Duration of chronic kidney disease reduces attention and executive function in pediatric patients.

Chronic kidney disease (CKD) in childhood is associated with neurocognitive deficits. Affected children show worse performance on tests of intelligence than their unaffected siblings and skew toward the lower end of the normal range. Here we further assessed this association in 340 pediatric patients (ages 6-21) with mild-moderate CKD in the Chronic Kidney Disease in Childhood cohort from 48 pediatric centers in North America. Participants underwent a battery of age-appropriate tests including Conners' Continuous Performance Test-II (CPT-II), Delis-Kaplan Executive Function System Tower task, and the Digit Span Backward task from the age-appropriate Wechsler Intelligence Scale. Test performance was compared across the range of estimated glomerular filtration rate and duration of CKD with relevant covariates including maternal education, household income, IQ, blood pressure, and preterm birth. Among the 340 patients, 35% had poor performance (below the mean by 1.5 or more standard deviations) on at least one test of executive function. By univariate nonparametric comparison and multiple logistic regression, longer duration of CKD was associated with increased odds ratio for poor performance on the CPT-II Errors of Commission, a test of attention regulation and inhibitory control. Thus, in a population with mild-to-moderate CKD, the duration of disease rather than estimated glomerular filtration rate was associated with impaired attention regulation and inhibitory control.

Report from a multi-institutional randomized clinical trial examining computer-assisted problem-solving skills training for English- and Spanish-speaking mothers of children with newly diagnosed cancer.

OBJECTIVES: To evaluate the feasibility and efficacy of a handheld personal digital assistant (PDA)-based supplement for maternal Problem-Solving Skills Training (PSST) and to explore Spanish-speaking mothers' experiences with it. METHODS: Mothers (n = 197) of children with newly diagnosed cancer were randomized to traditional PSST or PSST + PDA 8-week programs. Participants completed the Social Problem-Solving Inventory-Revised, Beck Depression Inventory-II, Profile of Mood States, and Impact of Event Scale-Revised pre-, post-treatment, and 3 months after completion of the intervention. Mothers also rated optimism, logic, and confidence in the intervention and technology. RESULTS: Both groups demonstrated significant positive change over time on all psychosocial measures. No between-group differences emerged. Despite technological "glitches," mothers expressed moderately high optimism, appreciation for logic, and confidence in both interventions and rated the PDA-based program favorably. Technology appealed to all Spanish-speaking mothers, with younger mothers showing greater proficiency. CONCLUSIONS: Well-designed, supported technology holds promise for enhancing psychological interventions.

Problem solving and maternal distress at the time of a child's diagnosis of cancer in two-parent versus lone-parent households.

OBJECTIVE: To examine negative affectivity and problem-solving abilities for lone mothers and those who are married/partnered subsequent to a child's diagnosis with cancer. METHODS: Negative affectivity and problem-solving strategies were assessed for 464 mothers (87 lone and 377 married/partnered) within 2-16 weeks of their child's diagnosis with cancer. RESULTS: The two groups of mothers did not differ significantly on measures of perceived posttraumatic stress or problem-solving; lone mothers reported significantly more symptoms of depression. This difference was no longer significant when maternal education was taken into account. CONCLUSIONS: Negative affectivity and problem-solving abilities were similar for lone mothers and those that are married/partnered shortly after their child has been diagnosed with cancer. Findings are discussed within the context of contemporary strategies to assess marital status as proxy variable for various underlying constructs.

Brain structural abnormalities in survivors of pediatric posterior fossa brain tumors: a voxel-based morphometry study using free-form deformation.

Voxel-based morphometry was used to compare brain structure of survivors of posterior fossa brain tumor (PFBT) with that of normal sibling controls to investigate disease- or cancer treatment-induced changes. Two different spatial normalization approaches that are available in public domain software (free-form deformation (FFD) and discrete cosine transform (DCT)) were compared for accuracy of normalization in the PFBT patients. Anatomical landmark matching demonstrated that spatial normalization was more accurate with FFD than with DCT. Voxel-based morphometry of the FFD-normalized magnetic resonance images from PFBT survivors and sibling controls detected reduced gray matter density in the thalamus and entorhinal cortex and reduced white matter density in the internal capsule, hypothalamus, corpus callosum, and cuneus of the occipital lobe in the PFBT survivors. Identification of these morphologic lesions may help localize the neural substrates of disease- or therapy-induced cognitive deficits in survivors of childhood cancer.

