Summary
Objective
Family‐based interventions represent a potentially valuable route to increasing child physical activity (PA) in children. A dual meta‐analysis and realist synthesis approach ...examined existing interventions to assist those developing programmes to encourage uptake and maintenance of PA in children.
Design
Studies were screened for inclusion based on including participants aged 5–12 years, having a substantive aim of increasing PA by engaging the family and reporting on PA outcome. Duplicate data extraction and quality assessment were conducted. Meta‐analysis was conducted in STATA. Realist synthesis included theory development and evidence mapping.
Results
Forty‐seven studies were included, of which three received a ‘strong’ quality rating, 21 ‘moderate’ and 23 ‘weak’. The meta‐analysis (19 studies) demonstrated a significant small effect in favour of the experimental group (standardized mean difference: 0.41; 95%CI 0.15–0.67). Sensitivity analysis, removing one outlier, reduced this to 0.29 (95%CI 0.14–0.45). Realist synthesis (28 studies) provided insight into intervention context (particularly, family constraints, ethnicity and parental motivation), and strategies to change PA (notably, goal‐setting and reinforcement combined).
Conclusion
This review provides key recommendations to inform policy makers and other practitioners in developing evidence‐based interventions aimed at engaging the family to increase PA in children, and identifies avenues for future research.
Treatment planning for children with neuroblastoma requires accurate assessment of prognosis. The most recent Children's Oncology Group (COG) risk classification system used tumor stage as defined by ...the International Neuroblastoma Staging System. Here, we validate a revised classifier using the International Neuroblastoma Risk Group Staging System (INRGSS) and incorporate segmental chromosome aberrations (SCA) as an additional genomic biomarker.
Newly diagnosed patients enrolled on the COG neuroblastoma biology study ANBL00B1 between 2007 and 2017 with known age, International Neuroblastoma Staging System, and INRGSS stage were identified (N = 4,832). Tumor
status, ploidy, SCA status (1p and 11q), and International Neuroblastoma Pathology Classification histology were determined centrally. Survival analyses were performed for combinations of prognostic factors used in COG risk classification according to the prior version 1, and to validate a revised algorithm (version 2).
Most patients with locoregional tumors had excellent outcomes except for those with image-defined risk factors (INRGSS L2) with
amplification (5-year event-free survival and overall survival: 76.3% ± 5.8% and 79.9% ± 5.5%, respectively) or patients age ≥ 18 months with L2
nonamplified tumors with unfavorable International Neuroblastoma Pathology Classification histology (72.7% ± 5.4% and 82.4% ± 4.6%), which includes the majority of L2 patients with SCA. For patients with stage M (metastatic) and MS (metastatic, special) disease, genomic biomarkers affected risk group assignment for those < 12 months (
) or 12-18 months (
, histology, ploidy, and SCA) of age. In a retrospective analysis of patient outcome, the 5-year event-free survival and overall survival using COG version 1 were low-risk: 89.4% ± 1.1% and 97.9% ± 0.5%; intermediate-risk: 86.1% ± 1.3% and 94.9% ± 0.8%; high-risk: 50.8% ± 1.4% and 61.9% ± 1.3%; and using COG version 2 were low-risk: 90.7% ± 1.1% and 97.9% ± 0.5%; intermediate-risk: 85.1% ± 1.4% and 95.8% ± 0.8%; high-risk: 51.2% ± 1.4% and 62.5% ± 1.3%, respectively.
A revised 2021 COG neuroblastoma risk classifier (version 2) that uses the INRGSS and incorporates SCAs has been adopted to prospectively define COG clinical trial eligibility and treatment assignment.
Abstract Objectives To comprehensively review all observational and experimental studies examining the relationship between physical activity and cognitive development during early childhood (birth ...to 5 years). Design Systematic review. Methods Electronic databases were searched in July, 2014. No study design, date, or language limits were imposed on the search. Included studies had to be published, peer reviewed articles that satisfied the a priori determined population (apparently healthy children aged birth to 5 years), intervention (duration, intensity, frequency, or patterns of physical activity), comparator (various durations, intensity, or patterns of physical activity), and outcome (cognitive development) study criteria. Study quality and risk of bias were assessed in December 2014. Results A total of seven studies, representing 414 participants from five different countries met the inclusion criteria, including two observational and five experimental studies. Six studies found increased or higher duration/frequency of physical activity had statistically significant ( p < 0.05) beneficial effects on at least one cognitive development outcome, including 67% of the outcomes assessed in the executive function domain and 60% in the language domain. No study found that increased or higher duration/frequency of physical activity had statistically significant detrimental effects on cognitive development. Six of the seven studies were rated weak quality with a high risk of bias. Conclusions This review provides some preliminary evidence that physical activity may have beneficial effects on cognitive development during early childhood. Given the shortage of the information and the weak quality of available evidence, future research is needed to strengthen the evidence base in this area.
