Principles and Practices of Returning Individual Research Results to Participants in Large Studies of Pregnancy and Childhood.

Investigators conducting human subject research have typically conveyed only clinically actionable results back to individual participants. Shifting scientific culture around viewing participants as partners in research, however, is prompting investigators to consider returning as much data or results as the participant would like, even if they are not clearly actionable. Expanding return of individual results may add value for individual participants and their communities, refine future research questions and methods, build trust, and enhance retention of participants. Yet, gaps remain in understanding the implications of these changes for groups of 'vulnerable' participants, including pregnant and pediatric participants. We present the findings of a National Institutes of Health workshop on returning individual research results, particularly as applicable to pregnant and pediatric participants. Research participants who were panelists at the workshop agreed that they desire to receive their results. Workshop findings and current literature indicate that participants have differing preferences for what results they receive. One way to address the limits of current practice is to develop flexible digital platforms that convey individual results along with researchers' availability to answer questions, and to provide as much information as possible about actionable steps to control environmental exposures associated with disease risk.

Attention and executive functioning in children and adolescents treated for high-risk acute lymphoblastic leukemia: A report from the Children's Oncology Group (COG).

OBJECTIVES: Survivors of childhood B-acute lymphoblastic leukemia (B-ALL) are at risk for difficulties with attention and executive functioning (EF) as a late effect of treatment. The present study aimed to identify treatment and demographic factors associated with risk for difficulties with EF in youth treated for high-risk B-ALL. METHOD: Children and adolescents with B-ALL treated on Children's Oncology Group (COG) protocol AALL0232 were randomized to high-dose or escalating-dose methotrexate (MTX), and either dexamethasone or prednisone during the induction phase. Neuropsychological functioning was evaluated via protocol AALL06N1, including performance-based and parent-report measures, for 177 participants (57% female, 81% white; mean age at diagnosis = 8.4 years; SD = 5.0) 8-24 months following treatment completion. RESULTS: Mean scores for all attention and EF measures were within the average range, with no significant differences as a function of MTX delivery or steroid treatment (all p > 0.05). In multivariable models, participants with US public insurance exhibited significantly greater parent-reported EF difficulties than those with US private or non-US insurance (p ≤ 0.05). Additionally, participants diagnosed under 10 years of age performed significantly more poorly on measures of attention (i.e., continuous performance task, p ≤ 0.05) and EF (i.e., verbal fluency and tower planning task, p ≤ 0.05). CONCLUSIONS: For survivors of pediatric B-ALL, treatment-related factors were not associated with attention or EF outcomes. In contrast, outcomes varied by demographic characteristics, including age and insurance type, an indicator of economic hardship. Future research is needed to more directly assess the contribution of socioeconomic status on cognitive outcomes in survivors.

Reaching "The Other Half": Teacher Referral Increases Inclusivity in Intervention Research for Neurodivergent School-Age Children.

OBJECTIVE: Researchers employed two recruitment strategies in a school-based comparative effectiveness trial for students with a diagnosis of attention-deficit/hyperactivity disorder (ADHD) or autism. This study assessed the: 1) effectiveness of school-based referrals for identifying students meeting diagnostic criteria and 2) impact of eliminating requirements for existing diagnoses on recruitment, sample characteristics, and intervention response. METHOD: Autistic students and students with ADHD in schools serving underresourced communities were recruited for an executive functioning (EF) intervention trial over 2 years. In Year 1, school staff nominated students with previous diagnoses. In Year 2, school staff nominated students demonstrating EF challenges associated with ADHD or autism; previous diagnosis was not required. Study staff then confirmed diagnoses. RESULTS: More students were included in Year 2 (N = 106) than Year 1 (N = 37). In Year 2, 96% of students referred by school staff met diagnostic criteria for ADHD or autism, 53% of whom were not previously diagnosed. Newly identified students were less likely than previously diagnosed students to be receiving services and, for those with ADHD, were more likely to speak primarily Spanish at home. Previously diagnosed and newly identified students did not differ on other demographic variables or intervention response. Caregivers of previously diagnosed students reported more symptoms than caregivers of newly identified students for both diagnostic groups. Previously diagnosed students with ADHD had more researcher-rated symptoms than newly identified students. CONCLUSIONS: Recruitment for an intervention study using behavior-based referrals from school staff enhanced enrollment without compromising the sample's diagnostic integrity and engaged children who otherwise would have been excluded.

