Lived Experience and Patient Advocacy Module: Curriculum and Faculty Guide.

INTRODUCTION: Medical teachers frequently tell learners how some of the greatest challenges in clinical care are not associated with the scientific details of biomedicine but are instead related to patient interactions and the human dimensions of illness and recovery. Beyond providing direct care, physicians sometimes serve as advocates and supporters for their patient as the patient navigates through the health care system. Opportunities to discuss and reflect on these aspects of medical practice may not arise in the course of clinical experiences. METHODS: This video module and accompanying lesson plan provide the basis for a structured session on patient-physician communication and patient advocacy. In the video, learners hear from a patient who experienced a life-changing medical condition and who faced challenges both before diagnosis and during a long recovery. The video provides a basis for vital discussions about the patient-physician relationship, highlighting the importance of clear and continuing communication. RESULTS: Students indicated that this module effectively provided a patient perspective. The video format and fast pace of the presentation appealed to them. DISCUSSION: This module is ideally suited for use as a stimulus for a facilitated small-group discussion with medical students. It can be presented within a 1-hour session. It can also be used as a freestanding module for independent study. Though the patient suffered from a specific medical condition-a pituitary tumor and related complications-students do not need to be knowledgeable about those conditions or have in-depth clinical experience to readily comprehend the messages in this lesson.

Pharmacogenetic Discovery in CALGB (Alliance) 90401 and Mechanistic Validation of a VAC14 Polymorphism that Increases Risk of Docetaxel-Induced Neuropathy.

PURPOSE: Discovery of SNPs that predict a patient's risk of docetaxel-induced neuropathy would enable treatment individualization to maximize efficacy and avoid unnecessary toxicity. The objectives of this analysis were to discover SNPs associated with docetaxel-induced neuropathy and mechanistically validate these associations in preclinical models of drug-induced neuropathy. EXPERIMENTAL DESIGN: A genome-wide association study was conducted in metastatic castrate-resistant prostate cancer patients treated with docetaxel, prednisone and randomized to bevacizumab or placebo on CALGB 90401. SNPs were genotyped on the Illumina HumanHap610-Quad platform followed by rigorous quality control. The inference was conducted on the cumulative dose at occurrence of grade 3+ sensory neuropathy using a cause-specific hazard model that accounted for early treatment discontinuation. Genes with SNPs significantly associated with neuropathy were knocked down in cellular and mouse models of drug-induced neuropathy. RESULTS: A total of 498,081 SNPs were analyzed in 623 Caucasian patients, 50 (8%) of whom experienced grade 3+ neuropathy. The 1,000 SNPs most associated with neuropathy clustered in relevant pathways including neuropathic pain and axonal guidance. An SNP in VAC14 (rs875858) surpassed genome-wide significance (P = 2.12 × 10-8, adjusted P = 5.88 × 10-7). siRNA knockdown of VAC14 in stem cell-derived peripheral neuronal cells increased docetaxel sensitivity as measured by decreased neurite processes (P = 0.0015) and branches (P < 0.0001). Prior to docetaxel treatment, VAC14 heterozygous mice had greater nociceptive sensitivity than wild-type litter mate controls (P = 0.001). CONCLUSIONS: VAC14 should be prioritized for further validation of its potential role as a predictor of docetaxel-induced neuropathy and biomarker for treatment individualization. Clin Cancer Res; 22(19); 4890-900. ©2016 AACR.

Bevacizumab and the risk of arterial and venous thromboembolism in patients with metastatic, castration-resistant prostate cancer treated on Cancer and Leukemia Group B (CALGB) 90401 (Alliance).

