Research in Pediatric Residency: National Experience of Pediatric Chief Residents.

OBJECTIVE: To determine factors associated with increased research productivity, satisfaction, and perceived barriers to research within residency from the experience of pediatric chief residents. METHODS: An online cross-sectional survey was administered to academic year 2014-15 chief residents. Topics assessed included program demographic characteristics, career intentions, research productivity, satisfaction with research training and opportunities, and research barriers. Chi-square and Fisher exact tests were used for descriptive statistics. Multivariable logistic regression analysis was used to determine factors associated with productivity and research satisfaction. RESULTS: The response rate was 63% (165 of 261). Half (82 of 165) were productive in research. Most were satisfied with their quality of research training (55%; 90 of 165) and research opportunities (69%; 114 of 165). Chiefs reporting interest in research were 5 times more likely to be productive than those who did not (odds ratio [OR] = 5.2; 95% confidence interval [CI], 2.3-11.8). Productive chiefs were more likely to report including research time in future careers (P = .003). Most (83%; 137 of 165) thought their programs were supportive of resident research, but lack of time was frequently cited as a major barrier. Those satisfied with research opportunities were less likely to find lack of training (OR = 0.3; 95% CI, 0.1-0.7) or faculty mentorship (OR = 0.2; 95% CI, 0.0-0.9) as a major barrier. CONCLUSIONS: Pediatric chief resident interest in research is strongly associated with research productivity during residency, and research productivity is strongly associated with career plans including research time. By cultivating research interest through faculty mentorship, research training, and dedicated time, pediatric residency programs might help foster early research success and, potentially lead to continued engagement with research in trainees' future careers.

In Pursuit of Meaningful Use of Learning Goals in Residency: A Qualitative Study of Pediatric Residents.

PURPOSE: Medical education aims to equip physicians for lifelong learning, an objective supported by the conceptual framework of self-regulated learning (SRL). Learning goals have been used to develop SRL skills in learners across the medical education continuum. This study's purpose was to elicit residents' perspectives on learning goal use and to develop explanations suggesting how aspects of the learning environment may facilitate or hinder the meaningful use of learning goals in residency. METHOD: Resident focus groups and program director interviews were conducted in 2012-2013, audio-recorded, and transcribed. Programs were selected to maximize diversity of size, geographic location, type of program, and current use of learning goals. Data were analyzed using the constant comparative method associated with grounded theory. Further analysis compared themes frequently occurring together to strengthen the understanding of relationships between the themes. Through iterative discussions, investigators built a grounded theory. RESULTS: Ninety-five third-year residents and 12 program directors at 12 pediatric residency programs participated. The analysis identified 21 subthemes grouped into 5 themes: program support, faculty roles, goal characteristics and purposes, resident attributes, and accountability and goal follow-through. Review of relationships between the themes revealed a pyramid of support with program support as the foundation that facilitates the layers above it, leading to goal follow-through. CONCLUSIONS: Program support facilitates each step of the SRL process that leads to meaningful use of learning goals in residency. A strong foundation of program support should include attention to aspects of the implicit curriculum as well as the explicit curriculum.

Validation of a multi-marker model for the prediction of incident type 2 diabetes mellitus: combined results of the Inter99 and Botnia studies.

PURPOSE: To assess performance of a biomarker-based score that predicts the five-year risk of diabetes (Diabetes Risk Score, DRS) in an independent cohort that included 15-year follow-up. METHOD: DRS was developed on the Inter99 cohort, and validated on the Botnia cohort. Performance was benchmarked against other risk-assessment tools comparing calibration, time to event analysis, and net reclassification. RESULTS: The area under the receiver-operating characteristic curve (AUC) was 0.84 for the Inter99 cohort and 0.78 for the Botnia cohort. In the Botnia cohort, DRS provided better discrimination than fasting plasma glucose (FPG), homeostasis model assessment of insulin resistance, oral glucose tolerance test or risk scores derived from Framingham or San Antonio Study cohorts. Overall reclassification with DRS was significantly better than using FPG and glucose tolerance status (p < 0.0001). In time to event analysis, rates of conversion to diabetes in low, moderate, and high DRS groups were significantly different (p < 0.001). CONCLUSION: This study validates DRS performance in an independent population, and provides a more accurate assessment of T2DM risk than other methods.

Microfluidic strategies applied to biomarker discovery and validation for multivariate diagnostics.

