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Introduction The mucopolysaccharidoses (MPSs) are a group of rare genetic lysosomal disorders with progressive multisystem involvement. An MPS-specific physical symptom scale was developed and introduced a Physical Symptom Score (PSS) to quantify the somatic disease burden across MPS I, II and VI. Hypothesis Somatic burden of disease in patients with attenuated MPS I, II and VI as measured by the PSS will be positively associated with age and negatively associated with neuropsychological functions [i.e. full scale intelligence quotient (FSIQ) and attention]. Materials and methods Forty-eight patients with attenuated MPS I (n = 24), II (n = 14), and VI (n = 10) aged 6 to 32 years on enzyme replacement therapy who were enrolled in “Longitudinal Studies of Brain Structure and Functions in MPS Disorders” across seven centers. Somatic disease burden was measured by the PSS. Neuropsychological functions were measured by the Wechsler Abbreviated Scale of Intelligence (WASI) and Test of Variables of Attention (TOVA). Results PSS was positively associated with age in attenuated MPS I (P, Highlights • MPS-specific physical symptom scale introduced a Physical Symptom Score (PSS) by quantifying the somatic disease burden • PSS was significantly positively associated with age in attenuated MPS I, MPS II and MPS VI • PSS was significantly negatively associated with Full Scale IQ (FSIQ) in attenuated MPS I and in MPS VI • PSS was not statistically significantly associated with FSIQ in MPS II, but had similar direction as other two groups • • There were no previous studies that examined the association of PSS in MPS disorders with neuropsychological functions

Objectives: The behavioral, adaptive and quality of life characteristics of attenuated mucopolysaccharidosis type II (MPS II) have not been well studied. Understanding changes over time in the attenuated phenotype may assist in helping achieve better outcomes in long-term function. This longitudinal study investigates these outcomes in relation to age, somatic disease burden, and IQ. Specifically, somatic disease burden is a major challenge for these patients, even with treatment with enzyme replacement therapy. Methods: 15 patients, 10 between ages 6 and

BACKGROUND The months immediately after the completion of treatment for childhood acute lymphoblastic leukemia (ALL) are often regarded as a stressful time for children and families. In this prospective, longitudinal study, the prevalence and predictors of anxiety and depressive symptoms after the completion of treatment were examined. METHODS Participants included 160 children aged 2 to 9 years with standard-risk ALL who were enrolled on Children's Oncology Group protocol AALL0331. Parents completed standardized rating scales of their children's emotional-behavioral functioning and measures of coping and family functioning at approximately 1 month, 6 months, and 12 months after diagnosis and again 3 months after the completion of chemotherapy. RESULTS At 3 months off therapy, approximately 24% of survivors had at-risk/clinically elevated anxiety scores and 28% had elevated depression scores, which are significantly higher than the expected 15% in the general population (P = .028 and .001, respectively). Patients with elevated anxiety 1 month after diagnosis were at greater risk of off-therapy anxiety (odds ratio, 4.1; 95% confidence interval, 1.31-12.73 [P = .022]) and those with elevated depressive symptoms 6 months after diagnosis were at greater risk of off-therapy depression (odds ratio, 7.88; 95% confidence interval, 2.61-23.81 [P = .0002]). In adjusted longitudinal analyses, unhealthy family functioning (P = .008) and less reliance on social support coping (P = .009) were found to be associated with risk of emotional distress. Children from Spanish-speaking families (P = .05) also were found to be at a greater risk of distress. CONCLUSIONS A significant percentage of children experience emotional distress during and after therapy for ALL. These data provide a compelling rationale for targeted early screening and psychosocial interventions to support family functioning and coping skills. Cancer 2016;122:1608–17. © 2015 American Cancer Society.

Behavioral weight loss programs help people achieve clinically meaningful weight losses (8–10% of starting body weight). Despite data showing that only half of participants achieve this goal, a “one size fits all” approach is normative. This weight loss intervention science gap calls for adaptive interventions that provide the “right treatment at the right time for the right person.” Sequential Multiple Assignment Randomized Trials (SMART), use experimental design principles to answer questions for building adaptive interventions including whether, how, or when to alter treatment intensity, type, or delivery. This paper describes the rationale and design of the BestFIT study, a SMART designed to evaluate the optimal timing for intervening with sub-optimal responders to weight loss treatment and relative efficacy of two treatments that address self-regulation challenges which impede weight loss: 1) augmenting treatment with portion-controlled meals (PCM) which decrease the need for self-regulation; and 2) switching to acceptance-based behavior treatment (ABT) which boosts capacity for self-regulation. The primary aim is to evaluate the benefit of changing treatment with PCM versus ABT. The secondary aim is to evaluate the best time to intervene with sub-optimal responders. BestFIT results will lead to the empirically-supported construction of an adaptive intervention that will optimize weight loss outcomes and associated health benefits.

