The Effect of Time to Treatment With Antiarrhythmic Drugs on Survival and Neurological Outcomes in Shock Refractory Out-of-Hospital Cardiac Arrest.

OBJECTIVES: Examining the association of time to treatment (drug or placebo) with survival to hospital discharge and neurologic outcome. DESIGN: Post hoc analysis of the Resuscitation Outcomes Consortium Amiodarone, Lidocaine, Placebo randomized controlled trial. SETTING: Emergency medical services enrolled patients with out-of-hospital cardiac arrest (OHCA) at multiple North American sites. PATIENTS: Adults with nontraumatic OHCA and an initial rhythm of ventricular fibrillation or pulseless ventricular tachycardia refractory to at least one defibrillation attempt were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We used logistic regression to examine the association of time to treatment with survival to hospital discharge and favorable neurologic status at discharge (modified Rankin Scale ≤ 3) for the three treatment groups including an interaction term between treatment and time to treatment to determine the effect of time on treatment effects. Time to treatment data were available for 2,994 out of 3,026 patients (99%). The proportion of patients who survived to hospital discharge decreased as time to drug administration increased, in amiodarone (odds ratio [OR], 0.91; 95% CI, 0.90-0.93 per min), lidocaine (OR, 0.93; 95% CI, 0.91-0.96), and placebo (OR, 0.91; 95% CI, 0.90-0.93). Comparing amiodarone to placebo, there was improved survival at all times of drug administration (OR, 1.32; 95% CI, 1.05-1.65). Comparing lidocaine to placebo, survival was not different with shorter times to drug administration (< 11 min), whereas survival was higher with lidocaine at longer times to drug administration with an interaction between treatment effect and time to treatment (p = 0.048). Survival with good neurologic outcome showed similar results for all analyses. CONCLUSIONS: Survival and favorable neurologic outcomes decreased with longer times to drug administration. Amiodarone improved survival at all time points whereas lidocaine improved survival only at later time points, compared with placebo.

Identifying clinical subtypes in sepsis-survivors with different one-year outcomes: a secondary latent class analysis of the FROG-ICU cohort.

BACKGROUND: Late mortality risk in sepsis-survivors persists for years with high readmission rates and low quality of life. The present study seeks to link the clinical sepsis-survivors heterogeneity with distinct biological profiles at ICU discharge and late adverse events using an unsupervised analysis. METHODS: In the original FROG-ICU prospective, observational, multicenter study, intensive care unit (ICU) patients with sepsis on admission (Sepsis-3) were identified (N = 655). Among them, 467 were discharged alive from the ICU and included in the current study. Latent class analysis was applied to identify distinct sepsis-survivors clinical classes using readily available data at ICU discharge. The primary endpoint was one-year mortality after ICU discharge. RESULTS: At ICU discharge, two distinct subtypes were identified (A and B) using 15 readily available clinical and biological variables. Patients assigned to subtype B (48% of the studied population) had more impaired cardiovascular and kidney functions, hematological disorders and inflammation at ICU discharge than subtype A. Sepsis-survivors in subtype B had significantly higher one-year mortality compared to subtype A (respectively, 34% vs 16%, p < 0.001). When adjusted for standard long-term risk factors (e.g., age, comorbidities, severity of illness, renal function and duration of ICU stay), subtype B was independently associated with increased one-year mortality (adjusted hazard ratio (HR) = 1.74 (95% CI 1.16-2.60); p = 0.006). CONCLUSIONS: A subtype with sustained organ failure and inflammation at ICU discharge can be identified from routine clinical and laboratory data and is independently associated with poor long-term outcome in sepsis-survivors. Trial registration NCT01367093; https://clinicaltrials.gov/ct2/show/NCT01367093 .

Children's screen use and school readiness at 4-6 years: prospective cohort study.

BACKGROUND: The primary aim of this study was to determine if screen use in early childhood is associated with overall vulnerability in school readiness at ages 4 to 6 years, as measured by the Early Development Instrument (EDI). Secondary aims were to: (1) determine if screen use was associated with individual EDI domains scores, and (2) examine the association between screen use and EDI domains scores among a subgroup of high screen users. METHODS: This prospective cohort study was carried out using data from young children participating in a large primary care practice-based research network in Canada. Logistic regression analyses were run to investigate the association between screen use and overall vulnerability in school readiness. Separate linear regression models examined the relationships between children's daily screen use and each separate continuous EDI domain. RESULTS: A total of 876 Canadian participants participated in this study. Adjusted logistic regression revealed an association between increased screen use and increased vulnerability in school readiness (p = 0.05). Results from adjusted linear regression demonstrated an association between higher screen use and reduced language and cognitive development domain scores (p = 0.004). Among high screen users, adjusted linear regression models revealed associations between increased screen use and reduced language and cognitive development (p = 0.004) and communication skills and general knowledge domain scores (p = 0.042). CONCLUSIONS: Screen use in early childhood is associated with increased vulnerability in developmental readiness for school, with increased risk for poorer language and cognitive development in kindergarten, especially among high users.

