Renal Response Outcomes of the EuroLupus and National Institutes of Health Cyclophosphamide Dosing Regimens in Childhood-Onset Proliferative Lupus Nephritis.

OBJECTIVE: We compared clinical characteristics and renal response in patients with childhood-onset proliferative lupus nephritis (LN) treated with the EuroLupus versus National Institutes of Health (NIH) cyclophosphamide (CYC) regimen. METHODS: A retrospective cohort study was conducted at 11 pediatric centers in North America that reported using both CYC regimens. Data were extracted from the electronic medical record at baseline and 3, 6, and 12 months after treatment initiation with CYC. To evaluate the adjusted association between CYC regimen (EuroLupus vs NIH) and renal response over time, generalized estimating equations with a logit link were used. An interaction between time and CYC regimen was included, and a contrast between CYC regimens at 12 months was used to evaluate the primary outcome. RESULTS: One hundred forty-five patients (58 EuroLupus, 87 NIH) were included. EuroLupus patients were on average older at the start of current CYC therapy, had longer disease duration, and more commonly had relapsed or refractory LN compared with the NIH group. After multivariable adjustment, there was no significant association between CYC regimen and achieving complete renal response at 12 months (odds ratio [OR] of response for the EuroLupus regimen, reference NIH regimen: 0.76; 95% confidence interval [CI] 0.29-1.98). There was also no significant association between CYC regimen and achieving at least a partial renal response at 12 months (OR 1.35, 95% CI 0.57-3.19). CONCLUSION: Our study failed to demonstrate a benefit of the NIH regimen over the EuroLupus CYC regimen in childhood-onset proliferative LN. However, future prospective outcome studies are needed.

Creative Arts Therapy Among Children With Cancer: Symptom Assessment Reveals Reduced Anxiety.

BACKGROUND: Symptom distress is related to decreased quality of life (QOL) among children with cancer, with high levels of pain, nausea, and anxiety reported. Creative arts therapy (CAT) has been related to improved QOL and symptoms in pediatric oncology, but the quality of evidence is mixed. OBJECTIVE: This article aims to examine the QOL symptom subscales in relation to CAT over time in children during the first year of cancer treatment. METHODS: A secondary analysis of prospective data was performed with linear mixed modeling on 267 observations with predictors of 2 groups: No CAT (n = 18) vs CAT (n = 65). The covariate of time (6 months) was used to explore the CAT relationship with the Pediatric Quality of Life Inventory (PedsQL) symptom subscales (pain and hurt, nausea, procedural anxiety, treatment anxiety, worry, cognitive problems, perceived physical appearance, and communication). RESULTS: Children (n = 83) were between 3 and 17 years old (M = 6), 51.2% female, and 32% minority. All tumor types were represented: liquid (37.3%), solid (24.1%), and central nervous system (38.6%). Reduced child report of procedural anxiety was significantly related to receiving CAT with a medium magnitude of association (adjusted effect size = 0.58, P = .01). CONCLUSION: Creative arts interventions were associated with a longitudinal improvement in anxiety in children with cancer. Further work is needed to target interventions to the appropriate specific burdensome symptoms. IMPLICATION FOR PRACTICE: Pediatric oncology nurses can advocate for CAT as an effective intervention to ameliorate the burdensome procedural anxiety experienced by patients.

Medication Adherence Rates in Adolescents With Eosinophilic Esophagitis Are Low and Are Associated With Health Habits.

Although swallowed topical steroids are effective in inducing histological remission in eosinophilic esophagitis (EoE), their efficacy is limited by treatment nonadherence. In this study, we objectively measured adherence rates to swallowed topical steroids in adolescents with EoE over the course of 8 weeks and analyzed the association between adherence rate, disease and demographic features, symptom severity, and medication-taking habit strength. We found that approximately 20% of adolescents with EoE were over-dosing on their medications. After excluding these patients, mean adherence rate was 67.0% (±19.4%) and median adherence rate was 63% (interquartile range 53%-88%). Adherence was not associated with demographic features, disease history, symptom severity, or quality of life but was associated with habit strength (Pearson r = 0.48, P = 0.04). These findings suggest that habit strength may serve as a potential target for interventions aimed at improving adherence in adolescents with EoE.

Examining Disparities in Pediatric Eosinophilic Esophagitis.

