[Show abstract][Hide abstract] ABSTRACT: The OptEC trial aims to evaluate the effectiveness of oral iron in young children with non-anemic iron deficiency (NAID). The initial sample size calculated for the OptEC trial ranged from 112-198 subjects. Given the uncertainty regarding the parameters used to calculate the sample, an internal pilot study was conducted. The objectives of this internal pilot study were to obtain reliable estimate of parameters (standard deviation and design factor) to recalculate the sample size and to assess the adherence rate and reasons for non-adherence in children enrolled in the pilot study.
The first 30 subjects enrolled into the OptEC trial constituted the internal pilot study. The primary outcome of the OptEC trial is the Early Learning Composite (ELC). For estimation of the SD of the ELC, descriptive statistics of the 4 month follow-up ELC scores were assessed within each intervention group. The observed SD within each group was then pooled to obtain an estimated SD (S2) of the ELC. Correlation (ρ) between the ELC measured at baseline and follow-up was assessed. Recalculation of the sample size was performed using analysis of covariance (ANCOVA) method which uses the design factor (1- ρ(2)). Adherence rate was calculated using a parent reported rate of missed doses of the study intervention.
The new estimate of the SD of the ELC was found to be 17.40 (S2). The design factor was (1- ρ2) = 0.21. Using a significance level of 5 %, power of 80 %, S2 = 17.40 and effect estimate (Δ) ranging from 6-8 points, the new sample size based on ANCOVA method ranged from 32-56 subjects (16-28 per group). Adherence ranged between 14 % and 100 % with 44 % of the children having an adherence rate ≥86 %. Information generated from our internal pilot study was used to update the design of the full and definitive trial, including recalculation of sample size, determination of the adequacy of adherence, and application of strategies to improve adherence.
ClinicalTrials.gov Identifier: NCT01481766 (date of registration: November 22, 2011).
[Show abstract][Hide abstract] ABSTRACT: Despite their wide usage, it has recently been suggested that stroller use may reduce physical activity levels of young children. However, there have been no studies on stroller use as it relates to physical activity outcomes. The objectives of this study were to understand the context of stroller use for young children and parents' perceptions of the relationship between stroller use and their children's physical activity.
Parents of children 1 to 5 years of age were recruited through two sites of TARGet Kids!, a primary-care, practice-based research network in Toronto, Canada. Fourteen semi-structured interviews were conducted. Interviews were audio recorded and transcribed verbatim and two independent reviewers conducted thematic analysis. A number of strategies were employed to ensure the trustworthiness of the data.
Parents discussed reasons for stroller use (i.e., transportation; storage; leisure; supervision/confinement; parent physical activity; and sleep), factors that influence the decision to use a stroller (i.e., caregiver choice; convenience, timing, distance; family lifestyle; and child preference), and perceived impact of stroller use on physical activity (i.e., most parents did not recognize a connection between stroller use and physical activity).
This study provides a context for researchers and policy makers to consider when developing stroller related physical activity guidelines for young children.
BMC Public Health 12/2015; 15(1):808. DOI:10.1186/s12889-015-1989-6 · 2.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Three decades of research suggests that prevention of iron deficiency anemia (IDA) in the primary care setting may be an unrealized and unique opportunity to prevent poor developmental outcomes in children. A longitudinal study of infants with IDA showed that the developmental disadvantage persists long term despite iron therapy. Early stages of iron deficiency, termed non-anemic iron deficiency (NAID), provide an opportunity for early detection and treatment before progression to IDA. There is little research regarding NAID, which may be associated with delayed development in young children. The aim of this study is to compare the effectiveness of four months of oral iron treatment plus dietary advice, with placebo plus dietary advice, in improving developmental outcomes in children with NAID and to conduct an internal pilot study.
From a screening cohort, those identified with NAID (hemoglobin ≥110 g/L and serum ferritin <14 μg/L) are invited to participate in a pragmatic, multi-site, placebo controlled, blinded, parallel group, superiority randomized trial. Participating physicians are part of a primary healthcare research network called TARGet Kids! Children between 12 and 40 months of age and identified with NAID are randomized to receive four months of oral iron treatment at 6 mg/kg/day plus dietary advice, or placebo plus dietary advice (75 per group). The primary outcome, child developmental score, is assessed using the Mullen Scales of Early Learning at baseline and at four months after randomization. Secondary outcomes include an age appropriate behavior measure (Children's Behavior Questionnaire) and two laboratory measures (hemoglobin and serum ferritin levels). Change in developmental and laboratory measures from baseline to the end of the four-month follow-up period will be analyzed using linear regression (analysis of covariance method).