Impaired neurocognitive functioning 3 months following diagnosis of high-risk acute lymphoblastic leukemia: A report from the Children's Oncology Group.

PURPOSE: Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer diagnosis. Cognitive late effects develop in 20%-40% of ALL survivors, but the course of declines is unclear. The aim of this paper is to characterize cognitive functioning, and its association with patient-reported outcomes, early in treatment. PATIENTS AND METHODS: A total of 483 children with high-risk ALL, aged 6-12 years at diagnosis, consented to the neurocognitive study embedded in a prospective therapeutic trial, Children's Oncology Group (COG) AALL1131. A computerized neurocognitive battery (Cogstate) was administered 3 months post diagnosis assessing reaction time, visual attention, working memory, visual learning, and executive functioning. Parent-reported executive functioning and patient-reported physical symptoms were also collected. RESULTS: Data from 390 participants (mean age at diagnosis = 9.2 years, 55.4% male) were obtained. Relatively few patients reported pain (16.0%) or nausea (22.6%), but a majority (68.5%) reported feeling at least some fatigue at testing. Mean Cogstate Z-scores were within normal limits across tasks; however, rates of impairment (Z-scores ≤ -1.5) for reaction time, working memory, visual learning, and visual attention were all higher than expected compared to the standardization sample. Patients reporting fatigue were significantly more likely to have impaired reaction time and visual attention compared to those reporting no fatigue. CONCLUSION: Findings support feasibility of computerized cognitive assessments and suggest higher-than-expected rates of impaired cognitive performance early during treatment for pediatric ALL, notably within 3 months of diagnosis, suggesting intervention efforts may be indicated. These results also highlight acute factors that may impact reliability of "baseline" assessments conducted soon after diagnosis.

Suicidal ideation and executive functioning in pediatric cancer.

OBJECTIVE: Neurocognitive impairments and psychological distress are among the most common difficulties experienced by children treated for cancer. Elevated rates of suicidal ideation (SI) are documented among cancer survivors, and a link between neurocognitive deficits and SI is evident, yet the relationship between SI and pediatric cancer-related neurocognitive effects has not yet been studied. PARTICIPANTS AND METHODS: Participants were 166 pediatric cancer patients (57.8% Brain Tumor, 31.3% leukemia, 10.8% other cancers) aged 6-23 (M = 11.57, SD = 3.82; 45.8% female) referred for neuropsychological surveillance. SI prevalence was measured by parent, teacher, or patient endorsement of self-harm related items on informant-report measures (e.g., the Child Behavior Checklist). Executive functioning (Behavior Rating Inventory of Executive Function), ADHD symptoms (ADHD Rating Scale), and performance-based measures were compared between those with SI and those without. RESULTS: 17.5% of pediatric cancer patients experienced SI, of which 44.7% had self-endorsement only, 58.5% parent-endorsement only, 20.6% teacher-endorsement only, and 24.1% had two endorsements. Those with SI had significantly greater impairments in global executive composite scores by both parent- and teacher-report (ps < 0.05). Parents of children with SI endorsed significantly more inattention symptoms (M = 6.10, SD = 15.48) than those without SI (M = 50.56, SD = 8.70; p < 0.01), but hyperactivity symptoms did not differ. Intellectual and executive function performance did not differ between those with and without SI (ps > 0.1). CONCLUSIONS: An elevated number of children treated for cancer experience SI and related neurocognitive problems. Screening for SI and further assessment of the connection between executive functioning and SI in pediatric cancer populations is needed.

Parents matter: Parent acceptance of school-based executive functions interventions relates to improved child outcomes.

OBJECTIVES: School-based interventions with parent-training components might improve access among lower-income families to effective help for children with neurodevelopmental disorders. This potential might be realized, however, only if parents perceive the interventions as acceptable and therefore engage with treatment. METHODS: Parents (N = 124) of 3rd-5th grade students diagnosed with Autism Spectrum Disorder or Attention-Deficit/Hyperactivity Disorder rated the acceptability of their child's treatment (one of two culturally responsive behavioral interventions). Parent engagement was measured through attendance at parent training sessions and the extent to which they read a corresponding workbook. RESULTS: Education and income correlated inversely with parent perceptions of treatment acceptability. Acceptability correlated positively with engagement, more strongly among lower-income families. Acceptability had an indirect effect on treatment outcome, mediated by parent engagement. CONCLUSIONS: Treatment providers should focus on strategies to increase parent acceptability, with particular attention to improving access for lower-income families.