Frailty status among older critically ill patients with severe acute kidney injury.

BACKGROUND: Frailty status among critically ill patients with acute kidney injury (AKI) is not well described despite its importance for prognostication and informed decision-making on life-sustaining therapies. In this study, we aim to describe the epidemiology of frailty in a cohort of older critically ill patients with severe AKI, the outcomes of patients with pre-existing frailty before AKI and the factors associated with a worsening frailty status among survivors. METHODS: This was a secondary analysis of a prospective multicentre observational study that enrolled older (age > 65 years) critically ill patients with AKI. The clinical frailty scale (CFS) score was captured at baseline, at 6 months and at 12 months among survivors. Frailty was defined as a CFS score of ≥ 5. Demographic, clinical and physiological variables associated with frailty as baseline were described. Multivariable Cox proportional hazard models were constructed to describe the association between frailty and 90-day mortality. Demographic and clinical factors associated with worsening frailty status at 6 months and 12 months were described using multivariable logistic regression analysis and multistate models. RESULTS: Among the 462 patients in our cohort, median (IQR) baseline CFS score was 4 (3-5), with 141 (31%) patients considered frail. Pre-existing frailty was associated with greater hazard of 90-day mortality (59% (n = 83) for frail vs. 31% (n = 100) for non-frail; adjusted hazards ratio [HR] 1.49; 95% CI 1.11-2.01, p = 0.008). At 6 months, 68 patients (28% of survivors) were frail. Of these, 57% (n = 39) were not classified as frail at baseline. Between 6 and 12 months of follow-up, 9 (4% of survivors) patients transitioned from a frail to a not frail status while 10 (4% of survivors) patients became frail and 11 (5% of survivors) patients died. In multivariable analysis, age was independently associated with worsening CFS score from baseline to 6 months (adjusted odds ratio [OR] 1.08; 95% CI 1.03-1.13, p = 0.003). CONCLUSIONS: Pre-existing frailty is an independent risk factor for mortality among older critically ill patients with severe AKI. A substantial proportion of survivors experience declining function and worsened frailty status within one year.

Ventilator Weaning and Discontinuation Practices for Critically Ill Patients.

Importance: Although most critically ill patients receive invasive mechanical ventilation (IMV), few studies have characterized how IMV is discontinued in practice. Objective: To describe practice variation in IMV discontinuation internationally, associations between initial discontinuation events and outcomes, and factors associated with the use of select discontinuation strategies and failed initial spontaneous breathing trials (SBTs). Design, Setting, and Participants: Prospective, multinational, observational study of critically ill adults who received IMV for at least 24 hours from 142 intensive care units (ICUs) in 19 countries within 6 regions (27 in Canada, 23 in India, 22 in the UK, 26 in Europe, 21 in Australia/New Zealand, and 23 in the US). Exposures: Receiving IMV. Main Outcomes and Measures: Primary analyses characterized types of initial IMV discontinuation events (extubation, SBT, or tracheostomy) and associations with clinical outcomes (including duration of ventilation, ICU and hospital mortality, and ICU and hospital length of stay). Secondary analyses examined the associations between SBT outcome and SBT timing and clinical outcomes. Results: Among 1868 patients (median [interquartile range] age, 61.8 [48.9-73.1] years; 1173 [62.8%] men) 424 (22.7%) underwent direct extubation, 930 (49.8%) had an initial SBT (761 [81.8%] successful), 150 (8.0%) underwent direct tracheostomy, and 364 (19.5%) died before a weaning attempt. Across regions, there was variation in the use of written directives to guide care, daily screening, SBT techniques, ventilator modes, and the roles played by clinicians involved in weaning. Compared with initial direct extubation, patients who had an initial SBT had higher ICU mortality (20 [4.7%] vs 96 [10.3%]; absolute difference, 5.6% [95% CI, 2.6%-8.6%]), longer duration of ventilation (median of 2.9 vs 4.1 days; absolute difference, 1.2 days [95% CI, 0.7-1.6]), and longer ICU stay (median of 6.7 vs 8.1 days; absolute difference, 1.4 days [95% CI, 0.8-2.4]). Patients whose initial SBT failed (vs passed) had higher ICU mortality (29 [17.2%] vs 67 [8.8%]; absolute difference, 8.4% [95% CI, 2.0%-14.7%]), longer duration of ventilation (median of 6.1 vs 3.5 days; absolute difference, 2.6 days [95% CI, 1.6-3.6]), and longer ICU stay (median of 10.6 vs 7.7 days; absolute difference, 2.8 days [95% CI, 1.1-5.2]). Compared with patients who underwent early initial SBTs, patients who underwent late initial SBTs (>2.3 days after intubation) had longer duration of ventilation (median of 2.1 vs 6.1 days; absolute difference, 4.0 days [95% CI, 3.7-4.5]), longer ICU stay (median of 5.9 vs 10.8 days; absolute difference, 4.9 days [95% CI, 4.0-6.3]), and longer hospital stay (median of 14.3 vs 22.8 days; absolute difference, 8.5 days [95% CI, 6.0-11.0]). Conclusions and Relevance: In this observational study of invasive mechanical ventilation discontinuation in 142 ICUs in Canada, India, the UK, Europe, Australia/New Zealand, and the US from 2013 to 2016, weaning practices varied internationally. Trial Registration: ClinicalTrials.gov Identifier: NCT03955874.

