Robert W. Butler

Attentional processes and their remediation in children treated for cancer: A literature review and the development of a therapeutic approach

It is now generally accepted that central nervous system treatments for childhood cancer can result in significant cognitive impairment, most commonly in the areas of attention/concentration. We review the literature on attentional and neurocognitive deficits in this population, and also efforts to remediate attentional deficits in other brain injured populations. It was our goal to develop an innovative, psychologically based outpatient rehabilitation program that would improve dysfunctional attentional processes and associated neuropsychological deficits. The characteristics of this program and a pilot study of its effectiveness are described. Participants were 31 off-therapy cancer survivors with documented attention deficits. Twenty-one completed the cognitive remediation program (CRP) and 10 served as comparisons. All participants completed a test of vigilance attention, 2 tests with an attentional component, and an arithmetic academic achievement measure. When the scores of the 2 groups were compared, the CRP group exhibited statistically significant improvement on all attentional measures. In contrast, the comparison group did not manifest any significant changes. Neither group demonstrated statistically significant changes on the arithmetic achievement test. We believe that the CRP has potential for improving attention/concentration, but generalization to academic achievement remains unproven. Phase 3 clinical trials and the documentation of long-term treatment gains are needed. Furthermore, it will be necessary to demonstrate the ecological validity of the CRP. With these caveats, this therapeutic approach may be helpful in other populations of cognitively impaired children and young adults, such as patients who have suffered traumatic brain injury.

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 childrens 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.

Neuropsychologic effects of cranial irradiation, intrathecal methotrexate, and systemic methotrexate in childhood cancer.

PURPOSE To investigate the neuropsychologic effects of cranial irradiation (CRT), intrathecal methotrexate (IT-MTX), and systemic methotrexate (SYS-MTX) in a cohort of pediatric patients with cancer who had either received no, moderate, or high doses of these treatments alone or in various combinations. PATIENT AND METHODS Data were collected on 120 pediatric cancer patients from a large variety of diagnostic groups. Patients completed a comprehensive neuropsychologic test battery designed to assess most areas of cognitive functioning. In analyzing cancer treatment effects, the following variables were statistically controlled: (1) age, (2) socioeconomic status (SES), (3) age at diagnosis, (4) months since both onset and cessation of CNS treatments, (5) time missed from schooling, and (6) presence/type of CNS cancer. RESULTS CRT, largely in combination with IT-MTX, was significantly associated with deficits in several, primarily nondominant, hemispheric neuropsychologic functions, even after control and other treatment variables were addressed. This relationship was somewhat, but not highly, dose-dependent at CRT doses greater than approximately 18 Gy, at least over the first several years posttreatment. While there was statistically significant evidence for cognitive impairment, absence from school during treatment and age at diagnosis were more predictive of reading and spelling academic achievement than having received CRT. IT-MTX and SYS-MTX alone were not associated with significant degrees of neuropsychologic involvement. CONCLUSION CRT, especially when administered with IT-MTX, at currently used dosages was associated with significant neuropsychologic impairment in children. These impairments are most likely to be reflected in nonverbal intelligence, perceptual abilities, and susceptibility to distraction. IT-MTX and SYS-MTX did not result in a consistent pattern of cognitive deficit.

Relation of cognitive coping and catastrophizing to acute pain and analgesic use following breast cancer surgery.

This study investigated the relation of cognitive coping and catastrophizing to acute postoperative pain and analgesic use. Fifty-nine women who had just undergone breast cancer surgery rated their pain on 3 consecutive days and completed a self-report measure of cognitive coping and catastrophizing prior to hospital discharge. Analgesic use over the 3-day period was tabulated from pharmacy records. Based on prior research, it was hypothesized that increased catastrophizing and decreased use of cognitive coping strategies would be associated with greater pain and analgesic use. Results partially confirmed these hypotheses. Catastrophizing, but not cognitive coping, was associated with individual differences in pain intensity and analgesic use. Additional analyses indicated that age was a significant predictor of both catastrophizing and postoperative pain. Specifically, younger patients were more likely to catastrophize and to report increased postoperative pain. Theoretical and clinical implications of these findings are discussed.