Assessing neuropsychological phenotypes of pediatric brain tumor survivors.

INTRODUCTION: Pediatric brain tumor survivors (PBTS) are at risk for both neurocognitive impairments and psychological difficulties, yet these two domains have historically been discretely examined, with assessment of psychosocial outcomes rarely included in studies of cognitive outcomes. Taking a person-centered approach, the current study aimed to more comprehensively evaluate PBTS late effect profiles, including both neurocognitive and psychological sequelae, and predictors of these profiles. METHOD: PBTS (N = 89) were assessed in a pediatric neuropsychological clinic between May 2009 and May 2018, diagnosed at least 1 year prior, and off-treatment for at least 3 months (Mage  = 6.57 years, SD = 4.53; 46.1% female). Parent- and teacher-report of psychological symptoms, and performance-based measures of neurocognitive functioning were examined using latent profile analysis. The R3STEP procedure identified predictors of class membership. RESULTS: The optimal model identified four classes characterized by: (1) average functioning across all measures ("Average," n = 47), (2) average psychosocial functioning and impaired neurocognitive functioning ("Cognitive Deficit," n = 25), (3) elevated social problems and significant neurocognitive impairments ("Social/Cognitive Deficit," n = 9), and (4) impaired visual planning and problem-solving and elevated parent-reported psychosocial problems, but average processing speed, working memory, and teacher-reported psychosocial outcomes ("Discrepant," n = 8). Ethnicity, race, radiation treatment, and diagnoses of neurofibromatosis 1, hydrocephalus, and cerebellar mutism syndrome were significant predictors of class membership (ps < 0.05). CONCLUSION: The present study identified distinct phenotypes with unique patterns of relations among neurocognitive and psychological domains. These findings are a vital first step toward identifying those at highest risk for poor outcomes and informing interventions that effectively address interrelated treatment targets for specific groups.

Psychological, educational, and social late effects in adolescent survivors of Wilms tumor: A report from the Childhood Cancer Survivor Study.

OBJECTIVE: To delineate the impact of treatment exposures and chronic health conditions on psychological, educational, and social outcomes in adolescent survivors of Wilms tumor. METHODS: Parent reports from the Childhood Cancer Survivor Study were analyzed for 666 adolescent survivors of Wilms tumor and 698 adolescent siblings. Adjusting for race and household income, survivors were compared to siblings on the Behavior Problems Index and educational outcomes. Multivariable modified Poisson regression estimated relative risks (RR) for therapeutic exposures and chronic health conditions (CTCAE 4.03 graded) among survivors, adjusting for sex, race, income, and age at diagnosis. RESULTS: Compared to siblings, adolescent survivors of Wilms tumor were more likely to take psychoactive medication (9.4% vs. 5.1%, p < 0.001) and utilize special education services (25.5% vs. 12.6%, p < 0.001) but did not differ significantly in emotional and behavioral problems. Survivors were less likely to be friendless (7.2% vs. 10.1%, p = 0.04) but were more likely to have difficulty getting along with friends (14.5% vs. 7.8%, p < 0.001). Among survivors, use of special education services was associated with abdomen plus chest radiation (RR = 1.98, CI:1.18-3.34). Those with grade 2-4 cardiovascular conditions had higher risk for anxiety/depression (RR = 1.95, CI:1.19-3.19), headstrong behaviors (RR = 1.91, CI:1.26-2.89), and inattention (RR = 1.56, CI:1.02-2.40). CONCLUSIONS: Adolescent survivors of Wilms tumor were similar to siblings with respect to mental health concerns overall but were more likely to require special education. Monitoring of psychosocial and academic problems through adolescence is warranted, especially among those treated with radiation to the abdomen plus chest or with cardiac conditions.

Adaptive functioning and academic achievement in survivors of childhood acute lymphoblastic leukemia: A report from the Children's Oncology Group.