Consumption of Cow's Milk in Early Childhood and Fracture Risk: A Prospective Cohort Study.

Cow's milk is consumed by most North American children, yet the relationships between the volume and fat content of cow's milk consumed and childhood fracture risk are unclear. Our primary objectives in this study were to evaluate whether the volume or fat content of cow's milk consumed at 1-3 years of age was associated with the risk of fracture between 3 and 10 years of age. This was a prospective cohort study of 2,466 children enrolled in Toronto, Ontario, Canada, between 2008 and 2016. The primary exposure was volume of cow's milk consumed between the ages of 1 and 3 years, and the secondary exposure was average percentage of milk fat consumed by each child during the same period. The primary outcome was a parental report of child fracture at ages 3-10 years. In the primary and secondary adjusted analyses, no association between milk volume and fracture risk (adjusted relative risk = 1.04, 95% confidence interval: 0.87, 1.26) or between milk-fat content and fracture risk (adjusted relative risk = 1.05, 95% confidence interval: 0.84, 1.31) was observed. In this study, we did not identify a protective association of early childhood cow's milk volume or fat consumption with fracture risk in later childhood. Future prospective research is needed to understand whether cow's milk is beneficial for fracture prevention through the life course.

First-year Analysis of the Operating Room Black Box Study.

OBJECTIVE: To characterize intraoperative errors, events, and distractions, and measure technical skills of surgeons in minimally invasive surgery practice. BACKGROUND: Adverse events in the operating room (OR) are common contributors of morbidity and mortality in surgical patients. Adverse events often occur due to deviations in performance and environmental factors. Although comprehensive intraoperative data analysis and transparent disclosure have been advocated to better understand how to improve surgical safety, they have rarely been done. METHODS: We conducted a prospective cohort study in 132 consecutive patients undergoing elective laparoscopic general surgery at an academic hospital during the first year after the definite implementation of a multiport data capture system called the OR Black Box to identify intraoperative errors, events, and distractions. Expert analysts characterized intraoperative distractions, errors, and events, and measured trainee involvement as main operator. Technical skills were compared, crude and risk-adjusted, among the attending surgeon and trainees. RESULTS: Auditory distractions occurred a median of 138 times per case [interquartile range (IQR) 96-190]. At least 1 cognitive distraction appeared in 84 cases (64%). Medians of 20 errors (IQR 14-36) and 8 events (IQR 4-12) were identified per case. Both errors and events occurred often in dissection and reconstruction phases of operation. Technical skills of residents were lower than those of the attending surgeon (P = 0.015). CONCLUSIONS: During elective laparoscopic operations, frequent intraoperative errors and events, variation in surgeons' technical skills, and a high amount of environmental distractions were identified using the OR Black Box.

The Electronic Asthma Management System (eAMS) improves primary care asthma management.