OBJECTIVE: To prospectively examine the bidirectional relationship between parental feeding practices (eg, instrumental feeding, encouragement to eat) and child eating behaviors (eg, food responsiveness, emotional eating) in low-income, ethnically diverse preschool children over a 3-year period. STUDY DESIGN: Parent/child (age 2–4 years at baseline) pairs (n = 222 non-Hispanics; n = 312 Hispanics) participated in NET-Works (Now Everybody Together for Amazing and Healthful Kids), a randomized controlled trial carried out in community and in-home settings in urban areas of Minnesota. Data were collected at baseline and 12, 24, and 36 months. The present study is a secondary data analysis using cross-lagged models to identify bidirectional associations between parental feeding practices and child eating behaviors. RESULTS: Three models showed significant cross-lagged effects (P < .05): model 1, parental instrumental feeding influencing later child food responsiveness; model 2, parental emotional feeding influencing later child food responsiveness; and model 3, parental emotional feeding influencing later child eating satiety. Model 1 showed significant bidirectional temporal paths, whereas models 2 and 3 showed significant unidirectional temporal paths from parental feeding practices to child eating behaviors. CONCLUSIONS: Parental instrumental and emotional feeding practices prospectively influence child food responsiveness and satiety. This study demonstrates causal temporality between parental feeding practices and child eating behaviors. Heath care providers may want to use findings regarding parent feeding practices as part of their anticipatory guidance during well-child visits with parents of preschoolers.

SUMMARY: BACKGROUND: Pediatric primary care is an important setting for addressing obesity prevention. OBJECTIVE: The Healthy Homes/Healthy Kids 5‐10 randomized controlled trial evaluated the efficacy of an obesity prevention intervention integrating pediatric primary care provider counseling and parent‐targeted phone coaching. METHODS: Children aged 5 to 10 years with a BMI between the 70th and 95th percentile and their parents were recruited from pediatric primary care clinics. Participants received well‐child visit provider counseling about obesity and safety/injury prevention and were then randomized to a 14‐session phone‐based obesity prevention (OP; n = 212) or safety and injury prevention contact control (CC; n = 209) intervention. The primary outcome was 12 and 24‐month child BMI percentile. RESULTS: There was no overall significant treatment effect on child BMI percentile. Caloric intake was significantly lower among OP compared with CC participants at 12 months (P < .005). In planned subgroup analyses, OP condition girls had significantly lower BMI percentile (P < .05) and BMI z‐score (P < .02) at 12 and 24 months relative to CC girls and were less likely to be overweight (38.0% vs 53.0%, P < .01) or (obese 3.4% vs 8.8%, P < .10) at follow‐up. CONCLUSIONS AND RELEVANCE: An obesity prevention intervention integrating brief provider counseling and parent‐targeted phone counseling did not impact 12 and 24‐month BMI status overall but did have a significant impact on BMI in girls.

Objectives. To evaluate a multicomponent obesity prevention intervention among diverse, low-income preschoolers. Methods. Parent-child dyads (n = 534) were randomized to the Now Everybody Together for Amazing and Healthful Kids (NET-Works) intervention or usual care in Minneapolis, MN (2012-2017). The intervention consisted of home visits, parenting classes, and telephone check-ins. The primary outcomes were adjusted 24- and 36-month body mass index (BMI). Results. Compared with usual care, the NET-Works intervention showed no significant difference in BMI change at 24 (-0.12 kg/m2; 95% confidence interval [CI] = -0.44, 0.19) or 36 months (-0.19 kg/m2; 95% CI = -0.64, 0.26). Energy intake was significantly lower in the NET-Works group at 24 (-90 kcal/day; 95% CI = -164, -16) and 36 months (-101 kcal/day; 95% CI = -164, -37). Television viewing was significantly lower in the NET-Works group at 24 (rate ratio = 0.84; 95% CI = 0.75, 0.93) and 36 months (rate ratio = 0.88; 95% CI = 0.78, 0.99). Children with baseline overweight or obesity had lower BMI in the NET-Works group than those in usual care at 36 months (-0.71 kg/m2; 95% CI = -1.30, -0.12). Hispanic children had lower BMI in the NET-Works group than those in usual care at 36 months (-0.59 kg/m2; 95% CI = -1.14, -0.04). Conclusions. In secondary analyses, NET-Works significantly reduced BMI over 3 years among Hispanic children and children with baseline overweight or obesity. Trial Registration: ClinicalTrials.gov Identifier: NCT01606891.

