A Fully Remote Randomized Trial of Transcranial Alternating Current Stimulation for the Acute Treatment of Major Depressive Disorder.

Objective: Major depressive disorder (MDD) is common, but current treatment options have significant limitations in terms of access and efficacy. This study examined the effectiveness of transcranial alternating current stimulation (tACS) for the acute treatment of MDD.Methods: We performed a triple-blind, fully remote, randomized controlled trial comparing tACS with sham treatment. Adults aged 21-65 years meeting DSM 5 criteria for MDD and having a score on the Beck Depression Inventory, Second Edition (BDI-II), between 20 and 63 were eligible to participate. Participants utilized tACS or sham treatment for two 20-minute treatment sessions daily for 4 weeks. The primary outcome was change in BDI-II score from baseline to the week 2 time point in an intent-to treat analysis, followed by analyses of treatment-adherent participants. Secondary analyses examined change at the week 1 and 4 time points, responder rates, subgroup analyses, other self-report mood measures, and safety. The study was conducted from April to October 2022.Results: A total of 255 participants were randomized to active or sham treatment. Improvement in intent-to-treat analysis was not statistically significant at week 2 (P= .056), but there were significant effects in participants with high adherence (P= .005). Significantly greater improvement at week 1 (P= .020) and greater response at week 4 (P= .028) occurred following tACS. Improvements were significantly larger for female participants. There were no significant effects on secondary mood measures. Side effects were minimal and mild.Conclusions: Rapid, clinically significant improvement in depression in adults with MDD was associated with tACS, particularly for women. Compared to other depression therapies, tACS has 3 key advantages: rapid, clinically significant treatment effect, the ability of patients to use the treatment on their own at home, and the rarity and low impact of adverse events.Trial Registration: ClinicalTrials.gov identifier: NCT05384041.

Pediatric Sedation/Anesthesia for MRI: Results From the Pediatric Sedation Research Consortium.

BACKGROUND: Magnetic resonance imaging (MRI) is the most common imaging procedure requiring sedation/anesthesia in children. Understanding adverse events associated with sedation/anesthesia is important in making decisions regarding MRI vs. other imaging modalities. No large studies have evaluated the practice of pediatric sedation/anesthesia for MRI by a variety of pediatric specialists. PURPOSE: Utilize a large pediatric sedation database to characterize the patients and adverse events associated with sedation/anesthesia for pediatric MRI. STUDY TYPE: Retrospective analysis of prospectively collected data. SUBJECTS: The Pediatric Sedation Research Consortium (PSRC) has 109,947 entries for sedations for MRI from November 10, 2011 through December 18, 2017. ASSESSMENT: Patient demographics, sedative medications, interventions, and adverse events are described. Associations with adverse events were assessed. Trends in sedative medications used over time are examined. STATISTICAL TESTS: Descriptive statistics, Chi-Squared and Fisher's Exact tests for categorical variables, logistic regression and assessment of trend using logistic regression and other method. RESULTS: A total of 109,947 MRI-related sedations were examined. Most subjects (66.2%) were 5 years old or younger. Seizure or other neurologic issue prompted MRI in 63.7% of cases. Providers responsible for sedation/anesthesia included intensivists (49.3%), emergency medicine physicians (28.2%), hospitalists (10.2%), and anesthesiologists (9.8%). The most commonly used sedative agent was propofol (89.1%). The most common airway intervention was supplemental oxygen (71.7%), followed by head/airway repositioning (20.6%). Airway-related adverse events occurred in 8.4% of patients. Serious adverse events occurred in only 0.06% of patients, including three cases of cardiac arrest. No mortality was recorded. There was a statistically significant increase in the use of dexmedetomidine over time. DATA CONCLUSIONS: Overall, adverse event rates were low. Sedation/anesthesia with propofol infusion and natural airway was the most common method used by this varied group of sedation providers. The use of dexmedetomidine increased over time. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 5.

Total vascular resistance increases during volume-unloading in asymptomatic single ventricle patients.

