Introduction to the special section on school-related outcomes and success for youth with chronic medical conditions.

Chronic medical conditions permeate our schools with estimates showing that between 15% and 25% of students present with an ongoing illness or disease. Treatments for the most prevalent of these conditions (e.g., diabetes, epilepsy, cancer, juvenile arthritis, and asthma) include hospitalizations, home treatments, and frequent physician appointments-all of which are highly disruptive to children and families. Given the potential medical, cognitive/academic, social-emotional, and behavioral challenges encountered by students with chronic medical conditions, school psychologists are in a unique position to both identify and support the educational experiences of these students. Further, schools provide an ideal forum for outcomes research and intervention programs. This Introduction to the Special Issue on School-Related Outcomes and Success for Youth With Chronic Medical Conditions addresses definitional issues, identifies challenges, reviews the 7 empirical articles in this issue, and discusses areas for future research. This special issue includes scientifically rigorous papers, which feature innovative studies that emphasize real-time, momentary assessments; positive psychology frameworks; and intervention approaches. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Influence of Nitrosative Stress on Fatigue During Childhood Leukemia Treatment.

The focus on a cure for childhood leukemia over the last three decades has resulted in survival rates of more than 80%. However, efforts to manage leukemia-treatment symptoms have not kept pace with new therapies. Symptom toxicity during treatment can result in complications, treatment delays, and therapy dose reductions. Compromise in therapy can negatively influence the quality of life and, even more notably, jeopardize chances for long-term survival. This study examined biologic mechanisms that influence fatigue caused by increased reactive oxidative species (ROS) or actual failure of the antioxidant defense system due to genetic variation by investigating reactive nitrosative species, a "downstream" consequence of ROS. The specific aims of this study were to characterize the trajectory of nitrosative stress during acute lymphoblastic leukemia treatment and evaluate the influence of nitrosative stress on fatigue. A repeated measures design was used to evaluate the fatigue experienced by 186 children and adolescents, 3-18 years of age, with a diagnosis of leukemia during the most intense phase of treatment. An established biomarker of nitrosative stress, protein 3-nitrotyrosine (3NT) residues in the cerebral spinal fluid, was evaluated at diagnosis, postinduction, and consolidation phases of treatment. Higher fatigue was associated with higher 3NT levels at the beginning of treatment. Two distinct groups of children experienced either consistently high or consistently low 3NT levels across the treatment trajectory, from diagnosis to 12 months postinduction. Findings from this study support continued exploration into the phenotypic biochemical mechanisms that influence a reactive response to childhood cancer treatment.

Changes in Oxidant Defense, Apoptosis, and Cognitive Abilities During Treatment for Childhood Leukemia.

Aggressive central nervous system (CNS)-directed treatment for acute lymphoblastic leukemia (ALL), the most prevalent cancer among children and adolescents, prevents metastasis of leukemia cells into the brain. Up to 60% of survivors experience cognitive problems, but knowledge about risk factors for and mechanisms of neurologic injury is lacking. Objectives of the present study were to (1) quantify changes in oxidant defense and apoptosis over the course of ALL therapy and (2) elucidate risk factors for long-term cognitive problems. The sample included 71 children with ALL. Cerebrospinal fluid (CSF) samples were collected at diagnosis and during intrathecal chemotherapy administration. Oxidant defense was measured by reduced glutathione (GSH), oxidized glutathione (GSSG), and the ratio of GSH:GSSG. Apoptosis was measured by activity of several cysteine-dependent aspartate-specific protease (abbreviated as caspase) enzymes that initiate (caspases 8 and 9) or execute (caspases 3/7) apoptosis. Cognitive abilities were assessed by standardized measures of short-term memory, visual-motor integration, and attention 3 years after ALL diagnosis. GSH and GSSG concentration increased significantly during ALL therapy, and a low GSH:GSSG ratio was indicative of an oxidized extracellular environment. Caspase enzyme activity increased significantly, and caspases 3/7 activity was significantly and negatively associated with performance on measures of cognitive abilities. Younger age at time of ALL diagnosis was associated with some measures of attention. Efflux of glutathione into CSF maintains oxidant defense by scavenging free radicals and other reactive oxygen species and is an early event in apoptosis. These mechanisms may be involved in neurologic injury associated with CNS-directed treatment and subsequent cognitive problems.

