Mandatory labeling requirements and over-the-counter cough and cold medication use in early childhood.

OBJECTIVES: Due to rare but severe adverse events, Health Canada in October 2009 required manufacturers to relabel over-the-counter (OTC) cough and cold medication (CCM) to state that the products should not be used in children <6 years of age. The main objective of this study was to determine whether this labeling standard decreased OTC CCM use among young children with a recent cough, cold or flu. METHODS: An interrupted time series study was conducted using data from the TARGet Kids! practice-based research network. A total of 3,515 healthy children 1-5 years of age were recruited from 2008-2011; of these, 1,072 had a cough, cold or flu in the previous month. Parents completed a standardized survey instrument. For the primary analysis, use of OTC CCMs prior to and after October 1, 2009 was compared using time series analyses. For the secondary analysis, multivariable logistic regression was used to identify predictors of recent OTC CCM use. RESULTS: OTC CCM use was reported in 222 of 1,072 (20.7%) children with a cough, cold or flu within the previous month. OTC CCM use declined from 22.2% to 17.8% following the October 2009 Health Canada labeling standard (p = 0.014). Maternal age <35 years (OR 1.49; 95% CI: 1.05-2.13) and having older siblings (OR 1.65; 95% CI: 1.16-2.35) were independently associated with OTC CCM use. CONCLUSION: Labeling legislation against OTC CCM use for children <6 years resulted in a small decrease in OTC CCM use. Stronger measures may be needed to curtail OTC CCM use, particularly for younger parents and those with multiple children.

Severe iron-deficiency anaemia and feeding practices in young children.

OBJECTIVES: 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. DESIGN: Two prospective samples: a national surveillance programme sample and a regional longitudinal study sample. SETTING: Canada, 2009-2011. SUBJECTS: 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. RESULTS: 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). CONCLUSIONS: 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.

Comparison of isotonic and hypotonic intravenous maintenance fluids: a randomized clinical trial.

IMPORTANCE: Use of hypotonic intravenous fluids for maintenance requirements is associated with increased risk of hyponatremia that results in morbidity and mortality in children. Clinical trial data comparing isotonic and hypotonic maintenance fluids in nonsurgical hospitalized pediatric patients outside intensive care units are lacking. OBJECTIVE: To compare isotonic (sodium chloride, 0.9%, and dextrose, 5%) with hypotonic (sodium chloride, 0.45%, and dextrose, 5%) intravenous maintenance fluids in a hospitalized general pediatric population. DESIGN, SETTING, AND PARTICIPANTS: In this double-blind randomized clinical trial,we recruited 110 children admitted to a general pediatric unit of a tertiary care children's hospital from March 1, 2008, through August 31, 2012 (age range, 1 month to 18 years), with normal baseline serum sodium levels who were anticipated to require intravenous maintenance fluids for 48 hours or longer (intent-to-treat analyses). Children with diagnoses that required specific fluid tonicity and volumes were excluded. INTERVENTIONS: Patients were randomized to receive isotonic or hypotonic intravenous fluid at maintenance rates for 48 hours. MAIN OUTCOMES AND MEASURES: The primary outcome was mean serum sodium level at 48 hours. The secondary outcomes were mean sodium level at 24 hours, hyponatremia and hypernatremia, weight gain, hypertension, and edema. Confounding variables were included in multiple regression models. Post hoc analyses included change from baseline sodium level at 24 and 48 hours and subgroup analysis of children with primary respiratory diagnosis. RESULTS: Of 110 enrolled patients, 54 received isotonic fluids and 56 received hypotonic fluids. The mean (SD) sodium level at 48 hours was 139.9 (2.7) mEq/L in the isotonic group and 139.6 (2.6) mEq/L in the hypotonic group (95% CI of the difference, -0.94 to 1.74 mEq/L; P = .60). Two patients in the hypotonic group developed hyponatremia, 1 in each group developed hypernatremia, 2 in each group developed hypertension, and 2 in the isotonic group developed edema. Mean (SD) change from baseline to 48-hour sodium level was +1.3 (2.9) vs -0.12 (2.8) mEq/L, respectively (absolute difference, 1.4 mEq/L; 95% CI of the difference, -0.01 to 2.8 mEq/L; P = .05). CONCLUSIONS AND RELEVANCE: Our study results support the notion that isotonic maintenance fluid administration is safe in general pediatric patients and may result in fewer cases of hyponatremia. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00632775.

Predictors of long length of stay in infants hospitalized with urinary tract infection.

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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Non-Western immigrant children have lower 25-hydroxyvitamin D than children from Western families.