OBJECTIVE: While the surgical stages of single ventricle (SV) palliation serve to separate pulmonary venous and systemic venous return, and to volume-unload the SV, staged palliation also results in transition from parallel to series circulation, increasing total vascular resistance. How this transition affects pressure loading of the SV is as yet unreported. METHODS: We performed a retrospective chart review of Stage I, II, and III cardiac catheterization (CC) and echocardiographic data from 2001-2017 in all SV pts, with focus on systemic, pulmonary, and total vascular resistance (SVR, PVR, TVR respectively). Longitudinal analyses were performed with log-transformed variables. Effects of SVR-lowering medications were analyzed using Wilcoxon rank-sum testing. RESULTS: There were 372 total patients who underwent CC at a Stage I (median age of 4.4 months, n=310), Stage II (median age 2.7 years, n = 244), and Stage III (median age 7.3 years, n = 113). Total volume loading decreases with progression to Stage III (P< 0.001). While PVR gradually increases from Stage II to Stage III, and SVR increases from Stage I to Stage III, TVR dramatically increases with progress towards series circulation. TVR was not affected by use of systemic vasodilator therapy. TVR, PVR, SVR, and CI did not correlate with indices of SV function at Stage III. CONCLUSIONS: TVR steadily increases with an increasing contribution from SVR over progressive stages. TVR was not affected by systemic vasodilator agents. TVR did not correlate with echo-based indices of SV function. Further studies are needed to see if modulating TVR can improve exercise tolerance and outcomes.

Centralization of Prehospital Triage Improves Triage of Pediatric Trauma Patients.

INTRODUCTION: This study describes the experience at a level 1 pediatric trauma center before and after the centralization of prehospital trauma triage, focusing on the rate of undertriage of trauma patients. Before centralization, emergency physicians were responsible for triaging these patients with mainly physiology-based criteria; after centralization, paramedics in a communication center performed this function using the same criteria. METHODS: This retrospective study includes 10 years of pediatric trauma registry patients at our institution, 5 years before and after centralization of prehospital triage. Rates of undertriage were calculated by both the Cribari Method and by disposition from the emergency department. Logistic regression was used to assess the effect of centralization on the incidence of undertriage while adjusting for differences in case-mix. RESULTS: Over the 10-year study period, 1862 trauma activations meeting inclusion and exclusion criteria were recorded in the trauma registry: 893 patients in the precentralization and 969 in the postcentralization groups. After centralization of the triage process, there were statistically significant decreases in the rates of undertriage from 8.7% to 4.2% (adjusted odds ratio, 0.49; 95% confidence interval, 0.33-0.73) when analyzed by the Cribari Method and from 37.7% to 27.7% when analyzed by disposition from the emergency department (adjusted odds ratio, 0.66; 95% confidence interval, 0.64-0.81). This represents a reduction in undertriage by 51.7% and 26.5%, respectively. CONCLUSIONS: Centralization of prehospital trauma triage at a level 1 pediatric trauma facility significantly reduced undertriage rates. Trauma centers should consider similar processes to improve prehospital triage.

Provider education decreases opioid prescribing after pediatric umbilical hernia repair.

PURPOSE: To improve opioid stewardship for umbilical hernia repair in children. METHODS: An educational intervention was conducted at 9 centers with 79 surgeons. The intervention highlighted the importance of opioid stewardship, demonstrated practice variation, provided prescribing guidelines, encouraged non-opioid analgesics, and encouraged limiting doses/strength if opioids were prescribed. Three to six months of pre-intervention and 3 months of post-intervention prescribing practices for umbilical hernia repair were compared. RESULTS: A total of 343 patients were identified in the pre-intervention cohort and 346 in the post-intervention cohort. The percent of patients receiving opioids at discharge decreased from 75.8% pre-intervention to 44.6% (p < 0.001) post-intervention. After adjusting for age, sex, umbilicoplasty, and hospital site, the odds ratio for opioid prescribing in the post- versus the pre-intervention period was 0.27 (95% CI = 0.18-0.39, p < 0.001). Among patients receiving opioids, the number of doses prescribed decreased after the intervention (adjusted mean 14.3 to 10.4, p < 0.001). However, the morphine equivalents/kg/dose did not significantly decrease (adjusted mean 0.14 to 0.13, p = 0.20). There were no differences in returns to emergency departments or hospital readmissions between the pre- and post-intervention cohorts. CONCLUSIONS: Opioid stewardship can be improved after pediatric umbilical hernia repair using a low-fidelity educational intervention. TYPE OF STUDY: Retrospective cohort study. LEVEL OF EVIDENCE: Level II.

Genetic testing and cascade screening in pediatric long QT syndrome and hypertrophic cardiomyopathy.

