Incorporating Informatics for Integrating Biology and the Bedside (i2b2) into Predoctoral Trainee Curriculum to Evaluate Student‐Generated Hypotheses

As part of the Clinical and Translational Science Institute predoctoral TL1 training program at the Pennsylvania State University, a multidisciplinary team of predoctoral trainees representing the Chemistry, Neurosurgery, Nutritional Sciences, and Public Health Sciences departments were introduced to the NIH‐sponsored Informatics for Integrating Biology and the Bedside (i2b2) database to test the following student‐generated hypothesis: children with iron deficiency anemia (IDA) are at increased risk of attention deficit‐hyperactivity disorder (ADHD). Children aged 4–12 and 4–17 years were categorized into IDA and control groups. De‐identified medical records from the Penn State Milton S. Hershey Medical Center (HMC) and the Virginia Commonwealth University Medical Center (VCUMC) were used for the analysis. Overall, ADHD prevalence at each institution was lower than 2011 state estimates. There was a significant association between IDA and ADHD in the 4–17‐year‐old age group for all children (OR: 1.902 [95% CI: 1.363–2.656]), Caucasian children (OR: 1.802 [95% CI: 1.133–2.864]), and African American children (OR: 1.865 [95% CI: 1.152–3.021]). Clinical and Translational Science Award (CTSA) infrastructure is particularly useful for trainees to answer de novo scientific questions with minimal additional training and technical expertise. Moreover, projects can be expanded by collaborating within the CTSA network.     

Placebo response rates and potential modifiers in double-blind randomized controlled trials of second and newer generation antidepressants for major depressive disorder in children and adolescents: a systematic review and meta-regression analysis

Children and adolescents with major depressive disorder (MDD) appear to be more responsive to placebo than adults in randomized placebo-controlled trials (RCTs) of second and newer generation antidepressants (SNG-AD). Previous meta-analyses obtained conflicting results regarding modifiers. We aimed to conduct a meta-analytical evaluation of placebo response rates based on both clinician-rating and self-rating scales. Based on the most recent and comprehensive study on adult data, we tested whether the placebo response rates in children and adolescents with MDD also increase with study duration and number of study sites. We searched systematically for published RCTs of SNG-AD in children and/or adolescents (last update: September 2017) in public domain electronic databases and additionally for documented studies in clinical trial databases. The log-transformed odds of placebo response were meta-analytically analyzed. The primary and secondary outcomes were placebo response rates at the end of treatment based on clinician-rating and self-rating scales, respectively. To examine the impact of study duration and number of study sites on placebo response rates, we performed simple meta-regression analyses. We selected other potential modifiers of placebo response based on significance in at least one previous pediatric meta-analysis and on theoretical considerations to perform explorative analyses. We applied sensitivity analyses with placebo response rates closest to week 8 to compare our data with those reported for adults. We identified 24 placebo-controlled trials (2229 patients in the placebo arms). The clinician-rated placebo response rates ranged from 22 to 62% with a pooled response rate of 45% (95% CI 41–50%). The number of study sites was a significant modifier in the simple meta-regression analysis [odds ratio (OR) 1.01, 95% CI 1.01–1.02, p = 0.0003, k = 24) with more study sites linked to a higher placebo response. Study duration was not significantly associated with the placebo response rate. The explorative simple analyses revealed that publication year may be an additional modifier. However, in the explorative multivariable analysis including the number of study sites and the publication year only the number of study sites reached a p value ≤ 0.05. The self-rated placebo response rates ranged from 1 to 68% with a pooled response rate of 26% (95% CI 10–54%) (k = 6; n = 396). This meta-analysis confirms a high pooled placebo response rate in children and adolescents based on clinician ratings, which exceeds that observed in the most recent meta-analysis of placebo effects in adults (36%; 95% CI 35–37%) published in 2016. However, and similar to findings in adults, the pooled response rates based on self-ratings were substantially lower. In accordance with previous meta-analyses, we corroborated the number of study sites as significant modifier. In comparison to the recent adult meta-analysis, the substantially lower number of pediatric studies entails a reduced power to detect modifiers. Future studies should provide more precise and homogenous information to support discovery of potential modifiers and consider no-treatment—if ethically permissible—to allow differentiation between placebo and spontaneous remission rates. If these differ, practicing clinicians should facilitate placebo effects as an addition to the verum effect to maximize benefits. Further research is required to explain the discrepant response rates between clinician and self-ratings.     

Root canal preparation in mandibular premolars with TRUShape and Vortex Blue: A micro‐computed tomography study

A comparison of the preparation ability of two root canal instrumentation systems in oval‐shaped canals using micro‐computed tomography was undertaken. Thirty extracted, single‐rooted, human mandibular premolars with radiographically similar canal morphology were selected, allocated to two groups (N = 15) and prepared with TRUShape or Vortex Blue (VB). Each sample was subjected to three scans (20 μm resolution): pre‐preparation and after preparation to sizes #30 and #40. Three‐dimensional data sets were evaluated for canal volume, surface area and surface treatment. Matched axial slices in apical, middle and coronal root thirds were evaluated for cross‐sectional area, roundness and transportation. Preparation with both instruments increased canal volumes and surface areas similarly and significantly (P < 0.001) with no significant difference between groups. TRUShape significantly enhanced surface treatment at both apical sizes (P < 0.05). Transportation exceeded 100 μm in only eight out of 90 cross sections. Both instruments performed similarly during preparation. TRUShape, however, significantly enhanced surface treatment.     

Three-dimensional echocardiography for the assessment of the tricuspid valve

Tricuspid valve pathology is increasingly recognized as an important contributor to patient morbidity. Accordingly, interest in transcatheter interventions for tricuspid valve disease has continued to grow. Echocardiographic imaging of the tricuspid valve has therefore become an integral component of patient assessment and the essential imaging modality for interventional procedures. The need for improved tricuspid valve imaging has highlighted the variability in tricuspid valve anatomy and the difficulties of using two-dimensional (2D) echocardiography alone to determine the location and type of tricuspid valve disease. Here, three-dimensional (3D) imaging using tools such as biplane imaging, multiplanar reconstruction and live 3D acquisition allow a more accurate and efficient evaluation of the tricuspid valve. The 3D imaging of the tricuspid valve is often focused on transesophageal echocardiography, but the more anterior location of the tricuspid valve also lends itself to assessment with transthoracic echocardiography. In this review, we will examine how 3D imaging can complement and enhance the information obtained from 2D echocardiography, and present novel applications for the quantitation of valvular disease and its utility in intraprocedural imaging.