PURPOSE: To characterize academic and adaptive skill outcomes in survivors of high-risk B-lineage acute lymphoblastic leukemia (HR B-ALL). METHODS: Participants were 178 patients enrolled on a nontherapeutic clinical trial that aimed to characterize neurocognitive and functional outcomes (ie, academic achievement and adaptive skills) following treatment for childhood HR B-ALL. Eligible patients were treated on Children's Oncology Group AALL0232 clinical trial that included two treatment randomizations: methotrexate delivery (high or escalating dose) and corticosteroid (dexamethasone or prednisone). Academic achievement and adaptive skills were evaluated at one time point, 8-24 months after completing treatment. RESULTS: Multivariable logistic regression showed no significant association between treatment variables and outcomes after accounting for age at diagnosis, sex, and insurance status. In multivariable analyses accounting for sex and insurance status, survivors <10 years old at diagnosis had significantly lower scores in Math (P = .02). In multivariable analyses accounting for sex and age at diagnosis, scores for children with US public health insurance were significantly lower than those with US private or military insurance across all academic and adaptive skills (all P-values ≤.04). Results from univariate analyses showed that boys had significantly lower scores than girls across all adaptive skill domains (all P-values ≤.04). CONCLUSION: Regardless of treatment randomization, survivors of HR B-ALL <10 years at diagnosis are at risk for deficits in Math and overall adaptive functioning; overall adaptive skills for boys were significantly poorer. Screening and early intervention for patients at highest risk, particularly young patients and lower resourced families, should be prioritized.

A Randomized Controlled Trial of Working Memory Training in Pediatric Sickle Cell Disease.

OBJECTIVE: Youth with sickle cell disease (SCD) are at risk for neurocognitive deficits including problems with working memory (WM), but few interventions to improve functioning exist. This study sought to determine the feasibility and efficacy of home-based, digital WM training on short-term memory and WM, behavioral outcomes, and academic fluency using a parallel group randomized controlled trial design. METHODS: 47 children (7-16 years) with SCD and short-term memory or WM difficulties were randomized to Cogmed Working Memory Training at home on a tablet device (N = 24) or to a standard care Waitlist group (N = 23) that used Cogmed after the waiting period. Primary outcomes assessed in clinic included performance on verbal and nonverbal short-term memory and WM tasks. Secondary outcomes included parent-rated executive functioning and tests of math and reading fluency. RESULTS: In the evaluable sample, the Cogmed group (N = 21) showed greater improvement in visual WM compared with the Waitlist group (N = 22; p = .03, d = 0.70 [CI95 = 0.08, 1.31]). When examining a combined sample of participants, those who completed ≥10 training sessions exhibited significant improvements in verbal short-term memory, visual WM, and math fluency. Adherence to Cogmed was lower than expected (M = 9.07 sessions, SD = 7.77), with 19 participants (41%) completing at least 10 sessions. Conclusions: Visual WM, an ability commonly affected by SCD, is modifiable with cognitive training. Benefits extended to verbal short-term memory and math fluency when patients completed a sufficient training dose. Additional research is needed to identify ideal candidates for training and determine whether training gains are sustainable and generalize to real-world outcomes.

Eating behavior and reasons for exercise among competitive collegiate male athletes.

PURPOSE: Research concerning eating disorders among adolescent and young adult male athletes is limited compared with female counterparts, but increasing evidence indicates that they may be at unique risk for unhealthy exercise and eating behavior. The current study aimed to characterize unhealthy exercise and eating behavior according to competitive athlete status, as well as per sport type. METHOD: Collegiate male athletes (N = 611), each affiliated with one of the 10 National College Athletics Association (NCAA) Division I schools in the United States, completed an online survey, reporting on eating and extreme weight control behaviors, and reasons for exercise. RESULTS: Competitive athletes endorsed increased driven exercise and exercising when sick. Baseball players, cyclists, and wrestlers emerged as the sports with the most players reporting elevated Eating Disorder Examination-Questionnaire scores in a clinical range, and basketball players reported the highest rates of binge eating. overall, baseball players, cyclists, rowers, and wrestlers appeared to demonstrate the greatest vulnerability for unhealthy eating and exercise behavior. CONCLUSION: Findings revealed differences between competitive and non-competitive male athletes. Among competitive athletes, results identified unique risk for unhealthy eating and exercise behavior across a variety of sport categories and support continued examination of these attitudes and behaviors in a nuanced manner. LEVEL II: Evidence obtained from well-designed controlled trials without randomization.

