Publications by authors named "Kristina K Hardy"

52 Publications

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

Pediatr Blood Cancer 2021 Apr 31;68(4):e28913. Epub 2021 Jan 31.

University of Florida Colleges of Medicine, Public Health and Health Professions, Gainesville, Florida.

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.
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http://dx.doi.org/10.1002/pbc.28913DOI Listing
April 2021

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

Psychooncology 2020 Oct 28. Epub 2020 Oct 28.

Neuropsychology Division, Children's National Health System, Washington, District of Columbia, USA.

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.
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http://dx.doi.org/10.1002/pon.5584DOI Listing
October 2020

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

Pediatr Blood Cancer 2020 11 4;67(11):e28647. Epub 2020 Sep 4.

Vanderbilt University Ingram Cancer Center, Nashville, Tennessee.

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.
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http://dx.doi.org/10.1002/pbc.28647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808411PMC
November 2020

Impact of Intrathecal Triple Therapy Versus Intrathecal Methotrexate on Disease-Free Survival for High-Risk B-Lymphoblastic Leukemia: Children's Oncology Group Study AALL1131.

J Clin Oncol 2020 08 4;38(23):2628-2638. Epub 2020 Jun 4.

Department of Pediatrics and the Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA.

Purpose: The high-risk stratum of Children's Oncology Group Study AALL1131 was designed to test the hypothesis that postinduction CNS prophylaxis with intrathecal triple therapy (ITT) including methotrexate, hydrocortisone, and cytarabine would improve the postinduction 5-year disease-free survival (DFS) compared with intrathecal methotrexate (IT MTX), when given on a modified augmented Berlin-Frankfurt-Münster backbone.

Patients And Methods: Children with newly diagnosed National Cancer Institute (NCI) high-risk B-cell acute lymphoblastic leukemia (HR B-ALL) or NCI standard-risk B-ALL with defined minimal residual disease thresholds during induction were randomly assigned to receive postinduction IT MTX or ITT. Patients with CNS3-status disease were not eligible. Postinduction IT therapy was given for a total of 21 to 26 doses. Neurocognitive assessments were performed during therapy and during 1 year off therapy.

Results: Random assignment was closed to accrual in March 2018 after a futility boundary had been crossed, concluding that ITT could not be shown to be superior to IT MTX. The 5-year postinduction DFS and overall survival rates (± SE) of children randomly assigned to IT MTX versus ITT were 93.2% ± 2.1% 90.6% ± 2.3% ( = .85), and 96.3% ± 1.5% 96.7% ± 1.4% ( = .77), respectively. There were no differences in the cumulative incidence of isolated bone marrow relapse, isolated CNS relapse, or combined bone marrow and CNS relapse rates, or in toxicities observed for patients receiving IT MTX compared with ITT. There were no significant differences in neurocognitive outcomes for patients receiving IT MTX compared with ITT.

Conclusion: Postinduction CNS prophylaxis with ITT did not improve 5-year DFS for children with HR B-ALL. The standard of care for CNS prophylaxis for children with B-ALL and no overt CNS involvement remains IT MTX.
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http://dx.doi.org/10.1200/JCO.19.02892DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402996PMC
August 2020

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

Eat Weight Disord 2021 Feb 28;26(1):75-83. Epub 2019 Nov 28.

Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.

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.
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http://dx.doi.org/10.1007/s40519-019-00819-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253316PMC
February 2021

Social Functioning of Childhood Cancer Survivors after Computerized Cognitive Training: A Randomized Controlled Trial.

Children (Basel) 2019 Sep 27;6(10). Epub 2019 Sep 27.

St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

Childhood cancer survivors are at risk for cognitive and social deficits. Previous findings indicate computerized cognitive training can result in an improvement of cognitive skills. The current objective was to investigate whether these cognitive gains generalize to social functioning benefits. Sixty-eight survivors of childhood cancer were randomly assigned to a computerized cognitive intervention (mean age 12.21 ± 2.47 years, 4.97 ± 3.02 years off-treatment) or waitlist control group (mean age 11.82 ± 2.42 years, 5.04 ± 2.41 years off-treatment). Conners 3 Parent and Self-Report forms were completed pre-intervention, immediately post-intervention and six-months post-intervention. Piecewise linear mixed-effects models indicated no significant differences in Peer Relations between groups at baseline and no difference in change between groups from pre- to immediate post-intervention or post- to six-months post-intervention ( > 0.40). Baseline Family Relations problems were significantly elevated in the control group relative to the intervention group ( < 0.01), with a significantly greater decline from pre- to immediate post-intervention ( < 0.05) and no difference in change between groups from post- to six-months post-intervention ( > 0.80). The study results suggest cognitive gains from computerized training do not generalize to social functioning. Training focused on skill-based social processing (e.g., affect recognition) may be more efficacious.
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http://dx.doi.org/10.3390/children6100105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826733PMC
September 2019

The NIH Toolbox for cognitive surveillance in Duchenne muscular dystrophy.

Ann Clin Transl Neurol 2019 09 31;6(9):1696-1706. Epub 2019 Aug 31.