A multicenter, randomized clinical trial of a cognitive remediation program for childhood survivors of a pediatric malignancy.

Survivors of childhood cancer whose malignancy and/or treatment involved the central nervous system may demonstrate a consistent pattern of neurocognitive deficits. The present study evaluated a randomized clinical trial of the Cognitive Remediation Program (CRP). Participants were 6- to 17-year-old survivors of childhood cancer (N = 161; 35% female, 18% Hispanic, 10% African American, 64% Caucasian, 8% other) who were at least 1 year off treatment and who manifested an attentional deficit. They were enrolled at 7 sites nationwide. Two thirds of the participants were randomly assigned to cognitive remediation. All participants were assessed using a battery of academic achievement/neurocognitive tests and parent/teacher measures of attention. The CRP resulted in parent report of improved attention and statistically significant increases in academic achievement. Effect sizes were modest but were comparable with those for other clinical trials of brain injury rehabilitation and for psychological interventions in general. The CRP is presented as a potentially beneficial treatment for many survivors of pediatric cancer. Long-term clinical significance remains unproven. Further work is needed to improve effect sizes and treatment compliance and to address the needs of other populations with pediatric brain injury.

Using problem-solving skills training to reduce negative affectivity in mothers of children with newly diagnosed cancer: report of a multisite randomized trial.

Mothers of children with cancer experience significant distress associated with their children's diagnosis and treatment. The efficacy of problem-solving skills training (PSST), a cognitive-behavioral intervention based on problem-solving therapy, was assessed among 430 English- and Spanish-speaking mothers of recently diagnosed patients. Participants were randomized to usual psychosocial care (UPC; n=213) or UPC plus 8 sessions of PSST (PSST; n=217). Compared with UPC mothers, PSST mothers reported significantly enhanced problem-solving skills and significantly decreased negative affectivity. Although effects were largest immediately after PSST, several differences in problem-solving skills and distress levels persisted to the 3-month follow-up. In general, efficacy for Spanish-speaking mothers exceeded that for English-speaking mothers. Findings also suggest young, single mothers profit most from PSST.

Biofilm consumption and variable diet composition of western sandpipers (Calidris mauri) during migratory stopover.

Many shorebird species undertake long-distance migrations punctuated by brief stays at food-rich, estuarine stopover locations. Understanding use of these food resources helps guide conservation and responsible development decisions. We determined the extent and degree to which Western Sandpiper (Calidris mauri) utilized biofilm as a food resource across a large and variable stopover location during northward (spring) migration. We investigated the spatial heterogeneity in diet composition, to determine whether shorebirds were consistently feeding on biofilm or whether diet varied between naturally and anthropogenically delineated sites. We used stable isotope analysis to estimate that biofilm conservatively comprised 22% to 53% of Western Sandpiper droppings across all sampling sites and that prey composition differed significantly between areas within the stopover location. Widespread biofilm consumption demonstrates the importance of biofilm as a dietary component. Variable diet composition suggests that habitat heterogeneity may be an important component of high quality stopover locations in the context of "state-dependant trade-offs" of Western Sandpiper population sub-groups. Future management decisions must consider and address potential impacts on the biofilm community throughout a stopover location, as single site studies of diet composition may not be adequate to develop effective management strategies for entire stopover sites.

Western sandpipers have altered migration tactics as peregrine falcon populations have recovered.

The presence of top predators can affect prey behaviour, morphology and life history, and thereby can produce indirect population consequences greater and further reaching than direct depredation would have alone. Raptor species in the Americas are recovering since restrictions on the use of dichlorodiphenyltrichloroethane (DDT) and the implementation of conservation measures, in effect constituting a hemisphere-wide predator-reintroduction experiment, and profound effects on populations of their prey are to be expected. Here, we document changes in the behaviour of western sandpipers (Calidris mauri) at migratory stopover sites over two decades. Since 1985, migratory body mass and stopover durations of western sandpipers have fallen steadily at some stopovers in the Strait of Georgia, British Columbia. Comparisons between years, sites and seasons strongly implicate increasing danger from the recovery of peregrine falcons (Falco peregrinus) as a causal factor. A decade-long ongoing steep decline in sandpiper numbers censused on our study site is explained entirely by the shortening stopover duration, rather than fewer individuals using the site. Such behavioural changes are probably general among migratory shorebird species, and may be contributing to the widespread census declines reported in North America.