A high prevalence of suboptimal asthma control is attributable to known evidence-practice gaps. We developed a computerised clinical decision support system (the Electronic Asthma Management System (eAMS)) to address major care gaps and sought to measure its impact on care in adults with asthma.This was a 2-year interrupted time-series study of usual care (year 1) versus eAMS (year 2) at three Canadian primary care sites. We included asthma patients aged ≥16 years receiving an asthma medication within the last 12 months. The eAMS consisted of a touch tablet patient questionnaire completed in the waiting room, with real-time data processing producing electronic medical record-integrated clinician decision support.Action plan delivery (primary outcome) improved from zero out of 412 (0%) to 79 out of 443 (17.8%) eligible patients (absolute increase 0.18 (95% CI 0.14-0.22)). Time-series analysis indicated a 30.5% increase in physician visits with action plan delivery with the intervention (p<0.0001). Assessment of asthma control level increased from 173 out of 3497 (4.9%) to 849 out of 3062 (27.7%) eligible visits (adjusted OR 8.62 (95% CI 5.14-12.45)). Clinicians escalated controller therapy in 108 out of 3422 (3.2%) baseline visits versus 126 out of 3240 (3.9%) intervention visits (p=0.12). At baseline, a short-acting ß-agonist alone was added in 62 visits and a controller added in 54 visits; with the intervention, this occurred in 33 and 229 visits, respectively (p<0.001).The eAMS improved asthma quality of care in real-world primary care settings. Strategies to further increase clinician uptake and a randomised controlled trial to assess impact on patient outcomes are now required.

Association of accelerated body mass index gain with repeated measures of blood pressure in early childhood.

BACKGROUND/OBJECTIVES: We examined the association for rates of age- and sex-standardized body mass index (zBMI) gain between 0-3, 3-18, and 18-36 months with BP in children at 36-72 months of age. METHODS: We collected repeated measures of zBMI and BP in 2502 children. zBMI was calculated using the World Health Organization standards. Each child's zBMI at birth and rates of zBMI gain in each period from birth to 36 months were estimated using linear spline multilevel models. Generalized estimating equations were used to determine whether zBMI at birth and zBMI gain between 0-3, 3-18, and 18-36 months were each associated with repeated measures of BP at 36-72 months of age. We sequentially conditioned on zBMI at birth and zBMI gain in each period prior to each period tested, as covariates, and adjusted for important socio-demographic, familial, and study design covariates. We examined whether these associations were modified by birthweight or maternal obesity, by including interaction terms. RESULTS: After adjusting for all covariates and conditioning on prior zBMI gains, a 1 standard deviation unit faster rate of zBMI gain during 0-3 months, (ß = 0.59 mmHg; 95% CI 0.31, 0.86) and 3-18 months (ß = 0.74 mmHg; 95% CI 0.46, 1.03) were each associated with higher systolic BP at 36-72 months. No significant associations were observed, however, for zBMI at birth or zBMI gain in the 18-36 month growth period. zBMI gains from 0-3 and 3-18 months were also associated with diastolic BP. Birthweight significantly modified the relationship during the 3-18 month period (p = 0.02), with the low birthweight group exhibiting the strongest association for faster rate of zBMI gain with higher systolic BP (ß = 1.31 mmHg; 95% CI 0.14, 2.48). CONCLUSIONS: Given that long-term exposure to small elevations in BP are associated with subclinical cardiovascular disease, promoting interventions targeting healthy growth in infancy may be important.

A Positive Association Between Dietary Intake of Higher Cow's Milk-Fat Percentage and Non-High-Density Lipoprotein Cholesterol in Young Children.

OBJECTIVES: To determine the association between cow's milk-fat and non-high-density lipoprotein (non-HDL) cholesterol, a marker of cardiovascular disease (CVD) risk in young children, and whether this association is mediated by the typical volume of cow's milk consumed. STUDY DESIGN: A longitudinal study in 2- to 8-year-old children (n = 2890) was conducted through The Applied Research Group for Kids (TARGet Kids!), a practice-based research network in Toronto, Canada. Generalized estimating equations were used to examine the relationship between parent-reported cow's milk-fat percentage intake and serum non-HDL cholesterol concentrations as well as having high non-HDL cholesterol (≥3.75 mmol/L [145 mg/dL]), adjusting for covariates including age, sex, body mass index z score, breastfeeding duration, mother's ethnicity, and parental history of CVD. Bootstrap resampling (10 000 repetitions) was used to assess whether typical volume consumed mediated the association between cow's milk-fat percentage and non-HDL cholesterol. RESULTS: In total, 156 (5.4%) had high non-HDL cholesterol. Each percent increase in cow's milk-fat was associated with a 0.035 mmol/L (1.35 mg/dL) (P < .001) and 0.024 mmol/L (0.92 mg/dL) (P = .01) increase in non-HDL cholesterol, unadjusted and adjusted for covariates respectively. Cow's milk-fat percentage was not associated with greater odds of having high non-HDL cholesterol. Volume of cow's milk partially mediated the association between cow's milk-fat percentage and non-HDL cholesterol, accounting for 28% of the relationship (P < .001). CONCLUSIONS: Consumption of higher-fat cow's milk was associated with a small increase in non-HDL cholesterol but not greater odds of having high non-HDL cholesterol. Further research is needed to assess this relationship with other CVD risk factors in young children. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01869530.