BACKGROUND: Bevacizumab is associated with an increased risk of arterial thromboembolism (ATE); however, its effect on venous thromboembolism (VTE) remains controversial. Scant data exist on the factors that increase the risk of ATE/VTE in patients with prostate cancer. The authors investigated the association of bevacizumab treatment and clinical factors with ATE/VTE risk in patients who were treated on Cancer and Leukemia Group B (CALGB) trial 90401. METHODS: Patients with metastatic, castration-resistant prostate cancer were randomized to receive docetaxel and prednisone with or without bevacizumab once every 21 days. Cycle-to-event Cox regression models were used to investigate the association of bevacizumab with the incidence of grade 3 or greater (≥ 3) ATE and VTE. Age, prior ATE/VTE, baseline antiplatelet/anticoagulant use, and VTE risk score (based on leukocyte count, hemoglobin, platelet count, body mass index, and tumor location) were evaluated in univariate and multivariable analyses. RESULTS: Of 1008 randomized patients, the odds of experiencing grade ≥ 3 ATE were significantly greater in those who received bevacizumab compared with those who received placebo (odds ratio, 2.79; P = .02), whereas an opposite trend was noted for grade ≥ 3 VTE (odds ratio, 0.60; P = .08). In the multivariable analysis, bevacizumab treatment (hazard ratio [HR], 3.00; P = .01) and age (HR, 1.06; P = .02) were significantly associated with the risk of ATE; whereas age (HR, 1.05; P = .01) and VTE risk score (HR, 1.83; P = .03) were significantly associated with the risk of VTE. CONCLUSIONS: Bevacizumab was significantly associated with a greater risk of ATE in patients with metastatic, castration-resistant prostate cancer, but it was not significantly associated with the risk of VTE. Understanding clinical factors that increase the risk for experiencing ATE/VTE is essential to mitigate the risks and reduce the burden of these prevalent complications in cancer care.

The Virtual Pathology Instructor: a medical student teaching tool developed using patient simulator software.

Virtual microscopy has been adopted by many medical schools but often without addressing the need for students to understand how to integrate slide observations with other diagnostic information. The goal of this study was to develop an innovative tool for teaching pathology to medical students that presents a variety of virtual materials necessary for a complete pathology evaluation. The Virtual Pathology Instructor (V-PIN) is patient simulation software (vpSim) created and supported by the University of Pittsburgh School of Medicine, Laboratory for Educational Technology, and allows students to assume the role of a diagnostic pathologist. V-PIN utility was demonstrated by educationally significant improvement between pretest and posttest scores for 2 cases (mean, 3.8 versus 4.2; P = .0007; 1.9 versus 3.0; P = .0001). A third case did not perform as well (mean, 2.5 versus 2.3; P = .12) but detailed evaluation of the performance of the case identified possible improvements. Maximum posttest performance was seen following both the traditional workshop and the V-PIN case as compared to the case alone (posttest 4.2 versus 3.0; P < .0001). No significant difference was identified in student progress through V-PIN cases taken before or after the related traditional workshop, as demonstrated by total time on task, number of steps to complete, total score, number of incorrect answers, and number of requests for V-PIN help. Patient simulation software is an effective tool for teaching pathology to medical students and can provide individual instruction and immediate feedback as well as identify opportunities to refine and enhance the educational experience.

The effect of prior androgen synthesis inhibition on outcomes of subsequent therapy with docetaxel in patients with metastatic castrate-resistant prostate cancer: results from a retrospective analysis of a randomized phase 3 clinical trial (CALGB 90401) (Alliance).

BACKGROUND: Preliminary data suggest a potential decreased benefit of docetaxel in patients with metastatic, castration-resistant prostate cancer (mCRPC) who previously received abiraterone acetate, a novel androgen synthesis inhibitor (ASI). Cancer and Leukemia Group B (CALGB) trial 90401 (Alliance), a phase 3 trial in patients with mCRPC who received docetaxel-based chemotherapy, offered the opportunity to evaluate effect of prior ketoconazole, an earlier generation ASI, on clinical outcomes after docetaxel. METHODS: In CALGB trial 90401, 1050 men with chemotherapy-naive mCRPC were randomized to receive treatment with docetaxel and prednisone that included either bevacizumab or placebo. In total, 1005 men (96%) had data available regarding prior ketoconazole therapy. The observed effects of prior ketoconazole on overall survival (OS), progression-free survival (PFS), prostate-specific antigen (PSA) decline, and the objective response rate (ORR) were assessed using proportional hazards and Poisson regression methods adjusted for validated prognostic factors and treatment arm. RESULTS: Baseline characteristics between patients who did (N=277) and did not (N=728) receive prior ketoconazole therapy were similar. There were no statistically significant differences between patients who did and those who did not receive prior ketoconazole therapy with respect to OS (median OS, 21.1 months vs 22.3 months, respectively; stratified log-rank P=.635), PFS (median PFS, 8.1 months vs 8.6 months, respectively; stratified log-rank P=.342), the proportion achieving a decline ≥ 50% in PSA (61% vs 66%, respectively; relative risk, 1.09; adjusted P=.129), or ORR (39% vs 43%, respectively; relative risk, 1.11; adjusted P=.366). CONCLUSIONS: As measured by OS, PFS, PSA, and the ORR, there was no evidence that prior treatment with ketoconazole had an impact on the clinical outcomes of patients with mCRPC who received subsequent docetaxel-based therapy. The current results highlight the need for prospective studies to assess for potential cross-resistance with novel ASIs and to define the optimal sequence of therapy in mCRPC.

