Rebecca Ronsley

Increased Prevalence of Obesity and Glucose Intolerance in Youth Treated with Second—Generation Antipsychotic Medications

Objective: To compare the rates of obesity, impaired fasting glucose (IFG), and type 2 diabetes between second-generation antipsychotic (SGA)-treated and -naive youth. Methods: A retrospective chart review was conducted for all child and adolescent psychiatry emergency admissions over 2.5 years. Data collected included age, sex, psychiatric diagnosis, medications, height, weight, fasting glucose, and lipid profile. Body mass index (BMI) was standardized for age and sex and converted to a z score. Overweight was defined as a BMI between the 85th and 95th percentile and obese as a BMI at the 95th percentile or greater for age and sex. The 2007 American Diabetes Association criteria for IFG and type 2 diabetes were used. Results: Among the 432 admissions, 167 (39%) had both height and weight measured, and 145 (34%) had fasting glucose measured. The mean zBMI was higher in the SGA-treated (n = 68), compared with the SGA-naive group (n = 99) (mean difference 0.81; 95% CI 0.46 to 1.16). In the SGA-treated group, 31% were obese and 26% were overweight, compared with 15% and 8%, respectively, in the SGA-naive group (P < 0.01). In the SGA-treated group (n = 65), 21.5% had IFG or type 2 diabetes, compared with 7.5% in the SGA-naive group (n = 80) (P = 0.01). Conclusions: Youth treated with SGAs have significantly higher rates of obesity and glucose intolerance than SGA-naive youth. These data emphasize the need for consistent metabolic monitoring of youth with psychiatric disorders who are prescribed SGAs.

A population-based study of antipsychotic prescription trends in children and adolescents in British Columbia, from 1996 to 2011.

Objectives: To establish prevalence rates of antipsychotic (AP) prescriptions for children 18 years of age or younger in British Columbia (BC) from 1996 to 2011 by age, sex, AP type, and primary diagnosis; and to identify the predominant AP prescribers for children by specialty training. Methods: BC Ministry of Health administrative data were used to describe AP prescriptions for youth aged 18 years or younger. Comparisons were made using population prevalence based on sex; age group; AP; International Classification of Diseases, Ninth Revision, diagnosis; and prescriber specialty. Results: From 1996 to 2011, overall AP (both first and second generation) prescription prevalence rate increased 3.8-fold (1.66 to 6.37 per 1000 population); second-generation AP (SGA) prescriptions increased 18.1-fold (0.33 to 5.98 per 1000 population). The highest increase in all AP prescriptions occurred in males aged 13 to 18 years (3.3 to 14.4 per 1000 population; 4.4-fold), followed by similar increases in males aged 6 to 12 years (2.3 to 8.6 per 1000 population; 3.7-fold) and in females aged 13 to 18 years (2.8 to 10.7 per 1000 population; 3.8-fold). Overall, the 3 most common diagnoses associated with all AP prescriptions were depressive disorders (12.8%), hyperkinetic syndrome of childhood (11.7%), and neurotic disorders (11.1%); however, variation was observed by prescriber specialty training. Among all new AP prescriptions in 2010/11, 38.6%, 34.3%, and 15.6% were provided by psychiatrists, family physicians, and pediatricians, respectively. Conclusions: There has been an exponential rise in SGA prescriptions in BC secondary to extensive off-label use, not only by psychiatrists but also by family physicians and pediatricians. Knowledge translation initiatives promoting evidence-based prescribing and monitoring practices related to SGA treatment need to target all 3 prescriber groups and be tailored for age subgroups.

Waist Circumference Is a Sensitive Screening Tool for Assessment of Metabolic Syndrome Risk in Children Treated with Second-Generation Antipsychotics

