The burden of psychological trauma and post-traumatic stress disorder among adults with congenital heart disease: PTSD in ACHD.

Psychological trauma, symptoms of post-traumatic stress disorder (PTSD), and mental health conditions are common in adult congenital heart disease (ACHD). There is a gap in research examining PTSD in ACHD using the current Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) criteria in assessing patient characteristics and experiences with trauma-focused treatment. Surveys were offered to outpatients over a 6-month enrollment period to be completed by way of a QR code on their personal smart phone. Patient-reported items include a detailed medical and psychosocial history, the Oslo social support scale, adverse childhood experiences survey, and the PTSD checklist for DSM-5. Of 158 patients (77% moderate or complex heart disease) who provided complete data, a provisional diagnosis of PTSD was found in 48 patients (30%) using a PTSD checklist for DSM-5 cut-off score of ≥31. A positive PTSD screen was associated with younger age, nonwhite race, presence of heart failure, lower New York Heart Association functional class, lower linear quality of life score, lower Oslo social support scale score, an insecure caregiver relation, period of unemployment, emergency department visits, medication nonadherence, and coexisting mental health disorders. Complexity of heart disease and number of surgical and/or catheter-based interventions were not associated with PTSD, although having undergone no cardiac surgeries until adulthood (aged ≥18 years) was associated with a lower prevalence of PTSD. Those who screened positive for PTSD were more likely to report multiple traumatic events, including noncardiac traumatic events. Only 14 of 48 patients (29%) reported a known diagnosis of PTSD, although 44 patients (92%) reported having ever seen a mental health provider. A total of 18 patients (38%) reported currently having a mental health provider. A total of 30 patients (62%) had heard of at least 1 evidence-based trauma-informed therapy, and 14 (29%) had tried at least 1. In conclusion, using the DSM-5 criteria, we observed a high prevalence of potential PTSD in ACHD associated with several novel cardiac and psychosocial patient factors. Future longitudinal studies will be necessary to establish causality. Few patients with ACHD have been formally diagnosed with PTSD or have experience with evidence-based trauma-informed therapies.

Maternal Western diet is associated with distinct preclinical pediatric NAFLD phenotypes in juvenile nonhuman primate offspring.

Pediatric NAFLD has distinct and variable pathology, yet causation remains unclear. We have shown that maternal Western-style diet (mWSD) compared with maternal chow diet (CD) consumption in nonhuman primates produces hepatic injury and steatosis in fetal offspring. Here, we define the role of mWSD and postweaning Western-style diet (pwWSD) exposures on molecular mechanisms linked to NAFLD development in a cohort of 3-year-old juvenile nonhuman primates offspring exposed to maternal CD or mWSD followed by CD or Western-style diet after weaning. We used histologic, transcriptomic, and metabolomic analyses to identify hepatic pathways regulating NAFLD. Offspring exposed to mWSD showed increased hepatic periportal collagen deposition but unchanged hepatic triglyceride levels and body weight. mWSD was associated with a downregulation of gene expression pathways underlying HNF4α activity and protein, and downregulation of antioxidant signaling, mitochondrial biogenesis, and PPAR signaling pathways. In offspring exposed to both mWSD and pwWSD, liver RNA profiles showed upregulation of pathways promoting fibrosis and endoplasmic reticulum stress and increased BiP protein expression with pwWSD. pwWSD increased acylcarnitines and decreased anti-inflammatory fatty acids, which was more pronounced when coupled with mWSD exposure. Further, mWSD shifted liver metabolites towards decreased purine catabolism in favor of synthesis, suggesting a mitochondrial DNA repair response. Our findings demonstrate that 3-year-old offspring exposed to mWSD but weaned to a CD have periportal collagen deposition, with transcriptional and metabolic pathways underlying hepatic oxidative stress, compromised mitochondrial lipid sensing, and decreased antioxidant response. Exposure to pwWSD worsens these phenotypes, triggers endoplasmic reticulum stress, and increases fibrosis. Overall, mWSD exposure is associated with altered expression of candidate genes and metabolites related to NAFLD that persist in juvenile offspring preceding clinical presentation of NAFLD.

Web-Based Exercise Program Increases Cervical Strength in Adolescent Athletes.