Assessment of provider perspectives on otoprotection research for children and adolescents: A Children's Oncology Group Cancer Control and Supportive Care Committee survey.

BACKGROUND: Cisplatin-induced hearing loss (CIHL) is a common and debilitating toxicity for childhood cancer survivors. Understanding provider perspectives is crucial to developing otoprotection studies that are both informative and feasible. Two international trials (ACCL0431 and SIOPEL6) investigated the drug sodium thiosulfate (STS) as an otoprotectant, but definitive interpretation of the findings of these trials has been challenging. Adoption of STS has therefore been uneven, and provider perspectives on its role are unknown. PROCEDURE: The Children's Oncology Group (COG) Cancer Control and Supportive Care Neurotoxicity Subcommittee therefore conducted a survey of providers at COG institutions to determine perspectives on pediatric otoprotection practices and research surrounding three major themes: (1) prevalence of routine use of STS with cisplatin-based regimens, (2) application of audiometry to cisplatin therapy, and (3) preferred modalities for otoprotection research. RESULTS: Survey respondents (45%, 44/98 surveyed institutions) were of diverse institutional sizes, practice settings, and geographical locations primarily in the United States and Canada. Overall, respondents considered CIHL an important toxicity and indicated strong enthusiasm for future studies (98%, 40/41). Results indicated that while STS was the current or planned standard of care in a minority of responding institutions (36%, 16/44), most sites were receptive to its inclusion in appropriate study designs. Application of audiometry for ototoxicity monitoring varied widely across sites. For otoprotection research, systemic agents were preferred (68%, 28/41) as compared with intratympanic approaches. CONCLUSION: These results suggest that pediatric otoprotection trials remain of interest to providers; the emphasis of these trials should remain on systemic and not intratympanic therapy.

Cognitive Abilities Moderate the Effect of Disease Severity on Health-Related Quality of Life in Pediatric Sickle Cell Disease.

Objective: Complications that can arise from sickle cell disease (SCD) have the potential to negatively affect health-related quality of life (HRQL). SCD manifests in varying degrees of severity, but effects on HRQL are not uniform. Cognitive abilities influence HRQL in other pediatric groups, potentially through variability in treatment adherence and psychological coping. This study examined the effect of SCD severity on HRQL and explored cognitive abilities as a moderator of this relationship. Methods: A total of 86 children and adolescents with SCD (ages 7-16 years) completed a cognitive assessment (Wechsler Scale of Intelligence for Children, Fifth Edition), and primary caregivers rated their child's SCD severity and HRQL (PedsQL Sickle Cell Disease Module). A hierarchical linear regression was conducted to evaluate the interactive effect of SCD severity and cognitive functioning on HRQL. Results: Caregiver-rated SCD severity predicted HRQL and cognitive abilities interacted with disease severity to influence HRQL. Youth with milder SCD and cognitive abilities in the average range or higher demonstrated significantly better HRQL compared with youth with mild SCD but below average cognitive abilities. Youth with more severe disease appeared to exhibit similarly low levels of HRQL, with only a minimal influence of cognitive abilities. Conclusions: Cognitive factors modify the effect of SCD severity on HRQL, particularly among youth with milder forms of SCD. Future studies are warranted to clarify the role of cognitive abilities in determining HRQL. Clinicians should monitor youth with milder forms of SCD and limited cognitive abilities for worsening HRQL and opportunities to provide support around disease self-management.

Systematic Review: A Prevention-Based Model of Neuropsychological Assessment for Children With Medical Illness.

Objective: Many pediatric chronic illnesses have shown increased survival rates, leading to greater focus on cognitive and psychosocial issues. Neuropsychological services have traditionally been provided only after significant changes in the child's cognitive or adaptive functioning have occurred. This model of care is at odds with preventative health practice, including early identification and intervention of neuropsychological changes related to medical illness. We propose a tiered model of neuropsychological evaluation aiming to provide a preventative, risk-adapted level of assessment service to individuals with medical conditions impacting the central nervous system based on public health and clinical decision-making care models. Methods: Elements of the proposed model have been used successfully in various pediatric medical populations. We summarize these studies in association with the proposed evaluative tiers in our model. Results and Conclusions: This model serves to inform interventions through the various levels of assessment, driven by evidence of need at the individual level in real time.

Long-Term Efficacy of Computerized Cognitive Training Among Survivors of Childhood Cancer: A Single-Blind Randomized Controlled Trial.

