Citations

AbstractHairy cell leukemia is an uncommon hematologic malignancy characterized by pancytopenia and marked susceptibility to infection. Tremendous progress in the management of patients with this disease has resulted in high response rates and improved survival, yet relapse and an appropriate approach to re-treatment present continuing areas for research. The disease and its effective treatment are associated with immunosuppression. Because more patients are being treated with alternative programs, comparison of results will require general agreement on definitions of response, relapse, and methods of determining minimal residual disease. The development of internationally accepted, reproducible criteria is of paramount importance in evaluating and comparing clinical trials to provide optimal care. Despite the success achieved in managing these patients, continued participation in available clinical trials in the first-line and particularly in the relapse setting is highly recommended. The Hairy Cell Leukemia Foundation convened an international conference to provide common definitions and structure to guide current management. There is substantial opportunity for continued research in this disease. In addition to the importance of optimizing the prevention and management of the serious risk of infection, organized evaluations of minimal residual disease and treatment at relapse offer ample opportunities for clinical research. Finally, a scholarly evaluation of quality of life in the increasing number of survivors of this now manageable chronic illness merits further study. The development of consensus guidelines for this disease offers a framework for continued enhancement of the outcome for patients.

Purpose To examine internal medicine (IM) residency program directors’ (PDs’) perspectives on the Core Entrustable Professional Activities for Entering Residency (Core EPAs)—introduced into undergraduate medical education to further competency-based assessment—and on communicating competency-based information during transitions. Method A spring 2015 Association of Program Directors in Internal Medicine survey asked PDs of U.S. IM residency programs for their perspectives on which Core EPAs new interns must or should possess on day 1, which are most essential, and which have the largest gap between expected and observed performance. Their views and preferences were also requested regarding communicating competency-based information at transitions from medical school to residency and residency to fellowship/employment. Results The response rate was 57% (204/361 programs). The majority of PDs felt new interns must/should possess 12 of the 13 Core EPAs. PDs’ rankings of Core EPAs by relative importance were more varied than their rankings by the largest gaps in performance. Although preferred timing varied, most PDs (82%) considered it important for medical schools to communicate Core EPA-based information to PDs; nearly three-quarters (71%) would prefer a checklist format. Many (60%) would be willing to provide competency-based evaluations to fellowship directors/employers. Most (> 80%) agreed that there should be a bidirectional communication mechanism for programs/employers to provide feedback on competency assessments. Conclusions The gaps identified in Core EPA performance may help guide medical schools’ curricular and assessment tool design. Sharing competency-based information at transitions along the medical education continuum could help ensure production of competent, practice-ready physicians.

Background: Although the Affordable Care Act has been successful in expanding Medicaid to >17 million people, insurance alone may not translate into access to health care. Even among the insured, substantial barriers to accessing services inhibit health care utilization. Objectives: We examined the effect of selected barriers to health care access and the magnitude of those barriers on health care utilization. Research Design: Data come from a 2008 survey of adult enrollees in Minnesota’s public health care programs. We used multivariate logistic regression to estimate the effects of perceived patient, provider, and system-level barriers on past year delayed, foregone, and lack of preventive care. Subjects: A total of 2194 adults enrolled in Minnesota Health Care Programs who were mostly female (66%), high school graduates (76%), unemployed (62%), and living in metro areas (67%) were included in the analysis. Results: Reporting problems across all barriers increased the odds of delayed care from 2 times for provider-related barriers (OR=2.0; 95% CI, 1.2–3.3) to >6 times for access barriers (OR=6.2; 95% CI, 3.8–10.2) and foregone care from 2.6 times for family/work barriers (OR=2.6; 95% CI, 1.3–5.1) to >7 times for access barriers (OR=7.1; 95% CI, 3.9–13.1). Perceived discrimination was the only barrier consistently associated with all 3 utilization outcomes. Conclusions: Multiple types of barriers are associated with delayed and foregone care. System-level barriers and discrimination have the greatest effect on health care seeking behavior.