Center for Genetic Muscle Disorders, Kennedy Krieger Institute, Johns Hopkins School of Medicine, Baltimore, Maryland.

Objective: We performed a prospective, cross-sectional cognitive assessment in subjects with Duchenne Muscular Dystrophy (DMD) and their biological mothers.

Methods: Thirty subjects with out-of-frame mutations in the dystrophin (DMD) gene, and 25 biological mothers were evaluated using the National Institutes of Health Toolbox Cognition Battery (NIHTB-CB). A parent completed the Behavior Rating Inventory of Executive Functioning (BRIEF), a standardized rating scale of executive functioning, for their child. Mothers completed self-reports of BRIEF and Neuro Quality-of-Life (NeuroQoL) Cognitive Function.

Results: Overall, the subjects with DMD scored approximately one standard deviation (SD) below age-corrected norms on the NIHTB-CB Total Cognition score. They scored 1.5 SD below age-corrected norms in Fluid Cognition, which evaluates the cognitive domains of executive function, working memory, episodic memory, attention, and processing speed. Their performance was consistent with age expectations (i.e., within 1 SD below age-corrected norms) in Crystalized Cognition, which evaluates vocabulary and reading. Subjects with DMD had higher T-scores in several domains of BRIEF, demonstrating greater difficulty in executive functioning. The biological mothers had overall average or above average T-scores on NIHTB-CB. Mothers who were carriers of DMD mutation performed lower overall compared to mothers who were not carriers of DMD mutation (Cohen's d = -1.1). Carrier mothers performed lower than average (1.5 SD) in Executive Function, measured by Flanker Inhibitory Control and Attention. Biological mothers scored within expected score ranges for adults in BRIEF and NeuroQoL.

Interpretation: The NIHTB-CB, combined with standardized self-reported measures, can be a sensitive screening tool for cognitive surveillance in DMD.
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http://dx.doi.org/10.1002/acn3.50867DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6764624PMC
September 2019

Monitoring neurocognitive functioning in childhood cancer survivors: evaluation of CogState computerized assessment and the Behavior Rating Inventory of Executive Function (BRIEF).

BMC Psychol 2019 May 2;7(1):26. Epub 2019 May 2.

Yale University School of Medicine, 15 PO Box 208064, 16 333 Cedar Street, LMP-2073 (for courier mail), 17, New Haven, CT, 06520-8064, USA.

Background: Many childhood cancer survivors develop neurocognitive impairment, negatively affecting education and psychosocial functioning. Recommended comprehensive neuropsychological testing can be time- and cost- intensive for both institutions and patients and their families. It is important to find quick and easily administered surveillance measures to identify those in need of evaluation.

Methods: We evaluated, individually and in combination, the sensitivity and specificity of the 1) Behavior Rating Inventory of Executive Functioning-Metacognition Index (BRIEF-MCI), and 2) CogState Composite Index (computerized assessment of cognition) in identifying below grade-level performance on state-administered tests of reading and mathematics among childhood cancer survivors.

Results: The 45 participants (39% female) were a mean age of 7.1 ± 4.4 years at diagnosis, 14.0 ± 3.0 at evaluation, with a history of leukemia (58%), lymphoma (9%), central nervous system tumors (20%), and other tumors (13%). Impairment on the BRIEF-MCI was associated with low sensitivity (26% reading, 41% mathematics) but stronger specificity (88% reading, 96% mathematics). We found similar associations for the CogState Composite Index with sensitivity of 26% for reading and 29% for mathematics and specificity of 92% for both reading and mathematics. Combining the two measures did not improve sensitivity appreciably (47% reading, 59% mathematics) while reducing specificity (84% reading, 88% mathematics).

Conclusions: While individuals identified from the BRIEF-MCI or CogState Composite would likely benefit from a full neuropsychological evaluation given the strong specificity, use of these measures as screening tools is limited. With poor sensitivity, they do not identify many patients with academic difficulties and in need of a full neuropsychological evaluation. Continued effort is required to find screening measures that have both strong sensitivity and specificity.
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http://dx.doi.org/10.1186/s40359-019-0302-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6498488PMC
May 2019

Neurocognitive Outcomes and Interventions in Long-Term Survivors of Childhood Cancer.

J Clin Oncol 2018 07 6;36(21):2181-2189. Epub 2018 Jun 6.

Kevin R. Krull, St Jude Children's Research Hospital, Memphis, TN; Kristina K. Hardy, Children's National Medical Center, Washington, DC; Lisa S. Kahalley, Baylor College of Medicine; Shelli R. Kesler, University of Texas MD Anderson Cancer Center, Houston, TX; and Ilse Schuitema, Leiden University, Leiden, the Netherlands.