Randomized, double-blind, placebo-controlled phase III trial comparing docetaxel and prednisone with or without bevacizumab in men with metastatic castration-resistant prostate cancer: CALGB 90401.

PURPOSE: A randomized, placebo-controlled study based on preclinical and clinical data that supports the potential role of vascular endothelial growth factor in prostate cancer was performed to evaluate the addition of bevacizumab to standard docetaxel and prednisone therapy in patients with metastatic castration-resistant prostate cancer (mCRPC). PATIENTS AND METHODS: Patients with chemotherapy-naive progressive mCRPC with Eastern Cooperative Oncology Group performance status ≤ 2 and adequate bone marrow, hepatic, and renal function were randomly assigned to receive docetaxel 75 mg/m(2) intravenously (IV) over 1 hour for 21 days plus prednisone 5 mg orally twice per day (DP) with either bevacizumab 15 mg/kg IV every 3 weeks (DP + B) or placebo. The primary end point was overall survival (OS), and secondary end points were progression-free survival (PFS), 50% decline in prostate-specific antigen, objective response (OR), and toxicity. RESULTS: In total, 1,050 patients were randomly assigned. The median OS for patients given DP + B was 22.6 months compared with 21.5 months for patients treated with DP (hazard ratio, 0.91; 95% CI, 0.78 to 1.05; stratified log-rank P = .181). The median PFS time was superior in the DP + B arm (9.9 v 7.5 months, stratified log-rank P < .001) as was the proportion of patients with OR (49.4% v 35.5%; P = .0013). Grade 3 or greater treatment-related toxicity was more common with DP + B (75.4% v 56.2%; P ≤ .001), as was the number of treatment-related deaths (4.0% v 1.2%; P = .005). CONCLUSION: Despite an improvement in PFS and OR, the addition of bevacizumab to docetaxel and prednisone did not improve OS in men with mCRPC and was associated with greater toxicity.

Developing a measure of local agency adaptation to emergencies: a metric.

Local public health agencies often must respond to health-related emergencies or disasters, while continuing to fulfill all public health functions for which they are funded. This article reports the development and initial pilot test of a method for measuring the nature and degree of a public health agency's response to such an emergency or disaster. How the instrument was developed as well as the initial results from the pilot study of four local public health systems (LPHSs) are presented and discussed. The instrument measured the extent to which each function and division of each of the four LPHSs were affected and provided a metric that could be used across LPHSs to indicate the burden experienced by each due to the emergency. Results obtained from the pilot study indicate that size and complexity of an LPHS was not predictive of its ability to respond to the emergency. These results support the use of the framework and associated measurement procedures to provide valuable information to managers responsible for such LPHSs. Such information should provide a foundation for comparing variations in performance and outcomes to various types of emergencies that vary in their severity and focus.

Overcoming challenges to integrating public and population health into medical curricula.

Integrating public health into medical curricula poses a substantial challenge to educators. However, the needs of trainees and the population requirements of accrediting bodies provide a compelling call to action to improve how tomorrow's medical practitioners are prepared to incorporate public health into their practices. This article provides insights about the nature of the challenges, and it identifies opportunities and practical approaches to integrating public health content into medical school curricula. The paper incorporates authors' opinions with a synthesis of the discussions from a workshop at the 2010 "Patients and Populations: Public Health in Medical Education" conference.

Public Health Area of Concentration: a model for integration into medical school curricula.

Calls for more public health education for medical students date back at least 150 years. In recent years, medical schools have increased their required coursework in core public health topics such as epidemiology, biostatistics, and behavioral determinants of health. Some schools have created more in-depth alternatives, including combined or concurrent master's degrees; MD/PhD programs with a public health track; certificates in public health; or complete re-envisioning of the school into an integrated medical and public health institution. In 2009 the University of Pittsburgh School of Medicine began a Public Health Area of Concentration (AOC) that provides an optional, integrated curriculum that includes key elements of research, practice, and leadership. The AOC is a partnership between two schools at the University of Pittsburgh--Medicine and Public Health--and the local county health department. The result is a program that provides mentorship and training over 4 years of education designed to mend the long historical divide between the skills and constituencies of individual and population health. In addition, the AOC is relatively easy and inexpensive to implement and is modular in nature. The Public Health AOC is a simple model for incorporating many key aspects of public health into medical education and can be duplicated by any university that is willing to create partnerships and work across boundaries.