Tower of London test performance in children with poor arithmetic skills.

The Tower of London (TOL) has been used to assess executive functions in both children and adults with documented brain dysfunction. Like many other measures of executive function, it has not been widely used in the assessment of learning disabilities in children. However, if performance on the TOL discriminated among groups of children with different academic strengths and weaknesses, then it may be useful in identifying learning disability subtypes. The purpose of this study was to determine whether performance on the TOL would differ among 3 groups of children: those with arithmetic difficulties, those with reading difficulties, and those with no academic difficulties. The group with arithmetic difficulties exhibited significantly greater impairment on the TOL than either the group with reading difficulties or the group with no difficulties. The latter 2 groups performed similarly. The clinical utility of the TOL, as well as the relation between arithmetic deficits and executive functions, are discussed.

Problem-solving skills training for mothers of children with newly diagnosed cancer: a randomized trial.

Mothers of children with serious illnesses have lower levels of well-being than mothers in the general population. Problem-solving therapy (PST), a cognitive-behavioral intervention, has been shown to be effective in treating negative affectivity (depression, anxiety) and other manifestations of reduced well-being. This report describes a problem-solving skills training (PSST) intervention, based on problem-solving therapy, for mothers of newly diagnosed pediatric cancer patients. Ninety-two mothers were randomly assigned to receive PSST or to receive standard psychosocial care (Control Group). After the 8-week intervention, mothers in the PSST Group had significantly enhanced problem-solving skills and significantly decreased negative affectivity compared with controls. Analysis revealed that changes in self-reports of problem-solving behaviors accounted for 40% of the difference in mood scores between the two groups. Interestingly, PSST had the greatest impact on improving constructive problem solving, whereas improvement in mood was most influenced by decreases in dysfunctional problem solving. The implications of these findings for refinement of the PSST intervention and for extension to other groups of children with serious illnesses are discussed.

Evaluation of the psychometric properties of the Pediatric Parenting Stress Inventory (PPSI).

OBJECTIVE: This work evaluated the psychometric properties of the Pediatric Parenting Stress Inventory (PPSI), a new measure of problems and distress experienced by parents of children with chronic illnesses. METHOD: This secondary data analysis used baseline data from 1 sample of English-, Spanish-, and Hebrew-speaking mothers of children recently diagnosed with cancer (n = 449) and 1 sample of English- and Spanish-speaking mothers of children recently diagnosed with cancer (n = 399) who participated in 2 problem-solving skills training interventions. The PPSI was administered at baseline with other measures of maternal distress. Factor structure was evaluated using exploratory factor analysis (EFA) on the first sample and confirmatory factor analysis (CFA) on both samples. Internal consistency was evaluated using Cronbach's alpha. Construct validity was assessed via Spearman correlations with measures of maternal distress. RESULTS: EFA resulted in a stable four-factor solution with 35 items. CFA indicated that the four-factor solution demonstrated reasonable fit in both samples. Internal consistency of the subscales and full scale was adequate to excellent. Construct validity was supported by moderate to strong correlations with measures of maternal distress, depression, and posttraumatic stress symptoms. CONCLUSIONS: The PPSI demonstrated good psychometric properties in assessing current problems and distress experienced by mothers of children newly diagnosed with cancer. This tool may be used to identify individualized targets for intervention in families of children with cancer. Future studies could evaluate the utility and psychometrics of the PPSI with other pediatric populations.

Intellectual functioning and multi-dimensional attentional processes in long-term survivors of a central nervous system related pediatric malignancy.