BACKGROUND: Little is known regarding the impact of race, ethnicity, and socioeconomic status on the health outcomes of children with eosinophilic esophagitis (EoE). OBJECTIVE: To (1) identify demographic characteristics of children diagnosed with EoE in a large tertiary care center, and (2) determine associations between a patient's demographics and depth of evaluation or treatment choices. METHODS: This retrospective cohort study included children 0 to 18 years old seen in Children's Hospital Colorado between January 1, 2009, and December 31, 2020. Demographics were extracted from the electronic medical record. Rural-Urban Commuting Area taxonomy codes were used to classify urbanization. Area Deprivation Index (ADI) scores were used to categorize neighborhood advantage/disadvantage. Data were analyzed using descriptive statistics and regression analysis. RESULTS: The study included 2,117 children with EoE. Children with higher state ADI scores (greater neighborhood disadvantage) had less radiographic evaluation of their disease (odds ratio [95% CI] per unit increase in state ADI = 0.93 [0.89-0.97]; P = .0002) and had esophageal dilations at younger ages (r = -0.24; P = .007). Black children compared with White children were younger at diagnosis (8.3 y vs 10.0 y; P = .002). Children from rural areas were seen less by feeding therapy (3.9% vs 9.9%; P = .02), but were younger at their visits (2.3 y vs 4.3 y; P < .001). CONCLUSIONS: In this study of children with EoE cared for in a large tertiary care center, we found differences in presentation and care depending on race, urbanization, and socioeconomic status.

The spectrum of eating environments encountered in free living adults documented using a passive capture food intake wearable device.

Introduction: The aim of this feasibility and proof-of-concept study was to examine the use of a novel wearable device for automatic food intake detection to capture the full range of free-living eating environments of adults with overweight and obesity. In this paper, we document eating environments of individuals that have not been thoroughly described previously in nutrition software as current practices rely on participant self-report and methods with limited eating environment options. Methods: Data from 25 participants and 116 total days (7 men, 18 women, Mage = 44 ± 12 years, BMI 34.3 ± 5.2 kg/mm2), who wore the passive capture device for at least 7 consecutive days (≥12h waking hours/d) were analyzed. Data were analyzed at the participant level and stratified amongst meal type into breakfast, lunch, dinner, and snack categories. Out of 116 days, 68.1% included breakfast, 71.5% included lunch, 82.8% included dinner, and 86.2% included at least one snack. Results: The most prevalent eating environment among all eating occasions was at home and with one or more screens in use (breakfast: 48.1%, lunch: 42.2%, dinner: 50%, and snacks: 55%), eating alone (breakfast: 75.9%, lunch: 89.2%, dinner: 74.3%, snacks: 74.3%), in the dining room (breakfast: 36.7%, lunch: 30.1%, dinner: 45.8%) or living room (snacks: 28.0%), and in multiple locations (breakfast: 44.3%, lunch: 28.8%, dinner: 44.8%, snacks: 41.3%). Discussion: Results suggest a passive capture device can provide accurate detection of food intake in multiple eating environments. To our knowledge, this is the first study to classify eating occasions in multiple eating environments and may be a useful tool for future behavioral research studies to accurately codify eating environments.

Approaches to analyzing binary data for large-scale A/B testing.

An industry-academic collaboration was established to evaluate the choice of statistical test and study design for A/B testing in larger-scale industry experiments. Specifically, the standard approach at the industry partner was to apply a t-test for all outcomes, both continuous and binary, and to apply naïve interim monitoring strategies that had not evaluated the potential implications on operating characteristics such as power and type I error rates. Although many papers have summarized the robustness of the t-test, its performance for the A/B testing context of large-scale proportion data, with or without interim analyses, is needed. Investigating the effect of interim analyses on the robustness of the t-test is important, because interim analyses rely on a fraction of the total sample size and one should ensure that desired properties are maintained when a t-test is implemented not just at the end of the study, but for making interim decisions. Through simulation studies, the performance of the t-test, Chi-squared test, and Chi-squared test with Yate's correction when applied to binary outcomes data is evaluated. Further, interim monitoring through a naïve approach with no correction for multiple testing versus the O'Brien-Fleming boundary are considered in designs that allow early termination for futility, difference, or both. Results indicate that the t-test achieves similar power and type I error rates for binary outcomes data with the large sample sizes used in industrial A/B tests with and without interim monitoring, and naïve interim monitoring without corrections leads to poorly performing studies.

