Moral Distress in Pediatric Healthcare Providers.

Pediatric providers across professions and clinical settings experience moral distress. Higher moral distress correlates with intent to leave for all professionals. Physicians as professional group had the highest moral distress. Intensive care nurses had the highest moral distress for nurses. While all providers describe distressing scenarios as disturbing, physicians report situations as occurring more frequently. The most distressing situations include requests for aggressive treatments not in child's best interest, poor team communication and lack of provider continuity. Understanding moral distress as experienced by all pediatric providers is needed to create interventions with a goal of reducing provider turnover.

Heterozygous mutations of the kinesin KIF21A in congenital fibrosis of the extraocular muscles type 1 (CFEOM1).

Congenital fibrosis of the extraocular muscles type 1 (CFEOM1; OMIM #135700) is an autosomal dominant strabismus disorder associated with defects of the oculomotor nerve. We show that individuals with CFEOM1 harbor heterozygous missense mutations in a kinesin motor protein encoded by KIF21A. We identified six different mutations in 44 of 45 probands. The primary mutational hotspots are in the stalk domain, highlighting an important new role for KIF21A and its stalk in the formation of the oculomotor axis.

Caregiver measures for seizure control, efficacy, and tolerability of antiepileptic drugs for childhood epilepsy: results of a preference survey.

We sought to identify and quantify caregiver-defined characteristics of efficacy related to the perceived success of antiepileptic drug (AED) use. A 22-question survey was designed using physician input, focus groups, and clinical trial endpoints. Responses were pooled and analyzed with regard to seizure type and treatment, categorized as controlled (exposure to 1 AED), adjunctive (exposure to 2 AEDs), or refractory (exposure to ≥3 AEDs). Two hundred ninety-five surveys were completed: 109 (37%) controlled, 84 (28%) adjunctive, and 102 (35%) refractory. Seizure freedom and median seizure reduction >90% maintained for >1 year were reported as the most important indicators of medication efficacy by the majority of respondents. These measures were the same regardless of seizure type or treatment category. Our results demonstrate that current trial design may be inadequate to address the expectations of patients. Incorporating patient-defined AED efficacy measures may improve satisfaction and informed decision making regarding epilepsy treatment.

Attention mediates radiation's impact on daily living skills in children treated for brain tumors.

BACKGROUND: Radiotherapy is associated with an increased survival rate in children with brain tumors, but also with cognitive decline. This study examined the time-dependent effects of radiation treatment on adaptive functioning in children with brain tumors. The potentially mediating effects of attention span (Trial 1 of the Rey Auditory Verbal Learning Test [RAVLT]) assessed within 7 years of diagnosis were explored. PROCEDURE: Twenty-two children treated with cranial radiation for third ventricle or cerebellar tumors were included in this archival study. The mean age at diagnosis was 7.62 years (SD = 4.78) and 10.16 years (SD = 3.83) at evaluation. We examined the extent to which auditory attention span was able to mediate the relationship between time elapsed since the initiation of radiation treatment (M = 2.43 years; SD = 2.37) and adaptive functioning (Vineland Adaptive Behavior Scales [VABS]). RESULTS: Attention span was found to mediate the relationship between time since the initiation of radiation and daily living skills. These findings were shown to be specific to attention and not a reflection of generalized neuropsychological decline, nor were they a result of increasing time since diagnosis in and of itself. CONCLUSIONS: The results of this study suggest that time since radiation may directly decrease attention and poor attention in turn may be associated with lower adaptive functioning on tasks of daily living.

Quantifying pediatric neuro-oncology risk factors: development of the neurological predictor scale.

Pediatric neuro-oncology researchers face methodological challenges associated with quantifying the influence of tumor and treatment-related risk factors on child outcomes. The Neurological Predictor Scale was developed to serve as a cumulative index of a child's exposure to risk factors. The clinical utility of the Neurological Predictor Scale was explored in a sample of 25 children with heterogeneous brain tumors. Consistent with expectation, a series of regression analyses demonstrated that the Neurological Predictor Scale significantly predicted composite intellectual functioning (r(2) = 0.21, p < .05), short-term memory (r(2) = 0.16, p = .05), and abstract visual reasoning abilities (r(2) = 0.28, p < .05). With the exception of chemotherapy, the Neurological Predictor Scale accounted for a significant amount of the variance in child intellectual functioning above and beyond individually examined variables. The Neurological Predictor Scale can be used to quickly quantify the cumulative risk factors associated with pediatric brain tumor diagnoses.

The use of dextroamphetamine to treat obesity and hyperphagia in children treated for craniopharyngioma.

