A Pilot Study of Ketotifen in Patients Aged 8-17 Years with Functional Dyspepsia Associated with Mucosal Eosinophilia.

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.

If we know better, why don't we do better? A rapid quality improvement project to increase utilization of comfort measures to reduce pain and distress in children in a COVID-19 mass vaccination clinic.

INTRODUCTION: Many evidence-based tools exist to address pain and distress associated with injections; however, there remains a large gap between the knowledge of these tools and their utilization. Our hospital began a quality improvement (QI) project prior to COVID-19, with the goal of increasing the utilization of Comfort Promise measures during needle procedures. When COVID-19 vaccinations were approved, our mass vaccination clinics provided an opportunity to rapidly increase utilization across the institution. The primary aim was to increase the percentage of comfort measures (CM) offered with COVID-19 vaccinations. METHODS: Through this QI project, nurses and other professionals implemented CMs during COVID mass vaccination clinics. Clinics occurred in 3 age-based waves. Waves served as Plan-Do-Study-Act (PDSA) cycles. Families completed post-vaccination surveys to determine what CMs were offered and intention for future use with vaccinations. RESULTS: Uptake of CMs (PainEase, ShotBlockers, Comfort Positioning, Alternative Focus, Topical Lidocaine, and Breastfeeding/Sucrose) throughout the waves increased and generally remained stable. CMs also seemed to decrease pain/distress with vaccinations (70.5 to 88.7%), and children/caregivers intended to use some combination for future vaccinations (82.5 to 98.5%). CONCLUSIONS: Fast-paced mass vaccination clinics provided an ideal opportunity to significantly increase utilization of CMs. Across age groups CMs yielded high satisfaction and interest in future utilization. Clinic nurses returned to their own sub-specialties and became change agents. IMPLICATIONS: If all healthcare providers can work together to achieve consensus while incorporating comfort measures into daily practice, sustained change with incorporation of these evidence-based tools can be achieved. Future directions are discussed.

An Update on the Assessment and Management of Pediatric Abdominal Pain.

Chronic abdominal pain is very common in children and adolescent and results in high personal and social costs. Most youth with chronic abdominal pain fulfill criteria for a functional abdominal pain disorder (FAPD) as defined by Rome criteria. These are complex conditions with a wide array of biological, psychological, and social factors contributing to the experience of pain. The purpose of the current review is to provide an overview of the pathophysiology of FAPDs and an up-to-date summary of the literature related to FAPDs in children and adolescents, with additional focus on several areas (eg, diet and probiotics) where patients and families frequently have questions or implement self-directed care. We also provide an approach to the assessment and treatment of pediatric FAPDs focusing on the robust literature regarding psychological interventions and much sparser literature regarding medication treatment.

Heartburn in children and adolescents in the presence of functional dyspepsia and/or irritable bowel syndrome correlates with the presence of sleep disturbances, anxiety, and depression.

ABSTRACT: The aim of this study was to assess the relationship of heartburn in pediatric patients with functional dyspepsia (FD) and irritable bowel syndrome (IBS) with gastrointestinal symptoms, sleep disturbances, and psychologic distress.The overlap in symptoms of FD, IBS, and gastroesophageal reflux disease (GERD) predicts greater symptom severity and decreased quality of life and presents opportunities for improved diagnostic classification and personalized therapeutics.A cross-sectional observational study of 260 pediatric patients with abdominal pain was conducted. Patients completed standardized questionnaires assessing clinical symptoms, sleep quality, and psychologic symptoms during routine clinical care. Questionnaire data were compared for patients reporting heartburn and not reporting heartburn using χ2 and t tests where appropriate.Gastrointestinal symptoms were significantly more prevalent among patients with a positive report of heartburn (vs a negative report of heartburn): pain with eating (83% vs 67%, P = .007), bloating (63% vs 44%, P = .005), acid regurgitation (47% vs 24%, P ≤ .001), and chest pain (45% vs 20%, P ≤ .001). Likewise, initiating and maintaining sleep (P = .007), arousal/nightmares (P = .046), sleep-wake transition (P = .001), hyperhidrosis during sleep (P = .016), and anxiety (P = .001) and depression (P = .0018) were also significantly increased in patients who reported heartburn versus patients who did not report heartburn.Patients with a positive report of heartburn, whether classified as having FD and/or IBS, had increased gastrointestinal symptoms, sleep disturbances, anxiety, and depression than patients with a negative report of heartburn. A better understanding of these associations may allow for personalized treatment for youth with abdominal pain and heartburn as a primary symptom.