AIMS: Central nervous system (CNS) malignancies and/or their treatment in pediatric cancer survivors are known to be associated with deficits in neuropsychological functions. We report findings from a nation-wide study of childhood cancer survivors to investigate intelligence and attention/concentration from a multi-dimensional perspective in a diverse sample from this population. MAIN METHODS: Four hundred forty-four pediatric cancer survivors between 6 and 17 years of age, who had suffered CNS involvement associated with their malignancy, were evaluated. All patients completed a measure of general intelligence. Attention was measured by a continuous performance test (CPT) and by parental report using a standardized psychological inventory. KEY FINDINGS: Social economic status (SES) was a significant predictor of intellectual functioning and scores on independent measures of attention. After controlling for SES, cranial radiation therapy (CRT) was strongly predictive of impairments in intellectual functioning. Patients who had completed a transplant procedure did not have significant impairments in intellectual functioning when compared to other participants. CPT performance was most clearly influenced by a younger age at diagnosis and the presence of a supratentorial brain tumor. Reaction time was lower in patients who had received CRT. Gender did not correlate with CPT performance, but caregiver reports of deficits in attentional functioning were more prevalent in girls compared to boys. SIGNIFICANCE: These findings are important given the large, representative sample and multi-dimensional assessment of attentional functioning. The presence of a very strong SES effect on all dependent variables must be addressed in studies of this nature.

Specificity of problem-solving skills training in mothers of children newly diagnosed with cancer: results of a multisite randomized clinical trial.

PURPOSE: Diagnosis of cancer in a child can be extremely stressful for parents. Bright IDEAS, a problem-solving skills training (PSST) intervention, has been shown to decrease negative affectivity (anxiety, depression, post-traumatic stress symptoms) in mothers of newly diagnosed patients. This study was designed to determine the specificity of PSST by examining its direct and indirect (eg, social support) effects compared with a nondirective support (NDS) intervention. PATIENTS AND METHODS: This randomized clinical trial included 309 English- or Spanish-speaking mothers of children diagnosed 2 to 16 weeks before recruitment. Participants completed assessments prerandomization (T1), immediately postintervention (T2), and at 3-month follow-up (T3). Both PSST and NDS consisted of eight weekly 1-hour individual sessions. Outcomes included measures of problem-solving skill and negative affectivity. RESULTS: There were no significant between-group differences at baseline (T1). Except for level of problem-solving skill, which was directly taught in the PSST arm, outcome measures improved equally in both groups immediately postintervention (T2). However, at the 3-month follow-up (T3), mothers in the PSST group continued to show significant improvements in mood, anxiety, and post-traumatic stress; mothers in the NDS group showed no further significant gains. CONCLUSION: PSST is an effective and specific intervention whose beneficial effects continue to grow after the intervention ends. In contrast, NDS is an effective intervention while it is being administered, but its benefits plateau when active support is removed. Therefore, teaching coping skills at diagnosis has the potential to facilitate family resilience over the entire course of treatment.

Long-term cognitive function, neuroimaging, and quality of life in primary CNS lymphoma.

OBJECTIVE: To describe and correlate neurotoxicity indicators in long-term primary CNS lymphoma (PCNSL) survivors who were treated with high-dose methotrexate-based regimens with or without whole-brain radiotherapy (WBRT). METHODS: Eighty PCNSL survivors from 4 treatment groups (1 with WBRT and 3 without WBRT) who were a minimum of 2 years after diagnosis and in complete remission underwent prospective neuropsychological, quality-of-life (QOL), and brain MRI evaluation. Clinical characteristics were compared among treatments by using the χ(2) test and analysis of variance. The association among neuroimaging, neuropsychological, and QOL outcomes was assessed by using the Pearson correlation coefficient. RESULTS: The median interval from diagnosis to evaluation was 5.5 years (minimum, 2 years; maximum, 26 years). Survivors treated with WBRT had lower mean scores in attention/executive function (p = 0.0011), motor skills (p = 0.0023), and neuropsychological composite score (p = 0.0051) compared with those treated without WBRT. Verbal memory was better in survivors with longer intervals from diagnosis to evaluation (p = 0.0045). On brain imaging, mean areas of total T2 abnormalities were different among treatments (p = 0.0006). Total T2 abnormalities after WBRT were more than twice the mean of any non-WBRT group and were associated with poorer neuropsychological and QOL outcomes. CONCLUSIONS: Our results suggest that in patients treated for PCNSL achieving complete remission and surviving at least 2 years, the addition of WBRT to methotrexate-based chemotherapy increases the risk of treatment-related neurotoxicity. Verbal memory may improve over time. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that in patients treated for PCNSL achieving complete remission and surviving at least 2 years, the addition of WBRT to methotrexate-based chemotherapy increases the risk of treatment-related neurotoxicity.