This trial will provide evidence regarding the association between child development and NAID, and the effectiveness of oral iron to improve developmental outcomes in children with NAID. The sample size of the trial will be recalculated using estimates taken from an internal pilot study.
This trial was registered with Clinicaltrials.gov (identifier: NCT01481766 ) on 22 November 2011.
[Show abstract][Hide abstract] ABSTRACT: Objectives:
To determine the prevalence, risk factors, physician practice patterns and longitudinal hematological outcome of children following screening for non-anemic iron deficiency (NAID).
The present analysis was a longitudinal cohort study invovling healthy children one to five years of age. Descriptive statistics were used to describe the prevalence, risk factors, practice patterns and hematological outcome of children identified with NAID. The association between NAID and potential risk factors were examined using multivariate logistic regression analysis.
Of 2276 children undergoing screening, 155 had NAID, corresponding to a prevalence of 7% (95% CI 5.95% to 8.05%). Risk factors significantly associated with NAID included: younger age (OR 1.08 [95% CI 1.06 to 1.11]), higher body mass index z-score (OR 1.22 [95% CI 1.01 to 1.48]), longer duration of breastfeeding (OR 1.05 [95% CI 1.01 to 1.08]) and increased volume of cow's milk intake (OR 1.13 [95% CI 1.01 to 1.26]). An assessment of practice patterns revealed that for 37% of children, an intervention for NAID was documented; and for 8.4% a physician-ordered follow-up laboratory test was completed to re-evaluate iron status. A total of 58 (37%) children underwent a follow-up laboratory test, of whom 38 (65.5%) had resolution of NAID, 15 (25.9%) had persistence of NAID and two (3.4%) had progression of NAID to anemia.
NAID is common in early childhood and is associated with modifiable risk factors. Substantial practice variation exists in the management of NAID. Further research is necessary to understand the benefits of screening for NAID and evidence-informed practice guidelines may reduce practice variation in the management of NAID in early childhood.
Paediatrics & child health 10/2015; 20(6):302-6. · 1.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Vitamin D is associated with established cardiovascular risk factors such as low density lipoprotein (LDL) in adults. It is unknown whether these associations are present in early childhood. To determine whether serum 25-hydroxyvitamin D (25(OH)D) is associated with serum non-high density lipoprotein (non-HDL) cholesterol during early childhood we conducted a cross-sectional study of children aged 1 to 5 years. Healthy children were recruited through the TARGet Kids! practice based research network from 2008-2011 (n=1,961). The associations between 25(OH)D and non-fasting non-HDL cholesterol (the primary endpoint), total cholesterol, triglycerides, HDL, and low density lipoprotein (LDL) cholesterol, were evaluated using multiple linear regression adjusted for age, sex, skin pigmentation, milk intake, vitamin D supplementation, season, body mass index, outdoor play, and screen time. Each 10 nmol/L increase in 25(OH)D was associated with a decrease in non-HDL cholesterol concentration of -0.89 mg/dl (95% CI: -1.16,-0.50), total cholesterol of -1.08 mg/dl (95%CI: -1.49,-0.70), and triglycerides of -2.34 mg/dl (95%CI: -3.23,-1.45). The associations between 25(OH)D and LDL and HDL were not statistically significant. 25(OH)D concentrations were inversely associated with circulating lipids in early childhood, suggesting that vitamin D exposure in early life may be an early modifiable risk factor for cardiovascular disease.
PLoS ONE 07/2015; 10(7):e0131938. DOI:10.1371/journal.pone.0131938 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: The prevention of near and actual cardiopulmonary arrest in hospitalized children is a patient safety imperative. Prevention is contingent upon the timely identification, referral and treatment of children who are deteriorating clinically. We designed and validated a documentation-based system of care to permit identification and referral as well as facilitate provision of timely treatment. We called it the Bedside Paediatric Early Warning System (BedsidePEWS). Here we describe the rationale for the design, intervention and outcomes of the study entitled Evaluating Processes and Outcomes of Children in Hospital (EPOCH). Methods/Design: EPOCH is a cluster-randomized trial of the BedsidePEWS. The unit of randomization is the participating hospital. Eligible hospitals have a Pediatric Intensive Care Unit (PICU), are anticipated to have organizational stability throughout the study, are not using a severity of illness score in hospital wards and are willing to be randomized. Patients are >37 weeks gestational age and <18 years and are hospitalized in inpatient ward areas during all or part of their hospital admission. Discussion: Following funding by the Canadian Institutes of Health Research and local ethical approvals, site enrollment started in 2010 and was closed in February 2014. Patient enrollment is anticipated to be complete in July 2015. The results of EPOCH will strengthen the scientific basis for local, regional, provincial and national decision-making and for the recommendations of national and international bodies. If negative, the costs of hospital-wide implementation can be avoided. If positive, EPOCH will have provided a scientific justification for the major system-level changes required for implementation.
