESIGN: The impact of data quality improvement support to care centers was evaluated using statistical process control methodology. Data quality measures were defined, performance feedback of those measures using statistical process control charts was implemented, and reports that identified data items not following data quality checks were developed to enable centers to monitor and improve the quality of their data. PRINCIPAL FINDINGS: There was a pattern of improvement across measures of data quality. The proportion of visits with complete critical data increased from 72 percent to 82 percent. The percent of registered patients improved from 59 percent to 83 percent. Of three additional measures of data consistency and timeliness, one improved performance from 42 percent to 63 percent. Performance declined on one measure due to changes in network documentation practices and maturation. There was variation among care centers in data quality. CONCLUSIONS: A quality improvement based approach to data quality monitoring and improvement is feasible and effective.

Complementary and Alternative Medicine Use in Children With Inflammatory Bowel Disease.

Complementary and alternative medicine (CAM) consists of products and practices that are not considered to be a part of conventional medicine. This article reviews pediatric studies on CAM in inflammatory bowel disease (IBD) along with relevant adult studies. Prevalence of CAM use ranges from 22% to 84% in children with IBD all over the world. CAM use in IBD includes diet changes, supplements, herbals, botanicals, and mind-body therapies. Common reasons for using CAM include severe disease and concern for adverse effects of conventional medicines. Despite widespread use, there are limited studies on efficacy and safety of CAM in children. Small studies suggest a favorable evidence for use of probiotics, fish oil, marijuana, and mind-body therapy in IBD. Adverse effects of CAM are reported but are rare. The article provides current state of knowledge on the topic and provides guidance to physicians to address CAM use in pediatric patients with IBD.

Prevalence of Anti-tissue Transglutaminase Antibodies and Celiac Disease in Children With Inflammatory Bowel Disease.

OBJECTIVES: Celiac disease can occur in children with inflammatory bowel disease (IBD) and poses a diagnostic challenge. We evaluated the presence of anti-tissue transglutaminase (tTG) antibodies and celiac disease among children with IBD. METHODS: In a retrospective chart review, we assessed the prevalence of tTG antibodies and celiac disease and compared with a control group of children with gastrointestinal symptoms without IBD. RESULTS: Study population included 130 children with IBD and 257 in the control group. Abnormal tTG levels were found in 6 and 20 patients, respectively (4.6% vs 7.8%, P = 0.24). One patient with IBD and 12 in the control group had celiac disease (0.8% vs 4.7%, P = 0.07). CONCLUSIONS: False-positive tTG can occur in children with IBD. The prevalence of celiac disease is not increased in children with IBD compared with non-IBD children with gastrointestinal symptoms and is similar to that in the general population.

Correlation of Erythrocyte Sedimentation Rate and C-Reactive Protein With Pediatric Inflammatory Bowel Disease Activity.

We aimed to examine correlation of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) with diagnosis of inflammatory bowel disease and with clinical, endoscopic, histological, and radiographic disease activity during follow-up. We reviewed charts of 135 children with inflammatory bowel disease and correlated their ESR and CRP values with disease activity in various encounters during 5 years. Normal ESR and CRP values were observed in up to 28% of children with Crohn disease and 42% of children with ulcerative colitis at diagnosis, respectively. Correlation of ESR and CRP with Crohn disease clinical, endoscopic, and histologic activity during follow-up depended on their value at diagnosis and mode of analysis (continuous or dichotomous). Both markers were not useful in predicting clinical, endoscopic, or histologic ulcerative colitis disease activity and radiographic small bowel Crohn disease during follow-up.

Prevalence and Patterns of Marijuana Use in Young Adults With Inflammatory Bowel Disease.

OBJECTIVES: Recent studies in adults report symptom relief with marijuana use in patients with inflammatory bowel disease (IBD). We assessed the prevalence, pattern, effects, and adverse effects of marijuana use in young adults with IBD. METHODS: We conducted a prospective questionnaire survey study at a pediatric IBD clinic. All patients (18-21 years of age) answered anonymous questionnaires about demographics, IBD, medications, and marijuana use. RESULTS: Fifty-three patients (mean age 18.7 years, 32 boys) were enrolled. Thirty-seven patients (70%) reported using marijuana currently or in the past. There was no statistically significant difference between the users and nonusers of marijuana regarding demographics, disease activity, or medications. Despite prolonged use of marijuana, 70% of patients did not discuss it with their gastroenterologists. Twenty-four patients used marijuana medicinally for IBD symptoms in addition to medical therapy. Although majority found marijuana to be moderately/very helpful, complete relief of symptoms such as abdominal pain, poor appetite, nausea, and diarrhea was seen in 29%, 37%, 14%, and 10% of patients, respectively. Only half of patients reported knowledge of possible adverse effects of marijuana and 19% of patients reported mild neuropsychiatric adverse effects. Overall, 98% of patients supported legalization of marijuana and 85% were interested in using medical marijuana if it became legally available. CONCLUSIONS: We found a high rate of marijuana use in our cohort of young adults with IBD. Majority of users report symptom improvement but do not inform physicians. Future well-controlled studies are necessary to assess role of marijuana in IBD therapy.