Evidence of change in brain activity among childhood cancer survivors participating in a cognitive remediation program.

Increased understanding of the underlying mechanisms of cognitive remediation is needed to facilitate development of intervention strategies for childhood cancer survivors experiencing cognitive late effects. Accordingly, a pilot functional magnetic resonance imaging (fMRI) study was conducted with 14 cancer survivors (12.02 ± 0.09 years old), who participated in a cognitive remediation clinical trial, and 28 healthy children (12.7 ± 0.6 years old). The ventral visual areas, cerebellum, supplementary motor area, and left inferior frontal cortex were significantly activated in the healthy participants during a continuous performance task. In survivors, brain activation in these regions was diminished at baseline, and increased upon completion of remediation and at a 6-month follow-up. The fMRI activation index for each region of interest was inversely associated with the Conners' Clinical Competence Index (p<.01). The pilot study suggests that fMRI is useful in evaluating neural responses to cognitive remediation.

Neuropsychological rehabilitation for survivors of childhood and adolescent brain tumors: a view of the past and a vision for a promising future.

The neuropsychological sequelae associated with the diagnosis and treatment of a brain tumor in childhood or adolescence are well described. Providers in the oncology field have become more aware of these problems in recent years, and some treatment regimens are now aimed at limiting neurocognitive toxicity. Nevertheless, the likelihood of cure for many brain tumors is still relatively low and aggressive treatment courses often cannot be avoided. The neuropsychological side effects of surgery, radiation, chemotherapy, and even the tumor itself will remain difficult to avoid until tumor-directed therapy is improved in dramatic ways. After three decades of research and a multitude of published studies, the nature of these neurocognitive deficits and the associated risk factors are well-understood, but there is a paucity of research aimed at therapeutic interventions. This is the essential step that must be taken to translate our current understanding into improved quality of life for children who survive the underlying disease. Unfortunately, the current standard of care for treatment of these complex neurobehavioral deficits relies on a strained public school system. Recent advances and current approaches in treatment interventions for neuropsychological sequelae are reviewed in this article, including pharmacologic treatments, cognitive remediation derived from traumatic brain injury rehabilitation, and comprehensive school re-integration efforts. There is an acute need for further advances in this field, and a bright future of individualized school re-integration is within reach.

Abnormalities in parentally rated executive function in methamphetamine/polysubstance exposed children.

Methamphetamine/polysubstance abuse in women of childbearing age is a major concern because of the potential long-term detrimental effects on the brain function of the fetus following in utero exposure. A battery of established tests, including the Wechsler Abbreviated Scale of Intelligence, Conners' Continuous Performance Test II, Behavioral Rating Inventory of Executive Function, the CMS Family Pictures and Dot Location tests, the Spatial Span test from the WISC-IV-Integrated, and a recently developed spatial learning and memory measure (Memory Island), was used to assess the effects of prenatal drug exposure on neurobehavioral performance. Participants were 7 to 9 year old children from similar socioeconomic backgrounds who either had (N=31) or had not (N=35) been exposed to methamphetamine/polysubstance during pregnancy. Compared to unexposed children, exposed children showed pronounced elevations (i.e. more problems) in parental ratings of executive function, including behavioral regulation and metacognition. Exposed children also exhibited subtle reductions in spatial performance in the Memory Island test. In contrast, IQ, Spatial Span, Family Pictures, Dot Location, and vigilance performance were unaffected by prenatal drug exposure history. Thus, children of women who reported using methamphetamine and other recreational drugs during pregnancy showed a selective profile of abnormalities in parentally rated executive function.

Neurocognitive functioning of children and adolescents with mild-to-moderate chronic kidney disease.

