Improved Detection of Child Maltreatment with Routine Screening in a Tertiary Care Pediatric Hospital.

OBJECTIVES: To evaluate the impact of layering routine child abuse screening on top of a preexisting electronic health record-embedded Child Abuse Clinical Decision Support System (CA-CDSS) in a pediatric emergency department. STUDY DESIGN: The Pittsburgh Child Abuse Screening Tool (P-CAST) was performed in all children aged <13 years and in nonverbal children aged ≥13 years who presented to a pediatric tertiary care center over a 6-month period. The P-CAST was layered on top of a preexisting CA-CDSS that included passive triggers, alerts, and abuse-specific order sets. RESULTS: Of the 28 797 screens performed, 1.8% were positive in children aged <13 years and 1.6% were positive in nonverbal children aged ≥13 years. One-half of the children with a positive P-CAST also triggered the CA-CDSS; the other one-half triggered only because of the P-CAST. Nineteen percent of the patients with a positive P-CAST were reported to Child Protective Services (CPS). There was no relationship between race and the odds of a positive P-CAST or between race and the likelihood of a report being made to CPS. CONCLUSIONS: Active routine child abuse screening improves identification of suspected child maltreatment in a children's hospital above and beyond what is identified with a CA-CDSS, which depends on passive triggers. The lack of a relationship between race and a positive P-CAST or a report to CPS suggest that systematic child abuse screening may mitigate well-recognized racial disparities in identifying and reporting suspected child maltreatment.

Integration of physical abuse clinical decision support at 2 general emergency departments.

OBJECTIVE: The study sought to develop and evaluate an electronic health record-based child abuse clinical decision support system in 2 general emergency departments. MATERIALS AND METHODS: A combination of a child abuse screen, natural language processing, physician orders, and discharge diagnoses were used to identify children <2 years of age with injuries suspicious for physical abuse. Providers received an alert and were referred to a physical abuse order set whenever a child triggered the system. Physician compliance with clinical guidelines was compared before and during the intervention. RESULTS: A total of 242 children triggered the system, 86 during the preintervention and 156 during the intervention. The number of children identified with suspicious injuries increased 4-fold during the intervention (P < .001). Compliance was 70% (7 of 10) in the preintervention period vs 50% (22 of 44) in the intervention, a change that was not statistically different (P = .55). Fifty-two percent of providers said that receiving the alert changed their clinical decision making. There was no relationship between compliance and provider or patient demographics. CONCLUSIONS: A multifaceted child abuse clinical decision support system resulted in a marked increase in the number of young children identified as having injuries suspicious for physical abuse in 2 general emergency departments. Compliance with published guidelines did not change; we hypothesize that this is related to the increased number of children identified with suspicious, but less serious injuries. These injuries were likely missed preintervention. Tracking compliance with guidelines over time will be important to assess whether compliance increases as physician comfort with evaluation of suspected physical abuse in young children improves.

Early Protocolized Versus Usual Care Rehabilitation for Pediatric Neurocritical Care Patients: A Randomized Controlled Trial.

OBJECTIVE: s: Few feasibility, safety, and efficacy data exist regarding ICU-based rehabilitative services for children. We hypothesized that early protocolized assessment and therapy would be feasible and safe versus usual care in pediatric neurocritical care patients. DESIGN: Randomized controlled trial. SETTING: Three tertiary care PICUs in the United States. PATIENTS: Fifty-eight children between the ages of 3-17 years with new traumatic or nontraumatic brain insult and expected ICU admission greater than 48 hours. INTERVENTIONS: Early protocolized (consultation of physical therapy, occupational therapy, and speech and language therapy within 72 hr ICU admission, n = 26) or usual care (consultation per treating team, n = 32). MEASUREMENTS AND MAIN RESULTS: Primary outcomes were consultation timing, treatment type, and frequency of deferrals and safety events. Secondary outcomes included patient and family functional and quality of life outcomes at 6 months. Comparing early protocolized (n = 26) and usual care groups (n = 32), physical therapy was consulted during the hospital admission in 26 of 26 versus 28 of 32 subjects (p = 0.062) on day 2.4 ± 0.8 versus 7.7 ± 4.8 (p = 0.001); occupational therapy in 26 of 26 versus 23 of 32 (p = 0.003), on day 2.3 ± 0.6 versus 6.9 ± 4.8 (p = 0.001); and speech and language therapy in 26 of 26 versus 17 of 32 (p = 0.011) on day 2.3 ± 0.7 versus 13.0 ± 10.8 (p = 0.026). More children in the early protocolized group had consults and treatments occur in the ICU versus ward for all three services (all p < 0.001). Eleven sessions were discontinued early: nine during physical therapy and two during occupational therapy, none impacting patient outcome. There were no group differences in functional or quality of life outcomes. CONCLUSIONS: A protocol for early personalized rehabilitation by physical therapy, occupational therapy, and speech and language therapy in pediatric neurocritical care patients could be safely implemented and led to more ICU-based treatment sessions, accelerating the temporal profile and changing composition of interventions versus usual care, but not altering the total dose of rehabilitation.