ABSTRACT: Wilson, JC, Levek, C, Daoud, AK, Brewer, M, Brooks, K, Sochanska, A, Randall, M, and Provance, AJ. Web-based exercise program increases cervical strength in adolescent athletes. J Strength Cond Res 35(4): 1149-1155, 2021-This cohort study aimed to evaluate the efficacy of a web-based 6-week cervical strengthening program on cervical strength in adolescent athletes. It was hypothesized that subjects completing the program would demonstrate significant increase in cervical muscle strength compared with baseline strength. Eighty-three high school soccer athlete subjects were recruited from 2 local nationally competitive soccer clubs. Teams were assigned to either control or intervention groups to minimize information crossover. Fifty subjects were recruited to the intervention group (29 male, 21 female; average age 15.1 years). Thirty-three subjects were recruited to the control group (21 male, 12 female; average age 15.1 years). Intervention group subjects completed a web-based progressive cervical strengthening program over 6 weeks. Cervical strength in flexion, extension, right and left lateral flexion (LLF) was measured in Newton (N) of force at 3 time points during the competitive season for both control and intervention groups. Intervention group subjects significantly increased cervical strength [mean difference (95% confidence interval)] in LLF [24.1 (15.9-32.4)], extension [27.9 (18.4-37.5)], right lateral flexion [18.8 (11.6-26.1)], and flexion [mean ratio: 1.2 (1.1-1.2)] at follow-up testing; whereas control subjects did not see significant changes in strength. A web-based progressive cervical strengthening program improves cervical muscular strength in a population of adolescent athletes over a period of 6 weeks. Such a program could be used by researchers in future studies evaluating the influence on concussion risk and by practitioners as a means of reducing sport-related head and neck injuries.

Thromboelastography-guided management of coagulopathy in neonates with congenital diaphragmatic hernia supported by extracorporeal membrane oxygenation.

PURPOSE: Congenital diaphragmatic hernia (CDH) can cause severe hemodynamic deterioration requiring support with extracorporeal membrane oxygenation (ECMO). ECMO is associated with hemorrhagic and thromboembolic complications. In 2015, we standardized anti-coagulation management on ECMO, incorporating thromboelastography (TEG) as an adjunct to manage hemostasis of CDH patients. The purpose of this study is to evaluate our blood product utilization, choice of blood product use in response to abnormal TEG parameters, and the associated effect on bleeding and thrombotic complications. METHODS: We retrospectively reviewed all CDH neonates supported by ECMO between 2008 and 2018. Blood product administration, TEG data, and hemorrhagic and thrombotic complications data were collected. We divided subjects into two groups pre-2015 and post-2015. RESULTS: After 2015, platelet transfusion was administered for a low maximum amplitude (MA) more frequently (77% compared to 65%, p = 0.0007). Cryoprecipitate was administered less frequently for a low alpha-angle (28% compared to 41%, p = 0.0016). There was no difference in fresh frozen plasma use over time. After standardizing the use of TEG, we observed a significant reduction in hemothoraces (18% compared to 54%, p = 0.026). CONCLUSION: Institutional standardization of anti-coagulation management of CDH neonates on ECMO, including the use of goal-directed TEG monitoring may lead to improved blood product utilization and a decrease in bleeding complications in neonates with CDH supported by ECMO. LEVEL OF EVIDENCE/TYPE OF STUDY: Level III, Retrospective comparative study.

Diuretic Use and Subsequent Electrolyte Supplementation in a Level IV Neonatal Intensive Care Unit.