Readiness to Change and Prospective Effects of Weight Management Programs in Pediatric Nonalcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is an increasing problem in pediatrics with limited treatment options. We prospectively assessed outcomes in patients managed in a hepatology clinic (HC) alone vs. those managed in combination with a multidisciplinary weight management program (MWMP). We describe each group's readiness to change at the time of NAFLD diagnosis. Patients diagnosed with NAFLD were given a modified Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES) at enrollment (T1) to assess readiness to change. They were then followed at 3-9 months (T2) and at 10-15 months (T3). Linear mixed models were used to evaluate changes in body mass index (BMI), BMI z-score, and transaminases over time and between the two groups. There were no significant treatment group main effects or treatment × time interactions for our primary end points for HC alone (n = 75) or with MWMP (n = 18). There was a significant main effect for time for BMI z-score, with BMI z-scores declining on average by 0.0568 (P = 0.004) from visit to visit. Low SOCRATES subscales scores in HC alone (n = 33) or with MWMP (n = 4) suggested a patient population with low recognition of disease and likelihood of taking steps for change. Patients with obesity and NAFLD had low scores on all three SOCRATES subscales. Despite this, both groups had improvement in BMI z-score without significant difference between the two treatment groups in other primary end points. Further study is needed to identify the most effective patient selection and treatment strategies for pediatric patients with NAFLD, including pharmacotherapy and surgery.

Electrogastrographic and autonomic nervous system responses to solid and liquid meals in youth with functional dyspepsia.

BACKGROUND: Meal-related symptoms are common in paediatric functional dyspepsia (FD). There are only a small number of paediatric studies assessing mechanisms for meal-related symptoms, and these have not utilized Rome IV criteria. The aim of the current study was to assess gastric myoelectric and autonomic nervous system (ANS) responses to both liquid and solid meals in youth with Rome IV-defined FD. METHODS: In healthy controls (N = 14) and youth with FD (N = 12), we recorded electrocardiograph (to assess heart rate variability; HRV) and electrogastrograph (EGG) signals before and after two test meals, one liquid and one solid. EGG parameters and HRV were assessed for the entire pre- and postprandial periods and in short time intervals. Additionally, liquid gastric emptying was assessed utilizing a 13 C-acetate breath test. KEY RESULTS: During the EGG, the dominant power increased with both meals in controls but not patients with FD. During HRV assessment, the low frequency to high frequency ratio was higher after the liquid meal in controls, despite being similar preprandial, as compared to patients with FD. In controls, both standard deviation of normal to normal waves (SDNN) and root mean square of successive ECG R peaks (R-R interval) differences (rMSSD) increased after the liquid meal (but not after the solid meal) in controls but not patients with FD. CONCLUSIONS AND INFERENCES: Youth with Rome IV-defined FD lacks the normal postprandial EGG dominant power response or autonomic nervous system response following a liquid meal. The latter appears to indicate a lack of ANS flexibility.

Heart Rate Variability and Gastric Electrical Response to a Cold Pressor Task in Youth with Functional Dyspepsia.

BACKGROUND/AIMS: While stress has been implicated in functional dyspepsia (FD), the mechanisms by which stress results in symptoms are not well defined. The aim of the current study was to assess gastric myoelectric and autonomic changes in response to a physical stressor in youth with FD. METHODS: In a group of healthy controls and pediatric FD subjects, we recorded ECG and EGG signals 30 min before and 60 min after, a cold pressor task (CPT). Gastric EGG and heart rate variability (HRV) parameters were calculated in pre- and post-CPT stages and in short intervals. RESULTS: The pre-CPT percent tachygastria was higher in FD subjects as compared to controls. However, CPT did not induce any EGG changes in either controls or FD subjects and the two groups did not differ from each other post-CPT. The CPT resulted in an increase in HRV and standard deviation of NN intervals in controls; there was no change in any HRV parameter in FD subjects. CONCLUSIONS: Acute physical stress does not appear to induce gastric electrical abnormalities in youth with FD. Youth with FD appear to lack the normal flexible autonomic response to a physical stressor.

