Factors associated with postpartum depression among high-risk women during the COVID-19 pandemic.

The purpose of this study was to investigate the impacts of the COVID-19 pandemic on multi-level factors associated with depression among a high-risk sample of postpartum women using longitudinal data collected at two timepoints. High-risk postpartum participants in the United States were recruited to participate in a parent study focused on mitigating risk of cardiometabolic disease in postpartum women. Individuals completed a baseline survey which included the Edinburgh Postpartum Depression Scale (EPDS) at 6-weeks postpartum between 2017 through 2019. A modified survey with the inclusion of selected questions from the Coronavirus Health Impact Survey (CRISIS) questionnaire was administered again during the first 6-months of the COVID-19 pandemic and individuals who completed both the baseline assessment and the COVID-19 assessment were included for analyses (n = 46). Multivariate models were run to investigate the impacts of individual-, interpersonal-, and structural-level factors on change in EPDS scores across the postpartum period. Findings suggest that losing contact with social supports (ß = 4.5, SE = 1.9, p = .02) and individuals who reported a total household income of less than $75,000 (ß = 3.4, SE = 1.7, p = .05) were more likely to report significantly worsening postpartum depression scores compared to others. Recommendations to mitigate the stressors that have been amplified by the COVID-19 pandemic and resulting mental health disparities include screening all high-risk postpartum women for depression and anxiety during both postpartum and pediatric healthcare visits, providing informational flyers with tips related to healthy coping behaviors and free/affordable community resources, and linking individuals to peer-led support groups.

Impact of State Prioritization of Safe Infant Sleep Programs on Supine Sleep Positioning for Non-Hispanic White and Non-Hispanic Black Infants.

OBJECTIVE: Investigate whether safe infant sleep prioritization by states through the Title V Maternal and Child Block Grant in 2010 differentially impacted maternal report of supine sleep positioning (SSP) for Non-Hispanic White (NHW) and Non-Hispanic Black (NHB) U.S.-born infants. STUDY DESIGN: We analyzed retrospective cross-sectional data from the Pregnancy Risk Assessment Monitoring System (PRAMS) from 2005 to 2015 from 4 states: WV and OK (Intervention) and AR and UT (Control). PRAMS is a population-based surveillance system of maternal perinatal experiences which is linked to infant birth certificates. Piece-wise survey linear regression models were used to estimate the difference in the change in slopes of SSP percents in the pre- (2005-2009) and post- (2011-2015) periods, controlling for maternal and infant characteristics. Models were also stratified by race/ethnicity. RESULTS: From 2005 to 2015, for NHW infants, SSP improved from 61.5% and 70.2% to 82.8% and 82.3% for intervention and control states, respectively. For NHB infants, SSP improved from 30.6% and 26.5% to 64.5% and 53.1% for intervention and control states, respectively. After adjustment for maternal characteristics, there was no difference in the rate of SSP change from the pre- to post- intervention periods for either NHW or NHB infants in intervention or control groups. CONCLUSION: Compared with control states that did not prioritize safe infant sleep in their 2010 Title V Block Grant needs assessment, intervention states experienced no difference in SSP improvement rates for NHW and NHB infants. While SSP increased for all infants during the study period, there was no causal relationship between states' prioritization of safe infant sleep and SSP improvement. More targeted approaches may be needed to reduce the racial/ethnic disparity in SSP and reduce the risk for sleep-associated infant death. KEY POINTS: · Supine sleep positioning improved for Black and White infants in the U.S.. · State prioritization of safe infant sleep did not directly impact SSP for NHB or NHW infants.. · More targeted approaches may be needed to reduce racial/ethnic disparities in safe sleep practices.

Hearing outcomes in children with pneumococcal meningitis in the PCV13 era.

