Citations

242 Background: We evaluated plasma cell free based genomic aberrations for prognosticating survival of newly diagnosed metastatic hormone sensitive prostate cancer (mHSPC) patients (pts). Methods: Plasma was collected from mHSPC pts enrolled between 2009-2014. Platelet poor plasma (PPP) fractions were processed uniformly and cell free DNA (cfDNA) extracted using Qiagen kits. Pts were followed after initiating hormonal therapy until death. Next Gen Sequencing (NGS) of cfDNA was performed using Illumina HiSeq X for a preselected panel of 128 genes (PredicineDDR-77 cancer driver genes; 29 genes in BRCA-FA homologous recombination deficiency (HRD) pathway; 22 DNA damage repair pathway genes). Statistical analyses of plasma genome based aberrations with overall survival (OS) were performed in R 3.5.1. Cox proportional-hazard models were used for survival analysis. Results: An average of 2.5 ml PPP from 99 pts yielded a median of 10.5 ng (range: 2.8-702) cfDNA per sample. 15/99 pt samples with a yield < 5 ng were excluded from sequencing; 9/99 samples failed NGS. Median follow-up time was 80.2 months (mths) (Range: 74.7, 87]); median OS was 69.1 mths (range: 54,NR). 29 pts with full NGS data had high volume metastatic disease. cfDNA yield correlated with metastatic volume (P = 0.01). Univariate analysis revealed both variables prognostic for OS (Metastatic volume: log-rank P=0.01, HR=2.1, 95% CI: 1.1-3.8; cfDNA yield: P =0.04, HR = 1.3, 95% CI: 1.03-1.7). Multivariate regression showed prognostic value of cfDNA yield remained independent of metastatic volume (P = 0.03, HR = 1.34, 95% CI: 1.02-1.76). 54/67 samples with NGS data had at least one mutation/copy number variation detected. Top mutated genes included TP53 (N=18), ATM (N=9), CHEK2 (N=7), FANCM (N=6), RB1 (N=6), BRCA2 (N=5), PIK3CA (N=4) and 37/67 pts harbored 1≥ variant in HDR pathways. These pts had a shorter survival (median: 58.6 mths) (P=0.04, HR= 2.28, 95% CI: 1.01-5.18) and pts with ATM mutations did significantly worse (median survival: 47.4 mths) (HR=4.03, P=0.0005, 95% CI: 1.73-9.37). Conclusions: Plasma cfDNA yield is prognostic for survival in newly diagnosed mHSPC state and presence of HRD pathway genomic aberrations in plasma cfDNA are associated with poor survival.

Purpose To begin to quantify and understand the use of the flipped classroom (FC)—a progressive, effective, curricular model—in internal medicine (IM) education in relation to residency program and program director (PD) characteristics. Method The authors conducted a survey that included the Flipped Classroom Perception Instrument (FCPI) in 2015 regarding programs’ use and PDs’ perceptions of the FC model. Results Among the 368 IM residency programs, PDs at 227 (61.7%) responded to the survey and 206 (56.0%) completed the FCPI. Regarding how often programs used the FC model, 34 of the 206 PDs (16.5%) reported “never”; 44 (21.4%) reported “very rarely”; another 44 (21.4%) reported “somewhat rarely”; 59 (28.6%) reported “sometimes”; 16 (7.8%) reported “somewhat often”; and 9 (4.4%) reported “very often.” The mean FCPI score (standard deviation [SD]) for the in-class application factor (4.11 [0.68]) was higher (i.e., more favorable) than for the preclass activity factor (3.94 [0.65]) ( P < .001). FC perceptions (mean [SD]) were higher among younger PDs (≤ 50 years, 4.12 [0.62]; > 50 years, 3.94 [0.61]; P = .04) and women compared with men (4.28 [0.56] vs. 3.91 [0.62]; P < .001). PDs with better perceptions of FCs had higher odds of using FCs (odds ratio, 4.768; P < .001). Conclusions Most IM programs use the FC model at least to some extent, and PDs prefer the interactive in-class components over the independent preclass activities. PDs who are women and younger perceived the model more favorably.

25 Background: Women with diabetes are at an increased risk of developing breast cancer, present with later stage disease, and experience higher breast cancer-specific mortality compared to nondiabetic women. Thus, it is imperative that diabetic women undergo routine screening mammography. Previous studies have shown conflicting results with smaller studies showing lower screening mammography rates among diabetics while a study using national self-report data showed that diabetic women were equally likely to be screened compared to nondiabetic women. Given the conflicting data and limitations of previous studies, we aimed to study receipt of mammography in diabetic women using a nationally representative administrative claims database. Methods: This was a retrospective study using a nationally representative administrative claims database from January 1, 2010, through December 31, 2012. We compared rates of receipt of mammography within a 2-year time frame in diabetic and nondiabetic women ages 40 to 64. We used Healthcare Effectiveness Data and Information Set (HEDIS) logic to define women with diabetes. We used CPT and ICD-9 codes to identify mammogram services received. We calculated odds ratios with 95% confidence intervals to compare mammogram rates among diabetics compared to nondiabetics. Results: 1,723,674 nondiabetic women and 133,973 diabetic women were identified. Among women ages 40 to 49, diabetic women had significantly decreased mammography rates compared to nondiabetic women (OR 0.84; 95% CI 0.83, 0.85). Rates were also lower in diabetic women ages 50 to 64 (OR 0.88; 95% CI 0.88, 0.91). Despite lower mammography rates among diabetics, diabetic women had 1.78 times more visits than nondiabetic women. Conclusions: Women with diabetes are less likely to undergo routine screening mammography than women without diabetes, despite having more encounters with health care providers. This study serves as a reminder to provide timely preventive health services to all patients regardless of medical comorbidities.