Fatigue and Oxidative Stress in Children Undergoing Leukemia Treatment.

Fatigue is a frequent and distressing symptom in children undergoing leukemia treatment; however, little is known about factors influencing this symptom. Antioxidants such as glutathione can decrease symptom severity in adult oncology patients, but no study has evaluated antioxidants' effects on symptoms in pediatric oncology patients. This study describes fatigue patterns and associations of fatigue with antioxidants represented by reduced glutathione (GSH) and the reduced/oxidized glutathione (GSH/GSSG) ratio among children receiving leukemia treatment. A repeated measures design assessed fatigue and antioxidants among 38 children from two large U.S. cancer centers. Fatigue was assessed among school-age children and by parent proxy among young children. Antioxidants (GSH and GSH/GSSG ratio) were assessed from cerebrospinal fluid at four phases during leukemia treatment. Young children had a steady decline of fatigue from the end of induction treatment through the continuation phase of treatment, but no significant changes were noted among the school-age children. Mean antioxidant scores varied slightly over time; however, the GSH/GSSG ratios in these children were significantly lower than the normal ratio. Mean GSH/GSSG ratios significantly correlated to fatigue scores of the school-age children during early phases of treatment. Children with low mean GSH/GSSG ratios demonstrated oxidative stress. The low ratios noted early in therapy were significantly correlated with higher fatigue scores during induction and postinduction treatment phases. This finding suggests that increased oxidative stress during the more intensive phases of therapy may explain the experience of fatigue children report.

Effects of Intraventricular Methotrexate on Neuronal Injury and Gene Expression in a Rat Model: Findings From an Exploratory Study.

Central nervous system (CNS)-directed treatment for acute lymphoblastic leukemia, used to prevent disease recurrence in the brain, is essential for survival. Systemic and intrathecal methotrexate, commonly used for CNS-directed treatment, have been associated with cognitive problems during and after treatment. The cortex, hippocampus, and caudate putamen, important brain regions for learning and memory, may be involved in methotrexate-induced brain injury. Objectives of this study were to (1) quantify neuronal degeneration in selected regions of the cortex, hippocampus, and caudate putamen and (2) measure changes in the expression of genes with known roles in oxidant defense, apoptosis/inflammation, and protection from injury. Male Sprague Dawley rats were administered 2 or 4 mg/kg of methotrexate diluted in artificial cerebrospinal fluid (aCSF) or aCSF only into the left cerebral lateral ventricle. Gene expression changes were measured using customized reverse transcription (RT)(2) polymerase chain reaction arrays. The greatest percentage of degenerating neurons in methotrexate-treated animals was in the medial region of the cortex; percentage of degenerating neurons in the dentate gyrus and cornu ammonis 3 regions of the hippocampus was also greater in rats treated with methotrexate compared to perfusion and vehicle controls. There was a greater percentage of degenerating neurons in the inferior cortex of control versus methotrexate-treated animals. Eight genes involved in protection from injury, oxidant defense, and apoptosis/inflammation were significantly downregulated in different brain regions of methotrexate-treated rats. To our knowledge, this is the first study to investigate methotrexate-induced injury in selected brain regions and gene expression changes using a rat model of intraventricular drug administration.

Neurocognitive Predictors of Academic Outcomes Among Childhood Leukemia Survivors.