BACKGROUND: Obesity and attention difficulties are known complications following surgical treatment for craniopharyngioma. Treatments to date have been largely disappointing. OBJECTIVE: To examine the use of the central nervous system stimulant dextroamphetamine sulfate to regulate appetite and subsequent weight gain in children treated for craniopharyngioma. SETTING: A multidisciplinary clinic specializing in pediatric brain tumors. PATIENTS: Five consecutive patients with significant weight gain and poor attention following surgical treatment for craniopharyngioma were selected for the study. INTERVENTION: Children enrolled in the study were treated with dextroamphetamine, and growth, laboratory, and behavioral assessments were conducted for 24 months. RESULTS: Mean +/- SD body mass index (weight in kilograms divided by height in meters squared) increased from 21 +/- 3.5 before the operation to 32 +/- 2.8 by the start of the protocol. Body mass indices remained stable throughout the protocol. No changes were observed in insulin levels or caloric intake, but the children were more active when taking dextroamphetamine. Parents noted a significant improvement in hyperactivity (mean +/- SD, 1.2 +/- 0.4 to 0.6 +/- 0.2; P =.05), scored with the Conners Parent and Teacher Rating Scales. Teachers noted a similar improvement. CONCLUSIONS: During dextroamphetamine treatment, weight gain stabilized in children who had experienced obesity following surgical resection for craniopharyngioma. In addition, parents and teachers noted significant improvements in children's overall activity and attention. Further studies are needed to determine if the improvements are stable and if earlier intervention can prevent the initial obesity.

Parent report of attention problems predicts later adaptive functioning in children with brain tumors.

Children with brain tumors are at risk for psychological and behavioral difficulties. This study examined the ability of parent report of attention problems, withdrawal, anxiety, and depression, as well as IQ, to predict later adaptive functioning in 42 children treated for brain tumors. Age at diagnosis, SES, gender, and scores on the Neurological Predictor Scale (NPS) also were examined as predictors. Parent report of attention problems, SES, and NPS were significant predictors of later adaptive functioning across domains. This finding highlights the ability of parent report of attention problems to predict later adaptive functioning in children treated for brain tumors.

Cognitive predictors of adaptive functioning vary according to pediatric brain tumor location.

This archival study sought to determine if the relationship between cognitive and adaptive abilities varied according to brain tumor location. Participants were 36 children treated for brain tumors. The best cognitive predictors of adaptive functioning were hypothesized to be attention span within the cerebellar group and verbal memory within the third ventricle group. Auditory attention span significantly predicted communication skills for the cerebellar group, whereas verbal memory significantly predicted socialization skills for the third ventricle group. These findings suggest that cognitive predictors vary according to tumor location, and highlight the need for more research examining adaptive functioning and its correlates.

Mechanism of transient adrenal insufficiency with megestrol acetate treatment of cachexia in children with cancer.

Megestrol acetate (MA) is used to stimulate appetite in children with cancer, but it can impair adrenal function and cause adrenal insufficiency. Three children with brain tumors were treated with MA to improve weight gain. Standard low-dose ACTH stimulation tests were performed on and off MA. All patients failed the low-dose ACTH stimulation while on MA and responded normally once off MA. The suppression of the adrenal axis was at the level of the hypothalamus/pituitary. Adrenal suppression can occur in patients treated with MA. Awareness of this possibility and the use of glucocorticoid stress coverage are advised.

Aggregation of actin and cofilin in identical twins with juvenile-onset dystonia.

The neuropathology of the primary dystonias is not well understood. We examined brains from identical twins with DYT1-negative, dopa-unresponsive dystonia. The twins exhibited mild developmental delays until age 12 years when they began developing rapidly progressive generalized dystonia. Genetic, metabolic, and imaging studies ruled out known causes of dystonia. Cognition was subnormal but stable until the last few years. Death occurred at ages 21 and 22 years. The brains were macroscopically unremarkable. Microscopic examination showed unusual glial fibrillary acidic protein-immunoreactive astrocytes in multiple regions and iron accumulation in pallidal and nigral neurons. However, the most striking findings were 1) eosinophilic, rod-like cytoplasmic inclusions in neocortical and thalamic neurons that were actin depolymerizing factor/cofilin-immunoreactive but only rarely actin-positive; and 2) abundant eosinophilic spherical structures in the striatum that were strongly actin- and actin depolymerizing factor/cofilin-positive. Electron microscopy suggested that these structures represent degenerating neurons and processes; the accumulating filaments had the same dimensions as actin microfilaments. To our knowledge, aggregation of actin has not been reported previously as the predominant feature in any neurodegenerative disease. Thus, our findings may shed light on a novel neuropathological change associated with dystonia that may represent a new degenerative mechanism involving actin, a ubiquitous constituent of the cytoskeletal system.