INTRODUCTION: Streptococcus pneumoniae, is associated with the highest incidence of post-meningitic SNHL. The exact impact of 13-valent pneumococcal conjugate vaccine (PCV) on pediatric SNHL from pneumococcal meningitis is unknown. We aimed to identify clinical factors associated with post-meningitic SNHL (pmSNHL) from pneumococcal meningitis and describe its rates based on three time periods: pre-PCV, PCV-7 and PCV13 eras. METHODS: A retrospective case-control study was performed for patients 18 years and younger diagnosed with pneumococcal meningitis from January 1, 2010 to December 31, 2020 at Children's Hospital Colorado. Demographic and clinical risk factors between those with or without SNHL were compared. Detailed hearing outcomes of those with resulting SNHL are described. RESULTS: 23 patients with CSF cultures or Meningitis/Encephalitis Panel positive for pneumococcal meningitis were identified. Twenty patients both survived the infection and had audiologic evaluation. Six patients had pmSNHL, with 50 % affected bilaterally. The rate of pmSNHL from S. pneumoniae in the PCV-13 era at our institution was similar to historical rates from the pre-PCV and PCV-7 eras. Similar proportions of patients with pmSNHL completed PCV vaccination (66.7 %) compared to those without (71.4 %). Non-PCV-13 serotypes were responsible 83 % of patients with pmSNHL versus 57 % of patients without pmSNHL. CONCLUSIONS: Despite high rates of PCV-13 uptake in our cohort, pmSNHL was still common, severe, and commonly associated with non-PCV-13 serotypes. Non-PCV-13 serotypes may be contributing to the persistently high rate of post-meningitic SNHL and the severity of SNHL. Newer pneumococcal conjugate vaccines with expanded serotypes may help mitigate the SNHL associated with pneumococcal meningitis.

Implementation of the Cardiac Inpatient Neurodevelopmental Care Optimization (CINCO) programme: an interdisciplinary, generalisable approach to inpatient neurodevelopmental care.

BACKGROUND: Children with CHD are at risk for neurodevelopmental delays, and length of hospitalisation is a predictor of poorer long-term outcomes. Multiple aspects of hospitalisation impact neurodevelopment, including sleep interruptions, limited holding, and reduced developmental stimulation. We aimed to address modifiable factors by creating and implementing an interdisciplinary inpatient neurodevelopmental care programme in our Heart Institute. METHODS: In this quality improvement study, we developed an empirically supported approach to neurodevelopmental care across the continuum of hospitalisation for patients with CHD using three plan-do-study-act cycles. With input from multi-level stakeholders including parents/caregivers, we co-designed interventions that comprised the Cardiac Inpatient Neurodevelopmental Care Optimization (CINCO) programme. These included medical/nursing orders for developmental care practices, developmental kits for patients, bedside developmental plans, caregiver education and support, developmental care rounds, and a specialised volunteer programme. We obtained data from the electronic health record for patients aged 0-2 years admitted for at least 7 days to track implementation. RESULTS: There were 619 admissions in 18 months. Utilisation of CINCO interventions increased over time, particularly for the medical/nursing orders and caregiver handouts. The volunteer programme launch was delayed but grew rapidly and within six months, provided over 500 hours of developmental interaction with patients. CONCLUSIONS: We created and implemented a low-cost programme that systematised and expanded upon existing neurodevelopmental care practices in the cardiac inpatient units. Feasibility was demonstrated through increasing implementation rates over time. Key takeaways include the importance of multi-level stakeholder buy-in and embedding processes in existing clinical workflows.

Cerebrospinal fluid amino acids glycine, serine, and threonine in nonketotic hyperglycinemia.

Nonketotic hyperglycinemia (NKH) is caused by deficient glycine cleavage enzyme activity and characterized by elevated brain glycine. Metabolism of glycine is connected enzymatically to serine through serine hydroxymethyltransferase and shares transporters with serine and threonine. We aimed to evaluate changes in serine and threonine in NKH patients, and relate this to clinical outcome severity. Age-related reference values were developed for cerebrospinal fluid (CSF) serine and threonine from 274 controls, and in a cross-sectional study compared to 61 genetically proven NKH patients, categorized according to outcome. CSF d-serine and l-serine levels were stereoselectively determined in seven NKH patients and compared to 29 age-matched controls. In addition to elevated CSF glycine, NKH patients had significantly decreased levels of CSF serine and increased levels of CSF threonine, even after age-adjustment. The CSF serine/threonine ratio discriminated between NKH patients and controls. The CSF glycine/serine aided in discrimination between severe and attenuated neonates with NKH. Over all ages, the CSF glycine, serine and threonine had moderate to fair correlation with outcome classes. After age-adjustment, only the CSF glycine level provided good discrimination between outcome classes. In untreated patients, d-serine was more reduced than l-serine, with a decreased d/l-serine ratio, indicating a specific impact on d-serine metabolism. We conclude that in NKH the elevation of glycine is accompanied by changes in l-serine, d-serine and threonine, likely reflecting a perturbation of the serine shuttle and metabolism, and of one-carbon metabolism. This provides additional guidance on diagnosis and prognosis, and opens new therapeutic avenues to be explored.