Objective This study examined cancer knowledge in adolescent and young adult (AYA) survivors and pilot tested a Web-based resource to provide individually tailored information regarding cancer treatment history, late effects risk, and resources. Methods Fifty-two survivors (15–28 years old) who completed cancer treatment were recruited from the University of Minnesota oncology clinics. Participants were randomly assigned to receive access to personalized health history, late effects information, and resources via a password-protected Web portal or to standard of care (physician counseling) only. Participants completed surveys measuring cancer knowledge, health locus of control, and psychosocial well-being prior to randomization and approximately 1 year later. Results Overall, few participants accurately reported their chemotherapy history with detail (19% at baseline and 33% at follow-up), and many did not recognize that previous cancer treatments could impact future health (60% at baseline and 54% at follow-up). Among those randomized to the receive access to the website, utilization was very low, making it difficult to draw conclusions about efficacy. Nonetheless, these data suggest that offering tailored information through the Web was not more effective than standard of care at improving cancer knowledge. Anxiety and health beliefs were associated with cancer knowledge, including knowledge of steps survivors could take to mitigate late effects risks (p

Background A better understanding of the optimal “dose” of behavioral interventions to affect change in weight-related outcomes is a critical topic for childhood obesity intervention research. The objective of this review was to quantify the relationship between dose and outcome in behavioral trials targeting childhood obesity to guide future intervention development. Methods A systematic review and meta-regression included randomized controlled trials published between 1990 and June 2017 that tested a behavioral intervention for obesity among children 2–18 years old. Searches were conducted among PubMed (Web-based), Cumulative Index to Nursing and Allied Health Literature (EBSCO platform), PsycINFO (Ovid platform) and EMBASE (Ovid Platform). Two coders independently reviewed and abstracted each included study. Dose was extracted as intended intervention duration, number of sessions, and length of sessions. Standardized effect sizes were calculated from change in weight-related outcome (e.g., BMI-Z score). Results Of the 258 studies identified, 133 had sufficient data to be included in the meta-regression. Average intended total contact (# sessions x length of sessions) was 27.7 (SD 32.2) hours and average duration was 26.0 (SD 23.4) weeks. When controlling for study covariates, a random-effects meta-regression revealed no significant association between contact hours, intended duration or their interaction and effect size. Conclusions This systematic review identified wide variation in the dose of behavioral interventions to prevent and treat pediatric obesity, but was unable to detect a clear relationship between dose and weight-related outcomes. There is insufficient evidence to provide quantitative guidance for future intervention development. One limitation of this review was the ability to uniformly quantify dose due to a wide range of reporting strategies. Future trials should report dose intended, delivered, and received to facilitate quantitative evaluation of optimal dose. Trial registrations The protocol was registered on PROSPERO (Registration #CRD42016036124). Electronic supplementary material The online version of this article (10.1186/s12966-017-0615-7) contains supplementary material, which is available to authorized users.

Figure S1. Forest plot demonstrating a visual representation of the variability in standardized effect size. Table S1. Dose of behavioral intervention and intervention characteristics by study and a full reference list of all studies reviewed. Table provides details of all articles reviewed in this meta-regression. Table S2. Meta-regression evaluating the relationship between dose and standardized effect size stratified by study characteristics. (PDF 1938 kb)

Childhood obesity in the United States is a significant public health concern. Prevalence estimates from 2009-2010 indicate that approximately 17% of U.S. children ages 2-19 are obese and 15% are overweight.1 Obesity is associated with multiple health comorbidities in childhood and adolescence, including type 2 diabetes,2,3 hypertension,2-4 and weight-related stigma.5 The negative health effects of obesity extend beyond childhood; children who are overweight or obese are at a greater risk for obesity and its health consequences in adulthood.6 The health risks associated with obesity and its high prevalence among U.S. children highlight the need for obesity prevention efforts. Parents are key partners in efforts to prevent childhood obesity, given their influence on multiple risk factors for overweight and obesity in children. Parent-level factors, such as encouraging child physical activity (PA),7 and setting rules about child TV use,8 and modeling of healthy eating behaviors9,10 are among the determinants of child PA level, media use, and dietary intake, all of which affect a child’s risk of obesity. Parental recognition of and concern about child weight status are other factors that may influence children’s weight status. Interestingly, there is a lack of concordance between the actual weight status of the child and parent perceptions of child weight. It is well documented that many parents do not recognize when their child is overweight or obese11-14 and many report low levels of concern about their child’s weight.15-17 Additionally, a recent study found that many parents of overweight or obese children did not recognize that their child’s weight posed a health risk, even among parents who accurately perceived their child as overweight.18 Parental misperception of child weight status, coupled with low levels of parental concern about child weight and its health consequences, are potential barriers to obesity prevention efforts.14,18 Perception of health risk is often viewed as a key component of behavior change,19,20 and several studies have recommended intervention strategies and clinical care practices targeting components of risk perception, including parental awareness and concerns about child weight.15,17,18,21 It is important that these strategies activate parent’s recognition of child weight-related health risks in a way that facilitates practices promoting healthy child growth, rather than contributing to anxiety and unhealthy weight control strategies. However, prior research in this area does not provide clear or consistent evidence indicating how parental beliefs regarding child weight are associated with weight-related parenting practices, parent engagement in child obesity prevention and/or treatment interventions, or child weight outcomes. In this study, we focus on parental concern regarding child weight. Few studies have examined the relationship between parental concern about child weight and weight-related parenting practices, and those that have reach varying conclusions about whether parental concern is associated with healthy parental behaviors. A recent study of average weight and overweight children and adolescents found parents who were concerned about child weight, compared to those who were unconcerned, reported greater use of several strategies to promote healthy child weight, including limiting child screen time, decreasing restaurant use, and decreasing soda intake.21 Similarly, an Australian study of average weight and overweight children ages 5-6 and 10-12 years found parental concern about a child’s future weight was associated with parental action to prevent child overweight.16 Conversely, maternal concern about child weight has been associated with potentially negative weight-related parenting practices, such as greater use of restrictive feeding practices among mothers of preschoolers,22 elementary school children,23 and early adolescents24 across the BMI spectrum, as well as with pressure to eat feeding strategies among mothers of early adolescents.24 These studies suggest parental concern about child weight may be associated with weight–related parenting practices, but additional research is needed to more fully examine these relationships given the small number of studies in this area, differences in study populations, and mixed findings. In the present study, we describe parental perception of child weight and concern about child weight among parents of young children between the ages of 5 and 10, who are overweight (BMI percentiles 85-95th) or are at-risk for becoming overweight (BMI percentiles 70-84th). We then investigate the relationship between parental concern about child weight and child-, household-, and parent-level factors in 3 domains: diet, PA, and media use. In doing so, we sought to: 1) assess accuracy of parental perceptions of child weight status and describe parental concerns about child weight; 2) assess demographic correlates of accuracy of parental perceptions of child weight status and parental concern about child weight; and 3) examine the relationship between parental concern about child weight and weight-related dietary, PA, and media factors at the child, household, and parent levels.