Integration of physical abuse clinical decision support into the electronic health record at a Tertiary Care Children's Hospital.

Objective: To evaluate the effect of a previously validated electronic health record-based child abuse trigger system on physician compliance with clinical guidelines for evaluation of physical abuse. Methods: A randomized controlled trial (RCT) with comparison to a preintervention group was performed. RCT-experimental subjects' providers received alerts with a direct link to a physical abuse-specific order set. RCT-control subjects' providers had no alerts, but could manually search for the order set. Preintervention subjects' providers had neither alerts nor access to the order set. Compliance with clinical guidelines was calculated. Results: Ninety-nine preintervention subjects and 130 RCT subjects (73 RCT-experimental and 57 RCT-control) met criteria to undergo a physical abuse evaluation. Full compliance with clinical guidelines was 84% pre-intervention, 86% in RCT-control group, and 89% in RCT-experimental group. The physical abuse order set was used 43 times during the 7-month RCT. When the abuse order set was used, full compliance was 100%. The proportion of cases in which there was partial compliance decreased from 10% to 3% once the order set became available (P = .04). Male gender, having >10 years of experience and completion of a pediatric emergency medicine fellowship were associated with increased compliance. Discussion/Conclusion: A child abuse clinical decision support system comprised of a trigger system, alerts and a physical abuse order set was quickly accepted into clinical practice. Use of the physical abuse order set always resulted in full compliance with clinical guidelines. Given the high baseline compliance at our site, evaluation of this alert system in hospitals with lower baseline compliance rates will be more valuable in assessing the efficacy in adherence to clinical guidelines for the evaluation of suspected child abuse.

Validation of the Pittsburgh Infant Brain Injury Score for Abusive Head Trauma.

BACKGROUND: Abusive head trauma is the leading cause of death from physical abuse. Misdiagnosis of abusive head trauma as well as other types of brain abnormalities in infants is common and contributes to increased morbidity and mortality. We previously derived the Pittsburgh Infant Brain Injury Score (PIBIS), a clinical prediction rule to assist physicians deciding which high-risk infants should undergo computed tomography of the head. METHODS: Well-appearing infants 30 to 364 days of age with temperature <38.3°C, no history of trauma, and a symptom associated with an increased risk of having a brain abnormality were eligible for enrollment in this prospective, multicenter clinical prediction rule validation. By using a predefined neuroimaging paradigm, subjects were classified as cases or controls. The sensitivity, specificity, and negative and positive predictive values of the rule for prediction of brain injury were calculated. RESULTS: A total of 1040 infants were enrolled: 214 cases and 826 controls. The 5-point PIBIS included abnormality on dermatologic examination (2 points), age ≥3.0 months (1 point), head circumference >85th percentile (1 point), and serum hemoglobin <11.2g/dL (1 point). At a score of 2, the sensitivity and specificity for abnormal neuroimaging was 93.3% (95% confidence interval 89.0%-96.3%) and 53% (95% confidence interval 49.3%-57.1%), respectively. CONCLUSIONS: Our data suggest that the PIBIS accurately identifies infants who would benefit from neuroimaging to evaluate for brain injury. An implementation analysis is needed before the PIBIS can be integrated into clinical practice.