BACKGROUND: Acute lymphoblastic leukemia is the most common pediatric cancer, and survival approaches 90%. Acute lymphoblastic leukemia survivors are more likely than healthy peers or siblings to experience academic underachievement, yet little is known about neurocognitive predictors of academic outcomes. OBJECTIVES: Objectives were to compare neurocognitive abilities to age-adjusted standardized norms, examine change over time in neurocognitive abilities, and establish neurocognitive predictors of academic outcomes. METHODS: Seventy-one children were followed over the course of therapy. Cognitive abilities were assessed during induction when the child was in remission (baseline) and annually for 3 years (years 1, 2, and 3). Reading and mathematics abilities were assessed at year 3. RESULTS: Fine motor dexterity was significantly below age-adjusted norms at all data points but showed improvement over time. Baseline visual-motor integration was within the reference range but significantly declined by year 3, and mean scores at years 2 and 3 were significantly below age-adjusted norms. Verbal short-term memory was significantly below age-adjusted norms at all assessments. Visual-motor integration predicted reading and mathematics abilities. Verbal short-term memory predicted reading abilities, and visual short-term memory predicted mathematics abilities. CONCLUSIONS: Central nervous system-directed therapy is associated with specific neurocognitive problems. Visual-spatial skills and verbal and visual short-term memory predict academic outcomes. IMPLICATIONS FOR PRACTICE: Early assessment of visual-spatial perception and short-term memory can identify children at risk of academic problems. Children who are at risk of academic problems could benefit from a school-based individual educational program and/or educational intervention.

The influence of oxidative stress on symptom occurrence, severity, and distress during childhood leukemia treatment.

PURPOSE/OBJECTIVES: To explore the symptom trajectory during the first 16 months of childhood leukemia treatment and any associations with the oxidative stress pathway measured by cerebrospinal fluid (CSF) concentration of oxidized phosphatidylcholine (PC), the predominant glycerophospholipid in the brain and cell membranes. DESIGN: Prospective, longitudinal design. SETTING: Two cancer centers in the southwestern United States. SAMPLE: 36 children (aged 3-14 years) newly diagnosed with acute lymphoblastic leukemia. METHODS: Symptoms were measured using the Memorial Symptom Assessment Scale at six specific time points during treatment. Biochemical changes in oxidative stress were measured by oxidized PC in the CSF. MAIN RESEARCH VARIABLES: Childhood cancer symptoms, oxidized PC. FINDINGS: Significant differences were found in the number of symptoms experienced during the three phases of treatment. Symptom trajectory changes and influence of the oxidative stress pathway on symptom experiences were identified. CONCLUSIONS: Symptoms experienced during treatment for childhood leukemia are associated with increased oxidative stress. IMPLICATIONS FOR NURSING: Children with leukemia experience symptoms throughout treatment. Physiologic measures indicate the influence of oxidative stress on symptoms.

Symptom self-management strategies in patients with non-metastatic prostate cancer.

AIMS AND OBJECTIVES: To explore the association between symptoms, symptom distress and symptom self-management and to identify effective strategies of symptom self-management in men with non-metastatic prostate cancer following radical prostatectomy or radiation therapy. BACKGROUND: Men receiving treatments for localised prostate cancer experience symptoms of urinary incontinence, urinary obstruction/irritation, bowel difficulties and sexual dysfunction. Understanding patients' symptom experiences and identifying strategies that they use to manage these symptoms are imperative for symptom management planning. DESIGN: A descriptive, cross-sectional study was conducted with a sample of 53 men, who were within three months of the initiation of their treatment. METHODS: The Symptom Indexes and the Strategy and Effectiveness of Symptom Self-Management questionnaires were used to measure symptoms, symptom distress and symptom self-management. Descriptive statistics, t-tests, correlations and multiple regressions were used to analyse the data. RESULTS: Symptoms were significantly correlated with symptom-related distress (r = 0·67, p < 0·01). Frequency of symptoms was significantly associated with symptom self-management strategies for urinary (ß = 0·50, p < 0·01), bowel (ß = 0·71, p < 0·01) and sexual problems (ß = 0·28, p = 0·05). The most effective strategies were as follows: pads and doing Kegel exercise for managing urinary problems, rest and endurance for bowel symptoms, and expressing feelings and finding alternative ways to express affection for management of sexual dysfunction. CONCLUSIONS: Assessing symptom self-management among men with newly diagnosed prostate cancer can help healthcare providers develop strategies that will enhance health-related quality of life. RELEVANCE TO CLINICAL PRACTICE: Results provide information on effective strategies that patients with prostate cancer found to reduce their symptoms. The strategies used provide a foundation for developing and testing interventions for personalised symptom management.