ReviewNeurocognitive sequelae of childhood cancers and their treatment

The present review will focus on the neurocognitive aspects of the medical treatment of childhood cancer by discussing current knowledge of brain damage among patients and how it is reflected in their cognitive abilities. It will direct these efforts toward the two most common forms of childhood cancer, acute lymphoblastic leukaemia (ALL) and brain tumours. It will first provide the reader with a brief medical background followed by a review of the current literature. The literature review will provide an in-depth analysis of the types of cognitive impairments observed and known or suspected risk factors for impairments. Finally, the review will close with a section that discusses interventions with the potential to prevent or minimize cognitive deficits acquired in the course of cancer treatment as they impact on the quality of life of paediatric cancer survivors.

Positive symptoms of psychosis in posttraumatic stress disorder

The possible presence of hallucinations and delusional thoughts in posttraumatic stress disorder (PTSD) was investigated. Other symptom clusters were also assessed in order to further clarify the nature of PTSD. Twenty combat veterans with PTSD were compared to 18 combat veterans without PTSD on symptom rating scales. The subjects with PTSD exhibited a greater degree of depression, anxiety, agitation, anhedonia, and positive symptoms of psychosis than the comparison group. Specifically, the PTSD group manifested increased hallucinations, delusions, and bizarre behavior. Some of these positive symptoms did not appear to be due to reexperiencing of the trauma. The groups were not significantly different on indices of mania, thought disorder, or inertia. The clinical and diagnostic implications of the results are discussed. A diagnosis of PTSD should be considered with patients who have positive symptoms in the absence of thought disorder.

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

ABSTRACT. 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.

Routine mechanical ventricular assist following the Norwood procedure—improved neurologic outcome and excellent hospital survival

BACKGROUND Although excellent survival following the Norwood procedure for palliation of hypoplastic left heart syndrome (HLHS) is being achieved by some, most centers, especially the ones with small surgical volume and limited experience, continue to struggle with initial results. Survivors often showed evidence of significant neurologic injury. The early postoperative care is labor-intensive as attempts are made to balance the systemic and pulmonary circulation for these infants. We report our experience with routine use of mechanical circulatory assist to support the increased cardiac output requirements present following Norwood procedure. METHODS Eighteen consecutive infants undergoing Norwood operation for HLHS (Oregon Health & Science University [OHSU] 13; University of Louisville [UL] 5) were placed on a ventricular assist device (VAD) immediately following modified ultrafiltration in the operating room using the cardiopulmonary bypass (CPB) cannulas that were in the right atrium and the neoaorta. VAD flows were maintained at approximately 200 mL x kg(-1) x min(-1) and the patients were transported to the intensive care unit (ICU). Patients operated at OHSU also received neurodevelopmental testing before their Glenn procedure, approximately 4 to 6 months following their Norwood operation. RESULTS All patients were stable on VAD support and no attempt was made to balance the systemic and pulmonary circulation. The ventilator was manipulated to achieve systemic Pa0(2) between 30 and 45 mm Hg and PaC0(2) between 35 and 45 mm Hg. Evidence of hypoperfusion (increasing lactates) was managed by increasing the VAD flow. Lactates normalized [< 2 mmol/L]) by 1.8 +/- 1.1 days following surgery. Average time of VAD support was 3.1 +/- 1.0 (range, 2 to 5 days) and average time until chest closure was 3.4 +/- 1.5 (range, 2 to 8 days). There were two cases of postoperative bleeding (11.1%) requiring reexploration and one case of mediastinitis (5.5%) in a patient who has now gone on to successful Glenn. Sixteen of the eighteen patients survived (hospital survival mean 89% with a 95% confidence interval of 63.9% to 98.1%; 12/13 OHSU [92.3%]; 4/5 UL [80%]). Neurodevelopmental testing using the Mullen Scales of Early Learning and the Vineland Adaptive Behavior Scale were normal for all infants tested. CONCLUSIONS Routine postoperative use of VAD can support the increased cardiac output demands of infants following Norwood operation and results in a stable postoperative convalescence that does not require aggressive ventilator or inotrope manipulation. Although not a panacea, this strategy can simplify postoperative management, lead to excellent hospital survival, and possibly augment cerebral oxygen delivery, resulting in improved neurologic outcomes for this challenging group of patients.

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 m2, 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 ≥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.