Recent research has demonstrated that survivors of childhood cancer are at risk for a myriad of late effects that affect physical and mental quality of life. We discuss the patterns and prevalence of neurocognitive problems commonly experienced by survivors of CNS tumors and acute lymphoblastic leukemia, the two most commonly researched cancer diagnoses. Research documenting the direct effects of tumor location and treatment type and intensity is presented, and patient characteristics that moderate outcomes (eg, age at diagnosis and sex) are discussed. Potential biologic mechanisms of neurotoxic treatment exposures, such as cranial irradiation and intrathecal and high-dose antimetabolite chemotherapy, are reviewed. Genetic, brain imaging, and neurochemical biomarkers of neurocognitive impairment are discussed. Long-term survivors of childhood cancer are also at risk for physical morbidity (eg, cardiac, pulmonary, endocrine) and problems with health behaviors (eg, sleep); research is reviewed that demonstrates these health problems contribute to neurocognitive impairment in survivors with or without exposure to neurotoxic therapies. We conclude this review with a discussion of literature supporting specific interventions that may be beneficial in the treatment of survivors who already experience neurocognitive impairment, as well as in the prevention of impairment manifestation.
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http://dx.doi.org/10.1200/JCO.2017.76.4696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6553837PMC
July 2018

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

J Pediatr Psychol 2018 09;43(8):882-894

Children's National Health System.

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.
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http://dx.doi.org/10.1093/jpepsy/jsy019DOI Listing
September 2018

Disseminability of computerized cognitive training: Performance across coaches.

Appl Neuropsychol Child 2019 Apr-Jun;8(2):113-122. Epub 2017 Nov 21.

b Department of Psychology , St. Jude Children's Research Hospital , Memphis , Tennessee.

Cogmed is a computerized cognitive intervention utilizing coaches who receive standardized instruction in analyzing training indices and tailoring feedback to remotely monitor participant's performance. The goal of this study was to examine adherence, satisfaction, and efficacy of Cogmed across coaches. Survivors of pediatric brain tumors and acute lymphoblastic leukemia (N = 68) were randomized to intervention (Cogmed) or waitlist control. The intervention group was matched with one of two coaches. Cognitive assessments were completed before and after intervention, and participants and caregivers in the intervention group completed satisfaction surveys. T-tests showed no differences in adherence across coaches (number of sessions completed p = .38; d = .32). Noninferiority statistics were not consistently equivalent for satisfaction, but equivalence was supported for caregiver perceptions of pragmatic utility and participant perceptions of logistical ease of Cogmed. Equivalence was not consistently suggested for cognitive outcomes, but was supported on measures tapping relevant cognitive domains (attention, working memory, processing speed, academic fluency). This study suggests adherence can be maintained across coaches. While aspects of satisfaction and cognitive outcomes were equivalent, the possible influence of coach-based variables cannot be ruled out. Findings highlight challenges in standardizing the coaching component of multicomponent computerized interventions and the need for ongoing research to establish dessiminability.
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http://dx.doi.org/10.1080/21622965.2017.1394853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5962364PMC
September 2019

Reply to I.J. Cohen.

J Clin Oncol 2017 12 18;35(35):3989-3991. Epub 2017 Oct 18.

Kristina K. Hardy, Children's National Medical Center, Washington, DC; Leanne M. Embry, University of Texas at San Antonio, San Antonio, TX; John A. Kairalla, University of Florida, Gainesville, FL; Shanjun Helian, Merck, Upper Gwynedd, PA; Meenakshi Devidas, University of Florida, Gainesville, FL; F. Daniel Armstrong, University of Miami, Miami, FL; Stephen Hunger, Children's Hospital of Philadelphia, Philadelphia, PA; William L. Carroll, New York University, New York, NY; Eric Larsen, Maine Children's Cancer Program, Scarborough, ME; Elizabeth A. Raetz, University of Utah, Salt Lake City, UT; Mignon L. Loh, University of California at San Francisco, San Francisco, CA; Wenjian Yang and Mary V. Relling, St Jude Children's Research Hospital and University of Tennessee, Memphis, TN; Robert B. Noll, University of Pittsburgh, Pittsburgh, PA; and Naomi Winick, University of Texas Southwestern, Dallas, TX.

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http://dx.doi.org/10.1200/JCO.2017.75.7252DOI Listing
December 2017

Attention-mediated neurocognitive profiles in survivors of pediatric brain tumors: comparison to children with neurodevelopmental ADHD.

Neuro Oncol 2018 04;20(5):705-715

Children's National Health System, Washington, DC.

Background: Attention and working memory symptoms are among the most common late effects in survivors of pediatric brain tumors, and are often associated with academic and psychosocial difficulties. Diagnostic and treatment approaches derived from the literature on attention-deficit hyperactivity disorder (ADHD) have frequently been applied to survivors, yet the extent of overlap in cognitive profiles between these groups is unclear. The objective of the present study is to compare neurocognition in survivors of brain tumors and children with neurodevelopmental ADHD.

Methods: Neuropsychological data were abstracted from clinically referred brain tumor survivors (n = 105, Mage = 12.0 y, 52.4% male) and children with ADHD (n = 178, Mage = 11.1 y, 64.0% male). Data consist of a battery of parent-report questionnaires and performance-based neuropsychological measures.

Results: Twenty-five survivors (23.8%) of pediatric brain tumors met symptom criteria for ADHD. Participants with neurodevelopmental ADHD and survivors who met ADHD criteria had significantly greater parent- (P < 0.001) and teacher-reported (P < 0.001) working memory and behavior regulation difficulties than survivors of tumor who did not meet criteria. Children with ADHD symptoms also performed worse on measures of sustained attention than survivors without ADHD symptoms (P < 0.001). Additionally, survivors with ADHD symptoms had greater performance-based working memory difficulties than either survivors without attention problems or children with neurodevelopmental ADHD (P = 0.002).