BACKGROUND: The efficacy of cascade screening for the inherited heart conditions long QT syndrome (LQTS) and hypertrophic cardiomyopathy (HCM) is incompletely characterized. OBJECTIVE: The purpose of this study was to examine the use of genetic testing and yield of cascade screening across diverse regions in the United States and to evaluate obstacles to screening in multipayer systems. METHODS: An institutional review board-approved 6 United States pediatric center retrospective chart review of LQTS and HCM patients from 2008-2014 was conducted for (1) genetic test completion and results and (2) family cascade screening acceptance, methods, results, and barriers. RESULTS: The families of 315 index patients (mean age 9.0 ± 5.8 years) demonstrated a 75% (254) acceptance of cascade screening. The yield of relative screening was 39% (232/601), an average of 0.91 detected per family. Genetic testing was less utilized in HCM index patients and relatives. Screening participation was greater in families of gene-positive index patients (88%) (P <.001) compared to gene-negative patients (53%). Cascade method utilization: Cardiology-only 45%, combined genetic and cardiology 39%, and genetic only 16%. Screening yield by method: combined 57%, genetic-only 29%, and cardiology-only 20%. Family decisions were the leading barriers to cascade screening (26% lack of followthrough and 26% declined), whereas insurance (6%) was the least cited barrier. CONCLUSION: Family participation in cascade screening is high, but the greatest barriers are family mediated (declined, lack of followthrough). Positive proband genetic testing led to greater participation. Cardiology-only screening was the most utilized method, but combined cardiology and genetic screening had the highest detection.

Nurse-Patient Connectedness and Nurses' Professional Quality of Life: Experiences of Volunteering at a Pediatric Oncology Camp.

Objective: Pediatric oncology nurses can experience burnout, vicarious traumatization, and compassion fatigue related to the unique stressors of their profession. Opportunities to enhance nurses' professional commitment and nurse-patient connectedness may mitigate these stressors. This study explored the impact of volunteering at a local oncology camp on pediatric oncology nurses' professional quality of life and connectedness with their oncology patients. Method and Sample: Pediatric oncology nurses from a single institution were invited to participate in this mixed methods study. Participants completed a survey assessing professional quality of life, professional commitment, and patient connectedness. Nurses who had oncology camp volunteer experience were invited to participate in a qualitative interview. Results: Compared with noncamp nurses (n = 23), camp nurses (n = 25) had increased odds of a low burnout score (odds ratio = 6.74, 95% confidence interval [1.10, 41.43], p = .039) and increased odds of a high compassion satisfaction score (odds ratio = 4.69, 95% confidence interval [1.14, 19.32], p = .033). Qualitative interviews supported the impact of volunteering at camp on nurses' personal and professional perspective, nursing practice, and delivery of person-centered care. Conclusion: Volunteering at a pediatric oncology camp provided nurses the opportunity to engage with patients, share experiences, and view patients as individuals while still maintaining professional boundaries. Nurses who volunteer at camp described a perspective moving beyond patient-centered to person-centered care, and for some pediatric oncology nurses, camp volunteering may be a novel way to mitigate burnout and an important tool to enhance resiliency.

Prospective evaluation of a clinical decision tool to reduce childhood admissions to PICUs for poisoning: ReCAP2.

Aim: To prospectively validate a pediatric clinical prediction model to identify children at low risk of clinically significant ingestions to prevent unnecessary pediatric intensive care unit (PICU) admissions.Methods: Calls received by the Georgia Poison Center about children for acute ingestions between May 25, 2017 and May 17, 2018 were scored in real time using the full, age-stratified, and simplified clinical scoring tool to reduce childhood admissions to PICUs for poisoning (RECAP2). Clinically significant ingestions with a poison center recommendation of PICU admission are defined in the simple RECAP2 model as ingestion of clonidine, ethanol, an oral anti-hyperglycemic agent, or exposure to carbon monoxide, as well as the presence of symptoms occurring within 2 h for an immediate release, or 4 h for an extended release, medication exposure. Model statistics and percent reduction in PICU admissions were computed.Results: There were 886 children admitted after ingestions, of which 454 (51.2%) children were admitted to intensive care. At the time of the initial poison center call to report the ingestion, 44 cases (5%) were incomplete using the full, age-stratified model compared to the complete scoring using the simple scoring model. Seventy-two children (8.1%) required monitoring or interventions performed only in a PICU. Real-time application of the full model compared with the simple model would have reduced PICU admissions by 33.3 and 31.7%, respectively.Conclusions: The simple RECAP2 clinical scoring model is a sensitive prediction tool to identify children at very low risk for clinically significant ingestions for whom PICU admission can be avoided. Clinical implementation of the simple RECAP2 model and recommendation for admission to an inpatient unit versus PICU should be further evaluated, to reduce unnecessary PICU admissions following acute ingestions.