Background Neurocognitive late effects after childhood acute lymphoblastic leukemia (ALL) are well-documented, but their impact on quality of life (QOL) is not well understood. In this multi-site study, we examined the relative influence of neurocognitive functioning, steroid randomization (prednisone vs. dexamethasone), and demographic characteristics on QOL in first-remission survivors of childhood ALL. Methods Participants included 263 ALL survivors (ages 7–17 years at the time of evaluation; mean age at diagnosis 3.9 years) who were treated on similar legacy Children's Cancer Group chemotherapy protocols and did not receive cranial radiation. Children completed detailed neuropsychological performance tests. The Pediatric QOL Inventory was completed by children and their parents. Participants were a mean of 9 years from diagnosis at the time of assessment (with a range of 4 to 13 years). Results Children and their parents reported lower mean child psychosocial QOL than healthy population norms (p

PURPOSE: Skeletal disease causes significant morbidity in mucopolysaccharidoses (MPS), and bone remodeling processes in MPS have not been well characterized. The objective of this study was to determine if biomarkers of bone turnover are abnormal in children with specific MPS disorders (i.e. MSP-I, MPS-II, and MPS-VI) compared to healthy children. METHODS: A cross-sectional study was performed of serum biomarkers of bone formation (bone-specific alkaline phosphatase [BSAP], osteocalcin) and urine biomarkers of bone resorption (pyridinoline, deoxypyridinoline) in MPS and healthy controls. Measures of physical function and pain were obtained using the Children’s Health Questionnaire (CHQ). RESULTS: The cohort consisted of 39 children with MPS (MPS-I = 26; MPS-II = 11; MPS-VI = 4) and 51 healthy children. Adjusting for sex and Tanner stage group, MPS individuals had statistically significant increases for osteocalcin ( p< 0.001), with trends toward higher BSAP (p = 0.054) and urinary pyridinoline (p = 0.084). These biomarkers were not significantly associated with CHQ bodily pain and physical-function scores. CONCLUSION: Osteocalcin was increased in children with MPS disorders, with trends for increases in BSAP and urinary pyridinoline, suggesting that bone remodeling is altered in children with MPS. Future studies to assess the ability of these biomarkers to quantify and monitor MPS skeletal disease in response to therapy are needed.

Mucopolysaccharidosis I and II are lysosomal storage disorders that, despite treatment with hematopoietic cell transplantation (HCT) and/or enzyme replacement therapy (ERT), continue to cause significant skeletal abnormalities leading to pain, stiffness, physical dysfunction, and short stature. Tumor necrosis factor – alpha (TNF-α) is elevated in individuals with MPS I and II and associated with pain and physical dysfunction. Therefore, we evaluated the safety and effects of the TNF-α inhibitor adalimumab in patients with MPS I and II in a 32-week, randomized, double blind, placebo-controlled, crossover study of adalimumab at a dose of 20 mg (weight 15– 5° in seven of eight joints in Subject #1 and five of eight joints in Subject #2 (range 7.0° to 52.8°). There was no change in the PPQ, 6MWT, or hand dynamometer. Data from this small pilot study suggest that treatment with adalimumab is safe, tolerable, and may improve ROM, physical function, and possibly pain, in children with MPS I or II. However, additional clinical trials are needed before this therapy should be recommended as part of clinical care.