OBJECTIVETo report results of intrathecal nusinersen in children with later-onset spinal muscular atrophy (SMA).
METHODSAnalyses included children from a phase 1b/2a study (ISIS-396443-CS2; ...NCT01703988) who first received nusinersen during that study and were eligible to continue treatment in the extension study (ISIS-396443-CS12; NCT02052791). The phase 1b/2a study was a 253-day, ascending dose (3, 6, 9, 12 mg), multiple-dose, open-label, multicenter study that enrolled children with SMA aged 2–15 years. The extension study was a 715-day, single-dose level (12 mg) study. Time between studies varied by participant (196–413 days). Assessments included the Hammersmith Functional Motor Scale–Expanded (HFMSE), Upper Limb Module (ULM), 6-Minute Walk Test (6MWT), compound muscle action potential (CMAP), and quantitative multipoint incremental motor unit number estimation. Safety also was assessed.
RESULTSTwenty-eight children were included (SMA type II, n = 11; SMA type III, n = 17). Mean HFMSE scores, ULM scores, and 6MWT distances improved by the day 1,150 visit (HFMSESMA type II, +10.8 points; SMA type III, +1.8 points; ULMSMA type II, +4.0 points; 6MWTSMA type III, +92.0 meters). Mean CMAP values remained relatively stable. No children discontinued treatment due to adverse events.
CONCLUSIONSNusinersen treatment over ∼3 years resulted in motor function improvements and disease activity stabilization not observed in natural history cohorts. These results document the long-term benefit of nusinersen in later-onset SMA, including SMA type III.
CLINICALTRIALS.GOV IDENTIFIERNCT01703988 (ISIS-396443-CS2); NCT02052791 (ISIS-396443-CS12).
CLASSIFICATION OF EVIDENCEThis study provides Class IV evidence that nusinersen improves motor function in children with later-onset SMA.
Aim
Pre‐school wheeze is a common hospital presentation in Australasia. The aim of this study was to describe the regional hospital presentation and cost of pre‐school wheeze.
Methods
Audit of ...children diagnosed with pre‐school wheeze at two hospitals in Auckland, New Zealand from October 2017 to September 2019. Guideline adherence was determined.
Results
One hundred and ninety‐two children made 247 pre‐school wheeze hospital presentations. Pre‐school wheeze accounted for a larger proportion of acute hospital presentations for Māori versus non‐Māori children (rate ratio 1.76, 95% confidence intervals 1.32–2.31). Hospital representations with pre‐school wheeze occurred in 38/192 (20%) children. The proportion with a pre‐school wheeze representation was larger for Māori than non‐Māori (30% vs. 16%, P = 0.02). Pre‐school wheeze event median length of stay increased as household deprivation increased (P = 0.01). Clinical severity of 247 pre‐school wheeze episodes was mild (n = 64, 26%), moderate (n = 153, 62%) and severe (n = 30, 12%). Of 244 episodes, inhaled bronchodilators only were given for 149 (61%), oxygen for 54 (22%) and intravenous treatment for 41 (17%). Hospital guideline use was evident in 164/247 (66%) episodes. Neither clinical severity nor treatment intensity varied with child sex, age or ethnicity or household deprivation. The estimated median (interquartile range) direct medical costs of each pre‐school wheeze episode were NZ$1279 (NZ$774–2158).
Conclusions
In Auckland, pre‐school wheeze accounts for a larger proportion of acute hospital presentations for Māori compared with non‐Māori and Māori children have increased odds of pre‐school wheeze readmissions. Length of hospital stay for pre‐school wheeze episodes increased with household deprivation. In this audit pre‐school wheeze guideline adherence was poor.
Abstract
Background
Obesity (OB) is a serious epidemic in the United States.