OBJECTIVES: To evaluate the relationship between diuretic use, serum electrolyte concentrations, and supplementation requirements in infants admitted to the neonatal intensive care unit. METHODS: This was a single-center retrospective cohort study conducted in a freestanding children's hospital Level IV NICU. Data were collected for all infants younger than 6 months, admitted to the NICU between January 2015 and May 2017, who received 2 or more consecutive doses of furosemide, chlorothiazide, hydrochlorothiazide, and/or hydrochlorothiazide/spironolactone. The primary outcome was the composite of the incidence of electrolyte abnormalities and/or electrolyte supplementation requirement within 30 days of diuretic exposure. RESULTS: A total of 72 patients met inclusion criteria, with a median gestational age of 30 weeks. Overall, 92% of patients exposed to diuretics experienced derangement in at least 1 serum electrolyte and/or required electrolyte supplementation during diuretic therapy. Patients born at 36 to 41 weeks' gestational age, receiving thiazide diuretics, experienced a significantly lower rate of the primary outcome (37%, p ≤ 0.001). The most common electrolytes affected by diuretic use were potassium and bicarbonate, with the highest incidence of the primary outcome for potassium occurring in patients receiving furosemide (p = 0.0196). Last, the median total daily dose of chlorothiazide in patients with an adverse event was 15 mg/kg/day, compared with 10 mg/kg/day in patients without an adverse event (p = 0.0041). CONCLUSIONS: Use of diuretics in young infants is likely to cause electrolyte derangements and/or require electrolyte supplementation. Patients born at earlier gestational ages may be at higher risk for developing such adverse effects.

Sustainability of Handshake Stewardship: Extending a Hand Is Effective Years Later.

BACKGROUND: Children's Hospital Colorado created a unique method of antimicrobial stewardship, called handshake stewardship, that effectively decreased hospital anti-infective use and costs in its pilot year (2013). Handshake stewardship is distinguished by: (1) the lack of prior authorization; (2) a review of all prescribed anti-infectives; (3) a shared review by the physician and the pharmacist; and (4) a daily, rounding-based, in-person approach to supporting providers. We sought to reevaluate the outcomes of the program after 5 years of experience, totaling 8 years of data. METHODS: We retrospectively measured anti-infective (antibiotic, antiviral, antifungal) use hospital-wide by unit and by drug for an 8-year period spanning October 2010 to October 2018. Aggregated monthly use was measured in days of therapy per thousand patient days (DOT/1000 PD). The percentage of children admitted ever receiving an anti-infective was also measured, as well as severity-adjusted mortality, readmissions, and lengths of stay. RESULTS: Hospital-wide mean anti-infective use significantly decreased, from 891 (95% confidence interval [CI] 859-923) in the pre-implementation phase to 655 (95% CI 637-694) DOT/1000 PD in post-implementation Year 5; in a segmented regression time series analysis, this was a rate of -2.6 DOT/1000 PD (95% CI -4.8 to -0.4). This is largely attributable to decreased antibacterial use, from 704 (95% CI 686-722) to 544 (95% CI 525 -562) DOT/1000 PD. The percentage of children ever receiving an anti-infective during admission likewise declined, from 65% to 52% (95% CI 49-54). There were no detrimental effects on severity adjusted mortality, readmissions, or lengths of stay. CONCLUSIONS: The handshake method is an effective and sustainable approach to stewardship.

Prediction of Nonelective Central Venous Catheter Removal in Medically Complex Neonates.

INTRODUCTION: Central venous catheters (CVCs) are essential to neonatal care but associated with significant morbidity. Nonelective CVC removal (NER) is an inadequately studied outcome associated with increased morbidity, infant and family stress, and cost. This study describes prevalence and predictors of NER in infants admitted to a level IV neonatal intensive care unit and NER variation between peripherally inserted central catheters (PICCs), cutdown PICCs, and surgical CVCs. METHODS: In this study, we include patient and catheter data for infants admitted to a level IV neonatal intensive care unit (2010-2015). Demographic and clinical characteristics were compared using 1-way analysis of variance (ANOVA), Kruskal-Wallis, and chi-square tests for continuous, non-normally distributed continuous, and categorical variables, respectively. The association between NER due to complication and infant and catheter characteristics was assessed using generalized linear mixed models. RESULTS: Patient and catheter characteristics vary significantly by catheter type. The overall rate of NER is 15% (17% PICCs, 13% cutdown PICCs, and 19% surgical CVCs). The most common indications for NER are catheter breakage, blood stream infection(BSI)/central line-associated blood stream infection(CLABSI), catheter malposition, mechanical obstruction, and extravasation. Birth weight, patient diagnosis, catheter dwell time, and concurrent catheters are associated with increased odds of NER. CONCLUSIONS: Patient risk factors and potentially modifiable catheter characteristics, including catheter dwell time and concurrent catheters, are associated with increased NER. As NER is associated with a broad spectrum of adverse outcomes, we propose a quality improvement strategy to risk stratify patients and reduce exposure to high-risk, modifiable catheter characteristics.