Conclusions: Nearly a quarter of survivors with attention symptoms have functional profiles that are similar to children with neurodevelopmental ADHD. They also experience more neurocognitive impairments than survivors without attentional difficulties, particularly in working memory. Screening for ADHD symptoms may help providers triage a subset of individuals in need of earlier or additional neuropsychological assessment.
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http://dx.doi.org/10.1093/neuonc/nox174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5892167PMC
April 2018

Neurocognitive Functioning of Children Treated for High-Risk B-Acute Lymphoblastic Leukemia Randomly Assigned to Different Methotrexate and Corticosteroid Treatment Strategies: A Report From the Children's Oncology Group.

J Clin Oncol 2017 Aug 3;35(23):2700-2707. Epub 2017 Jul 3.

Kristina K. Hardy, Children's National Medical Center, Washington, DC; Leanne Embry, The University of Texas Health Science Center at San Antonio, San Antonio; Naomi Winick, University of Texas Southwestern Medical Center, Dallas, TX; John A. Kairalla and Meenakshi Devidas, Colleges of Medicine, Public Health and Health Professions, University of Florida, Gainesville; Daniel Armstrong, University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL; Shanjun Helian, Merck, Upper Gwynedd; Stephen Hunger, Children's Hospital of Philadelphia, Philadelphia; Robert B. Noll, University of Pittsburgh School of Medicine, Pittsburgh, PA; William L. Carroll, New York University Medical Center, New York, NY; Eric Larsen, Maine Children's Cancer Program, Scarborough, ME; Elizabeth A. Raetz, University of Utah, Salt Lake City, UT; Mignon L. Loh, University of California, San Francisco, San Francisco, CA; and Wenjian Yang and Mary V. Relling, St Jude Children's Research Hospital; University of Tennessee Health Science Center, Memphis, TN.

Purpose Survivors of childhood acute lymphoblastic leukemia (ALL) are at risk for neurocognitive deficits that are associated with treatment, individual, and environmental factors. This study examined the impact of different methotrexate (MTX) and corticosteroid treatment strategies on neurocognitive functioning in children with high-risk B-lineage ALL. Methods Participants were randomly assigned to receive high-dose MTX with leucovorin rescue or escalating dose MTX with PEG asparaginase without leucovorin rescue. Patients were also randomly assigned to corticosteroid therapy that included either dexamethasone or prednisone. A neurocognitive evaluation of intellectual functioning (IQ), working memory, and processing speed (PS) was conducted 8 to 24 months after treatment completion (n = 192). Results The method of MTX delivery and corticosteroid assignment were unrelated to differences in neurocognitive outcomes after controlling for ethnicity, race, age, gender, insurance status, and time off treatment; however, survivors who were age < 10 years at diagnosis (n = 89) had significantly lower estimated IQ ( P < .001) and PS scores ( P = .02) compared with participants age ≥ 10 years. In addition, participants who were covered by US public health insurance had estimated IQs that were significantly lower ( P < .001) than those with US private or military insurance. Conclusion Children with high-risk B-lineage ALL who were age < 10 years at diagnosis are at risk for deficits in IQ and PS in the absence of cranial radiation, regardless of MTX delivery or corticosteroid type. These data may serve as a basis for developing screening protocols to identify children who are at high risk for deficits so that early intervention can be initiated to mitigate the impact of therapy on neurocognitive outcomes.
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http://dx.doi.org/10.1200/JCO.2016.71.7587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5549456PMC
August 2017

Computerized cognitive training for children with neurofibromatosis type 1: A pilot resting-state fMRI study.

Psychiatry Res Neuroimaging 2017 Aug 6;266:53-58. Epub 2017 Jun 6.

Department of Pediatrics and Neurology, George Washington University, School of Medicine, Washington, DC, USA; Children's National Health System, Washington, DC, USA. Electronic address:

In this pilot study, we examined training effects of a computerized working memory program on resting state functional magnetic resonance imaging (fMRI) measures in children with neurofibromatosis type 1 (NF1). We contrasted pre- with post-training resting state fMRI and cognitive measures from 16 participants (nine males; 11.1 ± 2.3 years) with NF1 and documented working memory difficulties. Using non-parametric permutation test inference, we found significant regionally specific differences (family-wise error corrected) in two of four voxel-wise resting state measures: fractional amplitude of low frequency fluctuations (indexing peak-to-trough intensity of spontaneous oscillations) and regional homogeneity (indexing local intrinsic synchrony). Some cognitive task improvement was observed as well. These preliminary findings suggest that regionally specific changes in resting state fMRI indices may be associated with treatment-related cognitive amelioration in NF1. Nevertheless, current results must be interpreted with caution pending independent controlled replication.
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http://dx.doi.org/10.1016/j.pscychresns.2017.06.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5582983PMC
August 2017

The Flexibility Scale: Development and Preliminary Validation of a Cognitive Flexibility Measure in Children with Autism Spectrum Disorders.