Evaluation of clinical outcomes in an interdisciplinary abdominal pain clinic: A retrospective, exploratory review.

BACKGROUND: Pediatric functional gastrointestinal disorders (FGIDs) are common and well-accepted to be etiologically complex in terms of the contribution of biological, psychological, and social factors to symptom presentations. Nonetheless, despite its documented benefits, interdisciplinary treatment, designed to address all of these factors, for pediatric FGIDs remains rare. The current study hypothesized that the majority of pediatric patients seen in an interdisciplinary abdominal pain clinic (APC) would demonstrate clinical resolution of symptoms during the study period and that specific psychosocial variables would be significantly predictive of GI symptom improvement. AIM: To evaluate outcomes with interdisciplinary treatment in pediatric patients with pain-related FGIDs and identify patient characteristics that predicted clinical outcomes. METHODS: Participants were 392 children, ages 8-18 [M = 13.8; standard deviation (SD) = 2.7], seen between August 1, 2013 and June 15, 2016 in an interdisciplinary APC housed within the Division of Gastroenterology in a medium-sized Midwestern children's hospital. To be eligible, patients had to be 8 years of age or older and have had abdominal pain for ≥ 8 wk at the time of initial evaluation. Medical and psychosocial data collected as part of standard of care were retrospectively reviewed and analyzed in the context of the observational study. Logistic regression was used to model odds of reporting vs never reporting improvement, as well as to differentiate rapid from slower improvers. RESULTS: Nearly 70% of patients followed during the study period achieved resolution on at least one of the employed outcome indices. Among those who achieved resolution during follow up, 43% to 49% did so by the first follow up (i.e., within roughly 2 mo after initial evaluation and initiation of interdisciplinary treatment). Patient age, sleep, ease of relaxation, and depression all significantly predicted the likelihood of resolution. More specifically, the odds of clinical resolution were 14% to 16% lower per additional year of patient age (P < 0.001 to P = 0.016). The odds of resolution were 28% to 42% lower per 1-standard deviation (SD) increase on a pediatric sleep measure (P = 0.006 to P < 0.040). Additionally, odds of clinical resolution were 58% lower per 1-SD increase on parent-reported measure of depression (P = 0.006), and doubled in cases where parents agreed that their children found it easy to relax (P = 0.045). Furthermore, sleep predicted the rapidity of clinical resolution; that is, the odds of achieving resolution by the first follow up visit were 47% to 60% lower per 1-SD increase on the pediatric sleep measure (P = 0.002). CONCLUSION: Outcomes for youth with FGIDs may be significantly improved by paying specific attention to sleep, ensuring adequate skills for relaxation, and screening of and referral for treatment of comorbid depression.

Using quality improvement methods to increase use of pain prevention strategies for childhood vaccination.

AIM: To increase evidence-based pain prevention strategy use during routine vaccinations in a pediatric primary care clinic using quality improvement methodology. METHODS: Specific intervention strategies (i.e., comfort positioning, nonnutritive sucking and sucrose analgesia, distraction) were identified, selected and introduced in three waves, using a Plan-Do-Study-Act framework. System-wide change was measured from baseline to post-intervention by: (1) percent of vaccination visits during which an evidence-based pain prevention strategy was reported as being used; and (2) caregiver satisfaction ratings following the visit. Additionally, self-reported staff and caregiver attitudes and beliefs about pain prevention were measured at baseline and 1-year post-intervention to assess for possible long-term cultural shifts. RESULTS: Significant improvements were noted post-intervention. Use of at least one pain prevention strategy was documented at 99% of patient visits and 94% of caregivers were satisfied or very satisfied with the pain prevention care received. Parents/caregivers reported greater satisfaction with the specific pain prevention strategy used [t(143) = 2.50, P ≤ 0.05], as well as greater agreement that the pain prevention strategies used helped their children's pain [t(180) = 2.17, P ≤ 0.05] and that they would be willing to use the same strategy again in the future [t(179) = 3.26, P ≤ 0.001] as compared to baseline. Staff and caregivers also demonstrated a shift in attitudes from baseline to 1-year post-intervention. Specifically, staff reported greater agreement that the pain felt from vaccinations can result in harmful effects [2.47 vs 3.10; t(70) = -2.11, P ≤ 0.05], less agreement that pain from vaccinations is "just part of the process" [3.94 vs 3.23; t(70) = 2.61, P ≤ 0.05], and less agreement that parents expect their children to experience pain during vaccinations [4.81 vs 4.38; t(69) = 2.24, P ≤ 0.05]. Parents/caregivers reported more favorable attitudes about pain prevention strategies for vaccinations across a variety of areas, including safety, cost, time, and effectiveness, as well as less concern about the pain their children experience with vaccination [4.08 vs 3.26; t(557) = 6.38, P ≤ 0.001], less need for additional pain prevention strategies [3.33 vs 2.81; t(476) = 4.51, P ≤ 0.001], and greater agreement that their doctors' office currently offers pain prevention for vaccinations [3.40 vs 3.75; t(433) = -2.39, P ≤ 0.05]. CONCLUSION: Quality improvement methodology can be used to help close the gap in implementing pain prevention strategies during routine vaccination procedures for children.

