[Show abstract][Hide abstract] ABSTRACT: Performing well designed and ethical trials in pediatric inflammatory bowel diseases (IBD) is a priority to support optimal therapy and to reduce the unacceptable long lag between adult and pediatric drug approval. Recently, clinical trials in children have been incorporating placebo arms into their protocols under conditions that created controversy. Therefore, four organizations (ESPGHAN, ECCO, the Canadian Children IBD Network and the global pediatric IBD network (PIBDnet)) jointly provide a statement on the role of placebo in pediatric IBD trials. Consensus was achieved by 94/100 (94%) voting committees' members that placebo should only be used if there is genuine equipoise between the active treatment and placebo. For example, this may be considered in trials of drugs with new mechanisms of action without existing adult data, especially when proven effective alternatives do not exist outside the trial. Placebo may also be used in situations where it is an 'add-on" to an effective therapy or to evaluate exit-strategies of maintenance therapy after long-term deep remission. However, it has been agreed that no child enrolled in a trial should receive a known inferior treatment both within and outside the trial. This also includes withholding therapy in children who show clinical response after a short induction therapy. Given the similarity between pediatric and adult IBD in regards to pathophysiology and response to treatments, drugs generally cannot be considered being in genuine equipoise with placebo if it has proven efficacy in adults. Continued collaboration of all stakeholders is needed to facilitate drug development and evaluation in pediatric IBD.
Journal of pediatric gastroenterology and nutrition 11/2015; DOI:10.1097/MPG.0000000000001024 · 2.63 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background and aims:
X-linked chronic granulomatous disease (X-CGD) due to hemizygous mutations in CYBB is characterized by invasive bacterial and fungal infections and granulomatous inflammation. Inflammatory bowel disease (IBD) is an additional or isolated manifestation. Allogeneic hematopoietic stem cell transplantation (alloHSCT) is the standard curative treatment. X-CGD carriers are usually healthy but those with non-random X-chromosome inactivation (XCI) may develop infectious or autoinflammatory manifestations.
Methods and results:
We report on two female patients with severe treatment refractory Crohn-like IBD manifesting at age 23 and eight years, respectively. NADPH-oxidase activity testing and molecular genetics proved X-CGD carrier status with non-random XCI. As in CGD, histopathology from colonic biopsies disclosed pigment-laden macrophages and reduced CD68(+) macrophages. Following submyeloablative conditioning, the younger patient was treated with alloHSCT at age 20 years. She came into remission within three months after transplantation and shows complete mucosal healing after 16 months off all medications.We suggest that children and young adults with refractory IBD should obligatorily be tested for CGD. AlloHSCT should be considered as curative therapy in severely diseased female carriers of X-CGD with non-random XCI.
Journal of Crohn s and Colitis 10/2015; DOI:10.1093/ecco-jcc/jjv186 · 6.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Data on the long-term impact of hydrolyzed formulas on allergies are scarce.
To assess the association between early intervention with hydrolyzed formulas in high-risk children and allergic outcomes in adolescence.
GINI trial participants (N=2252) received one of four formulas in the first four months of life as breastmilk substitute if necessary: partial or extensive whey hydrolyzate (pHF-W, eHF-W), extensive casein hydrolyzate (eHF-C) or standard cow's milk formula (CMF) as reference. Associations between these formulas and the cumulative incidence and prevalence of parent reported physician-diagnosed asthma, allergic rhinitis (AR) and eczema, as well as spirometric indices and sensitization, were examined using generalized linear models.
Between 11 and 15 years, the prevalence of asthma was reduced in the eHF-C group compared to CMF (odds ratio (OR) 0.49, 95% confidence interval (CI) 0.26-0.89), which is consistent with the spirometric results. The cumulative incidence of AR was lower in eHF-C (Risk Ratio (RR) 0.77, 95% CI 0.59-0.99]) and the AR prevalence in pHF-W (OR 0.67, 95% CI 0.47-0.95) and eHF-C (OR 0.59, 95% CI 0.41-0.84). The cumulative incidence of eczema was reduced in pHF-W (RR 0.75, 95% CI 0.59-0.96) and eHF-C (RR 0.60, 95% CI 0.46-0.77), as was the eczema prevalence between 11 and 15 years in eHF-C (OR 0.42, 95% CI 0.23-0.79). No significant effects were found in the eHF-W group or for sensitization.