Diagnostic Value of CT in Detecting Peripheral Zone Prostate Cancer.

OBJECTIVE. The purpose of this study was to identify the sensitivity of contrast-enhanced CT in detecting high-grade prostate adenocarcinoma. MATERIALS AND METHODS. A retrospective analysis included 100 patients with prostate cancer proven by biopsy between January 2010 and December 2017 who underwent staging CT of the abdomen and pelvis within 3 months of diagnosis. The control subjects were 100 randomly selected aged-matched male outpatients with no known history of malignancy who underwent contrast-enhanced CT of the abdomen and pelvis in the same time period as the patients with cancer. Two readers, blinded to both groups, independently assessed the likelihood of prostate cancer on the basis of the CT finding of focal abnormally increased peripheral enhancement in the prostate. Binary classification of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) was used to assess the diagnostic utility of CT versus the reference standard of transrectal ultrasound-guided biopsy. RESULTS. Eighty-three of 100 patients with biopsy-proven prostate cancer and 92 of 100 control subjects were correctly identified (sensitivity, 0.83; specificity, 0.92; PPV, 0.91; NPV, 0.84). There was no significant difference in diagnostic accuracy among subjects with different Gleason scores. Interrater agreement on both the cancer and control patients was 0.76 as assessed by Cohen kappa statistic. CONCLUSION. Incidental detection of a focal area of increased enhancement in the periphery of the prostate at contrast-enhanced CT may represent a clinically significant cancer and deserves further workup with prostate-specific antigen measurement and correlation with clinical risk factors for prostate cancer.

Real-world health care utilization and effectiveness of omalizumab for the treatment of severe asthma.

BACKGROUND: Omalizumab is indicated for the treatment of moderate to severe asthma. There is limited observational evidence on the costs and effectiveness of omalizumab. OBJECTIVE: To examine the costs and effectiveness of omalizumab for treatment of severe asthma relative to nonusers. METHODS: We conducted a within-person repeated-measures matched cohort study in Ontario, Canada from April 1, 2012 to March 31, 2014. Continuous users of omalizumab were matched with up to 4 nonusers according to age, sex, recent specialist visits, oral corticosteroid use, asthma severity, and Charlson comorbidity score. The primary outcome was direct health care costs. Secondary outcomes were asthma-related hospitalizations or emergency department visits and oral corticosteroid use. The association between omalizumab use and each outcome was assessed using mixed-effects models adjusting for confounders. RESULTS: Ninety-five omalizumab users and 352 nonusers were matched. Among users, there was a significant increase in health care costs of $1,796 per person owing to the cost of the medication at treatment initiation (P < .0001). Costs did not change significantly among nonusers ($85 increase in average monthly costs per person; P = .59). We found no significant changes in the rates of asthma-related hospitalizations or emergency department visits among omalizumab users (P = .44) or nonusers (P = .99) between pre- and postintervention periods. CONCLUSION: The use of omalizumab was associated with increased costs but no evidence of lower rates of clinically important outcomes. These results suggest omalizumab had limited effectiveness in our study population. Future studies should further explore subsets of patients most likely to benefit from omalizumab therapy.

Iron deficiency among low income Canadian toddlers: a cross-sectional feasibility study in a Community Health Centre and non-Community Health Centre sites.

