Faculty Bibliography

PURPOSE: AZD6244 is a MEK1/2 inhibitor with significant preclinical activity in multiple myeloma cells. This phase II study used a two-stage Simon design to determine the AZD6244 response rate in patients with relapsed or refractory multiple myeloma. EXPERIMENTAL DESIGN: AZD6244 (75 mg) was administered orally, twice a day, continuously for 28-day cycles. Response was evaluated after three cycles. RESULTS: Thirty-six patients received therapy. The median age was 65 years (range: 43-81) and the median number of prior therapies was 5 (range: 2-11). The most common grade 3 and 4 toxicities included anemia, neutropenia, thrombocytopenia, diarrhea, and fatigue. Three deaths occurred possibly related to AZD6244 (2 due to sepsis, 1 due to acute kidney injury). After AZD6244 discontinuation, three additional deaths occurred due to disease progression. The response rate (CR + PR) was 5.6% with a mean duration of response of 4.95 months and median progression-free survival time of 3.52 months. One patient had a very good partial response (VGPR), 1 patient had a partial response, 17 patients had stable disease, 13 patients had progressive disease, and 4 patients could not be assessed for response. Pharmacodynamic studies revealed variable effects on bone marrow CD138(+) cell MEK1/2 and ERK1/2 phosphorylation. The best clinical response, a prolonged VGPR, occurred in a patient with an MMSET translocation. CONCLUSIONS: Single-agent AZD6244 was tolerable and had minimal activity in this heavily pretreated population.

OBJECTIVE: The Test of Integrated Professional Skills (TIPS) is an objective structured clinical examination-simulation hybrid examination that assesses resident integration of technical, cognitive, and affective skills in Obstetrics and Gynecology (OBGYN) residents. The aim of this study was to analyze performance patterns and reactions of residents to the test to understand how it may fit within a comprehensive assessment program. DESIGN: A retrospective, mixed methods review of the design and implementation of the examination, patterns of performance of trainees at different levels of training, focus group data, and description of use of TIPS results for resident remediation and curriculum development. SETTING: OBGYN residents at New York University Langone Medical Center, a tertiary-care, urban academic health center. PARTICIPANTS: OBGYN residents in all years of training, postgraduate year-1 through postgraduate year, all residents completing the TIPS examination and consenting to participate in focus groups were included. RESULTS: In all, 24 residents completed the TIPS examination. Performance on the examination varied widely among individuals at each stage of training, and did not follow developmental trends, except for technical skills. Cronbach alpha for both standardized patient and faculty ratings ranged from 0.69 to 0.84, suggesting internal consistency. Focus group results indicated that residents respond to the TIPS examination in complex ways, ranging from anxiety about performance to mixed feelings about how to use the data for their learning. CONCLUSION: TIPS assesses a range of attributes, and can support both formative and summative evaluation. Lack of clear developmental differences and wide variation in performance by learners at the same level of training support the argument for individualized learning plans and competency-based education.

Simulation in obstetrics and gynecology (OBGYN) training captures a range of interpersonal, cognitive, and technical skills. However, trainee perspectives on simulation-based assessment remain unexplored. After an observed structured clinical examination (OSCE) simulation hybrid exam, two focus groups of residents were conducted. Analysis grounded in a thematic coding guided the qualitative research process. Responses suggest a valuation of cognitive and technical skills over interpersonal skills. Realism was seen as critical and residents perceived the assessment as more valuable for the educator than the learner. Feedback was highly valued. Resident perspectives on this exam give insight into their perceptions of simulation-based assessment as well as their conceptions of their own learning through simulations.

Although there are many analytical methods available for estimation of metformin in biological samples and pharmaceutical preparations, to our knowledge there is no specific spectrophotometric method using its derivatization by the Mannich reaction. A simple spectrophotometric method was developed by studying the UV evolution of the complex obtained between metformin, formaldehyde and uranine using the Mannich reaction. Measurements of metformin were achieved at 437 nm using UV-visible spectroscopy. To assess the validity of the method in a clinical situation the extraction was adapted to extract metformin from human urine that had been tested by our method. The spectrometric correlation coefficient (R²) was found to be 0.98 over metformin concentrations of 5- 30 mug/mL. This range includes the clinical levels reached during treatment. The method was validated for linearity, accuracy, and precision. The within-assay limit of detection and quantification (sensitivity) were found to be 0.001 mug/mL. This method for quantification of metformin is simple, precise and accurate. It is suitable as an alternative to existing clinical methods and for the analysis of metformin in pharmacodynamic studies of urinary excretion as well as pharmaceutical formulations and in vitro dissolution studies

The December 2014 outbreak of measles in California impacted over 100 children and served as a reminder that this disease still plagues the USA, even 50 years following the first licensed vaccine. Refusal of vaccination is a complicated and multifaceted issue, one that clearly demands a closer look by paediatricians and public health officials alike. While medical doctors and scientists are trained to practice 'evidence-based medicine', and studies of vaccine safety and efficacy speak the language of statistics, there is reason to believe that this is not the most effective strategy for communicating with all groups of parents. Herein, we consider other methods such as narrative practices that employ stories and appeal more directly to parents. We also examine how doctors are trained to disseminate information and whether there are reasonable supplementary methods that could be used to improve vaccine communication and ultimately immunisation rates.

CONTEXT: HIV patients are at an increased risk for cardiometabolic disease secondary to depot-specific alterations in adipose function, but mechanisms remain poorly understood. OBJECTIVE: The endoribonuclease Dicer has been linked to the modulation of brown and white adipocyte differentiation. We previously demonstrated that Dicer knockout mice undergo transformation of brown adipose tissue to white adipose tissue and develop a lipodystrophic phenotype. We hypothesized reduced Dicer and brown adipose tissue gene expression from nonlipomatous sc fat among HIV patients with a lipodystrophic phenotype. DESIGN: Eighteen HIV (nine with and without lipodystrophic changes in fat distribution, characterized by excess dorsocervical adipose tissue [DCAT]) and nine non-HIV subjects underwent punch biopsy of abdominal sc fat to determine expression of Dicer and other adipose-related genes. RESULTS: HIV subjects with long-duration antiretroviral use demonstrated excess DCAT vs non-HIV subjects (9.8 +/- 1.0 vs 6.6 +/- 0.8 cm(2), P = .02) with similar body mass index. Dicer expression was decreased in abdominal sc fat of HIV vs non-HIV (4.88 [1.91, 11.93] vs 17.69 [10.72, 47.91], P = .01), as were PPARalpha, ZIC1, PRDM16, DIO2, and HSP60 (all P