OBJECTIVE: To determine if children aged 1-6 years from non-Western immigrant families have lower serum 25-hydroxyvitamin D (25(OH)D) levels than children from Western-born families and examine which factors influence this relationship. DESIGN: Cross-sectional study. SETTING: Toronto, Canada. SUBJECTS: Healthy children (n 1540) recruited through the TARGet Kids! practice-based research network. Serum 25(OH)D concentrations of non-Western immigrants were compared with those of children from Western-born families. Children from non-Western immigrant families were defined as those born, or their parents were born, outside a Western country. Univariate and multiple linear regression analyses were used to identify factors which might influence this relationship. RESULTS: Median age was 36 months, 51 % were male, 86 % had 'light' skin pigmentation, 55 % took vitamin D supplements, mean cow's milk intake was 1·8 cups/d and 27 % were non-Western immigrants. Median serum 25(OH)D concentration was 83 nmol/l, with 5 % having 25(OH)D < 50 nmol/l. Univariable analysis revealed that non-Western immigrant children had serum 25(OH)D lower by 4 (95 % CI 1·3, 8·0) nmol/l (P = 0·006) and increased odds of 25(OH)D < 50 nmol/l (OR = 1·9; 95 % CI 1·3, 2·9). After adjustment for known vitamin D determinants the observed difference attenuated to 0·04 (95 % CI -4·8, 4·8) nmol/l (P = 0·99), with higher cow's milk intake (P < 0·0001), vitamin D supplementation (P < 0·0001), summer season (P = 0·008) and increased age (P = 0·04) being statistically significant covariates. Vitamin D supplementation was the strongest explanatory factor of the observed difference. CONCLUSIONS: There is an association between non-Western immigration and lower 25(OH)D in early childhood. This difference appears related to known vitamin D determinants, primarily vitamin D supplementation, representing opportunities for intervention.

Successful discharge of children with gastroenteritis requiring intravenous rehydration.

BACKGROUND: Emergency Department (ED) revisits are very common in children with gastroenteritis administered intravenous rehydration. STUDY OBJECTIVES: To determine if bicarbonate values are associated with ED revisits in children with gastroenteritis. METHODS: We conducted a secondary analysis of prospectively collected data, which included children >3 months of age with gastroenteritis treated with intravenous rehydration. Regression analysis was employed to determine whether, among discharged children, bicarbonate independently predicts revisits within 7 days (primary outcome) and successful discharge (secondary outcome). The latter composite outcome measure was defined as discharge at the index visit and the absence of a revisit requiring intravenous rehydration. RESULTS: Of 226 potentially eligible children, 174 were discharged and were included in the primary outcome analysis. Of the eligible children, 18% (30/174) had a revisit that was predicted by a higher baseline bicarbonate (odds ratio [OR] 1.1; 95% confidence interval [CI] 1.0-1.3; p = 0.03), absence of a primary care provider (OR 7.8; 95% CI 1.2-51.0; p = 0.03), and ondansetron administration (OR 2.4; 95% CI 1.0-5.5; p = 0.05). Bicarbonate was not associated with successful discharge. Negatively associated independent predictors of successful discharge were volume of intravenous fluids administered (OR 0.84/10 mL/kg increase; 95% CI 0.76-0.93; p < 0.001), and baseline clinical dehydration score (OR 0.75/unit increase; 95% CI 0.58-0.97; p < 0.001). Revisits requiring intravenous rehydration and hospitalization were associated with higher bicarbonate values (21.2 ± 4.6 mEq, p = 0.001, and 22.3 ± 5.0 mEq/L, p < 0.001, respectively). CONCLUSION: Lower serum bicarbonate values at the time of intravenous rehydration are not associated with unfavorable outcomes after discharge.

Predictors of bacteremia among children with sickle cell disease presenting with fever.

INTRODUCTION: Bacterial sepsis is more common and potentially life threatening in children with sickle cell disease (SCD). Identification of variables that predict bacteremia may aid clinicians in recognizing patients with SCD at higher risk for sepsis. OBJECTIVE: To determine whether absolute neutrophil count (ANC) >20×10/L is an independent risk factor for bacteremia in children with SCD and to identify other predictors of bacteremia in this population. METHODS: A case-control study was conducted. Subjects were 0 to 18 years of age admitted to a tertiary care pediatric hospital over a 17-year period with SCD and fever at presentation. Cases had bacteremia, whereas controls had negative blood cultures. RESULTS: Data were analyzed for 40 cases and 120 controls. ANC>20×10/L was significantly more prevalent among cases (odds ratio [OR], 7.0; 95% confidence interval [CI], 2.6-18.9). Cases were more likely to have emesis (OR, 2.9; 95% CI, 1.0-8.4) and a higher proportion of band cells (OR, 1.3; 95% CI, 1.1-1.4) at presentation. CONCLUSIONS: In a febrile child with SCD, an ANC>20×10/L, a higher proportion of band cells, and the presence of vomiting were associated with an increased likelihood of bacteremia.