Persistent Racial/Ethnic Disparities in Supine Sleep Positioning among US Preterm Infants, 2000-2015.

OBJECTIVE: To assess trends in racial disparity in supine sleep positioning (SSP) across racial/ethnic groups of infants born early preterm (Early preterm; <34 weeks) and late preterm (Late preterm; 34-36 weeks) from 2000 to 2015. STUDY DESIGN: We analyzed Pregnancy Risk Assessment Monitoring System data (a population-based perinatal surveillance system) from 16 US states from 2000 to 2015 (Weighted N = 1 020 986). Marginal prevalence of SSP by year was estimated for infants who were early preterm and late preterm, adjusting for maternal and infant characteristics. After stratifying infants who were early preterm and late preterm, we compared the aOR of SSP trends across racial/ethnic groups by testing the time-race interaction. RESULTS: From 2000 to 2015, Non-Hispanic Black infants had lower odds of SSP compared with Non-Hispanic White infants for early preterm (aOR 0.61; 95% CI 0.47-0.78) and late preterm (aOR 0.44; 95% CI 0.34-0.56) groups. For Hispanic infants, there was no statistically significant difference for either preterm group when compared with Non-Hispanic White infants. aOR of SSP increased (on average) annually by 10.0%, 7.3%, and 7.7%, respectively, in Non-Hispanic White, Non-Hispanic Black, and Hispanic early preterm infants and by 5.8%, 5.9%, and 4.8% among Non-Hispanic White, Non-Hispanic Black, and Hispanic late preterm infants. However, there were no significant between-group differences in annual changes (Early preterm: P = .11; Late preterm: P = .25). CONCLUSIONS: SSP increased for all racial/ethnic preterm groups from 2000 to 2015. However, the racial/ethnic disparity in SSP among early preterm and late preterm groups persists.

Fassier-Duval Rod Failure: Is It Related to Positioning in the Distal Epiphysis?

BACKGROUND: The relationship between Fassier-Duval (FD) rod placement and rod failure rates has not previously been quantified. METHODS: Retrospective review was conducted on patients with osteogenesis imperfecta treated with FD rods between 2005 and 2017. Age at first surgery, sex, Sillence type of osteogenesis imperfecta, bisphosphonate treatment, location of rod (side of body and specific bone), and dates of surgeries, radiographs, and rod failures were collected. C-arm images determined rod fixation within the distal epiphysis at the time of surgery. C-arm variables included rod deviation (percent deviation from the midline of the distal epiphysis) and anatomical direction of deviation (anterior/posterior and medial/lateral). X-ray images were examined for rod failure, which was defined as bending, pulling out of the physis, protrusion out of the bone, and/or failure to telescope. Cox proportional hazards regression models were used to compare failure rates with location of placement within the distal epiphysis allowing for clustering of the data by side (left or right) and bone (femur or tibia). RESULTS: The cohort was 13 patients (11 female individuals and 2 male individuals) with a total of 66 rods and 75 surgeries. Mean time from the first surgery to the last follow-up visit was 8.9 years (SD=5 y). There was a 7% increase in hazard of failure per 1-mm increase in antero-posterior (AP) deviation [hazard ratio (HR), 1.07; 95% confidence interval (CI), 1.01-1.14; P=0.029)]. Similarly, there was a 9% increase in hazard of failure for every 1-mm increase in lateral deviation (HR, 1.09; 95% CI, 1.01-1.18; P=0.019). A 12% increase in hazard of failure per 10% increase in deviation from the midline for both AP and lateral radiograph views was also found, although this was only statistically significant for lateral deviation on the AP radiograph view (HR, 1.12; 95% CI, 1.01-1.25; P=0.030). CONCLUSIONS: FD rod placement within the distal epiphysis has significant impact on increasing rod survival. LEVEL OF EVIDENCE: Level III-therapeutic study.

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.