Methods
We examined OB patterns and time trends across socio-economic and geographic parameters and projected the future ...situation. Large national databases were used. Overweight (OW), OB and severe obesity (SOB) were defined using body mass index cut-points/percentiles; central obesity (CO), waist circumference cut-point in adults and waist:height ratio cutoff in youth. Various meta-regression analysis models were fit for projection analyses.
Results
OB prevalence had consistently risen since 1999 and considerable differences existed across groups and regions. Among adults, men’s OB (33.7%) and OW (71.6%) levelled off in 2009–2012, resuming the increase to 38.0 and 74.7% in 2015–2016, respectively. Women showed an uninterrupted increase in OB/OW prevalence since 1999, reaching 41.5% (OB) and 68.9% (OW) in 2015–2016. SOB levelled off in 2013–2016 (men: 5.5–5.6%; women: 9.7–9.5%), after annual increases of 0.2% between 1999 and 2012. Non-Hispanic Blacks had the highest prevalence in women’s OB/SOB and men’s SOB. OB prevalence in boys rose continuously to 20.6% and SOB to 7.5% in 2015–2016, but not in girls. By 2030, most Americans will be OB/OW and nearly 50% of adults OB, whereas ∼33% of children aged 6–11 and ∼50% of adolescents aged 12–19 will be OB/OW. Since 1999, CO has risen steadily, and by 2030 is projected to reach 55.6% in men, 80.0% in women, 47.6% among girls and 38.9% among boys. Regional differences exist in adult OB prevalence (2011–2016) and across ethnicities; South (32.0%) and Midwest (31.4%) had the highest rates.
Conclusions
US obesity prevalence has been rising, despite a temporary pause in 2009–2012. Wide disparities across groups and geographical regions persist. Effective, sustainable, culturally-tailored interventions are needed.
BACKGROUNDThe relationship among physical activity (PA), fitness, cognitive function, and academic achievement in children is receiving considerable attention. The utility of PA to improve cognition ...and academic achievement is promising but uncertain; thus, this position stand will provide clarity from the available science.
OBJECTIVEThe purpose of this study was to answer the following questions1) among children age 5–13 yr, do PA and physical fitness influence cognition, learning, brain structure, and brain function? 2) Among children age 5–13 yr, do PA, physical education (PE), and sports programs influence standardized achievement test performance and concentration/attention?
STUDY ELIGIBILITY CRITERIAThis study used primary source articles published in English in peer-reviewed journals. Articles that presented data on, PA, fitness, or PE/sport participation and cognition, learning, brain function/structure, academic achievement, or concentration/attention were included.
DATA SOURCESTwo separate searches were performed to identify studies that focused on 1) cognition, learning, brain structure, and brain function and 2) standardized achievement test performance and concentration/attention. PubMed, ERIC, PsychInfo, SportDiscus, Scopus, Web of Science, Academic Search Premier, and Embase were searched (January 1990–September 2014) for studies that met inclusion criteria. Sixty-four studies met inclusion criteria for the first search (cognition/learning/brain), and 73 studies met inclusion criteria for the second search (academic achievement/concentration).
STUDY APPRAISAL AND SYNTHESIS METHODSArticles were grouped by study design as cross-sectional, longitudinal, acute, or intervention trials. Considerable heterogeneity existed for several important study parameters; therefore, results were synthesized and presented by study design.
RESULTSA majority of the research supports the view that physical fitness, single bouts of PA, and PA interventions benefit children’s cognitive functioning. Limited evidence was available concerning the effects of PA on learning, with only one cross-sectional study meeting the inclusion criteria. Evidence indicates that PA has a relationship to areas of the brain that support complex cognitive processes during laboratory tasks. Although favorable results have been obtained from cross-sectional and longitudinal studies related to academic achievement, the results obtained from controlled experiments evaluating the benefits of PA on academic performance are mixed, and additional, well-designed studies are needed.
LIMITATIONSLimitations in evidence meeting inclusion criteria for this review include lack of randomized controlled trials, limited studies that are adequately powered, lack of information on participant characteristics, failure to blind for outcome measures, proximity of PA to measurement outcomes, and lack of accountability for known confounders. Therefore, many studies were ranked as high risk for bias because of multiple design limitations.