Evolution of postoperative care: marked reduction of opioid consumption when ERAC pathway added to wound soaker therapy for cesarean delivery.

OBJECTIVE: Achieving functional recovery after cesarean delivery is critical to a parturient's ability to care for herself and her newborn. Adequate pain control is vital, and without it, many other aspects of the recovery process may be delayed. Reducing opioid consumption without compromising analgesia is of paramount importance, and enhanced recovery pathways have generated considerable interest given their ability to facilitate this. Our group's process for reducing opioid consumption for cesarean delivery patients evolved over time. We first demonstrated that providing additional incisional pain control with continuous bupivacaine infusions through wound catheters, with the concurrent use of neuraxial morphine, reduced postoperative opioid use. Iterations of an enhanced recovery after cesarean (ERAC) delivery pathway were then implemented after the Society for Obstetric Anesthesia and Perinatology's consensus statement for ERAC was issued to eliminate variability in both hospital course and in the treatment of postoperative pain. In this retrospective cohort analysis, we sought to identify whether adding ERAC protocols to our existing combination of neuraxial morphine and wound soaker catheters further reduced opioid consumption after cesarean delivery. METHODS: A retrospective cohort analysis of cesarean deliveries from 2015 through 2020 was performed. Deliveries were divided by analgesic pathway into four time-periods - time-point 1 [January 2015-April 2016, previous standard of care (control, N = 61)]: neuraxial morphine in addition to as needed opioid and non-opioid analgesics; time-point 2 [May 2016-May 2019, introduction of wound soaker (wound-soaker, N = 40)]: continuous wound catheter infusions of local anesthetic, neuraxial morphine in addition to as needed opioid and non-opioid analgesics; time-point 3 [May 2019-December 2019, wound soaker + early ERAC pathway (early ERAC, N = 78)]: continuous wound catheter infusion of local anesthetic, neuraxial morphine, in addition to scheduled non-opioid analgesics (acetaminophen and ibuprofen) every 6 h, alternating in relation to one another so that one is given every 3 h; time-point 4 [January 2020-July 2020, wound soaker + late ERAC pathway (late ERAC, N = 57)]: continuous wound catheter infusion of local anesthetic, neuraxial morphine in addition to non-opioid analgesics scheduled together every 6 h (to facilitate periods of uninterrupted rest). Cumulative and average daily opioid use for postoperative days (POD) 1-4 were analyzed using ANOVA and a mixed effect model, respectively. RESULTS: Average daily opioid consumption and total cumulative opioid consumption POD 1-4 (morphine milligram equivalents) for both early and late ERAC groups (23.9 ± 31.1 and 29.4 ± 35.1) were significantly reduced compared to control and wound soaker groups (185.1 ± 93.7 and 134.8 ± 77.1) (p < .001). CONCLUSION: The addition of ERAC protocols to our standardized multimodal analgesic regimen (local anesthetic wound infusion catheters and neuraxial morphine) for cesarean delivery significantly reduced postoperative opioid consumption.

Body mass index and variability in meal duration and association with rate of eating.

Background: A fast rate of eating is associated with a higher risk for obesity but existing studies are limited by reliance on self-report and the consistency of eating rate has not been examined across all meals in a day. The goal of the current analysis was to examine associations between meal duration, rate of eating, and body mass index (BMI) and to assess the variance of meal duration and eating rate across different meals during the day. Methods: Using an observational cross-sectional study design, non-smoking participants aged 18-45 years (N = 29) consumed all meals (breakfast, lunch, and dinner) on a single day in a pseudo free-living environment. Participants were allowed to choose any food and beverages from a University food court and consume their desired amount with no time restrictions. Weighed food records and a log of meal start and end times, to calculate duration, were obtained by a trained research assistant. Spearman's correlations and multiple linear regressions examined associations between BMI and meal duration and rate of eating. Results: Participants were 65% male and 48% white. A shorter meal duration was associated with a higher BMI at breakfast but not lunch or dinner, after adjusting for age and sex (p = 0.03). Faster rate of eating was associated with higher BMI across all meals (p = 0.04) and higher energy intake for all meals (p < 0.001). Intra-individual rates of eating were not significantly different across breakfast, lunch, and dinner (p = 0.96). Conclusion: Shorter beakfast and a faster rate of eating across all meals were associated with higher BMI in a pseudo free-living environment. An individual's rate of eating is constant over all meals in a day. These data support weight reduction interventions focusing on the rate of eating at all meals throughout the day and provide evidence for specifically directing attention to breakfast eating behaviors.