A Simple Measure of Hepatocellular Carcinoma Burden Predicts Tumor Recurrence After Liver Transplantation: The Recurrent Hepatocellular Carcinoma-Initial, Maximum, Last Classification.

Risk of recurrent hepatocellular carcinoma (rHCC) after liver transplantation (LT) depends on the pre-LT HCC burden, tumor behavior, and response to locoregional therapy (LRT). In December 2017, LT priority for HCC was expanded to select patients outside the Milan criteria who respond to LRT. Our aims were to develop a novel objective measure of pre-LT HCC burden (model of recurrent hepatocellular carcinoma-initial, maximum, last [RH-IML]), incorporating tumor behavior over time, and to apply RH-IML to model post-LT rHCC. Using United Network for Organ Sharing data from between 2002-2014 (development) and 2015-2017 (validation), we identified adult LT recipients with HCC and assessed pre-LT HCC tumor behavior and post-LT rHCC. For each patient, HCC burden was measured at 3 points on the waiting list: initial (I), maximum (M) total tumor diameter, and last (L) exception petition. HCC burden at these 3 points were classified as (A) Milan to University of California, San Francisco (UCSF), and (D) >UCSF, resulting in each patient having a 3-letter RH-IML designation. Of 16,558 recipients with HCC, 1233 (7%) had any post-LT rHCC. rHCC rates were highest in RH-IML group CCC (15%) and DDD (18%). When M and L tumor burdens did not exceed Milan (class B or A), rHCC was low (≤10%) as in AAA, ABA, ABB, BBA, BBB; rHCC was also low (≤10%) with successful downstaging when L was A (

Brain imaging in classic nonketotic hyperglycinemia: Quantitative analysis and relation to phenotype.

Patients with severe nonketotic hyperglycinemia (NKH) have absent psychomotor development and intractable epilepsy, whereas attenuated patients have variable psychomotor development and absent or treatable epilepsy; differences in brain magnetic resonance imaging (MRI) between phenotypes have not been reported. In a retrospective cross-sectional study, we reviewed 38 MRI studies from 24 molecularly proven NKH patients, and 2 transient NKH patients. Quantitative analyses included corpus callosum size, apparent diffusion coefficient, automated brain volumetric analysis, and glycine/creatine ratio by spectroscopy. All patients age <3 months had restricted diffusion in the posterior limb of the internal capsule, anterior brainstem, posterior tegmental tracts, and cerebellum, not present in transient NKH. In older infants, the pattern evolved and included generalized diffusion restriction in the supratentorial white matter, which quantitatively peaked between 3 and 12 months. No patient had absent corpus callosum or gyral malformation. The corpus callosum was relatively short in severe compared to attenuated phenotypes, and thin in severe cases only. The corpus callosum growth rate differed by severity; age-matched Z-scores of thickness worsened in severe cases only. Cerebral volume was decreased in the hippocampus, globus pallidus, cerebral cortex, thalamus, and cerebellum. Severe patients had greatest glycine/creatine ratios. In this study, no brain malformations were identified. The growth failure of the corpus callosum is worse in severe NKH, whereas the diffusion restriction pattern, reflecting microspongiosis, does not discriminate by phenotypic severity. NKH is therefore a disorder of brain growth best recognized in the corpus callosum, whereas spongiosis is not prognostic.

Antibiotic ointment versus a silver-based dressing for children with extremity burns: A randomized controlled study.