Objective: To investigate the long-term efficacy of computerized cognitive training in improving cognitive outcomes among childhood cancer survivors. Methods: Sixty-eight survivors of childhood acute lymphoblastic leukemia (ALL) or brain tumor (BT) were randomly assigned to computerized cognitive intervention (23 ALL/11 BT, age = 12.21 ± 2.47) or a waitlist control group (24 ALL/10 BT, age = 11.82 ± 2.42). Cognitive assessments were completed pre-, immediately post-, and 6 months postintervention. Results: A prior report showed training led to immediate improvement in working memory, attention and processing speed. In the current study, piecewise linear mixed effects modeling revealed that working memory and processing speed were unchanged from immediate to 6 months postintervention (intervention ß = -.04 to .01, p = .26 to .95; control ß = -.06 to .01, p = .23-.97), but group differences on an attention measure did not persist. Conclusion: Cognitive benefits are maintained 6 months following computerized cognitive training, adding to potential clinical utility of this intervention approach.

Feasibility of Home-Based Computerized Working Memory Training With Children and Adolescents With Sickle Cell Disease.

BACKGROUND: Children with sickle cell disease (SCD) are at increased risk for neurocognitive deficits, yet the literature describing interventions to ameliorate these problems and promote academic achievement is limited. We evaluated the feasibility and preliminary efficacy of a home-based computerized working memory (WM) training intervention (Cogmed) in children with SCD. PROCEDURE: Youth with SCD between the age of 7 and 16 years completed an initial neuropsychological assessment; those with WM deficits were loaned an iPad on which they accessed Cogmed at home. Participants were instructed to work on Cogmed 5 days each week for 5 weeks (25 training sessions). We examined Cogmed usage characteristics and change on WM assessment scores following the intervention. RESULTS: Of the 21 participants (M age = 11.38, SD = 2.78; Mdn age = 10.00, interquartile range [IQR] = 5.00; 52% female) screened, 60% exhibited WM deficits (n = 12) and received the intervention and 50% (n = 6) completed Cogmed. The mean number of sessions completed was 15.83 (SD = 7.73; Mdn = 17.00, IQR = 16.00); females were more likely to complete Cogmed, χ(2) (1) = 6.00, P = 0.01. Participants who reported lower SCD-related pain impact completed more sessions (r = 0.71, P = 0.01). Children who completed Cogmed exhibited improvements in verbal WM, visuospatial short-term memory, and visuospatial WM. CONCLUSIONS: Initial findings suggest Cogmed is associated with WM improvement in youth with SCD; however, adherence was lower than expected. Home-based WM interventions may ameliorate SCD-related WM deficits but strategies are needed to address barriers to program completion.

Vision specific quality of life in children with optic pathway gliomas.

Children with optic pathway gliomas (OPGs) frequently experience vision loss from their tumors. Most pediatric OPG research has focused on radiographic and visual outcomes, yet the impact of vision loss on quality of life (QOL) in children with OPGs has not been studied. The present study prospectively recruited children ≤ 10 years of age with sporadic or neurofibromatosis type 1 (NF1)-related OPGs. Vision specific QOL was assessed by parent proxy using the Children's Visual Function Questionnaire (CVFQ), and scores were analyzed according to magnitude of visual acuity (VA) loss and presence of visual field (VF) loss. Thirty-six subjects completed the study (53 % female) with median age of 4.6 years. Children with mild, moderate and severe vision loss have lower CVFQ subscale scores, indicating a lower vision specific QOL, compared to those with normal vision. Lower Competence scores were noted in participants with more profound vision loss (p < 0.05), reflecting a decreased ability to complete activities of daily living (e.g., feeding, grooming). Children with two visually impaired eyes were rated as having greater difficulty with social interactions and pleasurable activities (Personality subscale, p = 0.039) compared to those with only one impaired eye. In summary, our findings demonstrate that children with vision loss secondary to their OPG have a decreased vision specific QOL compared to those with normal vision. Measuring vision specific QOL may be considered a meaningful secondary outcome measure for pediatric OPG clinical trials.

Impact of Propofol Exposure on Neurocognitive Outcomes in Children With High-Risk B ALL: A Children's Oncology Group Study.