J Autism Dev Disord 2017 08;47(8):2502-2518

Center for Autism Spectrum Disorders, Children's National Health System, Washington, DC, USA.

Flexibility is a key component of executive function, and is related to everyday functioning and adult outcomes. However, existing informant reports do not densely sample cognitive aspects of flexibility; the Flexibility Scale (FS) was developed to address this gap. This study investigates the validity of the FS in 221 youth with ASD and 57 typically developing children. Exploratory factor analysis indicates a five-factor scale: Routines/rituals, transitions/change, special interests, social flexibility, and generativity. The FS demonstrated convergent and divergent validity with comparative domains of function in other measures, save for the Generativity factor. The FS discriminated participants with ASD and controls. Thus, this study suggests the FS may be a viable, comprehensive measure of flexibility in everyday settings.
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http://dx.doi.org/10.1007/s10803-017-3152-yDOI Listing
August 2017

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

J Pediatr Psychol 2017 09;42(8):815-822

Division of Neuropsychology, Center for Neuroscience and Behavioral Medicine, Children's National Health System.

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.
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http://dx.doi.org/10.1093/jpepsy/jsx060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328686PMC
September 2017

Neurocognitive outcomes in neurofibromatosis clinical trials: Recommendations for the domain of attention.

Neurology 2016 Aug;87(7 Suppl 1):S21-30

From the Children's National Health System (K.S.W., K.K.H.), The George Washington School of Medicine, Washington, DC; Children's Hospital Colorado (J.J.), University of Colorado School of Medicine, Aurora; Pediatric Oncology Branch (P.L.W., S.M.), National Cancer Institute, Bethesda, MD; University of Wisconsin-Milwaukee (B.P.K.-T.); Clinical Research Directorate/Clinical Monitoring Research Program (M.A.T.-T.), Leidos Biomedical Research, Inc., NCI at Frederick, MD; California State University (H.L.T.), Sacramento; Murdoch Children's Research Institute (J.M.P.), Victoria, Australia; Rainbow Babies & Children's Hospital (P.d.B.), Cleveland, OH; Roosevelt University (C.S.), Chicago, IL; Boston Children's Hospital (L.S.G., N.U.), MA; and University of Vermont (S.E.S.), Burlington.

Neurofibromatosis type 1 (NF1) is associated with neurocognitive deficits that can impact everyday functioning of children, adolescents, and adults with this disease. However, there is little agreement regarding measures to use as cognitive endpoints in clinical trials. This article describes the work of the Neurocognitive Committee of the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration. The goal of this committee is to identify standardized and specific cognitive assessment tools for use in NF clinical trials. The committee first identified cognitive domains relevant to NF1 and prioritized attention as the first domain of focus given prior and current trends in NF1 cognitive clinical trials. Performance measures and behavioral rating questionnaires of attention were reviewed by the group using established criteria to assess patient characteristics, psychometric properties, and feasibility. The highest rated tests underwent side-by-side comparison. The Digit Span subtest from the Wechsler scales was given the highest ratings of the performance measures due to its good psychometrics, feasibility, utility across a wide age range, and extensive use in previous research. The Conners scales achieved the highest ratings of the behavioral questionnaires for similar reasons. Future articles will focus on other cognitive domains, with the ultimate goal of achieving agreement for cognitive endpoints that can be used across NF clinical trials.
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http://dx.doi.org/10.1212/WNL.0000000000002928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5578356PMC
August 2016

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

J Pediatr Psychol 2017 Mar;42(2):220-231

Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN, USA.

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 β  = -.04 to .01, p = .26 to .95; control β  = -.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.
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http://dx.doi.org/10.1093/jpepsy/jsw057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5896595PMC
March 2017

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

Pediatr Blood Cancer 2016 09 26;63(9):1578-85. Epub 2016 May 26.

Children's National Health System, Washington, District of Columbia.

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.
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http://dx.doi.org/10.1002/pbc.26019DOI Listing
September 2016

Feasibility and acceptability of a remotely administered computerized intervention to address cognitive late effects among childhood cancer survivors.

Neurooncol Pract 2015 Jun 13;2(2):78-87. Epub 2015 Mar 13.

Department of Psychology , St Jude Children's Research Hospital , Memphis, Tennessee (L.E.C., J.M.A., K.N.C., K.M-E., V.W.W., H.M.C.); Division of Radiation Oncology , St. Jude Children's Research Hospital, Memphis, Tennessee (T.E.M.); Division of Translational Imaging Research , St Jude Children's Research Hospital , Memphis, Tennessee (R.J.O.); Department of Oncology , St Jude Children's Research Hospital , Memphis, Tennessee (S.J.); Department of Biostatistics , St Jude Children's Research Hospital , Memphis, Tennessee (L.H., H.Z.); Center for Neuroscience and Behavioral Medicine , Neuropsychology Division, Children's National Medical Center , Washington, DC (K.K.H.); Department of Psychiatry and Behavioral Science , George Washington University School of Medicine , Washington, DC (K.K.H).

