Discriminative Accuracy of Procalcitonin and Traditional Biomarkers in Pediatric Acute Musculoskeletal Infection.

OBJECTIVES: Septic arthritis (SA) is responsible for 20% of pediatric musculoskeletal infections (MSKI) and can have significant consequences. Early detection of SA is critical, and procalcitonin (PCT) has emerged as a promising biomarker. This study assessed the test performance of PCT and traditional biomarkers for suspected SA. METHODS: We conducted a prospective study at two pediatric emergency departments (ED). Data collected measured serum levels of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cell (WBC) count, and PCT. Box and whisker plots were generated to compare the of the biomarkers by positive MSKI or a non-MSKI diagnosis. The diagnostic performance of biomarkers was examined using the area under the receiver operating characteristic curve (AUC), and optimal cut -points were identified using the Liu method. RESULTS: Procalcitonin performed reasonably well for detection of MSKI (AUC, 0.72; confidence interval [95% CI], 0.59-0.84). However, CRP and ESR performed better (AUC, 0.88 and 0.78, respectively). White blood cell count was not predictive of MSKI. Patients with a PCT value >0.1 ng/mL, ESR values >19.5 mm/h, and a temperature higher than 99.0°F were more than twice as likely to have acute MSKI. A high CRP level was most predictive of acute MSKI, and patients with levels >2.38 mg/dL were 3.5 times more likely to have acute MSKI. CONCLUSIONS: Procalcitonin is a potential biomarker for the clinical differential of MSKI in the pediatric ED. Additional research is warranted to establish the optimal diagnostic level for PCT, to increase sample size, and to examine any impact on cost.

Moderating the Risk for Attention Deficits in Children with Pre-Adoptive Adversity: The Protective Role of Shorter Duration of out of Home Placement and Children's Enhanced Error Monitoring.

Early institutional-deprivation has been found to increase risk for inattention/hyperactivity (ADHD). Notably, studies suggest that children with a history of adversity evidencing an enhanced ERP (the error-related-negativity; ERN) may be protected against attention problems. However, such protective effects of the ERN have been studied in children whom typically experienced residential instability. It is unknown whether error-monitoring is similarly protective for children with stable post-deprivation placements. The present study examined the protective effect of the ERN in a sample of children who experienced at least 3-years of stable, relatively enriched caregiving after being internationally-adopted as infants/toddlers from institutional-care. We included two groups of children adopted internationally before age three, one group adopted from institutional-care (PI:n = 80) and one comparison group adopted from foster-care (FC;n = 44). A second comparison group consisted of non-adopted children (NA;n = 48) from demographically comparable families. At five-years of age, we assessed child ADHD symptoms (parent-report) and behavioral performance and neural correlates of error-monitoring (Go/No-Go task). PI children displayed lower Go/No-Go accuracy relative to FC children, and higher levels of ADHD symptoms relative to NA controls. In both FC and PI groups, longer duration of pre-adoptive out-of-home placement was associated with inattention, especially for children with deficits in error-monitoring. Enhancing cognitive control in the form of error monitoring might be a useful intervention target to protect children from some of the negative outcomes associated with adverse early care. Furthermore, results underscore that regardless of type of pre-adoptive care, we should aim to place children in stable/permanent homes as early as possible.

Evidence of altered salivary cytokine concentrations in Rett syndrome and associations with clinical severity.

Background: Immune dysregulation may play a role in the development of Rett syndrome (RTT), a neurodevelopmental disorder caused by mutations of the MECP2 gene. Abnormal cytokine concentrations have been documented in the serum of individuals with RTT. Measurement of salivary cytokines has been investigated as a potential alternative approach to measurement in blood and serum, but it is unclear whether salivary cytokine concentrations can provide valid information about systemic immune function in neurodevelopmental disorders. The goal of this study was to evaluate the potential validity of salivary cytokines as biomarkers of immune dysregulation in RTT. Methods: Saliva samples from 16 individuals with RTT (all female; age range 2-40 years) and 16 healthy control females (age range 2-40 years) were analyzed for concentrations of 12 cytokines. Between-group differences in concentrations, and correlations with clinical severity in the RTT group were evaluated. Results: Concentrations of several salivary cytokines (IL-1ß, IL-6, IL-8, IL-10, GM-CSF, TNF-α, and VEGF) were increased in RTT compared to controls. The same cytokines showed significant positive correlations with clinical severity scores. There were no differences in concentrations of IL-2, IL-4, IL-5, IL-12p70, and IFN-γ. Conclusion: The results suggest that salivary cytokines may be a possible indicator of immune dysregulation in RTT. Future research should investigate whether these results can be applied to other neurodevelopmental disorders.