Macronutrient and Micronutrient Intake in Adolescents With Non-alcoholic Fatty Liver Disease: The Association With Disease Severity.

OBJECTIVES: While dietary changes are recommended to treat pediatric non-alcoholic fatty liver disease (NAFLD), the role of specific nutrients in disease progression is unclear. The objective of this study is to (1) assess the macronutrient and micronutrient intake in adolescents with liver biopsy proven NAFLD [with and without non-alcoholic steatohepatitis (NASH)] and lean controls; (2) determine nutritional predictors of disease severity amongst these groups. METHODS: Adolescents with biopsy-proven NAFLD and lean controls completed the Harvard Food Frequency Questionnaire. RESULTS: Twenty-eight NAFLD and 15 lean controls were studied. NAFLD with (n = 20) and without NASH (n = 8) had similar total calorie, protein, fat, and carbohydrate intake. Subjects with NASH had higher total sugar (122.3 ± 48.3 vs 83.1 ± 38.8 g), glucose (24.3 ± 9.3 vs 15.2 ± 7.5 g), sucrose (42.3 ± 16.9 vs 28.8 ± 11.7 g), and fructose (29.4 ± 12.5 vs 18.1 ± 8.0 g) intake than those with NAFLD but without NASH ( P < 0.05). Both NAFLD groups had similar micronutrient intake. Alanine aminotransferase (ALT) correlated with total caloric intake ( ρ = 0.4; P = 0.04). Total carbohydrate calories correlated with a higher NAS summary score ( ρ = 0.38; P = 0.04) and lobular inflammation ( ρ = 0.50; P = 0.007). Percent calories from added sugar and glucose correlated with worsening NAS summary score ( ρ = 0.44, P = 0.02; ρ = 0.48, P = 0.009) and lobular inflammation ( ρ = 0.51, P = 0.006; ρ = 0.53, P = 0.004). Percent calories from fructose correlated with lobular inflammation ( ρ = 0.56; P = 0.002). Total daily calories, protein, fat, carbohydrate, and micronutrient intake were similar between NAFLD and lean controls. CONCLUSIONS: NASH patients consume similar total calories, protein, and fat as those without NASH, but have significantly higher sugar intake. NAFLD and lean children, however, have similar macro/micronutrient intake. Histologic disease severity correlates with total carbohydrate and added sugar intake, supporting a role for simple sugar intake in NAFLD progression.

Quality of Life Outcomes With Creative Arts Therapy in Children With Cancer.

Introduction: Children with cancer experience distress and decreased quality of life (QOL). Creative arts therapy (CAT) is a therapeutic modality which may improve QOL. This study examined the relationship between CAT and QOL in children and adolescents with cancer. Secondary aims explored relationships between CAT and emotional reactions, resilience, and posture (to investigate future potential as an objective biomarker of QOL). Methods: Children aged 3-18 years undergoing cancer treatments and a parent proxy completed the PedsQL3.0 Cancer Module, Faces Scale for emotional reactions, Resilience Scale in adolescents (>12 years), and an inclinometer to measure thoracic kyphosis before and after CAT. CAT exposure (number of sessions) was recorded. Results: Ninety-eight children with cancer (mean age 7.8 years, range 3-17) and parent proxy were enrolled. Of the 83 participants included in the final analysis, 18 received no CAT, 32 received low dose, and 33 received high dose CAT. A significant improvement in QOL was seen with high dose CAT in (slope change, p = .015), but the overall time by group interaction was not significant. Slope change response patterns suggested that CAT led to improved posture as compared to no CAT (time by group interaction, p = .044). Discussion: CAT may be an effective intervention to improve QOL in this population. Because initial evidence suggests that posture also improves with CAT, further investigation of posture as a potential objective biomarker of QOL is supported. Further study with a randomized controlled trial is warranted.

Circulating cyclic adenosine monophosphate concentrations in milrinone treated paediatric patients after congenital heart surgery.