Outcomes of Single Ventricle Patients Undergoing the Kawashima Procedure: Can We Do Better?

OBJECTIVES: Current technology advances in virtual surgery modeling and computational flow dynamics allow preoperative individualized computer-based design of Fontan operation. To determine potential role of those innovations in patients undergoing hepatic vein incorporation (HVI) following Kawashima operation, we retrospectively examined historic cohort of patients who underwent HVI following Kawashima with focus on regression of pulmonary arteriovenous malformations (PAVMs). METHODS: Twenty-two children with single ventricle and interrupted inferior vena cava underwent Kawashima operation (2002-12). Twenty-one (96%) patients had left atrial isomerism and 21 (96%) had undergone prior first-stage palliation. Clinical outcomes were examined. RESULTS: Mean O2 saturation (SaO2) increased from 77% ± 8% to 85% ± 6% ( P = .002) after Kawashima. Fifteen (68%) patients developed PAVMs. Eighteen patients underwent HVI (median age and interval from Kawashima: 4.4 and 3.7 years, respectively). Mean SaO2 prior to HVI was 77% ± 8% and increased to 81% ± 10% at the time of hospital discharge ( P = .250), with five patients requiring home oxygen. On follow-up, mean SaO2 increased to 95% ± 4% ( P < .001). Overall ten-year survival following Kawashima was 94%. CONCLUSIONS: A large number of patients develop PAVMs and subsequent cyanosis after Kawashima operation. Early following HVI, SaO2 is commonly low and insignificantly different from that prior to HVI. Although SaO2 will improve on follow-up in most patients, a number of patients continue to have low saturations, indicating incomplete resolution of PAVMs. Given the heterogeneity of those patients and lack of preoperative predictors for complete PAVM regression, our findings suggest a role for virtual surgery to determine optimal individual procedure design that would provide even distribution of hepatic blood flow to both pulmonary arteries.

Effect of a Low Free Sugar Diet vs Usual Diet on Nonalcoholic Fatty Liver Disease in Adolescent Boys: A Randomized Clinical Trial.

Importance: Pediatric guidelines for the management of nonalcoholic fatty liver disease (NAFLD) recommend a healthy diet as treatment. Reduction of sugary foods and beverages is a plausible but unproven treatment. Objective: To determine the effects of a diet low in free sugars (those sugars added to foods and beverages and occurring naturally in fruit juices) in adolescent boys with NAFLD. Design, Setting, and Participants: An open-label, 8-week randomized clinical trial of adolescent boys aged 11 to 16 years with histologically diagnosed NAFLD and evidence of active disease (hepatic steatosis >10% and alanine aminotransferase level ≥45 U/L) randomized 1:1 to an intervention diet group or usual diet group at 2 US academic clinical research centers from August 2015 to July 2017; final date of follow-up was September 2017. Interventions: The intervention diet consisted of individualized menu planning and provision of study meals for the entire household to restrict free sugar intake to less than 3% of daily calories for 8 weeks. Twice-weekly telephone calls assessed diet adherence. Usual diet participants consumed their regular diet. Main Outcomes and Measures: The primary outcome was change in hepatic steatosis estimated by magnetic resonance imaging proton density fat fraction measurement between baseline and 8 weeks. The minimal clinically important difference was assumed to be 4%. There were 12 secondary outcomes, including change in alanine aminotransferase level and diet adherence. Results: Forty adolescent boys were randomly assigned to either the intervention diet group or the usual diet group (20 per group; mean [SD] age, 13.0 [1.9] years; most were Hispanic [95%]) and all completed the trial. The mean decrease in hepatic steatosis from baseline to week 8 was significantly greater for the intervention diet group (25% to 17%) vs the usual diet group (21% to 20%) and the adjusted week 8 mean difference was -6.23% (95% CI, -9.45% to -3.02%; P < .001). Of the 12 prespecified secondary outcomes, 7 were null and 5 were statistically significant including alanine aminotransferase level and diet adherence. The geometric mean decrease in alanine aminotransferase level from baseline to 8 weeks was significantly greater for the intervention diet group (103 U/L to 61 U/L) vs the usual diet group (82 U/L to 75 U/L) and the adjusted ratio of the geometric means at week 8 was 0.65 U/L (95% CI, 0.53 to 0.81 U/L; P < .001). Adherence to the diet was high in the intervention diet group (18 of 20 reported intake of <3% of calories from free sugar during the intervention). There were no adverse events related to participation in the study. Conclusions and Relevance: In this study of adolescent boys with NAFLD, 8 weeks of provision of a diet low in free sugar content compared with usual diet resulted in significant improvement in hepatic steatosis. However, these findings should be considered preliminary and further research is required to assess long-term and clinical outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT02513121.