Adaptation of the State-Trait Inventory for Cognitive and Somatic Anxiety for Use in Children: A Preliminary Analysis.

OBJECTIVE: Anxiety has both state/trait and cognitive/somatic dimensions, and these distinctions may be particularly relevant for children with medical problems. This two-part study adapted the State-Trait Inventory for Cognitive and Somatic Anxiety (STICSA) and confirmed its factor structure in a sample of children in a primary care clinic. METHODS: STICSA items were adapted for reading level and piloted in a small group of children. Next, 250 children (12.3 ± 2.7 years) completed the adapted version, the STICSA-C. RESULTS: Separate confirmatory factor analyses conducted on the State and Trait forms of the STICSA-C confirmed the two-factor structure of the original measure (i.e., cognitive and somatic anxiety) and suggested an improved parsimonious model. CONCLUSIONS: Support was found for use of the STICSA-C as a reasonably good internally consistent measure for assessing cognitive and somatic anxiety in pediatric samples. Further investigation of its reliability and validity with replication in pediatric populations is warranted.

Investigation of potential early Histologic markers of pediatric inflammatory bowel disease.

BACKGROUND: Early manifestations of pediatric inflammatory bowel disease (IBD) can be relatively nonspecific. Initial mucosal biopsies may not be conclusive, delaying the diagnosis until subsequent biopsies demonstrate typical histologic features of IBD. We hypothesized that certain inflammatory cell types may be utilized as early histologic indicators of IBD in children. METHODS: A retrospective analysis compared histologic findings from initially inconclusive or negative endoscopic studies in 22 patients who were subsequently diagnosed with IBD (after diagnostic endoscopy) to those of 20 comparison patients with functional abdominal pain matched for age, gender, and study type. A pediatric pathologist, blinded to study group, reviewed biopsies for histologic abnormalities. Eosinophil densities were obtained from the stomach, duodenum, and rectosigmoid areas. Immunohistochemistry (IHC) staining for tumor necrosis factor-α (TNF-α) and matrix metalloproteinase-9 (MMP-9) was performed on the stomach and rectosigmoid areas. RESULTS: Gastritis and colonic crypt distortion were present in the IBD group at a greater rate (61 % vs. 22 %, p = 0.020; 34 % vs. 4 %, p = 0.008, respectively). Peak and mean eosinophil densities in the rectosigmoid area were greater in the IBD group (17.0/hpf vs. 5.0/hpf, p = 0.0063; 12.3/hpf vs. 4.2/hpf, p = 0.0106, respectively). TNF-α and MMP-9 staining did not reveal any significant differences. CONCLUSIONS: Our data suggests that significantly greater inflammation in the stomach, crypt distortion in the colon, and eosinophilia in the rectosigmoid distinguished the IBD group from the comparison group at the time of the initial endoscopic evaluation.

No guts, no glory: models of integrated care within a GI subspecialty practice.

The focus in pediatric medicine has shifted from a concentration on mortality and morbidity to a more comprehensive view encompassing the physical, social, and psychological aspects of health. What follows is a description of four integrated, collaborative care clinics within the GI subspecialty at Children's Mercy Kansas City that specifically address this trend in pediatric healthcare. With these descriptions, we hope to inform broader acceptance and utilization of similar models across other pediatric populations.