Citations

BACKGROUND AND OBJECTIVE: Simulation-based medical education (SBME) is used to teach residents. However, few studies have evaluated its clinical impact. The goal of this study was to evaluate the impact of an SBME session on pediatric interns’ clinical procedural success. METHODS: This randomized trial was conducted at 10 academic medical centers. Interns were surveyed on infant lumbar puncture (ILP) and child intravenous line placement (CIV) knowledge and watched audiovisual expert modeling of both procedures. Participants were randomized to SBME mastery learning for ILP or CIV and for 6 succeeding months reported clinical performance for both procedures. ILP success was defined as obtaining a sample on the first attempt with <1000 red blood cells per high-power field or fluid described as clear. CIV success was defined as placement of a functioning catheter on the first try. Each group served as the control group for the procedure for which they did not receive the intervention. RESULTS: Two-hundred interns participated (104 in the ILP group and 96 in the CIV group). Together, they reported 409 procedures. ILP success rates were 34% (31 of 91) for interns who received ILP mastery learning and 34% (25 of 73) for controls (difference: 0.2% [95% confidence interval: –0.1 to 0.1]). The CIV success rate was 54% (62 of 115) for interns who received CIV mastery learning compared with 50% (58 of 115) for controls (difference: 3% [95% confidence interval: –10 to 17]). CONCLUSIONS: Participation in a single SBME mastery learning session was insufficient to affect pediatric interns’ subsequent procedural success.

Purpose To assess the effects of ruxolitinib on symptom burden and quality of life (QoL) and to evaluate the ability of the modified Myelofibrosis Symptom Assessment Form (MFSAF) v2.0 to measure meaningful changes in myelofibrosis-related symptoms in patients with myelofibrosis. Patients and Methods COMFORT-I (Controlled Myelofibrosis Study With Oral JAK Inhibitor Treatment–I) is a double-blind, placebo-controlled phase III study evaluating ruxolitinib in patients with intermediate-2 or high-risk myelofibrosis. Exploratory analyses were conducted on the following patient-reported outcomes (PROs) assessments: modified MFSAF v2.0 (individual symptoms and Total Symptom Score [TSS]), European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Scale, and Patient Global Impression of Change (PGIC). Results Patients receiving ruxolitinib experienced improvements in individual myelofibrosis-related symptoms, although patients receiving placebo experienced worsening (P < .001). The majority (91%) of ruxolitinib-treated patients designated as ≥ 50% TSS responders (≥ 50% TSS improvement) self-reported their condition as either “Much improved” or “Very much improved” on the PGIC. These patients achieved significant improvements in the EORTC QLQ-C30 functional domains and Global Health Status/QoL versus patients receiving placebo, who experienced worsening on these measures (P ≤ .0135). Ruxolitinib-treated patients with a lesser degree of symptom improvement (< 50% TSS responders) also achieved improvements over placebo on these measures. The degree of spleen volume reduction with ruxolitinib correlated with improvements in TSS, PGIC, PROMIS Fatigue Scale, and EORTC Global Health Status/QoL. Ruxolitinib-treated patients who achieved a ≥ 35% reduction in spleen volume experienced the greatest improvements in these PROs. Conclusion Ruxolitinib-treated patients achieved clinically meaningful improvements in myelofibrosis-related symptoms and QoL, but patients receiving placebo reported worsening of symptoms and other PROs.

ObjectiveObesity, insulin resistance, and diabetes disproportionately affect African‐American (AA) women. Abnormal adipose tissue free fatty acid (FFA) release is associated with these conditions. Resting energy expenditure (REE) and sex predict FFA release in Caucasians, but whether this is true in AA is unknown. The sex‐specific relationships between FFA release, REE, and race was compared.Design and Methods100 adults (47% AA, 50% male, age 32 ± 8 years [mean ± SD]) from three different centers underwent duplicate measures of FFA release ([U‐13C] palmitate) and REE (indirect calorimetry). Body composition was determined by DXA and abdominal imaging.ResultsAA participants had lower REE, but similar FFA concentrations and flux compared with Caucasian participants. The significant predictors of palmitate release were REE, sex, and race. REE and FFA flux were correlated in both sexes and both races. In a multiple linear regression analysis with palmitate flux as the dependent variable and REE, sex, race, total fat mass, fat‐free mass, and insulin as independent variables, REE was the only independent predictor of FFA release in men. Both REE and race predicted palmitate flux in women.ConclusionsFFA flux is related to REE, but the relationship differs in AA and Caucasian women.