Complex diseases are caused by combinatorial genetic, environmental and lifestyle factors. The emergence of multibiomarker tests to define these diseases and to identify the early, presymptomatic stages offers several advantages to the conventional use of single marker tests. The development of multibiomarker protein-based tests remains constrained by technological and operational limitations in assaying hundreds to thousands of proteins in thousands of samples. In order to develop a multibiomarker test that stratifies risk for Type 2 diabetes, we took a candidate-driven immunoassay approach utilizing a microfluidics platform to analyze 89 candidate proteins in thousands of samples, which allowed us to move from discovery to a commercial test in 2 years. Future multibiomarker test development will be enhanced by advancements in the number of proteins that can be analyzed, analytical sensitivity and throughput, and sample volume requirements, all of which depend on the further advancement of microfluidics, detection technologies and affinity-based reagents.

Newborn screening results in children with central hypothyroidism.

OBJECTIVE: To investigate newborn screening results in children with congenital hypopituitarism, including central hypothyroidism, and to determine whether there were differences between children who had abnormal results and children with normal newborn screening results. STUDY DESIGN: Medical records of children with central hypothyroidism observed in our pediatric endocrinology clinics from 1990 to 2006 were reviewed. RESULTS: Forty-two subjects (22 boys) were identified. Eight children (19%) had a low total thyroxine level (<5.0 mcg/dL) on the newborn screening test. The average total thyroxine level in the remaining 34 subjects was 9.8 +/- 3.4 mcg/dL. Thyrotropin levels were within the reference range in all children. No differences were found in the 2 groups for birth history, jaundice (53% overall), hypoglycemia (36% overall), or micropenis (43% of boys). Fifty-seven percent of children had septo-optic dysplasia, and 98% had multiple pituitary hormone deficiencies. Children with an abnormal newborn screening results were initially examined by a pediatric endocrinologist at an average age of 4.6 +/- 5.0 months, and children with normal newborn screening results were initially examined at an average age of 16.9 +/- 26.7 months (P = .037). CONCLUSIONS: Most children with congenital central hypothyroidism have normal thyroid function at birth. Normal newborn screening results can be falsely reassuring and may contribute to a delay in diagnosis of hypopituitarism despite classic clinical features.

Development of a type 2 diabetes risk model from a panel of serum biomarkers from the Inter99 cohort.

OBJECTIVE: The purpose of this study was to develop a model for assessing the 5-year risk of developing type 2 diabetes from a panel of 64 circulating candidate biomarkers. RESEARCH DESIGN AND METHODS: Subjects were selected from the Inter99 cohort, a longitudinal population-based study of approximately 6,600 Danes in a nested case-control design with the primary outcome of 5-year conversion to type 2 diabetes. Nondiabetic subjects, aged >or=39 years, with BMI >or=25 kg/m(2) at baseline were selected. Baseline fasting serum samples from 160 individuals who developed type 2 diabetes and from 472 who did not were tested. An ultrasensitive immunoassay was used to measure of 58 candidate biomarkers in multiple diabetes-associated pathways, along with six routine clinical variables. Statistical learning methods and permutation testing were used to select the most informative biomarkers. Risk model performance was estimated using a validated bootstrap bias-correction procedure. RESULTS: A model using six biomarkers (adiponectin, C-reactive protein, ferritin, interleukin-2 receptor A, glucose, and insulin) was developed for assessing an individual's 5-year risk of developing type 2 diabetes. This model has a bootstrap-estimated area under the curve of 0.76, which is greater than that for A1C, fasting plasma glucose, fasting serum insulin, BMI, sex-adjusted waist circumference, a model using fasting glucose and insulin, and a noninvasive clinical model. CONCLUSIONS: A model incorporating six circulating biomarkers provides an objective and quantitative estimate of the 5-year risk of developing type 2 diabetes, performs better than single risk indicators and a noninvasive clinical model, and provides better stratification than fasting plasma glucose alone.

Genome sequencing in microfabricated high-density picolitre reactors.

The proliferation of large-scale DNA-sequencing projects in recent years has driven a search for alternative methods to reduce time and cost. Here we describe a scalable, highly parallel sequencing system with raw throughput significantly greater than that of state-of-the-art capillary electrophoresis instruments. The apparatus uses a novel fibre-optic slide of individual wells and is able to sequence 25 million bases, at 99% or better accuracy, in one four-hour run. To achieve an approximately 100-fold increase in throughput over current Sanger sequencing technology, we have developed an emulsion method for DNA amplification and an instrument for sequencing by synthesis using a pyrosequencing protocol optimized for solid support and picolitre-scale volumes. Here we show the utility, throughput, accuracy and robustness of this system by shotgun sequencing and de novo assembly of the Mycoplasma genitalium genome with 96% coverage at 99.96% accuracy in one run of the machine.