Background: Childhood cancer survivors frequently develop working memory (WM) deficits as a result of disease and treatment. Medication-based and therapist-delivered interventions are promising but have limitations. Computerized interventions completed at home may be more appealing for survivors. We evaluated the feasibility and acceptability of a remotely administered, computerized WM intervention (Cogmed) for pediatric cancer survivors using a single-blind, randomized, wait-list control design.

Methods: Of 80 qualifying patients, 12 were excluded or declined to participate. Participants randomized to intervention ( = 34/68) included survivors of childhood brain tumors (32%) or acute lymphoblastic leukemia (ALL; 68%) between the ages of 8 and 16 years ([Formula: see text] = 12.2) who were at least 1 year post therapy ([Formula: see text] = 5.0). The majority of brain tumor participants were treated with cranial radiation therapy (72.7%), whereas most of the ALL participants were treated with chemotherapy only (87%). Participants completed 25 WM training sessions over 5-9 weeks at home with weekly phone-based coaching.

Results: Participants lived in 16 states. Compliance was strong, with 30 of the 34 participants (88%) completing intervention. Almost all participants completed pre- and postintervention neuroimaging exams (91% and 93%, respectively). Families had the necessary skills to utilize the computer program successfully. Caregivers reported they were generally able to find time to complete training (63%), viewed training as beneficial (70%), and would recommend this intervention to others (93%).

Conclusions: Cogmed is a feasible and acceptable intervention for childhood cancer survivors. It is a viable option for survivors who do not live in close proximity to cancer care centers. Efficacy and neural correlates of change are currently being evaluated.
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http://dx.doi.org/10.1093/nop/npu036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4820841PMC
June 2015

Benefit Finding in Maternal Caregivers of Pediatric Cancer Survivors: A Mixed Methods Approach.

J Pediatr Oncol Nurs 2016 09 25;33(5):353-60. Epub 2016 Jan 25.

Children's National Health System, Washington, DC, USA George Washington University School of Medicine, Washington, DC, USA

Objective: Benefit finding has been described as the identification of positive effects resulting from otherwise stressful experiences. In this mixed methods study, we examined the relations between qualitative themes related to benefit finding and quantitative measures of psychosocial adjustment and coping as reported by maternal caregivers of survivors of pediatric cancer.

Methods: Female caregivers of survivors of pediatric cancer (n = 40) completed a qualitative questionnaire about their experiences caring for their child, along with several quantitative measures. Qualitative questionnaires were coded for salient themes, including social support and personal growth. Correlation matrices evaluated associations between qualitative themes and quantitative measures of stress and coping.

Results: Identified benefits included social support and personal growth, as well as child-specific benefits. Total benefits reported were significantly positively correlated with availability of emotional resources. Coping methods were also associated, with accepting responsibility associated with fewer identified benefits.

Conclusion: Despite the stress of their child's illness, many female caregivers of survivors of pediatric cancer reported finding benefits associated with their experience. Benefit finding in this sample was associated with better adjustment.
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http://dx.doi.org/10.1177/1043454215620119DOI Listing
September 2016

Computerized Cognitive Training for Amelioration of Cognitive Late Effects Among Childhood Cancer Survivors: A Randomized Controlled Trial.

J Clin Oncol 2015 Nov 12;33(33):3894-902. Epub 2015 Oct 12.

Heather M. Conklin, Robert J. Ogg, Jason M. Ashford, Matthew A. Scoggins, Ping Zou, Kellie N. Clark, Karen Martin-Elbahesh, Thomas E. Merchant, Sima Jeha, Lu Huang, and Hui Zhang, St Jude Children's Research Hospital, Memphis, TN; and Kristina K. Hardy, Children's National Medical Center and George Washington University School of Medicine, Washington, DC.

Purpose: Children receiving CNS-directed therapy for cancer are at risk for cognitive problems, with few available empirically supported interventions. Cognitive problems indicate neurodevelopmental disruption that may be modifiable with intervention. This study evaluated short-term efficacy of a computerized cognitive training program and neural correlates of cognitive change.

Patient And Methods: A total of 68 survivors of childhood acute lymphoblastic leukemia (ALL) or brain tumor (BT) with identified cognitive deficits were randomly assigned to computerized cognitive intervention (male, n = 18; female, n = 16; ALL, n = 23; BT, n = 11; mean age ± standard deviation, 12.21 ± 2.47 years) or waitlist (male, n = 18; female, n = 16; ALL, n = 24; BT, n = 10; median age ± standard deviation, 11.82 ± 2.42 years). Intervention participants were asked to complete 25 training sessions at home with weekly, telephone-based coaching. Cognitive assessments and functional magnetic resonance imaging scans (intervention group) were completed pre- and postintervention, with immediate change in spatial span backward as the primary outcome.

Results: Survivors completing the intervention (n = 30; 88%) demonstrated greater improvement than controls on measures of working memory (mean ± SEM; eg, Wechsler Intelligence Scale for Children [fourth edition; WISC-IV] spatial span backward, 3.13 ± 0.58 v 0.75 ± 0.43; P = .002; effect size [ES], 0.84), attention (eg, WISC-IV spatial span forward, 3.30 ± 0.71 v 1.25 ± 0.39; P = .01; ES, 0.65), and processing speed (eg, Conners' Continuous Performance Test hit reaction time, -2.10 ± 1.47 v 2.54 ± 1.25; P = .02; ES, .61) and showed greater reductions in reported executive dysfunction (eg, Conners' Parent Rating Scale III, -6.73 ± 1.51 v 0.41 ± 1.53; P = .002; ES, 0.84). Functional magnetic resonance imaging revealed significant pre- to post-training reduction in activation of left lateral prefrontal and bilateral medial frontal areas.