Behavioural interventions for paediatric obesity are promising, but detailed information on treatment fidelity (i.e. design, training, delivery, receipt and enactment) is needed to optimize the implementation of more effective interventions. Little is known about current practices for reporting treatment fidelity in paediatric obesity studies. This systematic review, in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, describes the methods used to report treatment fidelity in randomized controlled trials. Treatment fidelity was double-coded using the National Institutes of Health Fidelity Framework checklist. Three hundred articles (N = 193 studies) were included. Mean inter-coder reliability across items was 0.83 (SD = 0.09). Reporting of treatment design elements within the field was high (e.g. 77% of studies reported designed length of treatment session), but reporting of other domains was low (e.g. only 7% of studies reported length of treatment sessions delivered). Few reported gold standard methods to evaluate treatment fidelity (e.g. coding treatment content delivered). General study quality was associated with reporting of treatment fidelity (p 0.01) as was the number of articles published for a given study (p 0.01). The frequency of reporting treatment fidelity components has not improved over time (p = 0.26). Specific recommendations are made to support paediatric obesity researchers in leading health behaviour disciplines towards more rigorous measurement and reporting of treatment fidelity.

Background Neurocognitive functioning is an important construct in childhood cancer survivorship, given the potential neurotoxicity of central nervous system (CNS) diseases and treatments and the relevance for important functional outcomes in adulthood. However, within pediatric oncology cooperative groups there have been significant barriers to neurocognitive data collection that have historically resulted in incomplete data (

Background Adult survivors of childhood cancer and their siblings are compared on one of the most salient developmental milestones of adulthood, the ability to live independently.

Objective: To identify risk factors for adverse psychological outcomes among adult siblings of long-term survivors of childhood cancer. Methods: Cross-sectional, self-report data from 3083 adult siblings (mean age 29 years, range 18–56 years) of 5 + year survivors of childhood cancer were analyzed to assess psychological outcomes as measured by the Brief Symptom Inventory-18 (BSI-18). Sociodemographic and health data, reported by both the siblings and their matched cancer survivors, were explored as risk factors for adverse sibling psychological outcomes through multivariable logistic regression. Results: Self-reported symptoms of psychological distress, as measured by the global severity index of the BSI-18, were reported by 3.8% of the sibling sample. Less than 1.5% of siblings reported elevated scores on two or more of the subscales of the BSI-18. Risk factors for sibling depression included having a survivor brother (OR 2.22, 95% CI 1.42–3.55), and having a survivor with impaired general health (OR 2.15, 95% CI 1.18–3.78). Siblings who were younger than the survivor reported increased global psychological distress (OR 1.81, 95% CI 1.05–3.12), as did siblings of survivors reporting global psychological distress (OR 2.32, 95% CI 1.08–4.59). Siblings of sarcoma survivors reported more somatization than did siblings of leukemia survivors (OR 2.07, 95% CI 1.05–3.98). Conclusions: These findings suggest that siblings of long-term childhood cancer survivors are psychologically healthy in general. There are, however, small subgroups of siblings at risk for long-term psychological impairment who may benefit from preventive risk-reduction strategies during childhood while their sibling with cancer is undergoing treatment. Copyright © 2010 John Wiley & Sons, Ltd.

Background Hematopoeitic cell transplantation (HCT) in childhood has been associated with late complications including endocrine, neurocognitive, and cardiopulmonary abnormalities. Little is known about the complications of transplantation in infants. Procedure Eligible subjects underwent HCT for acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML) at less than 3 years of age. Seventeen out of 33 eligible patients were evaluated, transplanted between 1981–2000. Eleven patients had AML, 11 were female. Preparative regimen included total body irradiation (TBI) for eleven. Age at HCT ranged from 0.58 to 2.97 years, and survival 3.25 to 22.33 years. Patients underwent physical and laboratory evaluation, dual-energy X-ray absorptiometry (DXA) scan, bone age X-ray, neuropsychological, and quality of life (QOL) evaluation. Results Identified abnormalities included: growth hormone deficiency (59%), hypothyroidism (35%), osteochondromas (24%), decreased bone mineral density (24%), and dyslipidemias (59%). Two patients developed a second malignancy. Neuropsychological testing revealed average intelligence quotient (IQ) with attention deficits and other weaknesses for most patients. There were no overall differences between QOL in these children when compared to population norms. Conclusions Of the survivors evaluated, typical late effects seen after radiation exposure are common, yet most subjects were doing well without major ongoing medical issues. Dyslipidemias affect more than half of patients and may be associated with metabolic syndrome, placing patients at increased risk for early cardiovascular disease. Even in this group of patients where the majority was exposed to TBI at a very young age, most are functioning at an average or above-average level. Pediatr Blood Cancer 2007;49:958–963. © 2007 Wiley-Liss, Inc.