Abstract Background: Associations of medical history, lifestyle, and family history of hematological disorders with risk of chronic lymphocytic leukemia (CLL) have been previously established (1), but these exposures have not been well-studied as contributing factors to CLL prognosis. Here we investigate the association of these exposures with time to first treatment (TTFT) in 730 CLL patients. Methods: Newly diagnosed CLL patients seen at the Mayo Clinic between 2002 and 2012 were enrolled. CLL was defined according to the 1996 NCI-Working Group criteria (2). Risk factor data (including body mass index, smoking, alcohol use, sun exposure, having lived on a farm, any allergy, asthma, eczema, blood transfusion, diabetes, rheumatoid arthritis, and family history of hematological malignancy) were collected from self-administered questionnaires. Clinical and prognostic characteristics for CLL were extracted from medical records. Analyses were performed using Cox regression with first treatment as the event. Hazard ratios (HR) and 95% confidence intervals were estimated. We used Bonferroni correction for multiple testing with statistical significance at 0.004. Results: The median age at CLL diagnosis was 63 years (range 36 - 89); 65% were male, and 95% had a Rai stage< III. The median follow up time was 6.3 years, and 40% received treatment. In unadjusted analyses, patients with any history of allergies had significantly longer TTFT (HR = 0.66, 95% CI: 0.51-0.85, P = 0.001). We also observed borderline significance with history of asthma (HR = 0.53, 95% CI: 0.34-0.85, P = 0.008). These associations held after adjusting for important prognostic factors including age, sex, Rai stage, and IGVH mutational status. The other risk factors had non-significant associations (P>0.1). Conclusions: We observed an improved CLL prognosis in patients with a history of any allergies or asthma. These results were independent of other prognostic markers and suggest that an overactive IgE level from environmental exposures may provide insight into the progression of CLL. Literature Cited 1. Slager SL, Benavente Y, Blair A, Vermeulen R, Cerhan JR, Costantini AS, et al. Medical history, lifestyle, family history, and occupational risk factors for chronic lymphocytic leukemia/small lymphocytic lymphoma: the InterLymph Non-Hodgkin Lymphoma Subtypes Project. J Natl Cancer Inst Monogr. 2014 Aug;2014(48):41-51. 2. Cheson BD, Bennett JM, Grever M, Kay N, Keating MJ, O’Brien S, et al. National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood. 1996 Jun 15;87(12):4990-7. Citation Format: Sara Beiggi, James M. Foran, O’Byrne Megan, Celine M. Vachon, Timothy G. Call, Neil E. Kay, Tait D. Shanafelt, James R. Cerhan, Susan L. Slager. Medical history, lifestyle, and family history exposures and chronic lymphocytic leukemia outcome. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3453.

Abstract Introduction. First-line chemoimmunotherapy (CIT) has significantly increased the complete remission (CR) rate for patients with CLL; however, relapse is a common event and strategies aimed at eradicating disease more effectively are needed. Vascular Epithelial Growth Factor (VEGF) plays a crucial role in the cross talk between CLL B cells and their microenvironment. In addition low baseline VEGF levels predict a better response to CIT. Testing the combination of an anti-VEGF agent with CIT was therefore assessed by us in upfront CLL patients. Methods. Here we report the results of a phase II open-label randomized trial comparing the combination of bevacizumab, an anti-VEGF monoclonal antibody, with pentostatin, cyclophosphamide and rituximab (PCR-B) to PCR alone as front-line therapy in previously untreated patients with CLL. VEGF, b-fibroblast growth factor (FGF), thrombospondin (TSP)-1, chemokine ligand (CCL)-3 and CCL-4 plasma levels were measured at baseline and at time of response assessment. Results. Between 01/2009 and 01/2013, 62 patients were accrued in the study, 32 in the arm A (PCR-B) and 30 in arm B (PCR alone). A higher rate of grade 3-4 cardiovascular toxicity was observed with the use of PCR-B (34% vs 0%, p<0.001): this included 7 cases of hypertension, 2 cases of congestive heart failure, 1 myocarditis, and 1 case of torsade de point. A higher CR rate (50% vs 33%, p = 0.21) and a significantly longer median progression-free (p = 0.04) and treatment-free (p = 0.05) survival were achieved with the use of PCR-B. No difference in chemokine kinetics was observed between the 2 arms, except for VEGF, which significantly increased after PCR-B. In the PCR-B arm, chemokine kinetics for CCL-3 (median drop 5.0 vs. median drop 31.8, respectively; p = 0.02) and CCL-4 (median drop 23.8 vs. median drop 120.9, respectively; p = 0.01) were significantly associated with achievement of CR. No significant correlations were found between cytokine plasma levels and responses for patients treated in the PCR only arm. Conclusions. The addition of bevacizumab to CIT is safe and effective, although associated with higher cardiovascular toxicity, in particular hypertension. The addition of bevacizumab produces higher CR rates, translating into improved progression-free survival, and is associated with decreased plasma levels of CCL-3 and CCL-4. Citation Format: PAOLO STRATI, TAIT D. SHANAFELT, BETSY LAPLANT, ADAM PETTINGER, CONNIE LESNICK, DANIEL NIKCEVICH, TIMOTHY CALL, WEI DING, CURTIS HANSON, NEIL KAY. The addition of bevacizumab to chemoimmunotherapy prolongs progression-free survival in patients with chronic lymphocytic leukemia (CLL) through modulation of the microenvironment. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1423.

Currently, no standard defines the clinical skills that medical students must demonstrate upon graduation. The Liaison Committee on Medical Education bases its standards on required subject matter and student experiences rather than on observable educational outcomes. The absence of such established outcomes for MD graduates contributes to the gap between program directors’ expectations and new residents’ performance. In response, in 2013, the Association of American Medical Colleges convened a panel of experts from undergraduate and graduate medical education to define the professional activities that every resident should be able to do without direct supervision on day one of residency, regardless of specialty. Using a conceptual framework of entrustable professional activities (EPAs), this Drafting Panel reviewed the literature and sought input from the health professions education community. The result of this process was the publication of 13 core EPAs for entering residency in 2014. Each EPA includes a description, a list of key functions, links to critical competencies and milestones, and narrative descriptions of expected behaviors and clinical vignettes for both novice learners and learners ready for entrustment. The medical education community has already begun to develop the curricula, assessment tools, faculty development resources, and pathways to entrustment for each of the 13 EPAs. Adoption of these core EPAs could significantly narrow the gap between program directors’ expectations and new residents’ performance, enhancing patient safety and increasing residents’, educators’, and patients’ confidence in the care these learners provide in the first months of their residency training.