INTRODUCTION: Antibiotic or silver-based dressings are widely used in burn wound care. Our standard method of dressing pediatric extremity burn wounds consists of an antibiotic ointment or nystatin ointment-impregnated nonadherent gauze (primary layer), followed by rolled gauze, soft cast pad, plaster and soft casting tape (3M™ Scotchcast™, St. Paul, MN). The aim of this study was to compare our standard ointment-based primary layer versus Mepitel Ag® (Mölnlycke Health Care, Gothenburg, Sweden) in the management of pediatric upper and lower extremity burn wounds. METHODS: Children with a new burn injury to the upper or lower extremities, who presented to the burn clinic were eligible. Eligible children were enrolled and randomized, stratified by burn thickness, to be dressed in an ointment-based dressing or Mepitel Ag®. Study personnel and participants were not blinded to the dressing assignment after randomization. Dressings were changed approximately once or twice per week, until the burn wound was healed or skin-grafted. The primary outcome was time to wound healing and p-value < 0.05 was considered significant. RESULTS: Ninety-six children with 113 upper or lower extremity burns were included in the analysis. Mepitel Ag® (hazard ratio [HR] 0.57 (95% Confidence Interval (CI) 0.40-0.82); p = 0.002) significantly reduced the rate of wound healing, adjusting for burn thickness and fungal wound infection. The incidence of fungal wound infections and skin grafting was similar between the two groups. Children randomized to standard ointment dressings were significantly less likely to require four or more burn clinic visits than those in the Mepitel Ag® (4% versus 27%; p = 0.004). CONCLUSION: Our study shows that our standard ointment-based dressing significantly increases the rate of wound healing compared to Mepitel Ag® for pediatric extremity burn injuries. LEVEL OF EVIDENCE: Treatment study; Level 1.

Prevalence and Predictors of Back-Transport Closer to Maternal Residence After Acute Neonatal Care in a Regional NICU.

Objectives To describe the demographics, clinical characteristics and referral patterns of premature infants to a regional level IV neonatal intensive care unit (NICU); to determine the prevalence and predictors of back-transport of infants ≤ 32 weeks gestational age in a level IV NICU; for infants not back-transported closer to maternal residence, determine the length of stay beyond attainment of clinical stability. Methods Data (2010-2014) from the Children's Hospital Neonatal Database and individual chart review for infants ≤ 32 weeks admitted to a level IV NICU whose maternal residence was outside the metro area were included. Bivariate associations of maternal and infant characteristics with back-transport were estimated using two-sample t tests and Fisher's exact test. Multivariable logistic regression was used to measure independent predictors of back-transport. Clinical stability was defined as the attainment of full volume enteral feedings and low flow nasal cannula. Results A total of 223 infants were eligible for analysis; of whom 26% were back-transported after acute care. In the adjusted analysis, insurance status, distance from maternal residence and gestational age were significantly associated with back-transport. For infants not back-transported closer to maternal residence, median length of stay in the level IV NICU beyond attainment of clinical stability was 28.5 days. Conclusion for Practice Predictors of back-transport include private insurance, greater distance of maternal residence from NICU and younger gestational age. Many preterm infants admitted to a regional NICU for acute care remained hospitalized in a level IV NICU after achieving clinical stability, for which care in a NICU closer to maternal residence may be appropriate.

Utility of gabapentin in meeting physical therapy goals following posterior spinal fusion in adolescent patients with idiopathic scoliosis.

OF BACKGROUND DATA: Posterior spinal fusion surgery for scoliosis requires extensive postoperative analgesic care. In 2014, we initiated the use of gabapentin as an adjunct for multimodal pain management in spine fusion patients. The effect of gabapentin on postoperative recovery in scoliosis patients was evaluated using the time to meet postoperative physical therapy goals. This measure was chosen because the actions required to achieve the goals are specific and reproducible. Secondary outcomes included morphine equivalents and maximum pain scores. AIMS: The purpose of this study was to evaluate the effects of gabapentin on time to achieve physical therapy goals following posterior spinal fusion in adolescents with scoliosis. METHODS: A retrospective chart review was performed and patients treated perioperatively with gabapentin were compared with those who did not receive gabapentin. Outcome measures included the postoperative day that physical therapy goals were met, days to discharge, morphine equivalents, and maximum pain scores. The 4 physical therapy goals included logroll, transition from lying to sitting, ambulate 250 feet, and ascend/descend at least 3 stairs. RESULTS: There were 50 patients in the gabapentin group and 51 patients in the control group. In the gabapentin group, there was a statistically significant decrease in the time required to meet physical therapy goals. Notably, gabapentin was independently associated with a 5.34 times higher odds of completion of the most challenging physical therapy goal (stairs) within 1 day (P = .04; 95% CI=1.24-37.44). There was not a statistically significant difference in length of hospital stay between the groups (P = .116; 95% CI=0-1). CONCLUSION: In this retrospective analysis, the use of perioperative gabapentin is associated with a statistically significant decrease in time to completing physical therapy goals after spinal fusion for adolescent idiopathic scoliosis.