Children and adults with the lysosomal storage diseases mucopolysaccharidosis (MPS) types I, II and VI live shortened lives permeated by chronic pain and physical disability. Current treatments do not alleviate these problems. Thus there is a critical need to understand the mechanism of chronic pain and disability in MPS in order to improve the way we treat patients. A potential target is inflammation.We hypothesized that excessive inflammation mediated by the tumor necrosis factor-α (TNF-α) inflammatory pathway is the fundamental cause of much of the chronic pain and physical disability in MPS.55 patients with MPS I, II, or VI were enrolled over the course of a 5-year prospective longitudinal natural history study and evaluated annually for 2-5years. 51 healthy controls were enrolled in a separate cross-sectional study of bone and energy metabolism. TNF-α was measured by ELISA. Pain and physical disability were measured by the Children's Health Questionnaire - Parent Form 50 (CHQ-PF50). Differences in log-transformed TNF-α levels and associations with CHQ domains were evaluated using a linear mixed effects model with random intercept.TNF-α levels were measured in 48 MPS (age: 5-17years; 35% female) and 51 controls (age: 8-17years; 53% female). Among MPS, 22 (46%) were treated with hematopoietic cell transplantation (HCT) alone, 24 (50%) with enzyme replacement therapy (ERT) alone, and 2 (4%) with both HCT and ERT. TNF-α levels are higher in MPS compared to healthy controls (p0.001). Higher TNF-α levels are associated with increased pain and decreased physical function, social limitations due to physical health, and physical summary score (all p0.05). TNF-α levels were not significantly associated with the general health score. TNF-α levels did not change significantly over time in MPS.Higher TNF-α levels are implicated in the pain and decreased physical function present in individuals with MPS despite treatment with ERT and/or HCT, suggesting that TNF-a inhibition could potentially be a useful adjunctive therapy. Further investigation into the role of TNF-α inhibition in MPS to decrease pain and improve physical function is indicated.

We quantified medical signs and symptoms to construct the Physical Symptom Score (PSS) for use in research to assess somatic disease burden in mucopolysaccharidoses (MPS) to track disease and monitor treatments. We examined scoring reliability, its concurrent validity with other measures, and relationship to age in MPS type I.Fifty-four patients with MPS I (36 with Hurler syndrome treated with hematopoietic cell transplant and 18 with attenuated MPS I treated with enzyme replacement therapy), ages 5 to 18 years, were seen longitudinally over 5 years. The summation of frequency and severity of signs of specific organ involvement, surgeries, and hydrocephalus drawn from medical histories comprise the PSS. We examined relationship to age and to daily living skills (DLS) from the Vineland Adaptive Behavior Scale and physical quality of life from the Child Health Questionnaire (CHQ) for each group.The PSS was associated with age in both groups, indicating increase in disease burden over time. The PSS was significantly negatively associated with DLS (r = -0.48) and CHQ (r = -0.55) in the attenuated MPS I but not in the Hurler group.The association of somatic disease burden with physical quality of life and ability to carry out daily living skills suggests that the PSS will be useful in the measurement of disease and treatment effects in the attenuated MPS I group. Earlier treatment with transplant and differing parental expectations are possible explanations for its lack of association with other outcomes necessitating an adaptation for Hurler syndrome in the future.

Children and adolescents are vulnerable to the neurotoxic effects of radiation and chemotherapy, which can include disruption of normal brain development. Children with central nervous system malignancies and those who have received cranial radiation therapy are at particularly high risk. However, neurological and cognitive impairments have also been observed in other disease groups even in the absence of cranial radiation therapy. Toxicities may be acute, subacute, or long-term. Contributing factors include the type (location, volume, dosage) of radiation therapy administered, cumulative dosage of neurotoxic chemotherapy agents, mode of chemotherapy delivery (intrathecal), age at exposure, gender, and inherited factors. Affected survivors struggle with educational attainment, emotional-behavior difficulties, and other aspects of quality of life. Therfore, children and adolescents exposed to neurotoxic therapies benefit from surveillance and early intervention for neurological and cognitive late effects.

This study examined cancer knowledge in adolescent and young adult (AYA) survivors and pilot tested a Web-based resource to provide individually tailored information regarding cancer treatment history, late effects risk, and resources.Fifty-two survivors (15-28 years old) who completed cancer treatment were recruited from the University of Minnesota oncology clinics. Participants were randomly assigned to receive access to personalized health history, late effects information, and resources via a password-protected Web portal or to standard of care (physician counseling) only. Participants completed surveys measuring cancer knowledge, health locus of control, and psychosocial well-being prior to randomization and approximately 1 year later.Overall, few participants accurately reported their chemotherapy history with detail (19% at baseline and 33% at follow-up), and many did not recognize that previous cancer treatments could impact future health (60% at baseline and 54% at follow-up). Among those randomized to the receive access to the website, utilization was very low, making it difficult to draw conclusions about efficacy. Nonetheless, these data suggest that offering tailored information through the Web was not more effective than standard of care at improving cancer knowledge. Anxiety and health beliefs were associated with cancer knowledge, including knowledge of steps survivors could take to mitigate late effects risks (p 01).Knowledge gaps exist among AYA survivors regarding important aspects of their treatment histories and ongoing health risks. Offering purely educational information (either in person by providers or via the Web) does not appear to be enough to close this gap. Copyright © 2015 John WileySons, Ltd.

