Lack of Age-Appropriate Reference Intervals Causing Potentially Missed Alerts in Clinical Reports of Dyslipidemia.

This study shows that only 12.5% of laboratory reports (2/16) included age-appropriate pediatric reference ranges for all lipid and lipoproteins. The use of erroneous reference range(s) could lead to missed alerts of dyslipidemia in up to 97.3% (total cholesterol), 93.6% (high-density lipoprotein cholesterol), 94.8% (low-density lipoprotein cholesterol), and 87.8% (triglycerides) of youth in the population-based National Health and Nutrition Examination Survey cohort. These findings highlight the potential missed opportunities for reinforcing lifestyle counseling for dyslipidemia in addition to obesity in youth.

Improving Cardiovascular Health in a Pediatric Preventive Cardiology Practice.

Poor childhood cardiovascular health translates into poor adult cardiovascular health. We hypothesized care in a preventive cardiology clinic would improve cardiovascular health after lifestyle counseling. Over a median of 3.9 months, mean cardiovascular health score (range 0-11) improved from 5.8 ± 2.2 to 6.3 ± 2.1 (P < .001) in 767 children.

Multiple Emergency Department Visits for a Diagnosis of Kawasaki Disease: An Examination of Risk Factors and Outcomes.

OBJECTIVES: To determine predictors of >1 emergency department (ED) visit for a Kawasaki disease diagnosis in a quaternary care pediatric hospital and compare outcomes between patients with 1 vs >1 visit for Kawasaki disease diagnosis. STUDY DESIGN: Medical records of patients evaluated for Kawasaki disease between January 2006 and August 2018 at Boston Children's Hospital were abstracted for demographic and clinical data. Predictors of >1 visit were explored using logistic regression and classification and regression tree analysis. RESULTS: Of 530 patients diagnosed with Kawasaki disease, 117 (22%) required multiple ED visits for Kawasaki disease diagnosis. Multivariable regression and classification and regression tree analysis identified ≤2 Kawasaki disease criteria (OR 33.9; 95% CI 18.1-63.6), <3 days of fever at the first visit (OR 3.47; 95% CI 1.77-6.84), and non-White race (OR 2.15; 95% CI 1.18-3.95) as predictors of >1 visit. There were no significant differences in duration of hospitalization, day of illness at initial Kawasaki disease treatment, intravenous immunoglobulin resistance, need for adjunctive therapies, or coronary artery outcomes between patients diagnosed with Kawasaki disease at initial visit vs subsequent visits. CONCLUSIONS: Incomplete Kawasaki disease criteria, fewer days of fever, and non-White race were significant predictors of multiple ED visits for Kawasaki disease diagnosis in this single institution study. Our findings underscore the importance of maintaining a high index of suspicion for Kawasaki disease in patients with <4 Kawasaki disease criteria. Further research is needed to determine causes for increased healthcare use in non-White patients to receive a Kawasaki disease diagnosis.

Children with Heterozygous Familial Hypercholesterolemia in the United States: Data from the Cascade Screening for Awareness and Detection-FH Registry.

OBJECTIVE: To describe enrollment characteristics of youth in the Cascade Screening for Awareness and Detection of FH Registry. STUDY DESIGN: This is a cross-sectional analysis of 493 participants aged <18 years with heterozygous familial hypercholesterolemia recruited from US lipid clinics (n = 20) between April 1, 2014, and January 12, 2018. At enrollment, some were new patients and some were already in care. Clinical characteristics are described, including lipid levels and lipid-lowering treatments. RESULTS: Mean age at diagnosis was 9.4 (4.0) years; 47% female, 68% white and 12% Hispanic. Average (SD) highest Low-density lipoprotein cholesterol (LDL-C) was 238 (61) mg/dL before treatment. Lipid-lowering therapy was used by 64% of participants; 56% were treated with statin. LDL-C declined 84 mg/dL (33%) among those treated with lipid-lowering therapy; statins produced the greatest decline, 100 mg/dL (39% reduction). At enrollment, 39% had reached an LDL-C goal, either <130 mg/dL or ≥50% decrease from pre-treatment; 20% of those on lipid-lowering therapy reached both goals. CONCLUSIONS: Among youth enrolled in the Cascade Screening for Awareness and Detection of FH Registry, diagnosis occurred relatively late, only 77% of children eligible for lipid-lowering therapy were receiving treatment, and only 39% of those treated met their LDL-C goal. Opportunities exist for earlier diagnosis, broader use of lipid-lowering therapy, and greater reduction of LDL-C levels.