5 Background: The 11/2009 USPSTF breast cancer screening update recommended against routine screening mammography for women age 40-49, created confusion and prompted organizations to release opposing statements. We aimed to determine if the USPSTF update for breast cancer screening impacted screening mammography utilization in women age 40-49. Methods: We conducted a time-series analysis utilizing administrative claims data from over 100 health plans. Women ages 40-64 with at least one month of enrollment from 01/2006-12/2010 were included. Medicare claims are not included and thus women ≥65 were excluded. The start date of 01/2006 was chosen to account for possible effects of the recent recession. We developed claims-based algorithms to identify the number of monthly screening mammograms. Time series models were fit using SAS PROC AUTOREG; strong seasonal fluctuations were adjusted by including an autoregressive error of order 12. Results: Over 7.9 million women were included. Prior to the intervention, the baseline monthly mammography rate was 40.9/1,000 women for the 40-49 group and 47.4/1,000 women for the 50-64 group. Based on projections from pre-intervention trends, the update was associated with a 5.72% (1.27,10.18) and 4.97% (1.11,8.84) decrease in mammography rate at 3 and 10 months post-intervention, respectively in the 40-49 group. The intervention had no effect on mammography rates in the 50-64 group. This translates to 53,969 fewer mammograms performed in the year following the update for women ages 40-49 in this dataset. Conclusions: We present the first estimates of the impact of the USPSTF breast cancer screening update using a large nationally representative database. The update was associated with a small but significant decrease in mammography rates for women ages 40-49, while no change was seen for women ages 50-64, which is consistent with the context of the guideline change. A modest effect is also in line with public backlash and the release of numerous conflicting guidelines. These findings underscore the need for further research on benefits and risks of screening mammography as it is difficult to act on numerous sources of contradictory information.

Purpose The flipped classroom (FC), in which instructional content is delivered before class with class time devoted to knowledge application, has the potential to engage residents. A Mayo Clinic Internal Medicine Residency Program study was conducted to validate an FC perception instrument (FCPI); determine whether participation improved FC perceptions; and determine associations between resident characteristics, change in quality improvement (QI) knowledge, and FC perception scores. Method All 143 internal medicine residents at Mayo Clinic, Rochester participated from 2014 to 2015; some experienced a flipped QI curriculum and others completed the traditional nonflipped course. The FCPI was developed, and factor analysis revealed an intuitive two-factor structure: preclass activity and in-class application. Residents were surveyed before and after the monthlong curriculum to measure changes in perception, and the QI Knowledge Assessment Tool was employed to measure knowledge improvement. Results Postcourse FCPI scores significantly increased for three of the eight items. QI knowledge increased significantly among residents who experienced the FC compared with residents who completed the non-FC curriculum. Those without prior FC exposure demonstrated a significant increase in QI knowledge compared with those with previous FC experience. The FCPI had compelling validity evidence with improved scores after curriculum exposure and associations with greater engagement in online modules. Conclusions Residents who participated in the FC demonstrated improved QI knowledge compared with the control group. Residents valued the in-class application sessions more than the online component. These findings have important implications for graduate medical education as residency training programs increasingly use FC models.

Context: Polycystic ovary syndrome (PCOS) is a prevalent disorder that affects women of childbearing age and may be related to obesity and insulin resistance. Objective: The purpose of this systematic review was to appraise the evidence of the impact of lifestyle modification (LSM) interventions on outcomes of women with PCOS. Data Sources: Sources included Ovid Medline, OVID Embase, OVID Cochrane Library, Web of Science, Scopus, PsycINFO, and CINAHL (up to January 2011). Study Selection: We included randomized controlled trials that enrolled woman of any age with PCOS who received LSM and compared them against women who received no intervention, minimal intervention, or metformin. Data Extraction: Two authors performed the data extraction independently. Data Synthesis: We included 9 trials enrolling 583 women with a high loss to follow-up rate, lack of blinding, and short follow-up. Compared with minimal intervention, LSM significantly reduced fasting blood glucose (weighted mean difference, −2.3 mg/dL; 95% confidence interval, −4.5 to −0.1, I2 = 72%, P = .04) and fasting blood insulin (weighted mean difference, −2.1 μU/mL, 95% confidence interval, −3.3 to −1.0, I2 = 0%, P &lt; .001). Changes in body mass index were associated with changes in fasting blood glucose (P &lt; .001). Metformin was not significantly better than LSM in improving blood glucose or insulin levels. We found no significant effect of LSM on pregnancy rate, and the effect on hirsutism was unclear. Conclusions: The available evidence suggests that LSM reduces fasting blood glucose and insulin levels in women with PCOS. Metformin has similar effects. Translation of these short-term effects to patient-important outcomes, beyond diabetes prevention, remains uncertain.

Abstract: To ensure that participants in randomized controlled trials are protected from harm, interim analyses and review of results by an independent data monitoring committee have become standard practice. If an analysis of accumulating data partway through a trial reveals an unanticipated degree of benefit or toxicity, or differences in outcomes between the intervention and control groups are so unimpressive that any prospect of a positive result with the planned sample size is extremely unlikely, investigators may stop the trial earlier than originally scheduled. The practice of stopping randomized controlled trials early is, however, problematic, especially if the trial is stopped for apparent benefit. Concerns in trials stopped early for apparent benefit include appropriate interpretation of results and ethical problems concerning trial participants, clinicians, and society as a whole. In this article, we review the epidemiology of trials stopped early and illustrate some of the problems and controversies associated with stopping randomized controlled trials early for apparent benefit. Finally, we offer guidance for clinicians, those running clinical trials, and authors of systematic reviews.