CONCLUSIONSThe present systematic review found evidence to suggest that there are positive associations among PA, fitness, cognition, and academic achievement. However, the findings are inconsistent, and the effects of numerous elements of PA on cognition remain to be explored, such as type, amount, frequency, and timing. Many questions remain regarding how to best incorporate PA within schools, such as activity breaks versus active lessons in relation to improved academic achievement. Regardless, the literature suggests no indication that increases in PA negatively affect cognition or academic achievement and PA is important for growth and development and general health. On the basis of the evidence available, the authors concluded that PA has a positive influence on cognition as well as brain structure and function; however, more research is necessary to determine mechanisms and long-term effect as well as strategies to translate laboratory findings to the school environment. Therefore, the evidence category rating is B. The literature suggests that PA and PE have a neutral effect on academic achievement. Thus, because of the limitations in the literature and the current information available, the evidence category rating for academic achievement is C.
Estimates of the worldwide incidence and mortality from 36 cancers and for all cancers combined for the year 2018 are now available in the GLOBOCAN 2018 database, compiled and disseminated by the ...International Agency for Research on Cancer (IARC). This paper reviews the sources and methods used in compiling the cancer statistics in 185 countries. The validity of the national estimates depends upon the representativeness of the source information, and to take into account possible sources of bias, uncertainty intervals are now provided for the estimated sex‐ and site‐specific all‐ages number of new cancer cases and cancer deaths. We briefly describe the key results globally and by world region. There were an estimated 18.1 million (95% UI: 17.5–18.7 million) new cases of cancer (17 million excluding non‐melanoma skin cancer) and 9.6 million (95% UI: 9.3–9.8 million) deaths from cancer (9.5 million excluding non‐melanoma skin cancer) worldwide in 2018.
What's new?
The GLOBOCAN database, compiled by the International Agency for Research on Cancer (IARC), is updated regularly, providing timely estimates on national cancer incidence and mortality. Here, the authors, associated with the IARC, describe the data sources and methods used to compute global cancer incidence and mortality estimates for 38 specific cancers detailed in GLOBOCAN 2018. The authors further describe novel uncertainty intervals, newly derived from a method incorporating covariates that contribute to uncertainty in cancer estimation. Uncertainty intervals are presented alongside overall estimates, which indicate that 18.1 million new cancer cases and 9.6 million cancer deaths occurred globally in 2018.
CD19 chimeric antigen receptor (CD19-CAR) T cells induce high response rates in children and young adults (CAYAs) with B-cell acute lymphoblastic leukemia (B-ALL), but relapse rates are high. The ...role for allogeneic hematopoietic stem-cell transplant (alloHSCT) following CD19-CAR T-cell therapy to improve long-term outcomes in CAYAs has not been examined.
We conducted a phase I trial of autologous CD19.28ζ-CAR T cells in CAYAs with relapsed or refractory B-ALL. Response and long-term clinical outcomes were assessed in relation to disease and treatment variables.
Fifty CAYAs with B-ALL were treated (median age, 13.5 years; range, 4.3-30.4). Thirty-one (62.0%) patients achieved a complete remission (CR), 28 (90.3%) of whom were minimal residual disease-negative by flow cytometry. Utilization of fludarabine/cyclophosphamide-based lymphodepletion was associated with improved CR rates (29/42, 69%) compared with non-fludarabine/cyclophosphamide-based lymphodepletion (2/8, 25%;
= .041). With median follow-up of 4.8 years, median overall survival was 10.5 months (95% CI, 6.3 to 29.2 months). Twenty-one of 28 (75.0%) patients achieving a minimal residual disease-negative CR proceeded to alloHSCT. For those proceeding to alloHSCT, median overall survival was 70.2 months (95% CI, 10.4 months to not estimable). The cumulative incidence of relapse after alloHSCT was 9.5% (95% CI, 1.5 to 26.8) at 24 months; 5-year EFS following alloHSCT was 61.9% (95% CI, 38.1 to 78.8).
We provide the longest follow-up in CAYAs with B-ALL after CD19-CAR T-cell therapy reported to date and demonstrate that sequential therapy with CD19.28ζ-CAR T cells followed by alloHSCT can mediate durable disease control in a sizable fraction of CAYAs with relapsed or refractory B-ALL (ClinicalTrials.gov identifier: NCT01593696).
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