Conclusion: Study findings show computerized cognitive training is feasible and efficacious for childhood cancer survivors, with evidence for training-related neuroplasticity.
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http://dx.doi.org/10.1200/JCO.2015.61.6672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4652013PMC
November 2015

Psychosocial and Neurocognitive Outcomes in Adult Survivors of Adolescent and Early Young Adult Cancer: A Report From the Childhood Cancer Survivor Study.

J Clin Oncol 2015 Aug 6;33(23):2545-52. Epub 2015 Jul 6.

Pinki K. Prasad, Louisiana State University School of Medicine, New Orleans, LA; Kristina K. Hardy, Children's National Medical Center, Washington, DC; Nan Zhang, Deokumar Srivastava, Gregory T. Armstrong, Leslie L. Robison, and Kevin Krull, St Jude Children's Research Hospital, Memphis, TN; Lonnie Zeltzer, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA; Marilyn Stovall, The University of Texas MD Anderson Cancer Center, Houston, TX; Nita L. Seibel, Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD; Wendy Leisenring, Fred Hutchinson Cancer Research Center, Seattle, WA; and Kim Edelstein, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.

Purpose: To characterize psychological and neurocognitive function in long-term cancer survivors diagnosed during adolescence and early young adulthood (AeYA).

Methods: Six thousand one hundred ninety-two survivors and 390 siblings in the Childhood Cancer Survivor Study completed the Brief Symptom Inventory-18 and a Neurocognitive Questionnaire. Treatment and demographic predictors were examined, and associations with social attainment (employment, education, and living independently) were evaluated. Logistic regression models were used to compute odds ratios (ORs) and corresponding 95% CIs.

Results: Among survivors, 2,589 were diagnosed when AeYA (11 to 21 years old). Adjusted for current age and sex, these survivors, compared with siblings, self-reported higher rates of depression (11.7% v 8.0%, respectively; OR, 1.55; 95% CI, 1.04 to 2.30) and anxiety (7.4% v 4.4%, respectively; OR, 2.00; 95% CI, 1.17 to 3.43) and more problems with task efficiency (17.2% v 10.8%, respectively; OR, 1.72; 95% CI, 1.21 to 2.43), emotional regulation (19.1% v 14.1%, respectively; OR, 1.74; 95% CI, 1.26 to 2.40), and memory (25.9% v 19.0%, respectively; OR, 1.44; 95% CI, 1.09 to 1.89). Few differences were noted between survivors diagnosed with leukemia or CNS tumor before 11 years old versus during later adolescence, although those diagnosed with lymphoma or sarcoma during AeYA were at reduced risk for self-reported psychosocial and neurocognitive problems. Unemployment was associated with self-reports of impaired task efficiency (OR, 2.93; 95% CI, 2.28 to 3.77), somatization (OR, 2.29; 95% CI, 1.77 to 2.98), and depression (OR, 1.94; 95% CI, 1.43 to 2.63).

Conclusion: We demonstrated that risk for poor functional outcome is not limited to survivors' diagnoses in early childhood. AeYA is a critical period of development, and cancer during this period can impact neurocognitive and emotional function and disrupt vocational attainment.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4525049PMC
http://dx.doi.org/10.1200/JCO.2014.57.7528DOI Listing
August 2015

The potential utility of parent-reported attention screening in survivors of childhood cancer to identify those in need of comprehensive neuropsychological evaluation.

Neurooncol Pract 2015 Mar 12;2(1):32-39. Epub 2014 Dec 12.

Center for Neuroscience and Behavioral Medicine, Neuropsychology Division, Children's National Medical Center, Department of Psychiatry & Behavioral Medicine, George Washington University School of Medicine , Washington, DC (K.K.H.); Department of Psychology & Neuroscience , Duke University, Durham, North Carolina (currently affiliated with Department of Psychology, St. Jude Children's Research Hospital, Memphis, Tennessee) (V.W.W., A.B.W., T.M.A.); Departments of Psychiatry and Surgery, Duke University Medical Center, Department of Psychology & Neuroscience , Duke University , Durham, North Carolina (M.J.B.).

Background: Survivors of childhood cancer are at risk for neuropsychological late effects, yet identifying those in need of evaluation and obtaining needed services can be challenging for the medical team. Finding time- and cost-effective screening measures that can be used to identify children in need of evaluation is a clinical priority. Our objective was to investigate the association between parent-rated attention problems and related neuropsychological impairments in childhood cancer survivors as a means of identifying those at high risk for difficulties.