BACKGROUND: Iron deficiency in early childhood has been associated with poor developmental outcomes. Little is known about the nutritional health of young children receiving care at Canadian Community Health Centres (CHCs). Our objectives were to describe iron deficiency among toddlers at an Ontario CHC, to compare young children attending CHCs and non-CHCs, and assess the feasibility of conducting research on children in CHC settings. METHODS: One CHC, Kingston Community Health Centres (CHC) with two clinical sites and one community programming site was added to the nine non-CHC pediatric and primary care clinics in the existing TARGet Kids! research network. A cross-sectional feasibilitystudy was conducted.and. Healthy children, ages 12-36 months were Enrolled. iron deficiency without inflammation (ferritin< 14 µg/L and CRP < 10 mg/L) and serum ferritin were assessed. Adjusted multivariable regression analyses were used to evaluate an association between CHC enrolment and iron status. RESULTS: The CHC cohort (n = 31) was older, had lower household income, lower maternal education, higher nutrition risk scores, higher cow's milk intake, shorter breastfeeding duration and higher prevalence of unhealthy weights compared with the non-CHC cohort (n = 875). There was no association between CHC status and serum ferritin (difference in median serum ferritin 4.78 µg/L, 95% confidence interval [CI] -2.5, 14.3, p = 0.22) or iron deficiency (OR 0.55, 95% CI 0.11, - 2.73, p = 0.46) using multivariable linear and logistic regression, respectively. CONCLUSION: Despite differences in sociodemographic variables, we did not detect a difference in iron status between toddlers enrolled at CHCs compared to non-CHC settings. Further research is needed to understand the health effects of poverty generally, and iron deficiency specifically among children receiving care at CHCs.

Prevalence of Fabry Disease and Outcomes in Young Canadian Patients With Cryptogenic Ischemic Cerebrovascular Events.

BACKGROUND AND PURPOSE: Previous studies reported Fabry disease in 0% to 4% of young patients with cryptogenic ischemic stroke (IS). We sought to determine the prevalence of Fabry and outcomes among young Canadians with cryptogenic IS or transient ischemic attack (TIA). METHODS: We prospectively enrolled individuals aged 18 to 55 with IS or speech or motor TIA, and no cause identified despite predetermined investigation. α-galactosidase-A gene was sequenced for Fabry diagnosis. National Institutes of Health Stroke Scale score was measured at presentation to quantify stroke severity. Modified Rankin Scale determined functional outcomes ≤7 days after presentation and 6 months later. RESULTS: We enrolled 365 patients with IS and 32 with TIA. α-galactosidase-A sequencing identified a single carrier of a genetic variant of unknown significance (p.R118C) and no well-recognized pathogenic variants. Mean National Institutes of Health Stroke Scale score was 3.1. Proportion of patients with modified Rankin Scale of 0 to 2 was 70.7% at ≤7 days and 87.4% at 6 months. National Institutes of Health Stroke Scale score at presentation and diabetes mellitus predicted 6-month modified Rankin Scale. Thirteen patients experienced 5 recurrent IS and 9 TIA during follow-up. No patient died. Most patients (98.7%) returned home. Among previous workers, 43% had residual working limitations. CONCLUSIONS: In this Canadian cohort of patients with cryptogenic IS or TIA, the prevalence of Fabry was 0.3% if p.R118C variant is considered as pathogenic. This suggests that more cost-effective methods should be applied for diagnosis of Fabry rather than systematic genetic screening in this population. Overall, cryptogenic IS in young adults is associated with favorable outcomes.

Persistent High Non-High-Density Lipoprotein Cholesterol in Early Childhood: A Latent Class Growth Model Analysis.

OBJECTIVES: To examine patterns of non-high-density lipoprotein (HDL) cholesterol in early childhood and identify factors associated with persistent high non-HDL cholesterol in healthy urban children. STUDY DESIGN: We identified all children enrolled in a primary care practice-based research network called TARGet Kids! (The Applied Research Group for Kids) with ≥3 laboratory measurements of non-HDL cholesterol. Latent class growth model analysis was performed to identify distinct trajectory groups for non-HDL cholesterol. Trajectory groups were then categorized into "normal" vs "persistent-high" non-HDL cholesterol based on guideline cut-off values and logistic regression was completed to examine the association between trajectory group and the presence of anthropometric and cardiometabolic risk factors. RESULTS: A total of 608 children met inclusion criteria for the trajectory analysis (median age at enrolment = 18.3, IQR = 27.9 months). Four trajectory groups were identified with 2 groups (n = 451) categorized as normal non-HDL cholesterol and 2 groups (n = 157) as persistent high non-HDL cholesterol. Family history of high cholesterol (OR 2.04, 95% CI 1.27-3.28) was associated significantly with persistent high non-HDL cholesterol, whereas East/Southeast Asian vs European ethnicity (OR 0.33, 95% CI 0.14-0.78), longer breastfeeding duration (OR 0.96, 95% CI 0.93-1.00), and greater birth weight (OR 0.69, 95% CI 0.48-1.00) were associated with lower odds of persistent high non-HDL cholesterol. CONCLUSIONS: Patterns of non-HDL cholesterol are identified during early childhood, and family history of high cholesterol was associated most strongly with persistent high non-HDL cholesterol. Future research should inform the development of a clinical prediction tool for lipids in early childhood to identify children who may benefit from interventions to promote cardiovascular health.