Examination of Pediatric Radiation Dose Delivered After Cervical Spine Trauma.

OBJECTIVES: Pediatric cervical spine injuries (CSIs) are rare but potentially fatal injuries. Plain radiographs (x-rays) and computed tomography (CT) are used to diagnose CSIs. Given concerns related to radiation exposure, the utility of x-rays in diagnosing CSIs compared with other forms of imaging must be examined. METHODS: Patients younger than 19 years presenting with possible CSI to an urban tertiary care hospital who received imaging for possible CSI between January 1, 2011, and December 31, 2013, were included. The dose-length product was abstracted from the PACS system. Test performance for x-ray, CT, and MRI were calculated and effective radiation dose by age group was analyzed using the Kruskal-Wallis Test. RESULTS: A total of 671 patient charts were reviewed, 574 children were included in the study cohort. Median age of enrolled children was 9.70 (interquartile range, 4.78-13.83) years; 42.5% were female. Test performance of x-ray, CT, and MRI to detect CSI were calculated. Cervical x-rays performed only slightly inferior to CT. Sensitivity was 83% (95% confidence interval [CI], 36-99%), and specificity was 97% (95% CI, 96%-99%) versus 100% (95% CI, 96%-100%) for CT. Median effective dose of radiation for cervical CTs was 4.51 mSv (interquartile range, 3.84-5.59 mSv). Median dose significantly increased with age (2.94-5.10 mSv, P < 0.001). CONCLUSIONS: Plain radiographs were largely sufficient to screen for CSIs, indicating their utility as a screening tool for CSIs. The incidence of CSIs in our sample was similar to prior reports. The effective radiation dose delivered during pediatric head and cervical CTs were lower than previously published estimates.

ADHD Symptoms in Post-Institutionalized Children Are Partially Mediated by Altered Frontal EEG Asymmetry.

Individual differences in the propensity for left versus right frontal electroencephalogram (EEG) asymmetry may underlie differences in approach/withdrawal tendencies and mental health deficits. Growing evidence suggests that early life adversity may shape brain development and contribute to the emergence of mental health problems. The present study examined frontal EEG asymmetry (FEA) following the transition to family care in children adopted internationally from institutional care settings between 15 and 36 months of age (N = 82; 46 female, 36 male). Two comparison groups were included: an international adoption control consisting of children adopted from foster care with little to no institutional deprivation (N = 45; 17 female, 28 male) and a post-adoption condition control consisting of children reared in birth families of the same education and income as the adoptive families (N = 48; 23 female, 25 male). Consistent with evidence of greater approach and impulsivity-related behavior problems in post-institutionalized (PI) children, PI status was associated with greater left FEA than found in the other two groups. In addition, left FEA served as a mediator between institutionalization and age 5 ADHD symptoms for girls. Age at adoption and other preadoption factors were examined with results suggesting that earlier adoption into a supportive family resulted in a more typical pattern of brain functioning. Findings support the idea that the capacity of brain activity to evidence typical functioning following perturbation may differ in relation to the timing of intervention and suggest that the earlier the intervention of adoption, the better.

Emotion understanding, parent mental state language, and behavior problems in internationally adopted children.