Cerebrospinal fluid phospholipid changes following traumatic brain injury.

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality, with approximately 1.4 million people suffering a TBI each year. With TBI, a cascade of events is initiated including the activation of phospholipases, which leads to the disruption of the lipid bilayer of the membrane of neurons and neuroglia. The purpose of this study is to describe phospholipid changes following TBI. A total of 39 cerebrospinal fluid samples were obtained from the ventricular catheter system of 10 participants who received a TBI as a result of a motor vehicle crash, being struck by a vehicle as a pedestrian, or a fall. Phospholipids were extracted from samples and measured by normal-phase high-performance liquid chromatography with ultraviolet detector at a wavelength of 206 nm. The highest mean concentration of lysophosphatidylcholine occurred on Day 1 after injury. The concentration of phosphatidylserine was variable, with the highest mean concentration occurring on Day 2 after injury. The highest mean concentrations of phosphatidylethanolamine, phosphatidylcholine, and sphingomyelin occurred on Day 4 after injury. Findings provide preliminary evidence for disruption of central nervous system membrane phospholipids following TBI.

Methotrexate-induced alterations in beta-oxidation correlate with cognitive abilities in children with acute lymphoblastic leukemia.

Treatment advances, including central nervous system (CNS) treatment with methotrexate, have led to significant gains in disease-free survival from childhood acute lymphoblastic leukemia (ALL). However, methotrexate has been associated with neurological problems such as declines in cognitive and academic abilities. The purpose of this study was to investigate methotrexate-induced changes in beta-oxidation in children with ALL receiving methotrexate for CNS treatment. Specific aims were to investigate effects of methotrexate on beta-oxidation of the two most prevalent fatty acids (palmitic acid and stearic acid) in cerebrospinal fluid (CSF) samples and correlate the ratio of monounsaturation to saturation of these fatty acids with cognitive and academic abilities. The sample included 12 females and 14 males with low-risk (n = 7), standard-risk ( n = 13), or high-risk (n = 6) ALL. Mean age at diagnosis was 94.1 months (SD = 34.4). CSF samples were obtained in conjunction with diagnostic lumbar punctures; subsequent samples were obtained prior to intrathecal methotrexate administration during the induction, consolidation, and continuation phases of treatment. Fatty acids were analyzed by gas chromatography. Results showed a significant increase in the ratio of monounsaturation to saturation of both fatty acids, which was greatest during the most intensive phase of treatment. Ratios of monounsaturated to saturated fatty acids were negatively correlated with full-scale IQ, verbal IQ, and math calculations. Findings suggest that methotrexate alters beta-oxidation and that the resulting increase in fatty acid monounsaturation is related to declines in some domains of cognitive ability.

Symptoms and symptom distress in localized prostate cancer.

For over a decade, symptom distress has been a key concept in several studies of cancer. However, the definition of symptom distress is still unclear, and there are few measures targeting symptom distress, in general, and specific cancers, in particular. Prostate cancer is the sixth most common cancer worldwide and the second leading cause of death in American men. Many men with clinically localized prostate cancer may experience unique and multidimensional symptoms that occur from diagnosis through treatment, and thereafter. These symptoms associated with the disease and its treatments are in the form of physical and psychological sequelae such as urinary and bowel problems and sexual dysfunction. The purposes of this article are to (1) systematically review literature on symptoms and symptom distress in localized prostate cancer and (2) synthesize evidence of symptom distress applications and measurement in this group. A comprehensive, systematic review was conducted to identify original, data-based studies of symptoms and symptom distress in localized prostate cancer. Clarification of symptom distress and more comprehensive information about symptoms and symptom distress will provide nurses with a better foundation for developing self-management interventions aimed at ameliorating symptom distress and, ultimately, enhancing the quality of life of patients with localized prostate cancer.