Duration of Fasting, Serum Lipids, and Metabolic Profile in Early Childhood.

OBJECTIVES: To evaluate the association between fasting duration and lipid and metabolic test results. STUDY DESIGN: A cross-sectional study was conducted in healthy children aged 0-6 years from The Applied Research Group for Kids! (TARGet Kids!) primary care practice network, Toronto, Canada, 2008-2013. The associations between duration of fasting at blood collection and serum lipid tests and metabolic tests were evaluated using linear regression. RESULTS: Among 2713 young children with blood tests the fasting time ranged from 0 to 5 hours (1st and 99th percentiles). Fasting duration was not significantly associated with total cholesterol (ß = 0.006; P = .629), high-density lipoprotein (HDL) (ß = 0.002; P = .708), low-density lipoprotein (ß = 0.0013; P = .240), non-HDL (ß = 0.004; P = .744), or triglycerides (ß = -0.016; P = .084) adjusted for age, sex, body mass index, maternal ethnicity, and time of blood draw. Glucose, insulin, and homeostasis model assessment of insulin resistance were significantly associated with fasting duration, and the average percent change between 0 and 5 hours was -7.2%, -67.1%, and -69.9%, respectively. The effect of fasting on lipid or metabolic test results did not differ by age or sex; HDL and triglycerides may differ by weight status. CONCLUSIONS: In this cohort of healthy young children, we found little evidence to support the need for fasting prior to measurement of lipids. The effect of fasting on glucose was small and may not be clinically important. When measuring serum lipid tests in early childhood, fasting makes a very small difference. TRIAL REGISTRATION: ClinicalTrials.gov: NCT0186953.

Determining rates of overweight and obese status in children using electronic medical records: Cross-sectional study.

OBJECTIVE: To determine the prevalence of overweight and obese status in children by age, sex, and visit type, using data from EMRALD® (Electronic Medical Record Administrative data Linked Database). DESIGN: Heights and weights were abstracted for children 0 to 19 years of age who had at least one well-child visit from January 2010 to December 2011. Using the most recent visit, the proportions and 95% CIs of patients defined as overweight and obese were compared by age group, sex, and visit type using the World Health Organization growth reference standards. SETTING: Ontario. PARTICIPANTS: Children 0 to 19 years of age who were rostered to a primary care physician participating in EMRALD and had at least one well-child visit from January 2010 to December 2011. MAIN OUTCOME MEASURES: Proportion and 95% CI of children with overweight and obese status by age group; proportion of children with overweight and obese status by sex (with male sex as the referent) within each age group; and proportion of children with overweight and obese status at the most recent well-child visit type compared with other visit types by age group. RESULTS: There were 28 083 well-child visits during this period. For children who attended well-child visits, 84.7% of visits had both a height and weight documented. Obesity rates were significantly higher in 1- to 4-year-olds compared with children younger than 1 (6.1% vs 2.3%; P < .001), and in 10- to 14-year-olds compared with 5- to 9-year-olds (12.0% vs 9.0%; P < .05). Both 1- to 4-year-old boys (7.2% vs 4.9%; P < .01) and 10- to 14-year-old boys (14.5% vs 9.6%; P < .05) had higher obesity rates compared with girls. Rates of overweight and obese status were lower using data from well-child visits compared with other visits. CONCLUSION: Electronic medical records might be useful to conduct population-based surveillance of overweight or obese status in children. Methodologic standards, however, should be developed.

Total Duration of Breastfeeding, Vitamin D Supplementation, and Serum Levels of 25-Hydroxyvitamin D.