Methods: Cognitive and psychosocial data of survivors who completed neuropsychological evaluations were retrospectively abstracted. Parents of 70 survivors of pediatric cancer (mean age, 11.6 years) completed the Conners Parent Rating Scale and the Child Behavior Checklist. Children also completed a measure of intellectual functioning. The 18 symptoms of inattention and hyperactivity were abstracted from the Conners questionnaire, and participants were classified according to whether or not they met attention deficit/hyperactivity disorder (ADHD) symptom criteria (≥6 inattentive symptoms).

Results: Survivors who met symptom criteria for ADHD (27%) demonstrated greater impairments in IQ and working memory, but not processing speed, than survivors who did not. Meeting ADHD symptom criteria was also associated with greater externalizing and social problems but not more internalizing symptoms. ADHD symptom screening was associated with low sensitivity (range = 26.3%-69.2%) but stronger specificity (range = 75.0%-82.7%) for neuropsychological difficulties.

Conclusion: Parental ratings of attentional symptoms may be a useful way to screen survivors who may be in need of a full neuropsychological assessment.
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http://dx.doi.org/10.1093/nop/npu026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4369708PMC
March 2015

Characterizing the factor structure of parent reported executive function in autism spectrum disorders: the impact of cognitive inflexibility.

J Autism Dev Disord 2014 Dec;44(12):3056-62

Children's National Medical Center, 15245 Shady Grove Road, Suite 350, Rockville, MD, 20850, USA,

Parents of children with autism spectrum disorders (ASD) consistently report executive functioning (EF) deficits. This study investigates the factor structure of the Behavior Rating Inventory of Executive Function (BRIEF) as reported by parents of children with ASD and typically developing children (TDC). BRIEFs for 411 children with ASD and 467 TDC were examined. Confirmatory factor analysis of a nine-factor model met thresholds for goodness-of-fit in TDC, but not in the ASD sample. We found globally elevated EF problems in the ASD sample, especially on the Shift scale. These findings confirm that children with ASD exhibit significant EF deficits. Further investigation is needed to understand the pervasive nature of cognitive inflexibility in children with ASD.
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http://dx.doi.org/10.1007/s10803-014-2169-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6084425PMC
December 2014

Prevalence and clinical significance of night eating syndrome in university students.

J Adolesc Health 2014 Jul 31;55(1):41-8. Epub 2014 Jan 31.

The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. Electronic address:

Purpose: Most studies of night eating syndrome (NES) fail to control for binge eating, despite moderate overlap between the two conditions. Establishing the independent clinical significance of NES is imperative for it to be considered worthy of clinical attention. We compared students with and without NES on eating disorder symptomatology, quality of life, and mental health, while exploring the role of binge eating in associations.

Methods: Students (N = 1,636) ages 18-26 years (M = 20.9) recruited from 10 U.S. universities completed an online survey including the Night Eating Questionnaire (NEQ), Eating Disorder Examination-Questionnaire (EDE-Q), Project Eating Among Teens, and the Health-Related Quality of Life-4. NES was diagnosed according to endorsement of proposed diagnostic criteria on the NEQ. Groups (NES vs. non-NES) were compared on all dependent variables and stratified by binge eating status in secondary analyses.

Results: The prevalence of NES in our sample was 4.2%; it decreased to 2.9% after excluding those with binge eating. Body mass index did not differ between groups, but students with NES were significantly more likely to have histories of underweight and anorexia nervosa. In students with NES, EDE-Q scores were significantly higher; purging, laxative use, and compulsive exercise were more frequent; quality of life was reduced; and histories of depression, attention-deficit/hyperactivity disorder, and self-injury were more common. Binge eating did not account for all of these differences; the presence of it and NES was associated with additive risk for psychopathology on some items.

Conclusions: NES may be a distinct clinical entity from other DSM-5 eating disorders.
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http://dx.doi.org/10.1016/j.jadohealth.2013.11.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4065810PMC
July 2014

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

J Neurooncol 2014 Jan 7;116(2):341-7. Epub 2013 Nov 7.

Department of Neurology, Children's National Medical Center, 111 Michigan Ave, NW, Washington, DC, 20010, USA,

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.
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http://dx.doi.org/10.1007/s11060-013-1300-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3947291PMC
January 2014

The Eating Disorder Examination Questionnaire (EDE-Q) among university men and women at different levels of athleticism.

Eat Behav 2013 Aug 28;14(3):378-81. Epub 2013 Apr 28.

Child and Adolescent Psychiatry, Stanford University School of Medicine, Department of Psychiatry and Behavioral Sciences, Stanford, CA 94305, USA.

The aim of the current study was to establish norms for the Eating Disorder (ED) Examination Questionnaire (EDE-Q) among competitive athletes and to explore the contribution of level of athletic involvement and gender to ED psychopathology, as measured by the EDE-Q. University students (n = 1637) from ten United States universities were recruited online via a social networking website and asked to complete an anonymous survey. The sample was then divided according to gender and level of sports participation. Females scored higher than males regardless of level of athleticism. Lower mean scores were frequently observed among those involved in competitive sports exclusively and highest scores among those involved in recreational sports (alone or in addition to competitive athletics). Recreational activity seems to be important in stratifying risk among competitive athletes; gender is an important interaction term in athletic populations.
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http://dx.doi.org/10.1016/j.eatbeh.2013.04.002DOI Listing
August 2013