Prevalence and Clinical, Endoscopic, and Pathological Features of Duodenitis in Children.

OBJECTIVES: Although gastritis and esophagitis are well studied in children, there is very limited literature on duodenitis in children. We aimed to assess the prevalence, etiology, clinical, endoscopic, and pathological features in a large cohort of unselected children with duodenitis. METHODS: We reviewed the pathology reports of all the upper endoscopies performed at our institution during 5 years to identify children with duodenitis. Biopsy sections were reviewed to confirm the diagnosis of duodenitis. Demographic, clinical, endoscopic data, and the presence of associated gastritis and esophagitis were noted in all of the children with duodenitis. The etiology of duodenitis was correlated with the patients' clinical diagnosis. RESULTS: Out of 2772 children who had endoscopy, 352 had duodenitis with the prevalence rate of 12.7%. Gastritis was seen in 64% of children with duodenitis compared with 46% of children without duodenitis (P < 0.001). Common indications for endoscopy in children with duodenitis were abdominal pain, positive celiac serology, and diarrhea. The most common etiology was celiac disease (32%), followed by Crohn disease (13%), ulcerative colitis (3%), and Helicobacter pylori infection (6%). In 63% of cases, the endoscopic appearance of duodenum was normal. Cryptitis, villous changes, and cellular infiltration were noted on histology. CONCLUSIONS: Prevalence of duodenitis is 12.7% in children undergoing endoscopy. Celiac disease and inflammatory bowel disease are common causes of duodenitis. Associated gastritis is common in children with duodenitis, and the correlation of endoscopic appearance with histology is poor.

Obesity and gastrointestinal disorders in children.

Obesity in children has become a global pandemic during the last decade. Recent studies have reported an association between obesity and functional gastrointestinal (GI) disorders. In addition, obesity is also becoming increasingly recognized at diagnosis of organic GI diseases such as celiac disease and inflammatory bowel disease. An awareness of all possible complications and associations of obesity by the practicing physician is crucial to provide comprehensive care to obese children. This article reviews the present data on the association between obesity and various common GI disorders. The possible mechanisms and the clinical significance of this association are also discussed.

Histopathology of duodenal mucosal lesions in pediatric patients with inflammatory bowel disease: statistical analysis to identify distinctive features.

Histopathologic lesions of the upper gastrointestinal tract (UGT) are common in inflammatory bowel disease (IBD) patients. Pediatric patients have a higher incidence of IBD-associated gastritis and duodenitis than do adults. This study aimed to identify histopathologic features of duodenal lesions in the pediatric population that are characteristic of IBD, compared to duodenal pathology of different etiopathogenesis. We performed a retrospective analysis of UGT biopsies from pediatric patients with a histopathologic diagnosis of duodenitis (0-18 years of age) over a 7-year period. We identified 40 cases of duodenitis associated with Crohn's disease (CD) and 10 cases associated with ulcerative colitis (UC) and compared the histopathologic characteristics of the duodenitis with age-matched controls consisting of 40 cases duodenitis associated with celiac disease and 40 non-Helicobacter pylori-associated (NOS) etiology duodenitis cases. The histologic features that were evaluated included presence of granulomas, duodenal cryptitis, erosion, lamina propria eosinophils, villous blunting, increased intraepithelial lymphocytes (IELs), and crypt hyperplasia, among others. Additionally, we evaluated the presence of associated gastritis in all of these groups. Statistical analysis to identify significant differences was performed using Kruskal-Wallis testing. Cryptitis was the most distinctive feature of IBD-associated duodenitis. Granulomas were exceptionally rare. The severity of villous blunting and presence of IELs was significantly different in the IBD versus the celiac group. There is a significant overlap with duodenal lesions of different etiopathogenesis, including villous blunting and eosinophilia. With the exclusion of granulomas, cryptitis seems the most distinctive feature of the duodenal lesions associated with IBD.