Lower tacrolimus exposure and time in therapeutic range increase the risk of de novo donor-specific antibodies in the first year of kidney transplantation.

De novo donor-specific antibodies (dnDSAs) have been associated with reduced graft survival. Tacrolimus (TAC)-based regimens are the most common among immunosuppressive approaches used in in clinical practice today, yet an optimal therapeutic dose to prevent dnDSAs has not been established. We evaluated mean TAC C0 (tacrolimus trough concentration) and TAC time in therapeutic range for the risk of dnDSAs in a cohort of 538 patients in the first year after kidney transplantation. A mean TAC C0  < 8 ng/mL was associated with dnDSAs by 6 months (odds ratio [OR] 2.51, 95% confidence interval [CI] 1.32-4.79, P = .005) and by 12 months (OR 2.32, 95% CI 1.30-4.15, P = .004), and there was a graded increase in risk with lower mean TAC C0 . TAC time in the therapeutic range of <60% was associated with dnDSAs (OR 2.05, 95% CI 1.28-3.30, P = .003) and acute rejection (hazard ratio [HR] 4.18, 95% CI 2.31-7.58, P < .001) by 12 months and death-censored graft loss by 5 years (HR 3.12, 95% CI 1.53-6.37, P = .002). TAC minimization may come at a cost of higher rates of dnDSAs, and TAC time in therapeutic range may be a valuable strategy to stratify patients at increased risk of adverse outcomes.

Infant cardiopulmonary bypass: CD73 kinetics, association with clinical outcomes, and influence on serum adenosine production capacity.

BackgroundExtracellular adenine nucleotides contribute to ischemia-reperfusion injury following infant cardiopulmonary bypass (CPB), whereas conversion to adenosine may be protective. Alkaline phosphatase (AP), a key enzyme responsible for this conversion, decreases after infant CPB. Indirect evidence suggests that soluble CD73 may simultaneously increase and partially offset this loss of AP. We sought to measure CD73 levels in infants undergoing CPB and determine its association with adenosine production capacity and postoperative support requirements.MethodsA prospective cohort study of infants ≤120 days of age undergoing CPB. CD73 was measured before CPB and during rewarming. Multivariable modeling evaluated the contributions of CD73/AP to adenosine production capacity and postoperative support requirements.ResultsSerum samples from 85 subjects were analyzed. The median CD73 concentration increased following CPB (95.2 vs. 179.8 ng/ml; P<0.0001). Rewarming CD73 was independently inversely associated with vasoactive inotropic support (P<0.005) and length of intensive care unit stay (P<0.005). Combined AP activity and CD73 concentration predicted adenosine production capacity (P<0.0001).ConclusionsSerum CD73 increases following infant CPB. Low rewarming CD73 is independently associated with increased postoperative support requirements. CD73 and AP together predict serum adenosine production capacity and may represent potential therapeutic targets to clear extracellular adenine nucleotides and improve outcomes following infant CPB.

Pediatric Fall Risk Assessment Tool Comparison and Validation Study.

PURPOSE: Compare two pediatric fall risk assessment tools (I'M SAFE and Humpty Dumpty) used at the same organization to determine if one is better able to predict which patients fall. DESIGN AND METHODS: Retrospective data was obtained from patients admitted in 2014. Each patient who experienced a fall during hospitalization was matched with two non-fallers based on age and diagnosis. Logistic regression was performed to identify which tool more accurately determines fall risk and reliability testing was completed for the I'M SAFE tool. RESULTS: Over 22,000 patient files were extracted for this study. One hundred seventy-seven falls were identified, seventy-one of them were intrinsic. Of those patients who fell, the majority were assessed to be at high risk for falls. There were too few falls during the study period using the Humpty Dumpty tool to assess and make formal conclusions. The results for the I'M SAFE tool were opposite of what was expected and showed an increased risk for falls for patients who scored low risk using this tool. CONCLUSIONS: At completion of this study the data reflected that the I'M SAFE tool was not adequately predicting patients at greatest risk for intrinsic falls for this particular population. PRACTICE IMPLICATIONS: Further research on these tools is needed in other populations or across multiple sites. Additional work to adapt the tools may be necessary to better predict fall risk without over identifying high risk patients.

Pediatric Renal Angiomyolipomas in Tuberous Sclerosis Complex.