Objective: To compare the prevalence of metabolic syndrome (MetS) and its components in second-generation antipsychotic (SGA)-treated and SGA-naive children; and to explore the utility of clinical markers, such as waist circumference (WC) and body mass index (BMI), as screening tools for MetS. Methods: Subjects were prospectively recruited from the Psychiatry Emergency Unit at British Columbia Childrens Hospital. As part of a quality-assurance project, a metabolic monitoring protocol was implemented, including collection of anthropomorphic and laboratory data. Results: From January 2008 to February 2010, there were 117 SGA-treated and 217 SGA-naive children recruited. The overall prevalence of MetS was 19.0% (16/84; median treatment duration = 14 months) in SGA-treated and 0.8% (1/127) in SGA-naive children (OR 29.7; 95% CI 3.85 to 228.40, P < 0.001), with an increased prevalence of all components except high-density lipoprotein cholesterol (HDL-C), respectively: elevated WC (40.7% and 10.1%; P < 0.001); hypertriglyceridemia (33.7% and 18.8%; P = 0.01); impaired fasting glucose (12.5% and 0.7%; P = 0.005); and elevated blood pressure (41.2% and 16.5%; P < 0.001). SGA treatment was the strongest predictor of MetS (OR 19.2; 95% CI 2.30 to 160.44, P = 0.006) followed by male sex (OR 5.7; 95% CI 1.08 to 30.62, P = 0.04). Presence of abdominal obesity was more sensitive (92.9%) than BMI (68.8%), while fasting glucose of 5.6 mmol/L or more and HDL-C of 1.03mmol/L or less were most specific (94.1%) in correctly identifying MetS. Conclusions: SGA treatment confers a significantly increased risk for MetS over the long term. WC measurement is a simple and sensitive screening tool for determining MetS risk in SGA-treated children. These data highlight the dangers of SGA treatment and the importance of standardized metabolic monitoring using sex- and age-adjusted tables in this population.

Increased Risk of Obesity and Metabolic Dysregulation Following 12 Months of Second-Generation Antipsychotic Treatment in Children: A Prospective Cohort Study

Objective: To determine the risk of developing obesity and related metabolic complications in children following long-term treatment with risperidone or quetiapine. Methods: This was a 1-year naturalistic longitudinal study conducted between February 2009 and March 2012. A total of 130 children aged 2 to 18 years without prior exposure to second-generation antipsychotics (SGAs) were enrolled at initiation of treatment with either risperidone or quetiapine. Metabolic parameters were measured at baseline and months 6 and 12. Data of 37 participants (20 treated with risperidone and 17 treated with quetiapine) who completed 12-month monitoring were used in the analysis. Results: After 1 year of SGA treatment, mean weight increased significantly by 10.8 kg (95% CI 7.9 kg to 13.7 kg) for risperidone and 9.7 kg (95% CI 6.5 kg to 12.8 kg) for quetiapine. Body mass index z score also increased significantly in both groups (P < 0.001). There was a high incidence of children becoming overweight or obese (6/15 [40.0%] for risperidone-treated and 7/14 [50.0%] for quetiapine-treated). The mean levels of fasting glucose (for risperidone-treated) and ratio of total cholesterol to high-density lipoprotein cholesterol (for quetiapine-treated) increased significantly by 0.23 mmol/L (95% CI 0.03 mmol/L to 0.42 mmol/L) and 0.48 mmol/L (95% CI 0.15 mmol/L to 0.80 mmol/L), respectively. Conclusion: Children treated with risperidone or quetiapine are at a significant risk for developing obesity, elevated waist circumference, and dyslipidemia during 12 months of treatment. These data emphasize the importance of regular monitoring for early identification and treatment of metabolic side effects.

The centre for healthy weights--shapedown BC: a family-centered, multidisciplinary program that reduces weight gain in obese children over the short-term.

The objective was to conduct a program evaluation of the Centre for Healthy Weights—Shapedown BC (CHW-SB), a family-centered, multidisciplinary program for obese children, by assessing the change in weight trajectories from program intake to completion. Secondary outcomes included changes in clinical, biochemical and psychological parameters, and in physical activity (PA) levels. The CHW-SB program was evaluated over 10 weeks. Data collection included anthropometric, metabolic, PA and psychological measures. Longitudinal mixed effects regression was performed to evaluate weight change from Phase 1 (before program on waitlist) to Phase 2 (during program). 238 children <18 years of age were referred to the program of which 119 were eligible for participation. There was a significant decrease in weight trajectory in children following program entry. Participants experienced an average .89% monthly increase before program entry, compared to a .37% monthly decline afterwards, a drop of 1.26% (p < 0.0001, 95%CI 1.08 to 1.44). zBMI (2.26 ± 0.33 to 2.20 ± 0.36, p < 0.001), waist circumference (99 ± 15.7 to 97 ± 16 cm, p < 0.0001) and fasting insulin (137 ± 94.8 to 121 ± 83.4 pmol/L, p < 0.001) also decreased in participants who attended the final visit. Significant improvements were seen in all measures of PA, self-concept, and anxiety. CHW-SB, a government-funded program, is the first obesity-treatment program to be evaluated in Canada. While short-term evaluation revealed significant improvements in adiposity, PA, and psychological measures, the lack of full follow-up is a limitation in interpreting the clinical effectiveness of this program, as drop-out may be associated with lack of success in meeting program goals. These data also emphasize the need for ongoing evaluation to assess the long-term implications of this unique program and ultimately optimize utilization of governmental resources.