Clobetasol propionate, 0.05%, vs hydrocortisone, 1%, for alopecia areata in children: a randomized clinical trial.

IMPORTANCE: Alopecia areata is an idiopathic cause of hair loss with limited therapeutic repertoire. OBJECTIVE: To compare the efficacy and safety of a high- vs low-potency topical corticosteroid in pediatric patients. DESIGN, SETTING, AND PARTICIPANTS: This single-center, randomized, blind, 2-arm, parallel-group, superiority trial was carried out over a 24-week period at a tertiary referral academic dermatology clinic at The Hospital for Sick Children in Toronto, Ontario, Canada. Forty-two children attending the outpatients clinic, 2 to 16 years of age with alopecia areata affecting at least 10% of scalp surface area, were eligible; 1 declined to participate. There were no withdrawals from the study. INTERVENTIONS FOR CLINICAL TRIALS: Patients were randomly assigned to receive clobetasol propionate, 0.05% cream, or hydrocortisone, 1%, cream. Patients applied a thin layer of the assigned cream twice daily to the areas of hair loss for 2 cycles of 6 weeks on, 6 weeks off, for a total of 24 weeks. MAIN OUTCOMES AND MEASURES: The primary outcome was the change in scalp surface area with hair loss over 24 weeks following enrollment. RESULTS All participants were assessed at 6, 12, 18, and 24 weeks (except 1 participant who missed the 6-week visit). After adjusting for baseline hair loss, the clobetasol group had a statistically significant (P < .001) greater decrease in the surface area with hair loss, compared with the hydrocortisone group at all time points except at 6 weeks. One patient with extensive alopecia areata experienced skin atrophy that resolved spontaneously in 6 weeks. There was no difference observed in the number of patients with abnormal urinary cortisol at the beginning and the end of the study. CONCLUSIONS AND RELEVANCE: Topical clobetasol propionate, 0.05%, cream is efficacious and safe as a first-line agent for limited patchy childhood alopecia areata. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01453686.

Prostate cancer-specific survival differences in patients treated by radical prostatectomy versus curative radiotherapy.

OBJECTIVE: We compared the cause-specific survival of patients who received radiotherapy to those who received surgery for cure of their prostate cancer using a number of design and analytic steps to mitigate confounding by indication. METHODS: This was a case-cohort study of 2213 patients in the Ontario Cancer Registry diagnosed between 1990 and 1998 who were either treatment candidates or received curative radiotherapy or surgery. Cases included patients who died of prostate cancer within 10 years. The study population was restricted to those who were candidates for either treatment (radiotherapy or surgery) based on disease severity (low and intermediate risk using the Genitourinary Radiation Oncologists of Canada risk groups). The median follow-up was 51 months. Cause-specific survival was analyzed using Cox-proportional hazards regression with case-cohort variance adjustment. Results from intent-to-treat analyses were compared to results by treatment received. RESULTS: Adjusted hazard ratios for risk of prostate cancer death for radiotherapy compared to surgery for the entire study population were 1.62 (95%CI 1.00-2.61) and 2.02 (1.19-3.43) analyzing by intent-to-treat and treatment received, respectively. Intent-to-treat hazard ratios for the low- and intermediate-risk groups were 0.87 (0.28-2.76) and 1.57 (0.95-2.61), respectively. CONCLUSION: Overall results were driven by the finding in the intermediate-risk group, which indicated that radiotherapy was not as effective as surgery in this group. Confirmation was needed with special attention paid to risk stratification and the impact of more contemporary delivery of these treatment options.

Modifiable determinants of serum 25-hydroxyvitamin D status in early childhood: opportunities for prevention.