PURPOSE: Tuberous sclerosis complex is a genetic disorder characterized by the growth of hamartomas in multiple organs. Up to 80% of patients with tuberous sclerosis complex will have at least 1 angiomyolipoma in their lifetime. We describe the incidence and natural history of angiomyolipoma in a pediatric tuberous sclerosis complex population and analyze tumor growth to determine optimal renal imaging intervals in an effort to improve counseling, treatment and followup. MATERIALS AND METHODS: We performed a retrospective chart review of all patients with tuberous sclerosis complex from 2004 to 2014. Patients were included if they had a clinical or genetic diagnosis of tuberous sclerosis complex and had undergone at least 1 renal imaging study. RESULTS: A total of 145 patients were analyzed. Median age was 14 years (range 0 to 28). Overall incidence of angiomyolipoma was 50.3%. Median age at first angiomyolipoma detection was 11 years (range 2 to 26). Median yearly angiomyolipoma growth rate stratified by age at first detection was 0.0 mm for patients 0 to 6 years old, 0.9 mm for those 7 to 11 years old, 2.5 mm for those 12 to 16 years old and 1.8 mm for those 17 years old or older. Median yearly angiomyolipoma growth rate stratified by tumor size at first detection was 0.1 mm for tumors 0.6 to 0.9 cm, 1.8 mm for those 1.0 to 1.9 cm and 4.3 mm for those 2.0 to 2.9 cm. A total of 35 patients (24.1%) received mTOR (mammalian target of rapamycin) inhibitors. Eight patients underwent a total of 13 surgical interventions, of whom 2 had previously been treated with mTOR inhibitors. Median patient age at surgical intervention was 18.0 years and median angiomyolipoma size was 5.0 cm. CONCLUSIONS: Angiomyolipoma growth in children with tuberous sclerosis complex can be rapid and unpredictable. We recommend yearly renal ultrasound in all patients with tuberous sclerosis complex, with consideration of magnetic resonance imaging in those at risk for rapid growth and future intervention (ie those older than 11 years and/or those with renal angiomyolipomas larger than 2 cm).

Alkaline Phosphatase in Infant Cardiopulmonary Bypass: Kinetics and Relationship to Organ Injury and Major Cardiovascular Events.

OBJECTIVES: To determine the kinetics of alkaline phosphatase (AP) activity and concentration after infant cardiopulmonary bypass, including isoform-specific changes, and to measure the association between postoperative AP activity and major postoperative cardiovascular events, organ injury/dysfunction, and postoperative support requirements STUDY DESIGN: Prospective cohort study of 120 infants ≤120 days of age undergoing cardiopulmonary bypass. AP total and isoform-specific activity was assessed at 6 time points (preoperation, rewarming, 6, 24, 48, and 72 hours postoperation). Low AP activity was defined as ≤80 U/L. AP concentrations and biomarkers of organ injury/dysfunction were collected through 24 hours postoperation. Major cardiovascular events were defined as cardiac arrest, mechanical circulatory support, or death. RESULTS: AP activity loss occurred primarily during the operation (median decrease 89 U/L; P < .0001) secondary to decreased bone and liver 2 isoforms. Activity declined through 24 hours in 27% of patients. AP activity strongly correlated with serum concentration (r = 0.87-0.91; P < .0001). Persistent low AP activity at 72 hours was associated independently with occurrence of a major cardiac event (OR 5.6; P < .05). Early AP activity was associated independently with subsequent vasoactive-inotropic score (P < .001), peak lactate (P < .0001), peak creatinine (P < .0005), N-terminal pro-brain natriuretic peptide (P < .05), and intestinal fatty acid binding protein (P < .005). CONCLUSIONS: AP activity decreases during infant cardiopulmonary bypass and may continue to decrease for 24 hours. Activity loss is secondary to decreased bone and liver 2 isoform concentrations. Early low AP activity is associated independently with subsequent postoperative support and organ injury/dysfunction, and persistence of AP activity ≤80 U/L at 72 hours is associated independently with increased odds of major cardiovascular events.

Risk factors for bacteremia and central line-associated blood stream infections in children with acute myelogenous leukemia: A single-institution report.