Impact of Socioeconomic Status on Outcomes of Patients with Kawasaki Disease.

OBJECTIVE: To evaluate the association of neighborhood socioeconomic status (SES) with time to intravenous immunoglobulin treatment, length of stay (LOS), and coronary artery aneurysms (CAAs) in patients with Kawasaki disease. STUDY DESIGN: We examined the relationship of SES in 915 patients treated at a large academic center between 2000 and 2017. Neighborhood SES was measured using a US census-based score derived from 6 measures related to income, education, and occupation. Linear and logistic regression were used to examine the association of SES with number of days of fever at time of treatment, LOS, and CAA. RESULTS: Patients in the lowest SES quartile were treated later than patients with greater SES (7 [IQR 5, 9] vs 6 [IQR 5, 8] days, P = .01). Patients in the lowest SES quartile were more likely to be treated after 10 days of illness, with an OR 1.9 (95% CI 1.3-2.8). In multivariable analysis, SES remained an independent predictor of the number of days of fever at time of treatment (P = .01). Patients in the lowest SES quartile had longer LOS than patients with greater SES (3 [IQR 2, 5] vs 3 [IQR 2, 4], P = .007). In subgroup analysis of white children, those in the lowest SES quartile vs quartiles 2-4 were more likely to develop large/giant CAA 17 (12%) vs 30 (6%), P = .03. CONCLUSIONS: Lower SES is associated with delayed treatment, prolonged LOS, and increased risk of large/giant CAA. Novel approaches to diagnosis and education are needed for children living in low-SES neighborhoods.

Safety and Efficacy of Warfarin Therapy in Kawasaki Disease.

OBJECTIVE: To describe the safety and efficacy of warfarin for patients with Kawasaki disease and giant coronary artery aneurysms (CAAs, ≥8 mm). Giant aneurysms are managed with combined anticoagulation and antiplatelet therapies, heightening risk of bleeding complications. STUDY DESIGN: We reviewed the time in therapeutic range; percentage of international normalization ratios (INRs) in range (%); bleeding events, clotting events; INRs ≥6; INRs ≥5 and <6; and INRs <1.5. RESULTS: In 9 patients (5 male), median age 14.4 years (range 7.1-22.8 years), INR testing was prescribed weekly to monthly and was done by home monitor (n = 5) or laboratory (n = 3) or combined (1). Median length of warfarin therapy was 7.2 years (2.3-13.3 years). Goal INR was 2.0-3.0 (n = 6) or 2.5-3.5 (n = 3), based on CAA size and history of CAA thrombosis. All patients were treated with aspirin; 1 was on dual antiplatelet therapy and warfarin. The median time in therapeutic range was 59% (37%-85%), and median percentage of INRs in range was 68% (52%-87%). INR >6 occurred in 3 patients (4 events); INRs ≥5 <6 in 7 patients (12 events); and INR <1.5 in 5 patients (28 events). The incidence of major bleeding events and clinically relevant nonmajor bleeding events were each 4.3 per 100 patient-years (95% CI 0.9-12.6). New asymptomatic coronary thrombosis was detected by imaging in 2 patients. CONCLUSIONS: Bleeding and clotting complications are common in patients with Kawasaki disease on warfarin and aspirin, with INRs in range only two-thirds of the time. Future studies should evaluate the use of direct oral anticoagulants in children as an alternative to warfarin.

Statin-Associated Myopathy in a Pediatric Preventive Cardiology Practice.

OBJECTIVES: To describe muscle-related statin adverse effects in real-world pediatric practice. STUDY DESIGN: Using prospectively collected quality improvement data from a pediatric preventive cardiology practice, we compared serum creatine kinase (CK) levels among patients prescribed and not prescribed statins, and pre-/poststatin initiation. Multivariable mixed-effect models were constructed accounting for repeated measures, examining the effect of statins on log-transformed CK (lnCK) levels adjusted for age, sex, weight, season, insurance type, and race/ethnicity. RESULTS: Among 1501 patients seen over 3.5 years, 474 patients (14?±?4 years, 47% female) had at least 1 serum CK measured. Median (IQR) CK levels of patients prescribed (n?=?188 patients, 768 CK measurements) and not prescribed statins (n?=?351 patients, 682 CK measurements) were 107 (83) IU/L and 113 (81) IU/L, respectively. In multivariable-adjusted models, lnCK levels did not differ based on statin use (??=?0.02 [SE 0.05], P?=?.7). Among patients started on statins (n?=?86, 130 prestatin and 292 poststatin CK measurements), median CK levels did not differ in adjusted models (? for statin use on lnCK?=?.08 [SE .07], P?=?.2). There was a clinically insignificant increase in CK over time (??=?.08 [SE .04], P?=?.04 per year). No muscle symptoms or rhabdomyolysis were reported among patients with high CK levels. CONCLUSIONS: In a real-world practice, pediatric patients using statins did not experience higher CK levels, nor was there a meaningful CK increase with statin initiation. These data suggest the limited utility to checking CK in the absence of symptoms, supporting current guidelines.

