[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: 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: 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 Pediatric 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).
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. Randomization is to either BedsidePEWS or control (no severity of illness score) in a 1:1 ratio within two strata (<200, ≥200 hospital beds). All-cause hospital mortality is the selected primary outcome. It is objective, independent of do-not-resuscitate status and can be reliably measured. The secondary outcomes include (1) clinical outcomes: clinical deterioration, severity of illness at and during ICU admission, and potentially preventable cardiac arrest; (2) processes of care outcomes: immediate calls for assistance, hospital and ICU readmission, and perceptions of healthcare professionals; and (3) resource utilization: ICU days and use of ICU therapies.
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.
NCT01260831 ClinicalTrials.gov date: 14 December 2010.
[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 · 2.48 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 · 9.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Canadian Medical Association Journal 10/2014; 186(17). DOI:10.1503/cmaj.140555 · 5.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
[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 · 30.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The Applied Research Group for Kids (TARGet Kids!) is an ongoing open longitudinal cohort study enrolling healthy children (from birth to 5 years of age) and following them into adolescence. The aim of the TARGet Kids! cohort is to link early life exposures to health problems including obesity, micronutrient deficiencies and developmental problems. The overarching goal is to improve the health of Canadians by optimizing growth and developmental trajectories through preventive interventions in early childhood. TARGet Kids!, the only child health research network embedded in primary care practices in Canada, leverages the unique relationship between children and families and their trusted primary care practitioners, with whom they have at least seven health supervision visits in the first 5 years of life. Children are enrolled during regularly scheduled well-child visits. To date, we have enrolled 5062 children. In addition to demographic information, we collect physical measurements (e.g. height, weight), lifestyle factors (nutrition, screen time and physical activity), child behaviour and developmental screening and a blood sample (providing measures of cardiometabolic, iron and vitamin D status, and trace metals). All data are collected at each well-child visit: twice a year until age 2 and every year until age 10. Information can be found at: http://www.targetkids.ca/contact-us/.
International Journal of Epidemiology 06/2014; 44(3). DOI:10.1093/ije/dyu123 · 9.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To identify sociodemographic, dietary, and biological factors associated with families who do not receive dental care in early childhood and to identify risk factors associated with having cavities among children who receive early dental care.
A cross-sectional study of healthy Canadian children seen for primary health care between September 2011 and January 2013 was conducted through the TARGet Kids! practice-based research network in Toronto, Canada. Adjusted logistic regression was used to determine factors associated with children who were not seen by a dentist in early childhood and to determine risk factors associated with having dental cavities among children who received early dental care.
Of the 2505 children included in the analysis, <1% were seen by a dentist by 1 year of age. Older children were less likely to have never been to the dentist (odds ratio [OR], 0.88; 95% confidence interval [CI], 0.87-0.90). Low family income (OR, 2.73; 95% CI, 1.47-5.06), prolonged bottle use (OR, 1.43; 95% CI, 1.03-2.00), and higher intakes of sweetened drinks (OR, 1.20; 95% CI, 1.01-1.42) were associated with increased risk for never having been to the dentist. Among those who had been to the dentist, older children (OR, 1.04; 95% CI, 1.03-1.05), children of low income families (OR, 1.90; 95% CI, 1.17-3.10), and those of East Asian maternal ethnicity (OR, 1.91; 95% CI, 1.10-3.29) were more likely to have dental cavities.
Among healthy urban children seen by a primary care provider, those most susceptible to cavities were least likely to receive early dental care. These findings support the need for publicly funded universal early preventive dental care and underscore the importance for primary care physicians to promote dental care in early childhood.