[Show abstract][Hide abstract] ABSTRACT: Fe-deficiency anaemia (IDA) occurs in 1-2 % of infants in developed countries, peaks at 1-3 years of age and is associated with later cognitive deficits. The objectives of the present study were to describe the characteristics of young children with severe IDA and examine modifiable risk factors in a developed-country setting.
Two prospective samples: a national surveillance programme sample and a regional longitudinal study sample.
Two samples of young children recruited from community-based health-care practices: a national sample with severe anaemia (Hb<80 g/l) due to Fe deficiency and a regional sample with non-anaemic Fe sufficiency.
Children with severe IDA (n 201, mean Hb 55·1 g/l) experienced substantial morbidity (including developmental delay, heart failure, cerebral thrombosis) and health-care utilization (including a 42 % hospitalization rate). Compared with children with Fe sufficiency (n 597, mean Hb 122·4 g/l), children with severe IDA consumed a larger volume of cow's milk daily (median 1065 ml v. 500 ml, P<0·001) and were more likely to be using a bottle during the day (78 % v. 43 %, OR=6·0; 95 % CI 4·0, 8·9) and also in bed (60 % v. 21 %, OR=6·5; 95 % CI 4·4, 9·5).
Severe IDA is associated with substantial morbidity and may be preventable. Three potentially modifiable feeding practices are associated with IDA: (i) cow's milk consumption greater than 500 ml/d; (ii) daytime bottle use beyond 12 months of age; and (iii) bottle use in bed. These feeding practices should be highlighted in future recommendations for public health and primary-care practitioners.
Public Health Nutrition 06/2015; DOI:10.1017/S1368980015001639 · 2.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Identifying modifiers of glioma risk in patients with type 1 neurofibromatosis (NF1) could help support personalized tumor surveillance, advance understanding of gliomagenesis and potentially identify novel therapeutic targets. Here we report genetic polymorphisms in the human adenylate cyclase gene ADCY8 which correlate with glioma risk in NF1 in a sex-specific manner, elevating risk in females while reducing risk in males. This finding extends earlier evidence of a role for cAMP in gliomagenesis based on results in a genetically engineered mouse model (Nf1 GEM). Thus, sexually dimorphic cAMP signaling might render males and females differentially sensitive to variation in cAMP levels. Using male and female Nf1 GEM, we found significant sex differences exist in cAMP regulation and in the growth promoting effects of cAMP suppression. Overall, our results establish a sex-specific role for cAMP regulation in human gliomagenesis, specifically identifying ADCY8 as a modifier of glioma risk in NF1.
Cancer Research 11/2014; 75(1). DOI:10.1158/0008-5472.CAN-14-1891 · 9.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Vitamin D fortification of non-cow's milk beverages is voluntary in North America. The effect of consuming non-cow's milk beverages on serum 25-hydroxyvitamin D levels in children is unclear. We studied the association between non-cow's milk consumption and 25-hydroxyvitamin D levels in healthy preschool-aged children. We also explored whether cow's milk consumption modified this association and analyzed the association between daily non-cow's milk and cow's milk consumption.
In this cross-sectional study, we recruited children 1-6 years of age attending routinely scheduled well-child visits. Survey responses, and anthropometric and laboratory measurements were collected. The association between non-cow's milk consumption and 25-hydroxyvitamin D levels was tested using multiple linear regression and logistic regression. Cow's milk consumption was explored as an effect modifier using an interaction term. The association between daily intake of non-cow's milk and cow's milk was explored using multiple linear regression.
A total of 2831 children were included. The interaction between non-cow's milk and cow's milk consumption was statistically significant (p = 0.03). Drinking non-cow's milk beverages was associated with a 4.2-nmol/L decrease in 25-hydroxyvitamin D level per 250-mL cup consumed among children who also drank cow's milk (p = 0.008). Children who drank only non-cow's milk were at higher risk of having a 25-hydroxyvitamin D level below 50 nmol/L than children who drank only cow's milk (odds ratio 2.7, 95% confidence interval 1.6 to 4.7).