BACKGROUND: Milrinone is a phosphodiesterase type 3 inhibitor that results in a positive inotropic effect in the heart through an increase in cyclic adenosine monophosphate. The purpose of this study was to evaluate circulating cyclic adenosine monophosphate and milrinone concentrations in milrinone treated paediatric patients undergoing congenital heart surgery. METHODS: Single-centre prospective observational pilot study from January 2015 to December 2017 including children aged birth to 18 years. Milrinone and circulating cyclic adenosine monophosphate concentrations were measured at four time points through the first post-operative day and compared between patients with and without low cardiac output syndrome, defined using clinical and laboratory criteria. RESULTS: Fifty patients were included. Nine (18%) developed low cardiac output syndrome. For all patients, 22% had single ventricle heart disease. The density and distribution of cyclic adenosine monophosphate concentrations varied between those with and without low cardiac output syndrome but were not significantly different. Milrinone concentrations increased in all patients. Paired t-tests demonstrated an increase in circulating cyclic adenosine monophosphate concentrations during the post-operative period among patients without low cardiac output syndrome. CONCLUSIONS: In this prospective observational study, circulating cyclic adenosine monophosphate concentrations increased in those without low cardiac output syndrome during the first 24 post-operative hours and milrinone concentrations increased in all patients. Further study of the utility of cyclic adenosine monophosphate concentrations in milrinone treated patients is necessary.

Higher Mortality in Pediatric Liver Transplant Candidates With Sarcopenia.

Little is known about the impact of sarcopenia (reduced muscle mass and function) in pediatric chronic liver disease. We compared psoas muscle surface area (PMSA), measured at the 4th lumbar vertebrae, in children listed for liver transplantation (LT) to that of healthy controls and studied the impact of sarcopenia on transplant-associated outcomes. The effect of PMSA (raw value and z score) on survival was studied using multivariable proportional hazards, whereas the impact of PMSA on other transplant-associated outcomes was assessed by multivariable linear or logistic regression. The correlation of PMSA with anthropometric values and markers of disease severity was studied using Spearman's rank-order correlation. Mean PMSA was significantly lower in LT candidates (n = 57, 699.4 ± 591.9 mm2 [mean ± SD]) than controls (n = 53, 1052.9 ± 960.7 mm2 ; P = 0.02). For LT candidates, there was an increased risk of death (either while on the waiting list or following transplantation) with lower PMSA (hazard ratio [HR], 1.6 per 100 mm2 [P = 0.03]; 95% confidence interval [CI], 1.1-2.8), amounting to a 4.9 times higher risk of death for every 1 unit decrease in PMSA z score (HR, 4.9 [P = 0.05], 95% CI, 1.2-34.5), adjusting for age and sex. PMSA did not correlate with posttransplant length of intubation, hospital length of stay, or perioperative complications. PMSA also did not correlate with calculated (r = 0.10, P = 0.60) or appealed Model for End-Stage Liver Disease/Pediatric End-Stage Liver Disease scores (r = 0.10, P = 0.69). Pediatric LT candidates have a significant reduction in muscle compared with controls. LT candidates with lower PMSA experience significant increases in mortality. As such, sarcopenia may provide a novel indicator of disease severity in children with chronic liver disease.

Quality Improvement Initiative to Improve Endoscopic Reassessment of Eosinophilic Esophagitis.

The eosinophilic esophagitis (EoE) endoscopic reference score (EREFS) is a validated system for description, recognition, and reporting of EoE findings during esophagogastroduodenoscopy (EGD). This scoring system correlates with esophageal eosinophilia and therapeutic responses and has validated diagnostic accuracy with good inter- and intraobserver reliability in pediatric and adult patients. In this study, we aimed to improve physician education on and documentation of EREFS and correlate EREFS scoring with eosinophil density on histology. Methods: Applying the "Plan, Do, Study, Act" methodology for quality improvement between October 2018 and November 2019, we established a baseline rate of EREFS completion by review of the electronic medical record (EMR). Key drivers were identified, and 3 interventions were implemented. Results: Over 12 months, 542 distinct endoscopies were performed on 410 patients for EoE surveillance. Patients were 68% male with a mean age of 10.9 years (SD 5.7 years), mean EREFS score of 2.14 (SD 1.88), and mean peak eosinophil count 30.9 eos/hpf (SD 37.1 eos/hpf). Baseline EREFS completion rate of 72.7% (90% CI, 67.4-77.4). Following all 3 PDSA cycles, EREFS completion rate significantly improved to greater than desired target of 90% (94.9%; 90% CI, 90.6-97.6; P < 0.001). Conclusion: Interventions including provider education and the inclusion of EREFS in documentation templates can increase adoption rates of EREFS among providers caring for patients with known EoE.