BACKGROUND: Central line-associated blood stream infections (CLABSIs) are a source of high morbidity and mortality in children with acute myelogenous leukemia (AML). PROCEDURE: To understand the epidemiology and risk factors associated with the development of CLABSI in children with AML. METHODS: We retrospectively reviewed all patients with AML over a 5-year period between 2007 and 2011 at the Children's Hospital Colorado. Cases and controls were classified on the basis of the presence of a CLABSI as defined by the National Healthcare Safety Network. RESULTS: Of 40 patients in the study, 25 (62.5%) developed at least one CLABSI during therapy. The majority of CLABSIs were due to oral or gastrointestinal organisms (83.0%). Skin organisms accounted for 8.5%. In a multivariable analysis, the strongest risk factors associated with CLABSI were diarrhea (odds ratio [OR] 6.7, 95% confidence interval [CI] 1.6-28.7), receipt of blood products in the preceding 4-7 days (OR 10.0, 95%CI 3.2-31.0), not receiving antibiotics (OR 8.3, 95%CI 2.8-25.0), and chemotherapy cycle (OR 3.5, 95%CI 1.4-8.9). CLABSIs led to increased morbidity, with 13 cases (32.5%) versus two controls (1.9%) requiring transfer to the pediatric intensive care unit (P < 0.001). Three (7.5%) of 40 CLABSI events resulted in or contributed to death. CONCLUSIONS: Intensified line care efforts cannot eliminate all CLABSIs in the patients with AML. Exploring the role of mucosal barrier breakdown and/or the use of antibiotic prophylaxis may be effective strategies for further prevention of CLABSIs, supporting ongoing trials in this patient population.

Validation of the Vasoactive-Inotropic Score in Pediatric Sepsis.

OBJECTIVES: To assess the validity of Vasoactive-Inotropic Score as a scoring system for cardiovascular support and surrogate outcome in pediatric sepsis. DESIGN: Secondary retrospective analysis of a single-center sepsis registry. SETTING: Freestanding children's hospital and tertiary referral center. PATIENTS: Children greater than 60 days and less than 18 years with sepsis identified in the emergency department between January 2012 and June 2015 treated with at least one vasoactive medication within 48 hours of admission to the PICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Vasoactive-Inotropic Score was abstracted at 6, 12, 24, and 48 hours post ICU admission. Primary outcomes were ventilator days and ICU length of stay. The secondary outcome was a composite outcome of cardiac arrest/extracorporeal membrane oxygenation/in-hospital mortality. One hundred thirty-eight patients met inclusion criteria. Most common infectious sources were pneumonia (32%) and bacteremia (23%). Thirty-three percent were intubated and mortality was 6%. Of the time points assessed, Vasoactive-Inotropic Score at 48 hours showed the strongest correlation with ICU length of stay (r = 0.53; p < 0.0001) and ventilator days (r = 0.52; p < 0.0001). On multivariable analysis, Vasoactive-Inotropic Score at 48 hours was a strong independent predictor of primary outcomes and intubation. For every unit increase in Vasoactive-Inotropic Score at 48 hours, there was a 13% increase in ICU length of stay (p < 0.001) and 8% increase in ventilator days (p < 0.01). For every unit increase in Vasoactive-Inotropic Score at 12 hours, there was a 14% increase in odds of having the composite outcome (p < 0.01). CONCLUSIONS: Vasoactive-Inotropic Score in pediatric sepsis patients is independently associated with important clinically relevant outcomes including ICU length of stay, ventilator days, and cardiac arrest/extracorporeal membrane oxygenation/mortality. Vasoactive-Inotropic Score may be a useful surrogate outcome in pediatric sepsis.

Clinical Associations of Early Dysnatremias in Critically Ill Neonates and Infants Undergoing Cardiac Surgery.