PURPOSE: Many children treated for ALL develop long-term neurocognitive impairments. Increased risk of these impairments is associated with treatment and demographic factors. Exposure to anesthesia is an additional possible risk factor. This study evaluated the impact of cumulative exposure to anesthesia on neurocognitive outcomes among a multicenter cohort of children with ALL. METHODS: This study was embedded in AALL1131, a Children's Oncology Group phase III trial for patients with high-risk B-ALL. In consenting patients age 6-12 years, prospective uniform assessments of neurocognitive function were performed during and at 1 year after completion of therapy. Exposure to all episodes of anesthetic agents was abstracted. Multivariable linear regression models determined associations of cumulative anesthetic agents with the primary neurocognitive outcome reaction time/processing speed (age-normed) at 1 year off therapy, adjusting for baseline neurocognitive score, age, sex, race/ethnicity, insurance status (as a proxy for socioeconomic status), and leukemia risk group. RESULTS: One hundred and forty-four children, 76 (52.8%) males, mean age of 9.1 (min-max, 6.0-12.0) years at diagnosis, underwent a median of 27 anesthetic episodes (min-max, 1-37). Almost all patients were exposed to propofol (140/144, 97.2%), with a mean cumulative dose of 112.3 mg/kg. One year after therapy, the proportion of children with impairment (Z-score ≤-1.5) was significantly higher compared with a normative sample. In covariate-adjusted multivariable analysis, cumulative exposure to propofol was associated with a 0.05 Z-score decrease in reaction time/processing speed per each 10 mg/kg propofol exposure (P = .03). CONCLUSION: In a multicenter and uniformly treated cohort of children with B-ALL, cumulative exposure to propofol was an independent risk factor for impairment in reaction time/processing speed 1 year after therapy. Anesthesia exposure is a modifiable risk, and opportunities to minimize propofol use should be considered.

Sluggish cognitive tempo in survivors of pediatric brain tumors.

The presence of neurocognitive late effects in survivors of pediatric brain tumors is well established. However, there remains some debate about how best to conceptualize these deficits. Sluggish cognitive tempo (SCT) is a proposed conceptual framework that has been used to describe a subset of children with ADHD who exhibit a particular profile characterized by lethargy, day dreaming and staring, and poor organization. Previous work has suggested that survivors of leukemia exhibit a similar profile, but it has not yet been examined in survivors of pediatric brain tumors. A sample of 65 survivors of pediatric brain tumors, 25 survivors of leukemia and 50 community controls completed the Child Behavior Checklist, with four items used to measure SCT. Survivors completed additional measures of neurocognitive functioning. Survivors of brain tumors demonstrated significantly greater symptoms of SCT than survivors of leukemia or controls. SCT was associated with attention problems and working memory deficits and the presence of a VP-shunt. Results provided conditional support for the presence of SCT in survivors of brain tumors, with further research needed to determine the clinical utility of the framework.

Working memory training in survivors of pediatric cancer: a randomized pilot study.

OBJECTIVES: Survivors of pediatric brain tumors and acute lymphoblastic leukemia (ALL) are at increased risk for neurocognitive deficits, but few empirically supported treatment options exist. We examined the feasibility and preliminary efficacy of a home-based, computerized working memory training program, CogmedRM, with survivors of childhood cancer. METHODS: Survivors of brain tumors or ALL (n = 20) with identified deficits in attention and/or working memory were randomized to either the success-adapted computer intervention or a non-adaptive, active control condition. Specifically, children in the adaptive condition completed exercises that became more challenging with each correct trial, whereas those in the non-adaptive version trained with exercises that never increased in difficulty. All participants were asked to complete 25 training sessions at home, with weekly, phone-based coaching support. Brief assessments were completed pre-intervention and post-intervention; outcome measures included both performance-based and parent-report measures of working memory and attention. RESULTS: Eighty-five percent of survivors were compliant with the intervention, with no adverse events reported. After controlling for baseline intellectual functioning, survivors who completed the intervention program evidenced significant post-training improvements in their visual working memory and in parent-rated learning problems compared with those in the active control group. No differences in verbal working memory functioning were evident between groups, however. CONCLUSIONS: Home-based, computerized cognitive training demonstrates good feasibility and acceptability in our sample. Children with higher intellectual functioning at baseline appeared to benefit more from the training, although further study is needed to clarify the strength, scope, and particularly the generalizability of potential treatment effects.