The Association Between Functional Status and Health-Related Quality of Life Following Discharge from the Pediatric Intensive Care Unit.

BACKGROUND: Despite one third of children with acquired brain injury (ABI) experiencing new functional impairments following critical care admission, there is limited research investigating the impact of new functional impairments on overall health-related quality of life (HRQOL) or among important HRQOL domains. We aimed to investigate the association between new functional impairments, measured by the Functional Status Scale (FSS), and HRQOL in pediatric patients with ABI after critical care. METHODS: We conducted a secondary analysis of a prospective observational study of 275 children aged 2 months to 18 years with ABI. The primary exposure evaluated was change in FSS from baseline at hospital discharge, categorized per prior work (no change, 1-2 point increase, and ≥ 3 point increase). The primary outcome was overall HRQOL 6 months after hospital discharge, measured by the Pediatric Quality of Life Inventory (PedsQL) total score. Secondary outcomes were PedsQL domain scores. PedsQL total and domain scores were transformed into age-standardized z scores for analyses. Multiple linear regression models evaluated the association between FSS change category and HRQOL (overall and domain z scores) when controlling for demographic and clinical characteristics and were reported as ß-coefficients with 95% confidence intervals. RESULTS: Complete data were analyzed for 195 (71%) children, including 127 with traumatic brain injury. New functional impairment was common with 32 (16%) patients experiencing FSS increases ≥ 3, 50 (26%) patients with FSS increases of 1-2 points, and 113 (58%) patients with no change from prehospital baseline. The majority of children (63%) demonstrated HRQOL ratings ≥ 1 standard deviation below healthy age-based standards (z scores ≤ - 1). Regression models demonstrated older age, female sex, presence of comorbidities, and preadmission cardiopulmonary resuscitation were all significantly associated with poorer overall HRQOL (all p < 0.05). FSS increase ≥ 3 at discharge was significantly associated with worse overall HRQOL at follow-up (ß = - 1.07; 95% confidence interval = - 1.63 to - 0.52) when controlling for the aforementioned significant factors, and significantly improved model fit (p value for change = 0.001). Similar findings in secondary analyses were found for physical domain scores, with FSS increase showing a significant association with worse physical HRQOL scores and improvements in model fit. Change in FSS was not significantly associated with other HRQOL domain scores (emotional, social, school, psychosocial). CONCLUSIONS: Many children with ABI after critical care experience new functional impairments (FSS increases) and worse HRQOL than healthy peers. FSS increase at discharge is a significant risk factor for worse HRQOL in the months after hospital discharge and improves HRQOL models beyond illness and demographic variables alone.

Autism Diagnostic Observation Schedule (ADOS-2) elevations in a clinical sample of children and adolescents who do not have autism: Phenotypic profiles of false positives.

OBJECTIVE: While the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2) shows high sensitivity for detecting autism spectrum disorder (ASD) when present (i.e. true positives), scores on the ADOS-2 may be falsely elevated for individuals with cognitive impairments or psychological concerns other than ASD (i.e. false positives). This study examined whether demographic, psychological, cognitive, and/or adaptive factors predict ADOS-2 false positives and which psychiatric diagnoses most often result in false positives. METHOD: Sensitivity, specificity, false positive, and false negative rates were calculated among 214 5- to 16-year-old patients who completed an ADOS-2 (module 3) as part of an ASD diagnostic evaluation. Additional analyses were conducted with the 101 patients who received clinically elevated ADOS-2 scores (i.e. 56 true positives and 45 false positives). RESULTS: Results revealed a 34% false positive rate and a 1% false negative rate. False positives were slightly more likely to be male, have lower restricted and repetitive behavior (RRB) severity scores on the ADOS-2, and demonstrate elevated anxiety during the ADOS-2. Neither IQ, adaptive functioning, nor caregiver-reported emotional functioning was predictive of false positive status. Trauma-related psychiatric diagnoses were more common among false positives. CONCLUSIONS: The ADOS-2 should not be used in isolation to assess for ASD, and, in psychiatrically-complex cases, RRB symptom severity may be particularly helpful in differentiating ASD from other psychiatric conditions. Additionally, heightened levels of anxiety, more so than overactivity or disruptive behavior, may lead to non-ASD specific elevations in ADOS-2 scores.