Dysnatremias (DN) are common electrolyte disturbances in cardiac critical illness and are known risk factors for adverse outcomes in certain populations. Little information exists on DN in children with cardiac disease admitted to the cardiac intensive care unit (CICU) after undergoing cardiac surgery, either corrective or palliative. The aim was to determine the incidence and adverse outcomes associated with DN in neonates and infants undergoing cardiac surgery. Retrospective cohort and single center study performed at Children's Hospital Colorado from May 2013 to May 2014, in children under 1 year old admitted to the CICU after undergoing surgery for congenital or acquired cardiac disease. 183 subjects were analyzed. EXCLUSIONS: subjects that demonstrated DN before surgery. Serum sodium levels were recorded for the first 72 h post-operatively. DN was present in 54% of the subjects (98/183): hypernatremia in 60 (33%), hyponatremia in 38 (21%). Multivariate analysis revealed that mild hypernatremia (146-150 mmol/dl) and moderate hypernatremia (151-155 mmol/dl) were associated with longer hospital length of stay (LOS, p < 0.05) and ventilation times (p < 0.05). No association was shown between mild/moderate hyponatremia (125-134 mmol/dl) with either outcome. Hours to DN were significantly lower in hypernatremic (median = 5.8 h) than hyponatremic (median = 43.8 h) patients (p < 0.001). Children younger than 30 days presented DN at an earlier stage than those 31 days-1 year old (median +2.2 vs. 17.3 h). No associations present between DN and the class of diuretic (loop vs. thiazide) administered, or the route of administration (intravenous bolus vs. constant infusion). Total median sodium bicarbonate administration was associated with hypernatremia, as was exposure to vasopressin within the first 72 h post-operatively. Dysnatremias are common in the early post-operative period in neonates and infants undergoing cardiac surgery. Mild to moderate hypernatremia, but not hyponatremia, is associated with longer LOS and longer ventilation time in infants undergoing cardiovascular surgery. Hypernatremia is also associated with younger infants, a higher surgical complexity, administration of bicarbonate and exposure to vasopressin. Diuretic type or interval timing of intravenous delivery did not demonstrate any effect. Prospective studies are needed in this population, in order to determine how DN, particularly hypernatremia, contributes to adverse outcomes, whether this association is independent of illness severity, and what may be safe treatments and interventions for these disorders.

Intranasal Fentanyl and Quality of Pediatric Acute Care.

BACKGROUND: Changes in the manner in which medications can be delivered can have significant effects on the quality of care in the acute care setting. OBJECTIVE: The objective of this study was to evaluate the change in three Institute of Medicine quality indicators (timeliness, safety, and effectiveness) in the pediatric emergency department (ED) after the introduction of the Mucosal Atomizer Device Nasal™ (MADn) for opioid analgesia. METHODS: This was a retrospective review of patients receiving opioid analgesia for certain conditions over a 5-year period. We compared patients receiving intravenous opioid (IVO) to those receiving intranasal fentanyl (INF). Timeliness outcomes include time from medication order to administration, time from dose to discharge, overall time to analgesia, and ED length of stay. Effectiveness outcomes include change in pain score and frequency of repeat dosing. Safety outcomes were the frequency of reversal agent administration or a documented oxygen desaturation of < 90%. Sensitivity analyses were performed to evaluate the effect of moderate sedation on all three outcomes. RESULTS: During the study period, 1702 patients received opioid analgesia, 744 before and 958 after MADn introduction, of whom, 233 (24%) received INF. After MADn introduction, patients receiving INF had a shorter time to discharge from dose (109 vs. 203 min; p < 0.05) and shorter ED length of stay (168 vs. 267 min; p < 0.05). There was no difference in pain score reduction; however, repeat dosing was less frequent for patients receiving INF (16% vs. 27%). There was no use of reversal medication and no difference in the frequency of oxygen desaturations. When patients undergoing moderate sedation were removed from the analysis, there was no difference in the direction of findings for all three outcomes. CONCLUSIONS: INF is associated with improved timeliness and equivalent effectiveness and safety when compared to IVO in the setting of the pediatric ED.

Effects of Maternal Valium Administration on Fetal MRI Motion Artifact: A Comparison Study at High Altitude.

PURPOSE: Fetal MRI is performed without sedation. In cases of maternal claustrophobia or when reduction of fetal motion is critical, benzodiazepines may help. The purpose of this study was to evaluate the effects of low-dose benzodiazepine on fetal motion MRI and its effect on maternal oxygen levels at higher elevation. METHODS: A total of 131 fetal MRI scans performed from March 2012 through December 2013 were studied. Nineteen of the cases were performed following Valium administration. Images were graded with a 5-point Likert scale. Using pulse oximetry, maternal oxygen levels were recorded. RESULTS: Results were analyzed for each category combining 3 readers' interpretations. Using a 2-sample t test model, the average imaging scores were better for the control than the Valium group (p = 0.0139). Maternal oxygen levels at different times and positions were compared using independent 2-sample t test between the Valium and control groups showing no change in O2 saturation, except when controlling for altitude and gestational age (p = 0.0326). CONCLUSION: Administration of low-dose Valium did not decrease fetal motion on MRI. Valium did not pose any risk of maternal hypoxemia, except when controlling for altitude and gestational age on supine position. Thus, caution should be exercised to prevent the risk of fetal hypoxemia.

