Fetal Echocardiographic Z Score Pilot Project: Study Design and Impact of Gestational Age and Variable Type on Reproducibility of Measurements Within and Across Investigators.

BACKGROUND: Fetal echocardiography is widely available, but normative data are not robust. In this pilot study, the authors evaluated (1) the feasibility of prespecified measurements in a normal fetal echocardiogram to inform study design and (2) measurement variability to assign thresholds of clinical significance and guide analyses in larger fetal echocardiographic Z score initiatives. METHODS: Images from predefined gestational age groups (16-20, >20-24, >24-28, and >28-32 weeks) were retrospectively analyzed. Fetal echocardiography expert raters attended online group training and then independently analyzed 73 fetal studies (18 per age group) in a fully crossed design of 53 variables; each observer repeated measures for 12 fetuses. Kruskal-Wallis tests were used to compare measurements across centers and age groups. Coefficients of variation (CoVs) were calculated at the subject level for each measurement as the ratio of SD to mean. Intraclass correlation coefficients were used to show inter- and intrarater reliabilities. Cohen's d > 0.8 was used to define clinically important differences. Measurements were plotted against gestational age, biparietal diameter, and femur length. RESULTS: Expert raters completed each set of measurements in a mean of 23 ± 9 min/fetus. Missingness ranged from 0% to 29%. CoVs were similar across age groups for all variables (P < .05) except ductus arteriosus mean velocity and left ventricular ejection time, which were both higher at older gestational age. CoVs were >15% for right ventricular systolic and diastolic widths despite fair to good repeatability (intraclass correlation coefficient > 0.5); ductal velocities and two-dimensional measures, left ventricular short-axis dimensions, and isovolumic times all had high CoVs and high interobserver variability despite good to excellent intraobserver agreement (intraclass correlation coefficient > 0.6). CoVs did not improve when ratios (e.g., tricuspid/mitral annulus) were used instead of linear measurements. Overall, 27 variables had acceptable inter- and intraobserver repeatability, while 14 had excessive variability between readers despite good intraobserver agreement. CONCLUSIONS: There is considerable variability in fetal echocardiographic quantification in clinical practice that may affect the design of multicenter fetal echocardiographic Z score studies, and not all measurements may be feasible for standard normalization. As missingness was substantial, a prospective design will be needed. Data from this pilot study may aid in the calculation of sample sizes and inform thresholds for distinguishing clinically significant from statistically significant effects.

Feeding methods for infants with single ventricle physiology are associated with length of stay during stage 2 surgery hospitalization.

BACKGROUND: Tube feedings are often needed to achieve the growth and nutrition goals associated with decreased morbidity and mortality in patients with single ventricle anatomy. Variability in feeding method through the interstage period has been previously described, however, comparable information following stage 2 palliation is lacking. OBJECTIVES: To identify types of feeding methods following stage 2 palliation and their influence on length of stay. DESIGN: Secondary analysis of the National Pediatric Cardiology Quality Improvement Collaborative registry was performed on 932 patients. Demographic data, medical characteristics, postoperative complications, type of feeding method, and length of stay for stage 2 palliation were analyzed. RESULTS: Type of feeding method remained relatively unchanged during hospitalization for stage 2 palliation. Gastrostomy tube fed only patients were the oldest at time of surgery (182.7 ± 57.7 days, P < .001) and had the lowest weight-for-age z scores at admission (-1.6 ± 1.4, P < .001). Oral + gastrostomy tube groups had the longest median bypass times (172.5 minutes, P = .001) and longest length of stay (median 12 days, P < .001). Multivariable modeling revealed that feeding by tube only (P < .001), oral + tube feeding (P ≤ .001), reintubation (P < .001), and prolonged intubation (P < .001) were associated with increased length of stay. Neither age (P = .156) nor weight-for-age z score at admission (P = .066) was predictive of length of stay. CONCLUSIONS: Feeding methods established at admission for stage 2 palliation are not likely to change by discharge. Length of stay is more likely to be impacted by tube feeding and intubation history than age or weight-for-age z score at admission. Better understanding for selection of feeding methods and their impact on patient outcomes is needed to develop evidence-based guidelines to decrease variability in clinical practice patterns and provide appropriate counseling to caregivers.

Acute-Onset Chest Pain in a 17-Year-Old Female Adolescent With Systemic Lupus Erythematosus.

We report the case of a 17-year-old adolescent girl with systemic lupus erythematosus with disseminated pneumococcal infection leading to purulent pericarditis with cardiac tamponade. Although pericarditis is not an uncommon entity in autoimmune diseases such as systemic lupus erythematosus, purulent pericarditis is a rare cause (<1%) of this presentation.

"Higher order" addiction molecular genetics: convergent data from genome-wide association in humans and mice.

Family, adoption and twin data each support substantial heritability for addictions. Most of this heritable influence is not substance-specific. The overlapping genetic vulnerability for developing dependence on a variety of addictive substances suggests large roles for "higher order" pharamacogenomics in addiction molecular genetics. We and others have now completed genome-wide association (GWA) studies of DNAs from individuals with dependence on a variety of addictive substances versus appropriate controls. Recently reported replicated GWA observations identify a number of genes based on comparisons between controls and European-American and African-American polysubstance abusers. Here we review the convergence between these results and data that compares control samples and (a) alcohol-dependent European-Americans, (b) methamphetamine-dependent Asians and (c) nicotine dependent samples from European backgrounds. We also compare these human data to quantitative trait locus (QTL) results from studies of addiction-related phenotypes in mice that focus on alcohol, methamphetamine and barbiturates. These comparisons support a genetic architecture built from largely polygenic contributions of common allelic variants to dependence on a variety of legal and illegal substances. Many of the gene variants identified in this way are likely to alter specification and maintenance of neuronal connections.