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In most cases, the results of a large clinical trial will agree with the meta-analysis of the smaller trials on that same topic. This was demonstrated by researchers who identified 79 meta-analyses that included one large study of 1,000 or more patients and 61 meta-analyses that included one large study based on statistical power. In 82% to 90% of the cases, the large trial confirmed the results of the meta-analysis. In the 15 cases where the large trial did not confirm the meta-analysis, most of the difference could be accounted for., Objective.--To evaluate the results of large clinical trials vs the pooled results of smaller trials. Data Identification.--Meta-analyses with at least I "large" study were identified from the Cochrane Pregnancy and Childbirth Database and from MEDLINE (1966-1995). Study Selection.--We used a sample size approach to select 79 meta-analyses with at least 1 large study of 1000 or more patients. We used a statistical power approach to select 61 meta-analyses with at least 1 large study based on statistical power considerations. Data Extraction.--The outcome of interest for each meta-analysis was the primary one stated in the original publication or, when not clearly specified, was decided on clinically. Data Synthesis.--By random effects calculations, we found agreement between large and smaller trials in 90% of the meta-analyses selected by the sample size approach and in 82% of the meta-analyses selected by the statistical power approach. Twice as many disagreements appeared when the variability among large studies and among smaller studies was not considered (ie, fixed effects calculations). Of the 15 disagreements between results of large and smaller trials using the random effects model, plausible explanations were identified in 10 meta-analyses: 5 with differences in the control rate of events between large and smaller trials, 4 with specific protocol or study differences, and 1 with potential publication bias. Two other disagreements were not clinically important, and tentative reasons could be identified for 2 of the remaining 3 disagreements. Conclusions.--Results of smaller studies are usually compatible with the results of large studies, but discrepancies do occur even when the diversity among both large studies and smaller studies is considered. Clinically important differences without a potential explanation are extremely uncommon. Future research should further examine sources of heterogeneity between the results of large and smaller trials. JAMA. 1996;276:1332-1338

Objective: Patients with Kawasaki disease (KD) with coronary artery enlargement at diagnosis are at the highest risk for persistent coronary artery aneurysms (CAAs) and may benefit from primary adjunctive anti-inflammatory therapy beyond intravenous immunoglobulin (IVIG). We evaluate the effect of primary adjunctive corticosteroid therapy on outcomes in patients with CAA at diagnosis.Design: Single-centre, retrospective review.Patients: Patients with KD diagnosed within 10 days of fever onset and with baseline CA z-score ≥2.5.Interventions: Primary treatment with IVIG (n=162) versus IVIG plus corticosteroids (n=48).Main Outcome Measures: Treatment resistance (persistent fever >36 hours after initial treatment), CAA regression rate.Results: Of the 92 patients with KD who received corticosteroids at our institution from 2012 to 2019, 48 met the inclusion criteria for primary adjunctive therapy. The corticosteroid group was younger and had larger baseline CAAs compared with historical controls. Demographics and laboratory values were otherwise similar between groups. The corticosteroid group had a less treatment resistance (4% vs 30%, p=0.003) and a greater improvement in C reactive protein. After adjusting for baseline CA z-score, age and baseline bilateral versus unilateral CAA, the corticosteroid group had a higher odds of (OR 2.77 (1.04, 7.42), p=0.042) and a shorter time to CAA regression (HR 1.94 (1.27, 2.96), p=0.002).Conclusion: Primary adjunctive corticosteroid therapy is associated with decreased initial treatment resistance, greater improvement in inflammatory markers and higher likelihood of CAA regression in patients who have CAA at diagnosis. Multi-centre, randomised controlled trials are needed to confirm the benefits of corticosteroids in patients with CAA at diagnosis and to compare corticosteroids with other adjunctive therapies. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Heart disease is the number one cause of death in women. Little is known about how adolescent and young adult women perceive their risk of heart disease. We conducted eight online, semistructured focus groups with 35 young women aged 15–24 years recruited from two primary care practices in Boston, MA. Focus group discussion topics built upon data from a larger sample of women who completed the American Heart Association Women's Health Study survey. Topics included health concerns salient to young women, perceived susceptibility to heart disease, and barriers to heart-healthy behaviors. We used qualitative coding and thematic analyses to synthesize data. Participants were surprised to learn that heart disease is the leading cause of death in women. Young women discussed age ("I feel like those are things I associate with older people like 40"), gender ("I usually hear more about men suffering from heart problems than women"), and social norms ("we're so pressured just to grow up and [be] more focused on pregnancies or depression or our weight") as reasons for their low perceived risk for heart disease. Participants noted several barriers to adopting heart-healthy behaviors including stress, lack of time, and low perceived risk. "We just don't have time to worry about hearts. Especially if our hearts aren't bothering us to begin with and we can't see it." Perceptions of age, gender, and social norms contribute to low heart disease awareness among young women, which in turn may limit heart-healthy behaviors. [ABSTRACT FROM AUTHOR]

The prevalence of nonnutritive sweeteners (NNSs) in the food supply has increased over time. Not only are more children and adolescents consuming NNSs, but they are also consuming a larger quantity of NNSs in the absence of strong scientific evidence to refute or support the safety of these agents. This policy statement from the American Academy of Pediatrics is intended to provide the pediatric provider with a review of (1) previous steps taken for approved use of NNSs, (2) existing data regarding the safety of NNS use in the general pediatric population, (3) what is known regarding the potential benefits and/or adverse effects of NNS use in children and adolescents, (4) identified gaps in existing knowledge and potential areas of future research, and (5) suggested talking points that pediatricians may use when discussing NNS use with families [ABSTRACT FROM AUTHOR]

To optimize treatment and prevent cardiovascular disease in subjects with type 1 diabetes, it is important to determine how cholesterol metabolism changes with type 1 diabetes. The objective of the study was to compare plasma levels of campesterol and β-sitosterol, markers of cholesterol absorption, as well as lathosterol, a marker of cholesterol synthesis, in youth with and without type 1 diabetes. Serum samples were obtained from adolescent subjects with type 1 diabetes (n = 175, mean age 15.2 years, mean duration of diabetes 8.2 years) and without diabetes (n = 74, mean age 15.4 years). Campesterol, β-sitosterol, and lathosterol, were measured using targeted liquid chromatography tandem mass spectrometry, compared between groups, and correlated with the available cardiometabolic variables. Campesterol and β-sitosterol levels were 30% higher in subjects with type 1 diabetes and positively correlated with hemoglobin A1c levels. In contrast, lathosterol levels were 20% lower in subjects with type 1 diabetes and positively correlated with triglycerides, body mass index, and systolic blood pressure. Plasma markers suggest that cholesterol absorption is increased, whereas cholesterol synthesis is decreased in adolescent subjects with type 1 diabetes. Further studies to address the impact of these changes on the relative efficacy of cholesterol absorption and synthesis inhibitors in subjects with type 1 diabetes are urgently needed. • Cholesterol absorption markers are increased in type 1 diabetes. • Cholesterol synthesis markers are decreased in type 1 diabetes. • Cholesterol absorption markers correlate with HbA1c in type 1 diabetes. • Cholesterol synthesis markers correlate with BMI, TG, and BP in type 1 diabetes. [ABSTRACT FROM AUTHOR]