Internationally adopted postinstitutionalized (PI) children are at risk for lower levels of emotion understanding. This study examined how postadoption parenting influences emotion understanding and whether lower levels of emotion understanding are associated with behavior problems. Emotion understanding and parent mental state language were assessed in 3-year-old internationally adopted PI children (N = 25), and comparison groups of children internationally adopted from foster care (N = 25) and nonadopted (NA) children (N = 36). At 5.5-year follow-up, PI children had lower levels of emotion understanding than NA children, a group difference not explained by language. In the total sample, parent mental state language at age 3 years predicted 5.5-year emotion understanding after controlling for child language ability. The association of parent mental state language and 5.5-year emotion understanding was moderated by adoption status, such that parent mental state language predicted 5.5-year emotion understanding for the internationally adopted children, but not for the NA children. While postadoption experience does not erase negative effects of early deprivation on emotion understanding, results suggest that parents can promote emotion understanding development through mental state talk. At 5.5 years, PI children had more internalizing and externalizing problems than NA children, and these behavioral problems related to lower levels of emotion understanding.

Reducing pediatric CT usage through web-based education.

A grant from the AHRA and Toshiba Putting Patients First program enabled Fairview Health System in Minneapolis, MN to launch an interactive education website which provides best practice information for CT usage in head trauma and appendicitis cases. The website, PEMguidelines.org contains educational sections geared toward both clinicians and patients and families. The site provides evidenced based guidelines for the management of head trauma and appendicitis. PEMguidelines.org was rolled out in 2012 as part of a three pronged intervention strategy. A linkto the website was included in new clinical order-sets within the Fairview electronic health system. Clinical decision support aids were also embedded in the medical record system. Fairview held provider education sessions for ED physicians and staff to introduce and promote the new approach. Results from a six month period after the initial roll out indicate a decrease of 15% in abdominal CT scans for suspected appendicitis cases, while the numbers of missed cases did not increase.This initial evidence supports the effectiveness of this multilevel strategy in improving the safety and cost-effectiveness of pediatric CT use in diagnosis of appendicitis.

Beyond stimulus deprivation: iron deficiency and cognitive deficits in postinstitutionalized children.

Children adopted from institutions have been studied as models of the impact of stimulus deprivation on cognitive development (Nelson, Bos, Gunnar, & Sonuga-Barke, 2011), but these children may also suffer from micronutrient deficiencies (Fuglestad et al., 2008). The contributions of iron deficiency (ID) and duration of deprivation on cognitive functioning in children adopted from institutions between 17 and 36 months of age were examined. ID was assessed in 55 children soon after adoption, and cognitive functioning was evaluated 11-14.6 months postadoption when the children averaged 37.4 months old (SD = 4.9). ID at adoption and longer duration of institutional care independently predicted lower IQ scores and executive function (EF) performance. IQ did not mediate the association between ID and EF.

Electrophysiological evidence of altered memory processing in children experiencing early deprivation.

Associations between early deprivation and memory functioning were examined in 9- to 11-year-old children. Children who had experienced prolonged institutional care prior to adoption were compared to children who were adopted early from foster care and children reared in birth families. Measures included the Paired Associates Learning task from the Cambridge Neuropsychological Test and Automated Battery (CANTAB) and a continuous recognition memory task during which ERPs were also recorded. Children who experienced prolonged institutionalization showed deficits in both behavioral memory measures as well as an attenuated P300 parietal memory effect. Results implicate memory function as one of the domains that may be negatively influenced by early deprivation in the form of institutional care.

Neurodevelopmental effects of early deprivation in postinstitutionalized children.

The neurodevelopmental sequelae of early deprivation were examined by testing (N = 132) 8- and 9-year-old children who had endured prolonged versus brief institutionalized rearing or rearing in the natal family. Behavioral tasks included measures that permit inferences about underlying neural circuitry. Children raised in institutionalized settings showed neuropsychological deficits on tests of visual memory and attention, as well as visually mediated learning and inhibitory control. Yet, these children performed at developmentally appropriate levels on similar tests where auditory processing was also involved and on tests assessing executive processes such as rule acquisition and planning. These findings suggest that specific aspects of brain-behavioral circuitry may be particularly vulnerable to postnatal experience.

Postinstitutionalized children's development: growth, cognitive, and language outcomes.