Cytosine arabinoside induces programmed endothelial cell death through the caspase-3 pathway.

The anti-cancer effects of cytosine arabinoside (ARA-C) are well known. However, effects on nonmalignant cells have not been elucidated and may be important to understanding treatment-related toxicity. The purpose of this study was to examine the effect of ARA-C on nondividing vascular endothelial cells. The objectives were to determine the effects of ARA-C on cell viability and to ascertain whether ARA-C caused apoptosis in cultured vascular endothelial cells and hydrocortisone blunted caspase-3-induced apoptosis. Endothelial cells were cultured until confluent and mitotically quiescent then exposed to ARA-C (10(-7)to 10(-3) M) for 1 to 4 days. Some experiments involved cotreatment with hydrocortisone (10(-11),10(-10),10(-4), and 10(-3) M). Light microscopy and the colorimetric MTS assay were used to measure viability. Fluorescent annexin-V and DNA fragmentation assays were used to measure apoptosis, and a fluorescence-based enzymatic assay was used to measure caspase-3 activity, which is one pathway involved in the apoptosis cascade. Two-way ANOVA or the appropriate nonparametric test was used to determine statistical significance in studies of viability and apoptosis. Oneway ANOVA was used to determine statistical significance for caspase-3 activity. Viability was decreased with higher concentrations of ARA-C and increased days of treatment. The percentage of apoptotic cells increased with higher concentrations of ARA-C and increased days of treatment. ARA-C-treated samples showed DNA fragmentation, indicative of apoptosis. Caspase-3 activity increased after ARA-C addition; hydrocortisone blunted this increase. ARA-C caused apoptosis in nondividing endothelial cells in culture. Hydrocortisone may protect against ARA-C-induced apoptosis by reducing caspase-3 activity.

Advancing biobehavioral research in childhood cancer.

Research on individual and family responses to a child's or adolescent's cancer diagnosis and treatment is important because of significant advances in the field of pediatric oncology. To date, the majority of research has been behavioral or psychosocial in nature. It could be argued that a more holistic perspective that includes psychological, sociocultural, and biological dimensions would advance knowledge about individual and family responses to the experience of childhood cancer. Biobehavioral research refers to investigations that link behavioral and biological underpinnings in specific areas of science. The purpose of this article is to review research in two broad areas that could benefit from a biobehavioral perspective-psychosocial functioning/behavioral adjustment, and CNS treatment outcomes. Studies that include biological measures are highlighted. Advantages, challenges, and strategies for advancing biobehavioral research in childhood cancer are proposed.

The care of my child with cancer: parents' perceptions of caregiving demands.

Parents are actively involved in the direct care of their ill child receiving cancer treatment by providing and monitoring therapy and by managing symptoms related to the therapy or to the disease itself. Little is known about parents' perception of what helps or hinders them with their caregiving responsibilities or what effect the caregiving role has on the parent. In this descriptive, exploratory study, 151 parents responded to one or more of six open-ended questions that were part of the newly developed instrument, Care of My Child with Cancer. The 1,280 responses were analyzed using a semantic content analysis technique. The most frequently reported effect on parental caregiving involved negative physical and emotional health. One parent responded, "You feel like you lose all control over your life. It's no longer your own." The most desired forms of assistance with the caregiving role were periodic relief from direct caregiving, ongoing assistance with household responsibilities, and different forms of conveniences that could save time and energy. Two types of actual assistance found to be most helpful by parental caregivers included timely education about their child's health status from health care providers and emotional support from family members, friends, and others. These study findings provide the basis for future interventions that may diminish the effect that caregiving demands place on parents of children with cancer.