Acute Kidney Injury in Children With Type 1 Diabetes Hospitalized for Diabetic Ketoacidosis

Importance Acute kidney injury (AKI) in children is associated with poor short-term and long-term health outcomes; however, the frequency of AKI in children hospitalized for diabetic ketoacidosis (DKA) has not been previously examined. Objectives To determine the proportion of children hospitalized for DKA who develop AKI and to identify the associated clinical and biochemical markers of AKI. Design, Setting, and Participants This medical record review of all DKA admissions from September 1, 2008, through December 31, 2013, was conducted at British Columbia Children’s Hospital, the tertiary pediatric hospital in British Columbia, Canada. Children aged 18 years or younger with type 1 diabetes and DKA and with complete medical records available for data analysis were included (nu2009=u2009165). All data collection occurred between September 8, 2014, and June 26, 2015. Data analysis took place from August 25, 2015, to June 8, 2016. Main Outcomes and Measures Acute kidney injury was defined using Kidney Disease/Improving Global Outcomes serum creatinine criteria. Multinomial logistic regression was used to identify potential factors associated with AKI. Results Of the 165 children hospitalized for DKA, 106 (64.2%) developed AKI (AKI stage 1, 37 [34.9%]; AKI stage 2, 48 [45.3%]; and AKI stage 3, 21 [19.8%]). Two children required hemodialysis. In the adjusted multinomial logistic regression model, a serum bicarbonate level less than 10 mEq/L (compared with ≥10 mEq/L) was associated with a 5-fold increase in the odds of severe (stage 2 or 3) AKI (adjusted odds ratio [aOR], 5.22; 95% CI, 1.35-20.22). Each increase of 5 beats/min in initial heart rate was associated with a 22% increase in the odds of severe AKI (aOR, 1.22; 95% CI, 1.07-1.39). Initial corrected sodium level of 145 mEq/L or greater (compared with 135-144 mEq/L) was associated with a 3-fold increase in the odds of mild (stage 1) AKI (aOR, 3.29; 95% CI, 1.25-8.66). There were no cases of mortality in patients with or without AKI. Conclusions and Relevance This study is the first to date to document that a high proportion of children hospitalized for DKA develop AKI. Acute kidney injury was associated with markers of volume depletion and severe acidosis. Acute kidney injury is concerning because it is associated with increased morbidity and mortality as well as increased risk of chronic renal disease, a finding that is especially relevant among children who are already at risk for diabetic nephropathy. Strategies are needed to improve the diagnosis, management, and follow-up of AKI in children with type 1 diabetes.

Ensuring the Safety of Children Treated with Second-Generation Antipsychotics

Second-generation antipsychotic (SGA) prescriptions for children have steadily increased over the past two decades. This is in part due to the perception of a reduction in neurological side effects with SGAs as compared to first-generation antipsychotics. However, the current literature shows that children treated with SGAs are at risk for metabolic side effects including central obesity, impaired glucose tolerance, hypertension, dyslipidemia, and metabolic syndrome. To ensure the safety of children treated with SGAs, it is important that (1) these medications are used for evidence-based indications only; (2) prescribing physicians monitor metabolic changes at regular time intervals per the current recommendations; and (3) metabolic complications are identified early and treated through promotion of a healthy lifestyle, use of the lowest effective dose of the SGA, and reduction in the use of multiple medications.

Adherence to a pediatric diabetic ketoacidosis protocol in children presenting to a tertiary care hospital

To review adherence to a provincial diabetic ketoacidosis (DKA) protocol and to assess factors associated with intravenous fluid administration and the length time on an insulin infusion.