Validation, Implementation, and Clinical Impact of the Oncomine Myeloid Targeted-Amplicon DNA and RNA Ion Semiconductor Sequencing Assay.

The identification of clinically significant genes recurrently mutated in myeloid malignancies necessitates expanding diagnostic testing with higher throughput, such as targeted next-generation sequencing. We present validation of the Thermo Fisher Oncomine Myeloid Next-Generation Sequencing Panel (OMP), targeting 40 genes and 29 fusion drivers recurrently mutated in myeloid malignancies. The study includes data from a sample exchange between two Canadian hospitals demonstrating high concordance for detection of DNA and RNA aberrations. Clinical validation demonstrates high accuracy, sensitivity, and specificity of the OMP, with a lower limit of detection of 5% for single-nucleotide variants and 10% for insertions/deletions. Prospective sequencing was performed for 187 samples from 168 unique patients presenting with suspected or confirmed myeloid malignancy and other hematological conditions to assess clinical impact of identifying variants. Of detected variants, 48% facilitated or clarified diagnoses, 29% affected prognoses, and 25% had the potential to influence clinical management. Of note, OMP was essential to identifying patients with premalignant clonal states likely contributing to cytopenias. We also found that the detection of even a single variant by the OMP assay, versus 0 variants, was predictive of overall survival, independent of age, sex, or diagnosis (P = 0.03). This study demonstrates that molecular profiling of myeloid malignancies with the OMP represents a promising strategy to advance molecular diagnostics.

Patterns of gestational diabetes diagnosis inside and outside of clinical guidelines.

BACKGROUND: Hospital discharge codes are often used to determine the incidence of gestational diabetes mellitus (GDM) at state and national levels. Previous studies demonstrate substantial variability in the accuracy of GDM reporting, and rarely report how the GDM was diagnosed. Our aim was to identify deliveries coded as gestational diabetes, and then to determine how the diagnosis was assigned and whether the diagnosis followed established guidelines. METHODS: We identified which deliveries were coded at discharge as complicated by GDM at the Brigham and Women's Hospital in Boston, MA for the year 2010. We reviewed medical records to determine whether the codes were appropriately assigned. RESULTS: Of 7883 deliveries, coding for GDM was assigned with 98% accuracy. We identified 362 cases assigned GDM delivery codes, of which 210 (58%) had oral glucose tolerance test (OGTT) results available meeting established criteria. We determined that 126 cases (34%) received a GDM delivery code due to a clinician diagnosis documented in the medical record, without an OGTT result meeting established guidelines for GDM diagnosis. We identified only 15 cases (4%) that were coding errors. CONCLUSIONS: Thirty four percent of women assigned GDM delivery codes at discharge had a medical record diagnosis of GDM but did not meet OGTT criteria for GDM by established guidelines. Although many of these patients may have met guidelines if guideline-based testing had been conducted, our findings suggest that clinician diagnosis outside of published guidelines may be common. There are many ramifications of this approach to diagnosis, including affecting population-level statistics of GDM prevalence and the potential impact on some women who may be diagnosed with GDM erroneously.

Risk of future cardiovascular disease in women with prior preeclampsia: a focus group study.

BACKGROUND: A history of preeclampsia is a risk factor for the future development of hypertension and cardiovascular disease (CVD). The objective of this study was to assess, in women with prior preeclampsia, the level of knowledge regarding the link between preeclampsia and CVD, motivators for and barriers to lifestyle change and interest in a lifestyle modification program to decrease CVD risk following a pregnancy complicated by preeclampsia. METHODS: Twenty women with a history of preeclampsia participated in 5 phone-based focus groups. Focus groups were recorded, transcribed, and analyzed. Qualitative content analysis was used to identify common themes across focus groups. Consensus was reached on a representative set of themes describing the data. RESULTS: Women with prior preeclampsia were in general unaware of the link between preeclampsia and future CVD but eager to learn about this link and motivated to achieve a healthy lifestyle. Major perceived barriers to lifestyle change were lack of time, cost of healthy foods and family responsibilities. Perceived facilitators included knowledge of the link between preeclampsia and CVD, a desire to stay healthy, and creating a healthy home for their children. Women with prior preeclampsia were interested in the idea of a web-based program focused on lifestyle strategies to decrease CVD risk in women. CONCLUSIONS: Women with prior preeclampsia were eager to learn about the link between preeclampsia and CVD and to take steps to reduce CVD risk. A web-based program to help women with prior preeclampsia adopt a healthy lifestyle may be an appropriate strategy for this population.