Exploratory study of serum ubiquitin carboxyl-terminal esterase L1 and glial fibrillary acidic protein for outcome prognostication after pediatric cardiac arrest.

INTRODUCTION: Brain injury is the leading cause of morbidity and death following pediatric cardiac arrest. Serum biomarkers of brain injury may assist in outcome prognostication. The objectives of this study were to evaluate the properties of serum ubiquitin carboxyl-terminal esterase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) to classify outcome in pediatric cardiac arrest. METHODS: Single center prospective study. Serum biomarkers were measured at 2 time points during the initial 72 h in children after cardiac arrest (n=19) and once in healthy children (controls, n=43). We recorded demographics and details of the cardiac arrest and resuscitation. We determined the associations between serum biomarker concentrations and Pediatric Cerebral Performance Category (PCPC) at 6 months (favorable (PCPC 1-3) or unfavorable (PCPC 4-6)). RESULTS: The initial assessment (time point 1) occurred at a median (IQR) of 10.5 (5.5-17.0)h and the second assessment (time point 2) at 59.0 (54.5-65.0)h post-cardiac arrest. Serum UCH-L1 was higher among children following cardiac arrest than among controls at both time points (p<0.05). Serum GFAP in subjects with unfavorable outcome was higher at time point 2 than in controls (p<0.05). Serum UCH-L1 at time point 1 (AUC 0.782) and both UCH-L1 and GFAP at time point 2 had good classification accuracy for outcome (AUC 0.822 and 0.796), p<0.05 for all. CONCLUSION: Preliminary data suggest that serum UCH-L1 and GFAP may be of use to prognosticate outcome after pediatric cardiac arrest at clinically-relevant time points and should be validated prospectively.

Serum D-dimer concentrations are increased after pediatric traumatic brain injury.

OBJECTIVE: To determine whether D-dimer would be increased in children with traumatic brain injury (TBI), specifically mild abusive head trauma. STUDY DESIGN: D-dimer was measured using multiplex bead technology in 195 children <4 years old (n = 93 controls without TBI, n = 102 cases with TBI) using previously collected serum. D-dimer was then measured prospectively in a clinical setting in 44 children (n = 24 controls, n = 20 cases). Receiver operator curves were generated for prospective data. RESULTS: In both the retrospective and prospective cohorts, median (25th-75th percentile) D-dimer was significantly higher in cases vs controls. A receiver operator curve demonstrated an area under the curve of 0.91 (95% CI 0.83-0.99) in the prospective cohort. At a cut-off of 0.59 µg/L, the sensitivity and specificity for identification of a case was 90% and 75%, respectively. CONCLUSIONS: Our data suggest that serum D-dimer may be able to be used to identify which young children at risk for abusive head trauma might benefit from a head computed tomography or other additional evaluation. Additional data are needed to better identify the clinical scenarios that may result in false positive or false negative D-dimer concentrations.

Serum biomarkers of brain injury to classify outcome after pediatric cardiac arrest*.

OBJECTIVES: Morbidity and mortality in children with cardiac arrest largely result from neurologic injury. Serum biomarkers of brain injury can potentially measure injury to neurons (neuron-specific enolase), astrocytes (S100b), and axons (myelin basic protein). We hypothesized that serum biomarkers can be used to classify outcome from pediatric cardiac arrest. DESIGN: Prospective observational study. SETTING: Single tertiary pediatric hospital. PATIENTS: Forty-three children with cardiac arrest. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We measured serum neuron-specific enolase, S100b, and myelin basic protein on days 1-4 and 7 after cardiac arrest. We recorded demographics, details of the cardiac arrest and resuscitation, and Pediatric Cerebral Performance Category at hospital discharge and 6 months. We analyzed the association of biomarker levels at 24, 48, and 72 hours with favorable (Pediatric Cerebral Performance Category 1-3) or unfavorable (Pediatric Cerebral Performance Category 4-6) outcome and mortality. Forty-three children (49% female; mean age of 5.9 ± 6.3) were enrolled and 17 (40%) died. Serum S100b concentrations peaked earliest, followed by neuron-specific enolase and finally myelin basic protein. Serum neuron-specific enolase and S100b concentrations were increased in the unfavorable versus favorable outcome group and in subjects who died at all time points (all p < 0.05). Serum myelin basic protein at 24 and 72 hours correctly classified survival but not good versus poor outcome. Using best specificity, serum S100b and neuron-specific enolase had optimal positive and negative predictive values at 24 hours to classify both favorable versus unfavorable outcome and survival, whereas serum myelin basic protein's best accuracy occurred at 48 hours. Receiver operator curves for serum S100b and neuron-specific enolase to classify favorable versus unfavorable outcome at 6 months were superior to clinical variables. CONCLUSIONS: Preliminary data show that serum S100b, neuron-specific enolase, and myelin basic protein may aid in outcome classification of children surviving cardiac arrest.