OBJECTIVES: To determine the association between total breastfeeding duration and serum 25-hydroxyvitamin D (25-OHD) and to explore whether vitamin D supplementation influences this association. METHODS: We conducted a cross-sectional study of healthy children between September 2011 and August 2013 through the TARGet Kids! primary health care research network. Of the 4533 eligible children, we included only the 2508 who had 25-OHD measured. We assessed adjusted associations of total breastfeeding duration (in months) with serum 25-OHD and in supplemented versus nonsupplemented children, with the odds of 25-OHD less than 20 nanograms per milliliter. RESULTS: Each 1-month increase in total breastfeeding duration was associated with a 0.12 nanograms per milliliter lower median serum 25-OHD (95% confidence interval [CI] = -0.21 ng/mL, -0.02 ng/mL) among children who were not supplemented. The odds of serum 25-OHD less than 20 nanograms per milliliter increased by 6% (odds ratio [OR] = 1.06; 95% CI = 1.03, 1.10) for every 1-month increase in total breastfeeding duration among nonsupplemented children. The interaction between vitamin D supplementation, duration of breastfeeding, and median serum 25-OHD was statistically significant (P = .04). CONCLUSIONS: Breastfed children who were not supplemented, particularly those breastfed more than 1 year, appear to have lower vitamin D status. Vitamin D supplementation may mitigate this risk. These findings support recommendations for supplementation during breastfeeding of any duration.

Body Mass Index, Waist Circumference, and the Clustering of Cardiometabolic Risk Factors in Early Childhood.

BACKGROUND: Obesity has its origins in early childhood; however, there is limited evidence of the association between anthropometric indicators and cardiometabolic risk factors in young children. Our aim was to evaluate the associations between body mass index (BMI) and waist circumference (WC) in relation to cardiometabolic risk factors and to explore the clustering of these factors. METHODS: A cross-sectional study was conducted in children aged 1-5 years through TARGet Kids! (n = 2917). Logistic regression was used to evaluate associations between BMI and WC z-scores and individual traditional and possible non-traditional cardiometabolic risk factors. The underlying clustering of these measures was evaluated using principal components analysis (PCA). RESULTS: Child obesity (BMI z-score >2) was associated with high (>90th percentile) leptin [odds ratio (OR) 8.15, 95% confidence interval (CI) 4.56, 14.58] and insulin (OR = 1.76; 95% CI 1.05, 2.94). WC z-score >1 was associated with high insulin (OR 1.59, 95% CI 1.11, 2.28), leptin (OR 5.48, 95% CI 3.48, 8.63) and 25-hydroxyvitamin D < 75 nmol/L (OR 1.39, 95% CI 1.08, 1.79). BMI and WC were not associated with other traditional cardiometabolic risk factors, including non-High Density Lipoprotein (HDL) cholesterol, and glucose. Among children 3-5 years (n = 1035) the PCA of traditional risk factors identified three components: adiposity/blood pressure, metabolic, and lipids. The inclusion of non-traditional risk factors identified four additional components but contributed minimally to the total variation explained. CONCLUSIONS: Anthropometric indicators are associated with selected cardiometabolic risk factors in early childhood, although the clustering of risk factors suggests that adiposity is only one distinct component of cardiometabolic risk. The measurement of other risk factors beyond BMI and WC may be important in defining cardiometabolic risk in early childhood.

Increase in Utilization of Afterhours Medical Imaging: A Study of Three Canadian Academic Centers.

OBJECTIVES: The objectives of our study were to assess trends in afterhours medical imaging utilization for emergency department (ED) and inpatient (IP) patient populations from 2006-2013, including analysis by modality and specialty and with adjustment for patient volume. METHODS: For this retrospective study, we reviewed the number of CT, MRI, and ultrasound studies performed for the ED and IP patients during the afterhours time period (5pm - 8am on weekdays and 24 hours on weekends and statutory holidays) from 2006-2013 at three different Canadian academic hospitals. We used the Jonckheere-Terpstra (JT) test to determine statistical significance of imaging and patient volume trends. A regression model was used to examine whether there was an increasing trend over time in the volume of imaging tests per 1000 patients. RESULTS: For all three sites from 2006-2013 during the afterhours time period: There was a statistically significant increasing trend in total medical imaging volume, which also held true when the volumes were assessed by modality and by specialty. There was a statistically significant increasing trend in ED and IP patient volume. When medical imaging volumes were adjusted for patient volumes, there was a statistically significant increasing trend in imaging being performed per patient. CONCLUSION: Afterhours medical imaging volumes demonstrated a statistically significant increasing trend at all three sites from 2006-2013 when assessed by total volume, modality, and specialty. During the same time period and at all three sites, the ED and IP patient volumes also demonstrated a statistically significant increasing trend with more medical imaging, however, being performed per patient.