Sex, a biological variable, and gender, a cultural variable, define the individual and affect all aspects of disease prevention, development, diagnosis, progression, and treatment. Sex and gender are essential elements of individualized medicine. However, medical education rarely considers such topics beyond the physiology of reproduction. To reduce health care disparities and to provide optimal, cost-effective medical care for individuals, concepts of sex and gender health need to become embedded into education and training of health professionals. In September 2012, Mayo Clinic hosted a 2-day workshop bringing together leading experts from 13 U.S. schools of medicine and schools of public health, Health Resources and Services Administration Office of Women's Health (HRSA OWH), the National Institutes of Health (NIH) Office of Research on Women's Health (ORWH), and the Canadian Institute of Health and Gender. The purpose of this workshop was to articulate the need to integrate sex- and gender-based content into medical education and training, to identify gaps in current medical curricula, to consider strategies to embed concepts of sex and gender health into health professional curricula, and to identify existing resources to facilitate and implement change. This report summarizes these proceedings, recommendations, and action items from the workshop.

Class B GPCRs (G-protein-coupled receptors) share heptahelical topology and G-protein binding with other superfamily members, yet have unique structures and modes of activation. Natural ligands for these receptors are moderate-length peptides with C-terminal α-helices. NMR and crystal structures of the peptide-bound disulfide-bonded receptor N-terminal domains demonstrate that these helices occupy a conserved groove; however, the details of this interaction vary from one receptor to another. In this review, we focus on the prototypic secretin receptor and use extensive intrinsic photoaffinity labelling, structure–activity series, alanine-replacement mutagenesis and fluorescence analysis to define the molecular basis for this interaction. Additionally, experimental validation of predictions coming from in silico molecular modelling has provided a basis for enhancement of binding affinity. Such insights will be useful in the rational development of drugs acting at this important group of targets.

Chromosomal microarray analysis (CMA) is standard of care, first‐tier clinical testing for detection of genomic copy number variation among patients with developmental disabilities. Although diagnostic yield is higher than traditional cytogenetic testing, management impact has not been well studied. We surveyed genetic services providers regarding CMA ordering practices and perceptions about reimbursement. Lack of insurance coverage because of perceived lack of clinical utility was cited among the most frequent reasons why CMA was not ordered when warranted. We compiled a list of genomic regions where haploinsufficiency or triplosensitivity cause genetic conditions with documented management recommendations, estimating that at least 146 conditions potentially diagnosable by CMA testing have published literature supporting specific clinical management implications. Comparison with an existing clinical CMA database to determine the proportion of cases involving these regions showed that CMA diagnoses associated with such recommendations are found in approximately 7% of all cases (n = 28,526). We conclude that CMA impacts clinical management at a rate similar to other genetic tests for which insurance coverage is more readily approved. The information presented here can be used to address barriers that continue to contribute to inequities in patient access and care in regard to CMA testing.

Abstract Purpose: Clinically validated biomarkers for anti-angiogenesis agents are not available. We have previously reported associations between candidate VEGFA single-nucleotide polymorphisms (SNP) and overall survival (OS) in E2100. The associations between tumor VEGFA amplification and outcome are evaluated here. Experimental Design: E2100 was a phase III trial comparing paclitaxel with or without bevacizumab for patients with metastatic breast cancer. FISH to assess gene amplification status for VEGFA was conducted on paraffin-embedded tumors from 363 patients in E2100. Evaluation for association between amplification status and outcomes was conducted. Results: Estrogen receptor (ER)+ or progesterone receptor (PR)+ tumors were less likely to have VEGFA amplification than ER/PR− tumors (P = 0.020). VEGFA amplification was associated with worse OS (20.2 vs. 25.3 months; P = 0.013) in univariate analysis with a trend for worse OS in multivariate analysis (P = 0.08). There was a significant interaction between VEGFA amplification, hormone receptor status, and study arm. Patients with VEGFA amplification and triple-negative breast cancers (TNBC) or HER2 amplification had inferior OS (P = 0.047); amplification did not affect OS for those who were ER+ or PR+ and HER2−. Those who received bevacizumab with VEGFA amplification had inferior progression-free survival (PFS; P = 0.010) and OS (P = 0.042); no association was seen in the control arm. Test for interaction between study arm and VEGFA amplification with OS was not significant. Conclusion: VEGFA amplification in univariate analysis was associated with poor outcomes; this was particularly prominent in HER2+ or TNBCs. Additional studies are necessary to confirm the trend for poor OS seen on multivariate analysis for patients treated with bevacizumab. Clin Cancer Res; 19(5); 1281–9. ©2012 AACR.