In high-risk children, early intervention using different hydrolyzed formulas has variable preventative effects on asthma, allergic rhinitis and eczema up to adolescence. This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: Background:
Untreated celiac disease is associated with increased morbidity and mortality. Until now, no up-to-date figures have been available on the prevalence of celiac disease among children and adolescents in Germany, or on the percentage of undiagnosed cases.
To estimate the prevalence of celiac disease, serum samples obtained from 2003 to 2006 from participants in the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) were studied for celiac disease-specific autoantibodies and total IgA.
Of the 12 741 study participants aged 1 to 17 years (6546 boys, 6195 girls), 9 (0.07%) had a reported history of celiac disease. An elevated concentration of serum autoantibodies to tissue transglutaminase was found in 91 children with a normal IgA concentration and in 7 with IgA deficiency. The prevalence of undiagnosed celiac disease, based on positive autoantibody findings, was 0.8% (95% confidence interval 0.6-1.0%), and the overall prevalence of the disease was 0.9%. Seropositive children and adolescents had lower ferritin and red blood cell folate concentrations than seronegative ones; they also tended to be shorter and to weigh less as reflected by age- and sex-standardized z-scores.
The 0.9% prevalence of celiac disease in Germany, as determined from a combination of serological findings and clinical histories, is similar to reported prevalences elsewhere in Europe and North America. Pediatricians, primary care physicians, internists, and other specialists should be aware of the broad spectrum of clinical manifestations of this disease. Children who have symptoms suggestive of celiac disease or belong to a group at risk for it should be tested for antibodies against tissue transglutaminase, as should symptomatic adults after the exclusion of other possible causes. It is not yet clear whether asymptomatic adults from high-risk groups should be tested.
Deutsches Ärzteblatt International 09/2015; 112(33-34):553-60. DOI:10.3238/arztebl.2015.0553 · 3.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Understanding changes in dietary intake during puberty could aid the mapping of dietary interventions for primary prevention. The present study describes dietary changes from childhood to adolescence, and their associations with parental education, family income, child education, body mass index (BMI), pubertal onset and screen-time sedentary behaviour.
Dietary data (n = 1232) were obtained from food frequency questionnaires at the 10- and 15-year follow-ups of the GINIplus birth cohort study. Intakes of 17 food groups, macronutrients and antioxidant vitamins, were described by a) paired Wilcoxon rank sum tests, comparing average intakes at each time-point, and b) Cohen's kappa "tracking" coefficients, measuring stability of intakes (maintenance of relative tertile positions across time). Further, associations of changes (tertile position increase or decrease vs. tracking) with parental education, family income, child education, pubertal onset, BMI, and screen-time, were assessed by logistic regression and multinomial logistic regression models stratified by baseline intake tertile.
Both sexes increased average intakes of water and decreased starchy vegetables, margarine and dairy. Females decreased meat and retinol intakes and increased vegetables, grains, oils and tea. Males decreased fruit and carbohydrates and increased average intakes of meat, caloric drinks, water, protein, fat, polyunsaturated fatty acids (PUFAs), vitamin C and alpha-tocopherol. Both sexes presented mainly "fair" tracking levels [κw = 0.21-0.40]. Females with high (vs. low) parental education were more likely to increase their nut intake [OR = 3.8; 95 % CI = (1.7;8.8)], and less likely to decrease vitamin C intakes [0.2 (0.1;0.5)], while males were less likely to increase egg consumption [0.2 (0.1;0.5)] and n3 PUFAs [0.2 (0.1;0.5)]. Females with a higher (vs. low) family income were more likely to maintain medium wholegrain intakes [0.2 (0.1;0.7) for decrease vs. tracking, and 0.1 (0.0;0.5) for increase vs. tracking], and were less likely to decrease vitamin C intakes [0.2 (0.1;0.6)]. Males with high education were less likely to increase sugar-sweetened foods [0.1 (0.1;0.4)]. Finally, BMI in females was negatively associated with decreasing protein intakes [0.7 (0.6;0.9)]. In males BMI was positively associated with increasing margarine [1.4 (1.1;1.6)] and vitamin C intakes [1.4 (1.1;1.6)], and negatively associated with increasing n3 PUFA.