Serum concentrations of ubiquitin C-terminal hydrolase-L1 and αII-spectrin breakdown product 145 kDa correlate with outcome after pediatric TBI.

Predicting outcome after pediatric traumatic brain injury (TBI) is important for providing information to families and prescribing rehabilitation services. Previously published studies evaluating the ability of serum biomarkers to predict outcome after pediatric TBI have focused on three markers: neuron-specific enolase (NSE), S100B, and myelin-basic protein (MBP), all of which have important limitations. The study objectives were to measure serum concentrations of two novel serum biomarkers, ubiquitin C-terminal hydrolase (UCH-L1) and αII-spectrin breakdown product 145 kDa (SBDP145), in children with TBI and healthy controls and to assess the ability of these markers to predict outcome as assessed by a dichotomous Glasgow Outcome Scale (GOS) score. We also sought to compare the predictive ability of UCH-L1 and SBDP145 to that of the clinical gold standard, the Glasgow Coma Scale (GCS) score, and to that of the well-accepted biomarkers NSE, S100B, and MBP. Serum UCH-L1 and SBDP145 concentrations were significantly greater in subjects than in controls. The increase in UCH-L1 and SBDP145 was exclusively seen in subjects with moderate and severe TBI; there was no increase after mild TBI. Both markers had a significant negative partial correlation with the GCS after controlling for age. Both UCH-L1 and SBDP145 were correlated with GOS, and this correlation was stronger than the correlations with NSE, S100B, or MBP. These results suggest that these two markers may be useful in assessing outcome after moderate and severe pediatric TBI.

Derivation and validation of an equation for adjustment of neuron-specific enolase concentrations in hemolyzed serum.

OBJECTIVE: To derive and validate a formula to allow for adjustment of serum neuron-specific enolase (NSE) concentrations based on the amount of hemolysis in the sample. To compare the accuracy of qualitative and quantitative assessment of hemolysis. DESIGN: Derivation and validation of a formula. SUBJECTS: Eighty-three children <11 years of age were used for the derivation. Twenty-three children <11 years without brain injury and 30 with brain injury were used for the validation. INTERVENTIONS: We evaluated the amount of hemolysis quantitatively using a hemocue and qualitatively by visualization. We measured NSE concentrations by enzyme-linked immunosorbent assay. Using a subset of subjects, we used linear regression analysis to derive an equation to adjust serum NSE concentrations based on the degree of hemolysis. We prospectively validated the formula in a different group. NSE < or =11.5 ng/mL was considered normal. RESULTS: The formula derived was as follow: Adjusted NSE = Unadjusted NSE - (1.659) (square root of the hemocue). In the validation, 96% of children without brain injury had a normal adjusted NSE; 93% of children with brain injury had an abnormal adjusted NSE. Qualitative analysis of hemolysis was inconsistent and both overassessed and under-assessed hemolysis as quantified by hemocue. CONCLUSIONS: We retrospectively derived and prospectively validated an equation for adjusting serum NSE concentrations based on the amount of hemolysis in the sample. Use of this formula will allow for accurate measurement of NSE even in hemolyzed sample and may improve its usefulness as a marker of brain injury in children. Qualitative assessment of the degree of hemolysis is not accurate and should not be used.