Characterization of Myocardial Dysfunction in Fluid- and Catecholamine-Refractory Pediatric Septic Shock and Its Clinical Significance.

PURPOSE:: Myocardial dysfunction is a known complication in patients with pediatric septic shock (PSS); however, its clinical significance remains unclear. The purpose of this study was to characterize left ventricular (LV) and right ventricular (RV) dysfunction and their prevalence in patients with PSS using echocardiography (echo) and to investigate their associations with the severity of illness and clinical outcomes. METHODS:: Retrospective chart review between 2010 and 2015 from 2 tertiary care pediatric intensive care units. Study included 78 patients (mean age 9.3 ± 7 years) from birth up to 21 years who fulfilled criteria for fluid- and catecholamine-refractory septic shock. Echocardiographic parameters of systolic, diastolic, and global function were measured offline. They were correlated with admission Pediatric Risk of Mortality III (PRISM III) and Pediatric Logistic Organ Dysfunction scores, vasoactive-inotrope score (VIS), ß-type natriuretic peptide (BNP), lactate, type of shock, duration of mechanical ventilation (MV), intensive care unit and hospital length of stay, and mortality. RESULTS:: Overall, 28-day mortality was 26%, and 88% patients required MV. Prevalence of LV dysfunction was 72% and RV dysfunction was 63%. LV systolic dysfunction (fractional shortening z score <-2) was significantly associated with PRISM III, VIS, and BNP. RV systolic dysfunction (tricuspid annular plane systolic excursion z score <-2) was significantly associated with cold shock. LV and RV diastolic dysfunction did not have any significant clinical associations. No echocardiographic measures were associated with mortality. CONCLUSION:: Myocardial dysfunction is highly prevalent in PSS but is not associated with mortality. LV systolic dysfunction is associated with a higher severity of illness, use of vasoactives, and BNP, whereas RV systolic dysfunction is associated with cold shock. Further studies are needed to determine the utility of echo in the bedside management of patients with PSS.

Parent reported long-term quality of life outcomes in children after congenital diaphragmatic hernia repair.

PURPOSE: The aim of this study was to determine long-term outcomes for congenital diaphragmatic hernia (CDH) patients including quality of life (QoL), symptom burden, reoperation rates, and health status. METHODS: A chart review and phone QoL survey were performed for patients who underwent CDH repair between 2007 and 2014 at a tertiary free-standing children's hospital. Comprehensive outcomes were collected including subsequent operations and health status. Associations with QoL were tested using Wilcoxon Rank-Sum tests and Pearson correlation coefficients. RESULTS: Of 102 CDH patients identified, 46 (45.1%) patient guardians agreed to participate with mean patient age of 5.8 (SD, 2.2) years at time of follow-up. Median PedsQLTM and PedsQLTM Gastrointestinal scores were 91.8 (IQR, 84.8-95.8) and 95.8 (IQR, 93.0-98.2), out of 100. Thoracoscopic repair was associated with higher PedsQLTM scores while defects with an intrathoracic stomach were associated with increased gas and bloating. No difference in QoL was found when comparing defect side, patch vs primary repair, prenatal diagnosis, extracorporeal membrane oxygenation, or recurrence. Older age weakly correlated with worse school functioning and heartburn. CONCLUSION: Children with CDH have reassuring QoL scores. Given the correlation between older age and poor school function, longer follow-up of patients with CDH may be warranted. LEVEL OF EVIDENCE: III (Retrospective comparative study).

Temporomandibular joint involvement in children with juvenile idiopathic arthritis: a preliminary report.