Cholesterol Screening and Treatment Practices and Preferences: A Survey of United States Pediatricians.

OBJECTIVES: To determine pediatricians' practices, attitudes, and barriers regarding screening for and treatment of pediatric dyslipidemias in 9- to 11-year-olds and 17- to 21-year-olds. STUDY DESIGN: American Academy of Pediatrics (AAP) 2013-2014 Periodic Survey of a national, randomly selected sample of 1627 practicing AAP physicians. Pediatricians' responses were described and modeled. RESULTS: Of 614 (38%) respondents who met eligibility criteria, less than half (46%) were moderately/very knowledgeable about the 2008 AAP cholesterol statement; fewer were well-informed about 2011 National Heart, Lung, and Blood Institute Guidelines or 2007 US Preventive Service Task Force review (both 26%). Despite published recommendations, universal screening was not routine: 68% reported they never/rarely/sometimes screened healthy 9- to 11-year-olds. In contrast, more providers usually/most/all of the time screened based on family cardiovascular history (61%) and obesity (82%). Screening 17- to 21-year-olds was more common in all categories (P?

Correlates of Achieving Statin Therapy Goals in Children and Adolescents with Dyslipidemia.

OBJECTIVE: To determine the real-world effectiveness of statins and impact of baseline factors on low-density lipoprotein cholesterol (LDL-C) reduction among children and adolescents. STUDY DESIGN: We analyzed data prospectively collected from a quality improvement initiative in the Boston Children's Hospital Preventive Cardiology Program. We included patients ≤21 years of age initiated on statins between September 2010 and March 2014. The primary outcome was first achieving goal LDL-C, defined as <130 mg/dL, or <100 mg/dL with high-level risk factors (eg, diabetes, etc). Cox proportional hazards models were used to assess the impact of baseline clinical and lifestyle factors. RESULTS: Among the 1521 pediatric patients evaluated in 3813 clinical encounters over 3.5 years, 97 patients (6.3%) were started on statin therapy and had follow-up data (median age 14 [IQR 7] years, 54% were female, and 24% obese, 62% with at least one lifestyle risk factor). The median baseline LDL-C was 215 (IQR 78) mg/dL, and median follow-up after starting statin was 1 (IQR 1.3) year. The cumulative probability of achieving LDL-C goal within 1 year was 60% (95% CI 47-69). A lower probability of achieving LDL-C goals was associated with male sex (HR 0.5 [95% CI 0.3-0.8]) and higher baseline LDL-C (HR 0.92 [95% CI 0.87-0.98] per 10 mg/dL), but not age, body mass index percentile, lifestyle factors, or family history. CONCLUSIONS: The majority of pediatric patients started on statins reached LDL-C treatment goals within 1 year. Male patients and those with greater baseline LDL-C were less likely to be successful and may require increased support.

Endothelial pulse amplitude testing: feasibility and reproducibility in adolescents.

OBJECTIVES: To test prospectively the reproducibility and feasibility of endothelial pulse amplitude testing (Endo-PAT), a novel Food and Drug Administration-approved technology, in healthy adolescents. STUDY DESIGN: We performed Endo-PAT testing on 2 different days separated by no more than 7 days in 30 healthy fasting adolescents, ages 13 to 19 years, to assess reproducibility and feasibility. The reported level of discomfort, as measured on a pain scale of 1 to 5, was documented. RESULTS: The mean difference in paired Endo-PAT indices was 0.12 (95% CI, -0.09-0.33; P = .24; intraclass correlation coefficient, 0.78), and the within-subject variation of Endo-PAT index was 0.16. The Endo-PAT index on test days 1 and 2 were 1.91 +/- 0.57 and 1.78 +/- 0.51 (mean plus or minus SD), respectively. All attempted studies (100%) were completed (95% CI, 88%-100%), and all completed studies (100%) could be analyzed (95% CI, 88%-100%). The median pain score was 1 on both days. CONCLUSION: In healthy adolescents, Endo-PAT is feasible and has excellent reproducibility. This technology may provide an easy and reliable means of assessing endothelial function in the pediatric population.