OBJECTIVES We evaluated eating behaviors and quality of life (QOL) in preadolescent children at risk for obesity, with and without abdominal pain (AP). METHODS Participants were parent-child dyads enrolled in a randomized, controlled obesity prevention trial. The children were between 5 and 10 years of age and at risk for obesity (70th-95th percentile of body mass index, n = 420). Parents completed measures of their child's eating behaviors, QOL, AP, and bowel function and their own depression status, concern about child weight, and feeding practices. Children's height and weight were also measured. RESULTS Children with frequent AP (≥2/month, n = 103) were compared with children reporting infrequent AP (

Objective To describe the proportion of children adhering to recommended physical activity and dietary guidelines, and examine demographic and household correlates of guideline adherence. Design Cross-sectional (pre-randomization) data from a behavioral intervention trial designed to prevent unhealthy weight gain in children. Participants A total of 421 children (aged 5–10 years) at risk for obesity (body mass index percentile, 70–95). Main Outcomes Measured Physical activity (accelerometry), screen time (parent survey), and fruit and vegetable and sugar-sweetened beverage intake (24-hour dietary recall). Analysis Proportions meeting guidelines were calculated. Logistic regression examined associations between demographic and household factors and whether children met recommended guidelines for (1) physical activity (≥ 60 min/d), (2) screen time (≤ 2 h/d), (3) fruit and vegetable intake (≥ 5 servings/d), and (4) sugar-sweetened beverage avoidance. Results Few children met more than 1 guideline. Only 2% met all 4 recommended guidelines and 19% met none. Each guideline had unique sociodemographic and domain-specific household predictors (ie, availability of certain foods and beverages, media, and active play and exercise equipment). Conclusions and Implications Families equipped to promote healthy child behavior patterns in 1 activity or dietary domain may not be in others. Results have implications for the development of interventions to affect children's weight-related behaviors and growth trajectories.

To provide one of the first prospective reports examining neuropsychological outcomes for children treated with 1800 cGy whole brain radiotherapy (WBRT) and prophylactic chemotherapy versus prophylactic chemotherapy alone for acute lymphoblastic leukemia (ALL). Acute and long-term neuropsychological toxicities associated with WBRT are compared.This multisite study included 188 children, ages 4-21 years at enrollment, who were assessed with standardized neuropsychological tests at 9, 21, and 48 months after diagnosis with intermediate risk ALL. All participating children were receiving treatment on a parent study CCG105.Verbal intelligence (VIQ) scores for children receiving WBRT was significantly lower than VIQ for prophylactic chemotherapy at the 48-month time point (p 0.05). A significant cross-level interaction between time since diagnosis and treatment condition was observed (p 0.05). WBRT did not result in differences in PIQ; both groups of children demonstrated comparable increases in PIQ. Neuropsychological findings at 48 months after diagnosis indicated diminished performance in neuromotor, visual-motor coordination, and executive functioning for children receiving WBRT. Academic achievement was unaffected by WBRT at 4 years after diagnosis.The measurement of verbal and performance IQ as a primary endpoint in ALL clinical trials is critical to characterizing neuropsychological late effects. A trajectory of decline in neuropsychological functioning, specifically verbal IQ, was observed. Missing data within the trial occurred at random and did not impact results observed. The impact of WBRT becomes evident at 48 months after diagnosis, suggesting the need for long-term follow-up beyond the time frame typically used in Phase III trials.

Neurocognitive late effects after childhood acute lymphoblastic leukemia (ALL) are well-documented, but their impact on quality of life (QOL) is not well understood. In this multi-site study, we examined the relative influence of neurocognitive functioning, steroid randomization (prednisone vs. dexamethasone), and demographic characteristics on QOL in first-remission survivors of childhood ALL.Participants included 263 ALL survivors (ages 7-17 years at the time of evaluation; mean age at diagnosis 3.9 years) who were treated on similar legacy Children's Cancer Group chemotherapy protocols and did not receive cranial radiation. Children completed detailed neuropsychological performance tests. The Pediatric QOL Inventory was completed by children and their parents. Participants were a mean of 9 years from diagnosis at the time of assessment (with a range of 4 to 13 years).Children and their parents reported lower mean child psychosocial QOL than healthy population norms (p 0.05), but were not in the impaired range. Physical QOL was similar to population norms. Though neurocognitive difficulties were predominantly mild for the sample as a whole, neurocognitive deficits, specifically problems in verbal cognitive abilities and visual-motor integration skills, were significantly associated with poor physical (p 0.01) and Psychosocial QOL (p 0.01). QOL was not associated with previous steroid randomization.ALL survivors with neurocognitive deficits are at risk for poor QOL, with broad implications for their physical, social, and school functioning.