OBJECTIVE: Children with juvenile idiopathic arthritis (JIA) are at risk for temporomandibular joint (TMJ) arthritis. This can lead to pain, limited mouth opening, facial asymmetry, and malocclusion. Our objective was to characterize patients with JIA and TMJ involvement in a single center. STUDY DESIGN: This was a retrospective study of children with JIA evaluated at Children's Healthcare of Atlanta. Inclusion criteria were confirmed JIA and jaw complaints. Medical records were reviewed to document demographics, JIA information, age at first TMJ complaint, and involvement of other joints. Descriptive statistics were computed. RESULTS: Majority of patients were white (mean age 13 years; range 5-18 years) with polyarticular rheumatoid factor (RF) negative or oligoarticular persistent JIA. Some were antinuclear antibody (ANA) positive, RF positive, or human leukocyte antigen (HLA)-B27 positive. Patients had involvement of other joints (e.g., fingers, knees, wrists). Of those with TMJ symptoms, 6 (10%) had TMJ arthritis. CONCLUSIONS: In our cohort, 60 (10%) of patients were diagnosed with TMJ arthritis. In this population, patients who are female, white, RF negative, HLA-B27 negative, ANA negative, and polyarticular RF-negative subtype and have involvement of other joints have a higher likelihood of having TMJ symptoms. If a patient meets these criteria, careful evaluation of TMJs should take place.

Primary versus secondary anastomosis in intestinal atresia.

PURPOSE: Neonates with intestinal atresia (IA) undergo either primary anastomosis (PA) or ostomy creation with secondary anastomosis (SA). Our purpose was to compare outcomes for PA and SA and to assess factors influencing procedure selection. METHODS: We conducted a retrospective cohort study of neonates with IA between 2009 and 2015. Patient characteristics, operative details, and outcomes were collected. Surgeon-level preferences (defined as performing >50% PA or SA) were assessed using logistic regression. RESULTS: Of 92 IA patients, 70 (76.1%) underwent PA and 22 (23.9%) underwent SA. Neonates with PA had shorter hospitalizations (27 days vs. 95 days, p < 0.001), shorter total parenteral nutrition duration (19 days vs. 74.5 days, p < 0.001), and fewer readmissions (33.3% vs. 63.2%, p = 0.024). On multivariable regression analysis, higher Apgar scores (Odds Ratio (OR) 4.16, 95% Confidence Interval (CI) 1.20-14.29) and uncomplicated atresia (OR 3.97, 95% CI 1.37-11.48) were associated with PA. At the surgeon-level, utilization of PA varied from 43.5% to 100%. Surgeon preference is not influenced by the demographic, presentation, or surgical findings of this patient population. CONCLUSIONS: PA has better outcomes than SA. Though procedural selection is influenced by the clinical status of the neonate, however surgeon preference plays a significant role in this clinical decision. LEVEL OF EVIDENCE: Level III Treatment Study.

Timing of infliximab and adalimumab initiation despite methotrexate in children with chronic non-infectious anterior uveitis.

AIMS: Methotrexate (MTX) is standard treatment in pediatric chronic anterior uveitis (CAU). Addition of tumor necrosis factor-α inhibitors (TNFi) is often needed. We describe the timing and risk factors for TNFi use in children with CAU on MTX. METHODS: In this retrospective study, we reviewed 51 records, and 46 met inclusion criteria. Primary outcome was the addition of TNFi due to active CAU per Standardization of Uveitis Nomenclature criteria. Time to TNFi and factors associated with their addition were assessed using survival analysis models. RESULTS: Of 46 children treated with MTX for uveitis (36 juvenile idiopathic arthritis-associated uveitis, 10 idiopathic CAU), 72% had ocular complications. MTX was started a median of 5.0 months, and TNFi 43 months from uveitis diagnosis. Kaplan-Meier estimates suggest that cumulatively, 12% (95% CI: 4-23%) start TNFi within 6 months of MTX, 21% (12-37%) within 1 year, and 39% (24-54%) within 2 years. On Cox Proportional Hazard regression analysis, children with idiopathic CAU required TNFi earlier in their uveitis course (at 3 months (Hazard Ratio 6.06; 95% confidence interval (1.25-29.41))). Females appeared less likely to require TNFi early. Children treated in 2012 and later were more likely to receive TNFi earlier than those treated before 2012. CONCLUSION: Little is known about optimal time to initiate treatment or factors associated with the need to add TNFi in children on MTX. Children with idiopathic CAU and males required TNFi earlier in their course. Factors associated with these potential risk factors for TNFi warrant further investigation.