Average dietary intakes changed significantly, despite fair tracking levels, suggesting the presence of trends in dietary behaviour during puberty. Family income and parental education predominantly influenced intake changes. Our results support the rationale for dietary interventions targeting children, and suggest that sex-specific subpopulations, e.g. low socio-economic status, should be considered for added impact.
BMC Public Health 09/2015; 15(1):841. DOI:10.1186/s12889-015-2189-0 · 2.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Asthma, rhinitis, and eczema often co-occur in children but their interrelationships at the population level have been poorly addressed. We assessed co-occurrence of childhood asthma, rhinitis, and eczema using unsupervised statistical techniques.
We included 17,209 children at 4 years and 14,585 at 8 years from seven European-population-based birth cohorts (MeDALL project). At each age period, children were grouped, using partitioning cluster analysis, according to the distribution of 23 variables covering symptoms "ever" and "in the last 12 months", doctor diagnosis, age of onset, and treatments of asthma, rhinitis, and eczema, IgE sensitisation, weight, and height. We tested the sensitivity of our estimates to subject and variable selections, and to different statistical approaches, including latent class analysis and self-organising maps.
Two groups were identified as the optimal way to cluster the data at both age periods and in all sensitivity analyses. The first (reference) group at 4 and 8 years (including 70 and 79% of children, respectively) was characterised by a low prevalence of symptoms and sensitisation, whereas the second (symptomatic) group exhibited more frequent symptoms and sensitisation. 99% children with comorbidities (co-occurrence of asthma, rhinitis, and/or eczema) were included in the symptomatic group at both ages. The children's characteristics in both groups were consistent in all sensitivity analyses.
At 4 and 8 years, at the population level, asthma, rhinitis, and eczema can be classified together as an allergic comorbidity cluster. Future research including time-repeated assessments and biological data will help understanding the interrelationships between these diseases. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: Physical inactivity in children is an important risk factor for the development of various morbidities and mortality in adulthood, physical activity already has preventive effects during childhood. The objective of this study is to estimate the association between physical activity, healthcare utilization and costs in children.
Cross-sectional data of 3356 children aged 9 to 12 years were taken from the 10-year follow-up of the birth cohort studies GINIplus and LISAplus, including information on healthcare utilization and physical activity given by parents via self-administered questionnaires. Using a bottom-up approach, direct costs due to healthcare utilization and indirect costs resulting from parental work absence were estimated for the base year 2007. A two-step regression model compared effects on healthcare utilization and costs for a higher (≥7 h/week) versus a lower (<7 h/week) level of moderate-to-vigorous physical activity (MVPA) adjusted for age, gender, BMI, education and income of parents, single parenthood and study region. Recycled predictions estimated adjusted mean costs per child and activity group.
The analyses for the association between physical activity, healthcare utilization and costs showed no statistically significant results. Different directions of estimates were noticeable throughout cost components in the first step as well as the second step of the regression model. For higher MVPA (≥7 h/week) compared with lower MVPA (<7 h/week) total direct costs accounted for 392 EUR (95% CI: 342-449 EUR) versus 398 EUR (95% CI: 309-480 EUR) and indirect costs accounted for 138 EUR (95% CI: 124-153 EUR) versus 127 EUR (95% CI: 111-146 EUR).
The results indicate that childhood might be too early in life, to detect significant preventive effects of physical activity on healthcare utilization and costs, as diseases attributable to lacking physical activity might first occur later in life. This underpins the importance of clarifying the long-term effects of physical activity as it may strengthen the promotion of physical activity in children from a health economic perspective.
BMC Public Health 04/2015; 15(1):437. DOI:10.1186/s12889-015-1721-6 · 2.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Whether the strength of associations between parental and child allergic diseases differs by whether the first onset of the parental disease is before or after a child's birth has never been examined and is the aim of this study. Yearly childhood asthma, allergic rhinitis and eczema diagnoses were longitudinally regressed against the effect of a parental disease (pre versus post child birth) of the same type separately for each parent using generalized estimation equations. Both a maternal and paternal history of asthma were associated with childhood asthma prevalence up to 15 years of age. Effect estimates were similar for parental asthma with first onset before and after the birth of the child. The results for allergic rhinitis and eczema were less consistent. Parental allergic diseases with first onsets before and after the birth of a child both pose risks to childhood allergic disease in the offspring, especially for asthma. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.