OBJECTIVES To determine the effect of modifiable dietary intake variables (current vitamin D supplementation and daily cow's milk intake) on 25-hydroxyvitamin D level in early childhood and to evaluate the relationship between these modifiable dietary factors and other largely nonmodifiable determinants of vitamin D status including skin pigmentation and season. DESIGN Cross-sectional study. SETTING Primary care pediatric and family medicine practices participating in the TARGet Kids! practice-based research network in Toronto, Ontario, Canada. PARTICIPANTS From December 2008 to June 2011, healthy children 1 to 5 years of age were recruited during a routine physician's visit. INTERVENTIONS Survey, anthropometric measurements, and laboratory data were collected. A multivariable linear regression model was developed to examine the independent effects of vitamin D supplementation and daily volume of cow's milk on 25-hydroxyvitamin D level. MAIN OUTCOME MEASURES 25-Hydroxyvitamin D level. RESULTS Blood was obtained in 1898 children. Two modifiable dietary intake variables, vitamin D supplementation and cow's milk, increased 25-hydroxyvitamin D level by 3.4 ng/mL (95% CI, 2-4 ng/mL) and 1.6 ng/mL per 250-mL cup per day (95% CI, 1-2 ng/mL), respectively. Two nonmodifiable variables reflecting cutaneous vitamin D synthesis (skin pigmentation and season) were also strongly associated with 25-hydroxyvitamin D status but accounted for a much smaller proportion of the explained variation in 25-hydroxyvitamin D level. The effect of vitamin D supplementation and milk intake on 25-hydroxyvitamin D level appeared similar regardless of skin pigmentation or season. CONCLUSION Two modifiable dietary intake variables (vitamin D supplementation and cow's milk intake) are the most important determinants of 25-hydroxyvitamin D status in early childhood.

Office-based randomized controlled trial to reduce screen time in preschool children.

OBJECTIVE: To determine if an intervention for preschool-aged children in primary care is effective in reducing screen time, meals in front of the television, and BMI. METHODS: A randomized controlled trial was conducted at a primary care pediatric group practice in Toronto, Canada. Three-year-old children and their parents were randomly assigned to receive a short behavioral counseling intervention on strategies to decrease screen time. The primary outcome 1 year later was parent reported screen time. Secondary outcomes included television in the child's bedroom, number of meals in front of the television, and BMI. RESULTS: In the intention-to-treat analysis at 1 year, there were no significant differences in mean total weekday minutes of screen time (60, interquartile range [IQR]: 35-120 vs 65, IQR: 35-120; P = .68) or mean total weekend day minutes of screen time (80, IQR: 45-130 vs 90, IQR: 60-120; P = .33) between the intervention and control group. Adjusting for baseline BMI, there was a reduction in the number of weekday meals in front of the television (1.6 ± 1.0 vs 1.9 ± 1.2; P = .03) but no differences in BMI or number of televisions in the bedroom. CONCLUSIONS: This pragmatic trial was not effective in reducing screen time or BMI but was effective in reducing meals in front of the screen. Short interventions focused solely on reducing screen time implemented in the primary care practice setting may not be effective in this age group.

Therapeutic value of lymph node dissection at radical prostatectomy: a population-based case-cohort study.

OBJECTIVE: • To examine the association between the number of lymph nodes removed in pelvic lymphadenectomy and the risk of prostate cancer death, particularly in low to intermediate risk prostate cancer patients. PATIENTS AND METHODS: • Data on a subset of patients from a population-based case-cohort study was used to assess the effect of lymph node removal on prostate cancer-specific mortality. • The subset included in this report were those 281 patients from the parent study who were treated with prostatectomy and had a pelvic lymph node dissection and for whom we had a record of the number of nodes removed (the sub-cohort) and 41 patients fitting the same criteria who died of their prostate cancer within 10 years (the cases). • Study variables included number of lymph nodes removed, lymph node status, age, pre-treatment PSA, T category, Gleason score and use of hormonal therapy. • We ran a Cox proportional hazards regression analysis that accounted for the study design and allowed us to consider these patient and disease characteristics as potential confounders of the association of interest. • In a secondary analysis, the results were stratified by nodal status. RESULTS: • The crude hazard ratio (HR), which is a measure of relative risk, was not statistically significantly associated with a reduction in the risk of prostate cancer mortality as the number of lymph nodes removed at PLND increased (HR: 0.97, 95% CI: 0.91-1.03). • None of the variables considered as potential confounders had an impact on the crude HR. Using two cut points to categorize the number of lymph nodes removed, one at 4 or more removed and the other at 10 or more removed resulted in HRs indicating a risk reduction of 25% in both cases, although these results were not statistically significant. • When we analyzed the association by pathological nodal status, we observed a possible increase in risk in the node-positive group (HR: 1.10, 95% CI: 0.86, 1.42), while those with negative lymph nodes may have benefited from increasing numbers removed (HR 0.95, 95% CI: 0.89,1.02). CONCLUSION: • The results of this study indicate a possible therapeutic benefit of lymph node removal in node negative patients. Future research should focus on gaining a better understanding of the biologic mechanisms of a possible therapeutic benefit of PLND, particularly for those lower risk patients with histologically negative lymph nodes.