Acute cellular rejection treatment outcomes stratified by Banff grade in pediatric kidney transplant.

INTRODUCTION: There are limited data to guide optimal treatment strategies for acute cellular rejection (ACR) based on Banff grade for pediatric kidney transplant recipients. This report reviews a large pediatric transplant center's experience with ACR. MATERIALS AND METHODS: A retrospective analysis of pediatric kidney transplant recipients at our center from 2007 to 2014 was performed. Primary outcomes were incidence of graft failure and graft function one year following ACR based on Banff grade and treatment received. RESULTS: A total of 204 patients were reviewed, of which 65 received rejection treatment with either an oral steroid cycle (n = 16), intravenous steroid pulse (n = 28), or anti-thymocyte globulin (rATG, n = 21). Overall, patients received rATG for treatment of more severe rejection associated with impaired graft function and as a group experienced statistically significant improvements in eGFR over the year following treatment, though most did not regain baseline graft function. DISCUSSION: Our data suggest that rATG is partially effective in treating ACR, but our study was underpowered to determine the effect of different treatments based on Banff grade. Since there is limited literature to guide clinical treatment of ACR in children, large transplant centers should collaborate to evaluate outcomes and establish evidence-based practice.

Enhancing Pain Assessment in Pediatric Sickle Cell Disease by Applying Quality Improvement Science.

OBJECTIVE: Standardized pain assessment and interventions are recommended for youth hospitalized for pain. This quality improvement (QI) project integrated into a pediatric psychology service aimed to increase the standardized assessment of pain-related functional ability for youth with sickle cell disease (SCD) hospitalized for pain. METHODS: Children and adolescents (n=102) with SCD referred for psychology consultation for poor coping in response to pain during hospitalization completed a validated self-report of functional ability in addition to pain intensity during inpatient psychology visits. At the time of the quality initiative, routine and standardized assessment of pain-related functional ability was not integrated into standard clinical care. Plan, Do, Study, Act (PDSA) cycles determined the feasibility and addressed common barriers of routine assessment and documentation of pain-related functional ability among youth with SCD during inpatient psychology visits with the primary goal to increase assessment of functional ability to at least 85% among patients with SCD referred for pediatric psychology consultation to address pain management within 1 year. RESULTS: Through iterative PDSA cycles, routine assessment of pain-related functional ability during psychology visits increased to an average of 93% over the course of 12 months. Routine, standardized assessment of functional ability was considered feasible within a pediatric psychology service. CONCLUSIONS/LESSONS LEARNED: This project supported the feasibility of integrating standardized assessment of functional ability to enhance pain assessment for youth hospitalized for SCD pain as part of routine clinical care in a multidisciplinary setting regardless of psychology referral.

Atrial Septal Defects Accelerate Pulmonary Hypertension Diagnoses in Premature Infants.

Between 4 and 16% of extremely premature infants have late pulmonary hypertension (PH) (onset >30 days of life), and infants with PH have a higher risk of tracheostomy and death. Atrial septal defects (ASD) increase pulmonary blood flow and may promote PH in at-risk infants. The objective of this study was to determine if infants with ASD develop PH sooner than those without ASD. Infants who were born at < 32 weeks' gestation, with an echocardiogram on day of life > 30, and without congenital anomalies were included. Infants with and without ASD were evaluated for the time to PH diagnosis, defined as the day of the first echocardiogram that showed PH. A multivariable model with ASD and significant variables on PH and a Cox proportional hazard model evaluating time to PH was determined. Of the 334 infants with echocardiograms, 57 had an ASD and 26% of these developed PH vs. 12% without ASD (p = 0.006). Infants with PH had lower gestational age (25.2 vs. 26.2 weeks, p = 0.005), smaller birthweight (699 vs. 816 gm, p = 0.001), and more prematurity complications than infants without PH. More PH infants had maternal African-American race (63.9 vs. 36.1%), right ventricular dysfunction (23.9 vs. 3.2%, p < 0.001), right ventricular dilation (52.1 vs. 8.6%, p < 0.001), or right ventricular hypertrophy (51.2 vs. 10.1%, p < 0.001), than infants without PH. At 150 days of life, 78.1% (95% CI 64.6-86.9%) of infants with ASD survived without PH, compared with 90.9% (95% CI 86.7-93.8%) of infants without ASD, and the unadjusted hazard for development of PH for infants with ASD was 2.37 (95% CI 1.29-4.36). When significant clinical variables were controlled, infants with ASD had a 2.44-fold (95% CI 1.27-4.68) increase in PH, compared with infants without ASD. Most PH in infants with or without ASD was diagnosed by day of life 150, but infants with ASD had an over 2-fold increased hazard for PH during their neonatal hospitalization. Premature infants with ASD should be followed closely for PH development and further studies to investigate the optimal timing of closure are needed.