BACKGROUND AND OBJECTIVES: Few data exist on the neurocognitive functioning of children with mild-to-moderate chronic kidney disease (CKD). The primary objectives of this paper are (1) to determine the neurocognitive status in this population and (2) to identify sociodemographic and health-status variables associated with neurocognitive functioning. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a cross-sectional study of 368 children, aged 6 to 16 years, from the Chronic Kidney Disease in Children (CKiD) cohort. Median iGFR was 43 ml/min per 1.73 m(2), and the median duration of CKD was 8.0 years. Approximately 26% had underlying glomerular disease. Measures of intelligence, academic achievement, attention regulation, and executive functioning were obtained at study entry. The prevalence of neurocognitive deficits was determined by comparing participant scores on each measure of neurocognitive functioning with normative data. The association between hypothesized predictors of neurocognitive dysfunction was evaluated using multivariate regression analyses. RESULTS: Neurocognitive functioning was within the average range for the entire group; however, 21% to 40% of participants scored at least one SD below the mean on measures of intelligence quotient (IQ), academic achievement, attention regulation, or executive functioning. Higher iohexol-based GFR (iGFR) predicted a lesser risk for poor performance on measures of executive function. Participants having elevated proteinuria (i.e., urine protein/creatinine >2) scored lower on verbal IQ, full-scale IQ, and attention variability than those without elevated proteinuria. CONCLUSIONS: Whereas most children with mild-to-moderate CKD have no major neurocognitive deficits, a substantial percentage did show neurocognitive dysfunction that places them at risk for poor long-term educational and occupational outcomes.

Health-related quality of life of children with mild to moderate chronic kidney disease.

OBJECTIVE: To compare the health-related quality of life (HRQoL) of children with chronic kidney disease (CKD) with healthy children; to evaluate the association between CKD severity and HRQoL; and to identity demographic, socioeconomic, and health-status variables that are associated with impairment in HRQoL in children with mild to moderate CKD. METHODS: This was a cross-sectional assessment of HRQoL in children who were aged 2 to 16 and had mild to moderate CKD using the Pediatric Inventory of Quality of Life Core Scales (PedsQL). Overall HRQoL and PedsQL domain means for parents and youth were compared with previously published norms by using independent sample t tests. Study participants were categorized by kidney disease stage (measured by iohexol-based glomerular filtration rate [iGFR]), and group differences in HRQoL were evaluated by using analysis of variance and Cuzick trend tests. The association between hypothesized predictors of HRQoL and PedsQL scores was evaluated with linear and logistic regression analyses. RESULTS: The study sample comprised 402 participants (mean age: 11 years, 60% male, 70% white, median iGFR: 42.5 mL/min per 1.73 m(2), median CKD duration: 7 years). Youth with CKD had significantly lower physical, school, emotional, and social domain scores than healthy youth. iGFR was not associated with HRQoL. Longer disease duration and older age were associated with higher PedsQL scores in the domains of physical, emotional, and social functioning. Older age was associated with lower school domain scores. Maternal education > or =16 years was associated with higher PedsQL scores in the domains of physical, school, and social functioning. Short stature was associated with lower scores in the physical functioning domain. CONCLUSIONS: Children with mild to moderate CKD, in comparison with healthy children, reported poorer overall HRQoL and poorer physical, school, emotional, and social functioning. Early intervention to improve linear growth and to address school functioning difficulties is recommended.

Qualitative analysis of the role of culture in coping themes of Latina and European American mothers of children with cancer.

It has been well established that mothers of children diagnosed with cancer experience high levels of distress. Latina mothers may be at risk for higher levels of distress related to language barriers, cultural factors, and economic, immigration, and acculturation stressors. Despite the increasing US Latino population, few studies have examined the role of culture within pediatric oncology, including how mothers cope with their child's cancer. This study used qualitative analysis of 24 sessions from 3 Latina and 3 European American mothers of children recently diagnosed with cancer. The session transcripts were divided into a total of 2328 thought segments that were then analyzed for themes using a collaborative iterative process. Analysis identified 9 shared coping themes that included, with some variations: gathering information, professional help-seeking, activities, problem solving, positive thinking, present orientation, reframing, avoidance, and religion. Three themes were culture specific: only European American mothers discussed compromise, whereas normalization and perspective taking were unique to the Latina mothers and suggest that the cultural value of simpatía influences coping. Clinical and research recommendations are discussed.