Consumption of non-cow's milk beverages was associated with decreased serum 25-hydroxyvitamin D levels in early childhood. This association was modified by cow's milk consumption, which suggests a trade-off between consumption of cow's milk fortified with higher levels of vitamin D and non-cow's milk with lower vitamin D content.
Canadian Medical Association Journal 10/2014; 186(17). DOI:10.1503/cmaj.140555 · 5.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective:
Urinary tract infection (UTI) is the most common serious bacterial infection in infants. To use resources optimally, factors contributing to costs through length of stay (LOS) must be identified. This study sought to identify clinical and health system factors associated with long LOS in infants with UTI.
Using a case-control design, we included infants <6 months old hospitalized with UTI. Cases had LOS ≥96 hours; controls had LOS <96 hours. Clinical and health system variables were extracted from medical records. Cases and controls were compared by using comparative statistics and multiple logistic regression analysis.
Cases (n = 71) and controls (n = 71) did not differ by gender; cases were more likely to be younger (4.2 vs 7.1 weeks, P = .04), born preterm (13% vs 3%, P = .03), have known genitourinary disease (17% vs 4%, P = .01), an ultrasound (85% vs 68%, P = .02) or voiding cystourethrogram (VCUG) (61% vs 34%, P = .001) ordered, longer wait for VCUG (53 vs 27 hours, P = .002), consult requested (54% vs 10%, P < .001), and longer duration of intravenous (IV) antibiotics (125 vs 62 hours, P < .001). Multiple logistic regression demonstrated that cases were more likely to be premature (odds ratio [OR] 7.6), have known genitourinary disease (OR 7.3), and have VCUG ordered in the hospital (OR 4.5).
Infants who are older, are born full term, have no genitourinary disease, receive shorter courses of IV antibiotics, and do not have a VCUG ordered have shorter stays and may be eligible for a short-stay unit. Earlier transition to oral antibiotics and delayed ordering of a VCUG may decrease LOS.
[Show abstract][Hide abstract] ABSTRACT: Importance
Routine use of pulse oximetry has been associated with changes in bronchiolitis management and may have lowered the hospitalization threshold for patients with bronchiolitis.Objective
To examine if infants with bronchiolitis whose displayed oximetry measurements have been artificially elevated 3 percentage points above true values experience hospitalization rates at least 15% lower compared with infants with true values displayed.Design, Setting, and Participants
Randomized, double-blind, parallel-group trial conducted from 2008 to 2013 in a tertiary-care pediatric emergency department in Toronto, Ontario, Canada. Participants were 213 otherwise healthy infants aged 4 weeks to 12 months with mild to moderate bronchiolitis and true oxygen saturations of 88% or higher.Interventions
Pulse oximetry measurements with true saturation values displayed or with altered saturation values displayed that have been increased 3 percentage points above true values.Main Outcomes and Measures
The primary outcome was hospitalization within 72 hours, defined as inpatient admission within this interval or active hospital care for greater than 6 hours. Secondary outcomes included the use of supplemental oxygen in the emergency department, level of physician agreement with discharge from the emergency department, length of emergency department stay, and unscheduled visits for bronchiolitis within 72 hours.Results
Forty-four of 108 patients (41%) in the true oximetry group and 26 of 105 (25%) in the altered oximetry group were hospitalized within 72 hours (difference, 16% [95% CI for the difference, 3.6% to 28.4%]; P = .005). Using the emergency department physician as a random effect, the primary treatment effect remained significant (adjusted odds ratio, 4.0 [95% CI, 1.6 to 10.5]; P = .009). None of the secondary outcomes were significantly different between the groups. There were 23 of 108 (21.3%) subsequent unscheduled medical visits for bronchiolitis in the true oximetry group and 15 of 105 (14.3%) in the altered oximetry group (difference, 7% [95% CI, −0.3% to 0.2%]; P = .18).Conclusions and Relevance
Among infants presenting to an emergency department with mild to moderate bronchiolitis, those with an artificially elevated pulse oximetry reading were less likely to be hospitalized within 72 hours or to receive active hospital care for more than 6 hours than those with unaltered oximetry readings. This suggests that oxygen saturation should not be the only factor in the decision to admit, and its use may need to be reevaluated.Trial Registration
clinicaltrials.gov Identifier: NCT00673946
JAMA The Journal of the American Medical Association 08/2014; 312(7):712-8. DOI:10.1001/jama.2014.8637 · 35.29 Impact Factor