OBJECTIVE: Children adopted internationally from institutions are a growing population presenting to professional care providers. Although postinstitutionalized (PI) children are adopted from multiple world regions, current knowledge is predominantly based on those adopted from Romania and Eastern European countries. This study examines and compares developmental outcomes of PI children adopted from multiple world regions. METHOD: Five to 11 years after adoption, 8- through 11-year-old PI children (N = 91), children internationally adopted early from foster care (N = 109), and nonadopted children (N = 69) completed screening measures assessing vision, hearing, growth, and cognitive and language abilities. Parents completed questionnaires on service utilization, school performance, preadoptive history, and postadoption environment. RESULTS: Forty-four percent of PI children's growth was stunted (height <10th percentile) at adoption. At assessment, although physically smaller, nearly all PI children had average growth parameters. Relative to nonadopted children and children adopted early from foster care, PI children performed more poorly on cognitive and language screens with increased time in institution related to lower performance. Notably, group means on these measures were within the average range. PI children were more likely to be falling behind academically and to use intervention services. Family environment did not differ between PI and nonadopted children. There were few differences for PI children by world region of adoption once accounting for duration of institutionalization. CONCLUSIONS: Despite currently living in similar environments, PI children have specific needs that differ from early-adopted and nonadopted children. Consideration of multiple factors, including length of institutionalization, is essential when providing care for these children.

Developmental changes in hypothalamus-pituitary-adrenal activity over the transition to adolescence: normative changes and associations with puberty.

Home baseline and laboratory stressor (Trier Social Stress Test for Children) measures of salivary cortisol were obtained from 82 participants (40 girls) aged 9, 11, 13, and 15 years. Measures of pubertal development, self-reported stress, parent reports of child depressive symptoms and fearful temperament, and cardiac measures of sympathetic and parasympathetic activity were also obtained. Significant increases in the home cortisol baselines were found with age and pubertal development. Cortisol stress reactivity differed by age group with 11-year-olds and 13-year-old boys showing blunted reactivity and 9-year-olds, 13-year-old girls, and 15-year-olds showing significant cortisol reactions. Cortisol reactivity correlated marginally with sexual maturation. Measures of sympathetic activity revealed increased sympathetic modulation with age. Higher sympathetic tone was associated with more fearful temperament, whereas greater cortisol reactivity was associated with more anxious and depressed symptoms for girls. The importance of these findings for the hypothesis that puberty-associated increases in hypothalamic-pituitary-adrenal axis activity heightens the risk of psychopathology is discussed.

Moderate versus severe early life stress: associations with stress reactivity and regulation in 10-12-year-old children.

Early life stress (ELS) is expected to increase reactivity of the hypothalamic-pituitary-adrenocortical (HPA) axis; however, several recent studies have shown diminished cortisol reactivity among adults and children with ELS exposure. The goal of this study was to examine cortisol activity in 10-12-year-old internationally adopted children to determine if moderate and severe ELS have different impacts on the HPA axis. Salivary cortisol and two measures of autonomic activity were collected in response to the Trier Social Stress Test for Children (TSST-C). Three groups reflecting moderate, severe, and little ELS were studied: early adopted children who came predominantly from foster care overseas (early adopted/foster care (EA/FC), n=44), later adopted children cared for predominantly in orphanages overseas (late adopted/post-institutionalized (LA/PI), n=42) and non-adopted (NA) children reared continuously by their middle- to upper-income parents in the United States (n=38). Diminished cortisol activity was noted for the EA/FC group (moderate ELS), while the LA/PI group (severe ELS) did not differ from the NA group. Overall, few children showed cortisol elevations to the TSST-C in any group. The presence/absence of severe growth delay at adoption proved to be a critical predictive factor in cortisol activity. Regardless of growth delay, however, LA/PI children exhibited higher sympathetic tone than did NA children. These results suggest that moderate ELS is associated with diminished cortisol activity; however, marked individual differences in cortisol activity among the LA/PI children suggest that child factors modify the impact of severe ELS. Lack of effects of severe ELS even for growth delayed children may reflect the restorative effects of adoption or the generally low responsiveness of this age group to the TSST-C.