Neurocognitive functioning is an important construct in childhood cancer survivorship, given the potential neurotoxicity of central nervous system (CNS) diseases and treatments and the relevance for important functional outcomes in adulthood. However, within pediatric oncology cooperative groups there have been significant barriers to neurocognitive data collection that have historically resulted in incomplete data (30% compliance), thereby limiting progress in understanding the neurocognitive functioning of survivors. This paper describes the development, feasibility, and potential efficacy of a brief neurocognitive battery to maximize collection of psychometrically robust neurocognitive data within a pediatric cooperative group. We hypothesized that a novel set of procedures could result in collection of data from over 80% of eligible children.A novel assessment battery (ALTE07C1) that evaluates a child's cognitive, social, emotional, and behavioral functioning was developed. It included measures that were psychometrically sound, normed, widely available, and could be administered by any licensed psychologist. The battery required approximately 1 hour of administration time. A data monitoring team was developed to ensure prompt data collection.Approximately 75% (105 of 140) of institutions with eligible patients opened ALTE07C1; 159 participants have been enrolled. The overall compliance rate for submission of neurocognitive data exceeded 90%.Our study supports the feasibility and potential efficacy of a brief neurocognitive battery and a data monitoring team to evaluate children participating in multi-site pediatric oncology trials. Future work will utilize ALTE07C1 as a primary or secondary endpoint for pediatric trials when there is risk for neurocognitive impairment.

Adult survivors of childhood cancer and their siblings are compared on one of the most salient developmental milestones of adulthood, the ability to live independently.Adult survivors of childhood cancers (n = 6,047) and siblings (n = 2,326), all 25 years of age and older, completed a long-term follow-up questionnaire that assessed adaptive, neurocognitive, and psychological functioning, as well as demographic and health status. Multivariable logistic regression analyses and structural equation modeling (SEM) were used to identify predictors of independent living.Compared to siblings (n = 206, 8.7%), survivors (n = 1063; 17.7%) were more than twice as likely to live dependently (OR 2.07; 95% confidence interval [CI] 1.77-2.42). Survivors diagnosed with CNS tumors (OR 0.13, 95% CI 0.10-0.18) or leukemia (OR 0.29, 95% CI 0.23-0.27) were significantly less likely to live independently compared to those diagnosed with Hodgkin lymphoma. Other risk factors for reduced independent living included cranial radiation (≤ 24 Gy OR 0.76, 95% CI 0.62-0.93;24 Gy OR 0.31, 95% CI 0.24-0.41), use of neuroleptic, anticonvulsant, or psychostimulant medication (OR 0.32, 95% CI 0.24-0.43), attention and processing speed problems (OR 0.58, 95% CI 0.47-0.71), poor physical functioning (OR 0.49, 95% CI 0.38-0.63), depression (OR 0.68, 95% CI 0.53-0.88), and racial/ethnic minority status (OR 0.39, 95% CI 0.30-0.51). SEM demonstrated that neurocognitive functioning had both direct effects on independent living status, and indirect effects through use of neurologically directed medication, depression, and poor mental health.Adult survivors of childhood cancer who experience neurocognitive, psychological, or physical late effects are less likely to live independently as adults.

To identify risk factors for adverse psychological outcomes among adult siblings of long-term survivors of childhood cancer.Cross-sectional, self-report data from 3083 adult siblings (mean age 29 years, range 18-56 years) of 5 + year survivors of childhood cancer were analyzed to assess psychological outcomes as measured by the Brief Symptom Inventory-18 (BSI-18). Sociodemographic and health data, reported by both the siblings and their matched cancer survivors, were explored as risk factors for adverse sibling psychological outcomes through multivariable logistic regression.Self-reported symptoms of psychological distress, as measured by the global severity index of the BSI-18, were reported by 3.8% of the sibling sample. Less than 1.5% of siblings reported elevated scores on two or more of the subscales of the BSI-18. Risk factors for sibling depression included having a survivor brother (OR 2.22, 95% CI 1.42-3.55), and having a survivor with impaired general health (OR 2.15, 95% CI 1.18-3.78). Siblings who were younger than the survivor reported increased global psychological distress (OR 1.81, 95% CI 1.05-3.12), as did siblings of survivors reporting global psychological distress (OR 2.32, 95% CI 1.08-4.59). Siblings of sarcoma survivors reported more somatization than did siblings of leukemia survivors (OR 2.07, 95% CI 1.05-3.98).These findings suggest that siblings of long-term childhood cancer survivors are psychologically healthy in general. There are, however, small subgroups of siblings at risk for long-term psychological impairment who may benefit from preventive risk-reduction strategies during childhood while their sibling with cancer is undergoing treatment.

Advances in the treatment of childhood cancers have greatly improved survivorship. Success has not come without cost, however, as survivors are at risk for late effects of treatment, including neurocognitive late effects (e.g., difficulties with thinking and reasoning). In the advent of chemotherapy-only protocols, researchers are examining neurocognitive sequelae of these agents to understand the specific role of chemotherapy in neurocognitive changes and the mechanism through which these occur. In this review, we examine the state of the literature on neurocognitive late effects after chemotherapy and their proposed neural mechanisms.