Importance of Compliance Audits for a Pediatric Complicated Appendicitis Clinical Practice Guideline.

Clinical practice guidelines (CPG) have been shown to decrease practice variation, reduce resource use, and improve patient outcomes. The purpose of this study was to audit compliance of a pediatric complicated appendicitis CPG to identify areas for continued improvement. A comprehensive complicated appendicitis CPG was implemented in a children's hospital system. Outcomes were compared for 48 months pre- (01/2012 to 12/2015) and 28 months post-implementation (01/2016 to 04/2018). A detailed compliance audit was nested within the post-implementation period in 60 consecutive patients from 11/2017 to 03/2018. Feedback was provided to care providers throughout the audit. Overall, 2370 children with complicated appendicitis were identified (1366 pre-CPG and 1004 post-CPG). The CPG resulted in decrease in mean length of stay from 5.3 days to 4.5 days (p = 0.751), postoperative returns to the system (13.0% to 10.1%, p = 0.030), and readmissions (5.3% to 4.3%, p = 0.237). Central line use decreased from 11.2% to 5.5% (p < 0.001) and antibiotic selection improved from 47.0% to 84.1% (p < 0.001). On audit, only 15% (9/60) had full CPG compliance and 49% (29/60) received recommended antibiotic durations. Compliance increased from 7% to 23% with audit-derived feedback. After stratifying by appendicitis severity, audits resulted in improved antibiotic duration compliance for patients with severe appendicitis (38.1% to 66.7%, p = 0.07) and postoperative ambulation for patients with lower grade disease (37.5% to 83.3%, p = 0.06). Audit cycles on a complicated appendicitis CPG and feedback to providers improved CPG compliance and more granular outcomes of interest.

Adrenocorticotropic Hormone for Childhood Nephrotic Syndrome: The ATLANTIS Randomized Trial.

BACKGROUND AND OBJECTIVES: There is renewed interest in adrenocorticotropic hormone (ACTH) for the treatment of nephrotic syndrome. We evaluated the efficacy and safety of ACTH in children with frequently relapsing or steroid-dependent nephrotic syndrome in a randomized trial. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Participants aged 2-20 years old with frequently relapsing or steroid-dependent nephrotic syndrome were enrolled from 16 sites in the United States and randomized 1:1 to ACTH (repository corticotropin injection) or no relapse-preventing treatment. ACTH treatment regimen was 80 U/1.73 m2 administered twice weekly for 6 months, followed by 40 U/1.73 m2 administered twice weekly for 6 months. The primary outcome was disease relapse during the first 6 months. Participants in the control group were offered crossover to ACTH treatment if they relapsed within 6 months. Secondary outcomes were relapse after ACTH dose reduction and treatment side effects. RESULTS: The trial was stopped at a preplanned interim analysis after enrollment of 31 participants because of a lack of discernible treatment efficacy. Fourteen out of 15 (93%) participants in the ACTH arm experienced disease relapse in the first 6 months, with a median time to first relapse of 23 days (interquartile range, 9-32), compared with 15 out of 16 (94%) participants and at a median of 21 days (interquartile range, 14-51) in the control group. There was no difference in the proportion of relapsed patients (odds ratio, 0.93; 95% confidence interval, 0.05 to 16.40; P>0.99) or time to first relapse (hazard ratio, 1.03; 95% confidence interval, 0.50 to 2.15; P=0.93). Thirteen out of 16 participants in the control group crossed over to ACTH treatment. Three out of 28 participants completed 12 months of ACTH treatment; the others exited the trial because of frequent relapses or side effects. There were no disease relapses after ACTH dose reduction among the three participants. Most side effects were mild and similar to side effects of corticosteroids. CONCLUSIONS: ACTH at 80 U/1.73 m2 administered twice weekly was ineffective at preventing disease relapses in pediatric nephrotic syndrome.