Biochemical and molecular predictors for prognosis in nonketotic hyperglycinemia.

OBJECTIVE: Nonketotic hyperglycinemia is a neurometabolic disorder characterized by intellectual disability, seizures, and spasticity. Patients with attenuated nonketotic hyperglycinemia make variable developmental progress. Predictive factors have not been systematically assessed. METHODS: We reviewed 124 patients stratified by developmental outcome for biochemical and molecular predictive factors. Missense mutations were expressed to quantify residual activity using a new assay. RESULTS: Patients with severe nonketotic hyperglycinemia required multiple anticonvulsants, whereas patients with developmental quotient (DQ) > 30 did not require anticonvulsants. Brain malformations occurred mainly in patients with severe nonketotic hyperglycinemia (71%) but rarely in patients with attenuated nonketotic hyperglycinemia (7.5%). Neonatal presentation did not correlate with outcome, but age at onset ≥ 4 months was associated with attenuated nonketotic hyperglycinemia. Cerebrospinal fluid (CSF) glycine levels and CSF:plasma glycine ratio correlated inversely with DQ; CSF glycine > 230 µM indicated severe outcome and CSF:plasma glycine ratio ≤ 0.08 predicted attenuated outcome. The glycine index correlated strongly with outcome. Molecular analysis identified 99% of mutant alleles, including 96 novel mutations. Mutations near the active cleft of the P-protein maintained stable protein levels. Presence of 1 mutation with residual activity was necessary but not sufficient for attenuated outcome; 2 such mutations conferred best outcome. Divergent outcomes for the same genotype indicate a contribution of other genetic or nongenetic factors. INTERPRETATION: Accurate prediction of outcome is possible in most patients. A combination of 4 factors available neonatally predicted 78% of severe and 49% of attenuated patients, and a score based on mutation severity predicted outcome with 70% sensitivity and 97% specificity.

Intermittent versus Persistent Wolff-Parkinson-White Syndrome in Children: Electrophysiologic Properties and Clinical Outcomes.

BACKGROUND: Intermittent Wolff-Parkinson-White (WPW) syndrome is considered to have a lower risk of sudden death. Fewer data exist regarding electrophysiologic (EP) characteristics and the natural history of intermittent WPW in children. METHODS: All patients with WPW age 1-18 years at a single institution (1996-2013) were reviewed. Patients with intermittent preexcitation were compared to those with loss of preexcitation on Holter/exercise testing and those with persistent preexcitation. High-risk accessory pathway (AP) was defined as AP effective refractory period (APERP), block cycle length, or shortest preexcited RR interval during atrial fibrillation ≤250 ms. RESULTS: A total of 295 patients were included: 226 (76.6%) persistent, 39 (13.2%) intermittent, and 30 (10.2%) loss of preexcitation Holter/exercise. There were no differences in symptoms between groups. Median interquartile range APERP was significantly longer in intermittent WPW (380 [320, 488] ms vs 320 [300, 350] ms persistent, 310 [290, 330] ms loss of preexcitation Holter/exercise; P = 0.0008). At baseline, there was no difference between groups in frequency of high-risk pathways. However, when isoproterenol values were included, high-risk pathways were more frequent among patients with loss of preexcitation on Holter/exercise (54% vs 16% persistent, 11% intermittent; P = 0.005). There was one death in a patient with loss of preexcitation on exercise testing, no EP study, and prior drug use. A second patient with persistent WPW and APERP 270 ms required resuscitation following a methadone overdose. CONCLUSION: Intermittent preexcitation in children does not connote a lower risk AP by EP criteria or reduced symptoms. The low number of pediatric WPW patients who develop preexcited atrial fibrillation or sudden death warrants larger studies to investigate these outcomes.