Serum biomarker concentrations and outcome after pediatric traumatic brain injury.

Predicting outcome after pediatric traumatic brain injury (TBI) is important for providing information to families and prescribing rehabilitation services. The study objective was to assess whether biomarkers concentrations obtained at the time of injury are associated with outcome. Serial serum concentrations of neuron-specific enolase (NSE), S100B and myelin basic protein (MBP) were measured in 152 children with acute TBI. Outcome was assessed with the Glasgow Outcome Scale (GOS) score and/or GOS-Extended Pediatric (GOS-E Peds). Spearman's rank correlation and binary logistic regression assessed the relationship between biomarker concentrations and outcome. For all biomarkers and time points, higher biomarker concentrations were associated with worse outcome. Initial and peak NSE concentrations and initial MBP concentrations were more strongly correlated with outcome in children < or =4 years compared with those >4 years of age. Using binary logistic regression to evaluate the simultaneous affect of all biomarkers on outcome, there was significant overall model fit predicting a dichotomous GOS from biomarker concentrations with a 77% correct classification rate and a negative and positive predictive value of 97% and 75%, respectively. We conclude that NSE, S100B, and MBP concentrations obtained at the time of TBI may be useful in predicting outcome. Future studies should focus on assessing the differential benefit of biomarkers compared with clinical variables and in assessing a continuous rather than categorical outcome variable.

Serum biomarkers after traumatic and hypoxemic brain injuries: insight into the biochemical response of the pediatric brain to inflicted brain injury.

Inflicted traumatic brain injury (iTBI) involves a combination of mechanical trauma and hypoxemia. Serum biomarker concentrations may provide objective information about their relative importance to the pathophysiology of iTBI. We compared the time course of neuron-specific enolase (NSE), S100B and myelin basic protein after pediatric hypoxic-ischemic brain injury, iTBI and noninflicted TBI (nTBI). The time to reach peak concentrations of all three biomarkers was shorter after nTBI. Initial and peak S100B, initial and peak myelin basic protein and peak NSE concentrations were no different between the three groups. Initial NSE concentration was highest after nTBI. These results suggest that the biochemical response of the brain to iTBI is distinct from the response to nTBI and shares temporal similarities with hypoxic-ischemic brain injury. This may have important implications for the treatment and prognosis of children with iTBI.

Identification of inflicted traumatic brain injury in well-appearing infants using serum and cerebrospinal markers: a possible screening tool.

OBJECTIVE: Inflicted traumatic brain injury (iTBI) is the leading cause of death from TBI in infants. Misdiagnosis of iTBI is common and results in increased morbidity and mortality. Biomarkers may be able to assist in screening infants who are at high risk for iTBI and whose injury might otherwise be missed. We investigated whether serum and/or cerebrospinal fluid (CSF) concentrations of neuron-specific enolase (NSE), S100B, and myelin-basic protein (MBP) are sensitive and specific for iTBI in high-risk infants. METHODS: A prospective case-control study was conducted of 98 well-appearing infants who presented with nonspecific symptoms and no history of trauma. Serum or CSF was collected. NSE, S100B, and MBP concentrations were measured by enzyme-linked immunosorbent assay. Abnormal marker concentrations were defined a priori. Patients were followed for 12 months to assess for subsequent abuse. RESULTS: Fourteen patients received a clinical diagnosis of iTBI. Using preestablished cutoffs, NSE was 77% sensitive and 66% specific and MBP was 36% sensitive and 100% specific for iTBI. S100B was neither sensitive nor specific for iTBI. Five patients who were not identified with iTBI at enrollment were identified at follow-up as being possible victims of abuse; 4 had an increased NSE concentration at enrollment. CONCLUSIONS: Serum and/or CSF concentrations of NSE and MBP may be useful as a screening test to identify infants who are at increased risk for iTBI and may benefit from additional evaluation with a head computed tomography scan. S100B is neither sensitive nor specific for iTBI in this study population. The ability to identify iTBI that might otherwise be missed has important implications for decreasing the morbidity and the mortality from iTBI.