Co-occurring Down Syndrome and Autism Spectrum Disorder: Cognitive, Adaptive, and Behavioral Characteristics.

The current study explores functioning in individuals with co-occurring Autism Spectrum Disorder and Down Syndrome (ASD+DS; n = 23), individuals with ASD and cognitive impairment (ASD+ID; n = 99) and individuals with idiopathic ID (n = 38). ANCOVA results revealed that individuals with ASD+DS showed strengths in behavioral functioning compared to individuals with ID and more similar behavioral functioning to those with ASD+ID (η2 = 0.12), with the exception of disruptive behaviors. Cognitive functioning (ɸc = 0.41) and ASD symptomatology (η2 = 0.11) were more comparable for children with ASD+DS and ASD + ID than for individuals with ID. Individuals with ASD+DS had the lowest overall adaptive skills (η2 = 0.11). Findings highlight similarities between ASD+DS and ASD+ID groups, emphasizing the importance of ASD identification within the DS population to provide access to specific interventions.

Emotional Aspects of Pediatric Post-Intensive Care Syndrome Following Traumatic Brain Injury.

Children with traumatic brain injury (TBI) requiring neurocritical care are at risk for neurocognitive, emotional, physical, and psychosocial difficulties, collectively known as Post-Intensive Care Syndrome. Our study assessed parent-reported emotional functioning and identified risk factors for emotional sequelae in the acute recovery phase. Fifty-three children between 5 and 18 years old hospitalized for TBI were assessed 1-month following discharge. Relevant injury-, child-, and family-specific variables were collected. Emotional functioning was assessed using PROMIS Parent Proxy Report Short Forms for Anxiety and Depressive Symptoms. We used Chi-square tests to evaluate differences between children with and without elevations in anxiety and depressive symptoms. Logistic regression determined predictors of elevations in symptoms among significant variables. Parents frequently endorsed moderate or worse anxiety (45.2%) and depressive (32.1%) symptoms among children. Mechanism of injury and elevated parent post-traumatic stress disorder (PTSD) symptoms were associated with elevated anxiety and depressive symptoms, while direct family involvement in the accident/injury was associated only with elevated anxiety symptoms. Results from logistic regression indicated that only elevated parent PTSD symptoms were a significant predictor for child anxiety and depressive symptoms. Anxiety and depressive symptoms are prevalent in the acute recovery phase of TBI. Consistent with previous research, elevations in anxiety and depressive symptoms were more related to psychosocial factors than injury severity. High levels of parent PTSD symptoms and their relationship with children's internalizing symptoms highlight the need for mental health treatment for TBI patients and their families.

Role of nuclear factor kappaB in ovarian hormone-mediated stress hypersensitivity in female mice.

BACKGROUND: The molecular mechanisms of stress-induced depressive behaviors have been characterized extensively in male rodents; however, much less is known about female subjects, despite the fact that human depression is far more prevalent in women. METHODS: To gain insight into these mechanisms, we performed microarray analysis in nucleus accumbens (NAc), a key brain reward region implicated in depression, in ovariectomized (OVX) and gonadally intact female mice after chronic unpredictable stress and measured stress-induced depression-like behavior in the forced swim test (FST). Male mice were studied in the FST for comparison. RESULTS: We find that stress regulation of genes in NAc of gonadally intact female mice is blunted in OVX mice. This pattern of gene regulation is consistent with behavioral findings on the FST: the pro-depression-like effect of stress in intact female mice is absent in OVX female and gonadally intact male mice. We identified, among many genes regulated by stress, several nuclear factor kappaB (NFkappaB) subunits-a pro-survival transcription factor involved in cellular responses to stress-as being highly upregulated in NAc of OVX mice. Given the role of NFkappaB during stress, we hypothesized that upregulation of NFkappaB by OVX decreases susceptibility to stress. Indeed, we show that inhibition of NFkappaB in NAc of OVX animals increases susceptibility to stress-induced depressive behaviors, whereas activation of NFkappaB in NAc of intact female subjects blocks susceptibility. CONCLUSIONS: These results suggest a hormonal mechanism of NFkappaB regulation that contributes to stress-induced depressive behaviors in female subjects and might represent a mechanism for gender differences in prevalence rates of these disorders in humans.