Defining the correctness of a diagnosis: differential judgments and expert knowledge.

Approaches that use a simulated patient case to study and assess diagnostic reasoning usually use the correct diagnosis of the case as a measure of success and as an anchor for other measures. Commonly, the correctness of a diagnosis is determined by the judgment of one or more experts. In this study, the consistency of experts' judgments of the correctness of a diagnosis, and the structure of knowledge supporting their judgments, were explored using a card sorting task. Seven expert pediatricians were asked to sort into piles the diagnoses proposed by 119 individuals who had worked through a simulated patient case of Haemophilus influenzae Type B (HIB) meningitis. The 119 individuals had varying experience levels. The expert pediatricians were asked to sort the proposed diagnoses by similarity of content, and then to order the piles based on correctness, relative to the known correct diagnosis (HIB meningitis). Finally, the experts were asked to judge which piles contained correct or incorrect diagnoses. We found that, contrary to previous studies, experts shared a common conceptual framework of the diagnostic domain being considered and were consistent in how they categorized the diagnoses. However, similar to previous studies, the experts differed greatly in their judgment of which diagnoses were correct. This study has important implications for understanding expert knowledge, for scoring performance on simulated or real patient cases, for providing feedback to learners in the clinical setting, and for establishing criteria that define what is correct in studies of diagnostic error and diagnostic reasoning.

Evidence-based and population-based medicine: national implementation under the UME-21 project.

BACKGROUND AND OBJECTIVES: The Undergraduate Medical Education for the 21st Century (UME-21) project developed and implemented innovations to medical school curricula at medical schools across the country. This report describes the development and implementation of innovative approaches to improving instruction in evidence-based medicine with a population-based perspective. METHODS: Each school participating in the UME-21 project designed, implemented, and evaluated its own unique curriculum initiatives. We examined these initiatives using data abstracted from written reports submitted to the project Executive Committee. Additional data were obtained by personal communication with project directors and evaluators at the various schools, student and preceptor comments, internal program evaluation at each school, and external evaluation by the UME-21 project leadership. The Association of American Medical Colleges Graduation Questionnaire was also used. RESULTS: Fourteen of 18 participating schools implemented a broad range of curricula to facilitate teaching and learning about evidence-based and population-based medicine. Common themes included the application of evidence to patient care, use of clinical practice guidelines and pathways, and the general incorporation of evidence-based techniques (literature searching, critical appraisal, etc) into the teaching of other content, such as clinical science and managed care. Teaching approaches included Web-based and other computer-based education, an emphasis on active and self-directed learning, use of small groups and workshops, and distribution of this content over multiple years. As an alternative to full-length evidence-based medicine courses, many schools incorporated an evidence-based approach into existing courses and clerkships. Data demonstrated an upward trend in student satisfaction with how topics were presented at UME-21 schools. CONCLUSIONS: These innovations successfully demonstrated that evidence-based and population-based medicine content can be introduced into medical school curricula. Introducing these constructs in ways that demonstrate their relevance to patient care facilitates student learning.

Collaborating to integrate curriculum in primary care medical education: successes and challenges from three US medical schools.

BACKGROUND AND OBJECTIVES: Traditional medical school department-based clerkship structures can lead to redundancy and/or gaps in curriculum, inefficient administrative systems, and academic isolation for clerkship directors. This paper describes the approaches, successes, and challenges three institutions experienced when implementing an interdepartmental collaboration to create an integrated primary care clerkship experience. METHODS: Each school combined family medicine, ambulatory pediatrics, and ambulatory medicine into contiguous clerkship blocks. In all institutions, each clerkship maintained certain distinct features while the integrated aspects contained longitudinal curriculum of certain primary care topics. RESULTS: Evaluations by students demonstrated favorable responses to the new content and integrated methods of teaching, as did results of the Association of American Medical Colleges graduation survey. Faculty at each institution reported that their multidisciplinary approach has stimulated important educational collaborations, many of which require an economy of scale not often achievable within a single clerkship. These included innovative evaluation/documentation efforts; centralization of administrative tasks; enhanced recruitment, retention, and development of community-based faculty; an increase in the active core group of local and national primary care leaders; and an increase in scholarly activities. The collaborations have not occurred without challenges, primarily in the need for identifying sustainable resources for these and future collaborative educational endeavors. CONCLUSIONS: The benefits involved in developing an integrated primary care experience include expansion of curriculum content and methods, as well as enhancement of collegial support and resources to community-based and academic faculty. These integrations do, however, bring added challenges, time, and costs to traditional independent clerkships.