Citations

Abstract Background: Human papillomavirus (HPV) is a causative agent in cervical cancer as well as anal, oropharyngeal, penile, and vaginal/vulvar cancers. Licensed, effective HPV vaccines have been available in the U.S. since mid-2006 for females and late 2011 for males and are recommended up to age 26. Despite this, in 2014, only 39.7% of U.S. girls and 21.6% of boys 13 to 17 years of age completed the three-dose vaccine series. ‘Lack of knowledge’ was a primary reason cited among parents for not vaccinating their children. HPV vaccination rates are lower still among 19-26 year olds, particularly among the uninsured. We assessed awareness and knowledge of HPV disease, HPV-related cancers, and HPV vaccines among working, uninsured adults and used 2014 data from the Health Information National Trends Survey (HINTS cycle 4) as a national benchmark against which to compare our data. Methods: Self-administered surveys were offered to patients attending appointments at the Volunteers in Medicine (VIM) clinic in Jacksonville, FL between September 10, 2014 and October 24, 2014. VIM provides free primary care for working individuals without insurance living and/or working in Duval County. Patients were eligible to participate if they were at least 18 years of age, not in acute distress, and had not completed a survey during pilot-testing. Surveys were available in English and Spanish and contained a validated HPV knowledge measure assessing disease knowledge and vaccine knowledge. Additionally, HPV-related cancer knowledge was assessed: 5 HPV-related (cervical, anal, throat, penile, vaginal/vulvar) and 4 not currently known to be HPV-related (lung, breast, prostate, skin). High knowledge was defined as having a knowledge score in the upper quartile of positive values. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression to assess the association of demographic characteristics with having high knowledge of HPV, HPV vaccines, and HPV-related cancer. Additional models assessed individual cancers. During the study period 356 patients were eligible to participate; of these, 55 declined (84% participation rate). Of the 301 surveys, 5 surveys were excluded from analysis due to excessive missing data; a total of 296 surveys were analyzed. Results: 50.3% of participants (n=149) had heard of HPV, 37.2% (n=110) correctly indicated that HPV is sexually transmitted, and 32.1% (n=95) had heard of the HPV vaccine. In HINTS 4, these estimates were 63.6%, 44.0%, and 62.7%, respectively. In adjusted models, high HPV disease knowledge was associated with race (OR non-white = 0.39 (0.19, 0.78)) and education (OR >high school = 2.34 (1.14, 4.84)) while high HPV vaccine knowledge was associated with race (OR non-white = 0.42 (0.21, 0.82)), education (OR >high school = 5.04 (2.30, 11.06)), and sex (OR male = 0.34 (0.12, 0.94)). Of the HPV-related cancers, 43.9% answered correctly for cervical, 9.1% for anal, 11.1% for mouth/throat, 11.5% for penile, and 30.7% for vaginal/vulvar cancer. Males were less likely than females to know that HPV is a causative agent for cervical (OR=0.41 (0.22, 0.75)) and vaginal/vulvar cancers (OR=0.43 (0.22, 0.86)). Conclusion: Using estimates obtained in HINTS 4 as a benchmark, awareness and knowledge of HPV, HPV-related cancers, and HPV vaccines were low among working, uninsured adult patients. In addition to improving access to HPV vaccination (e.g. volunteer clinics), the findings demonstrate a need for strategies to educate medically underserved adults about HPV. Maximizing access to HPV vaccination, including catch-up vaccination for adults up to age 26 are consistent with the recommendations of the President's Cancer Panel, the American College of Obstetricians and Gynecologists, the American College of Physicians, and the Advisory Committee on Immunization Practices. Citation Format: Carmen Radecki Breitkopf, Lila Finney Rutten, Debra Jacobson, Patrick Wilson, Monica Albertie, Robert M. Jacobson, Gerardo Colon-Otero. Awareness and knowledge of HPV, HPV-related cancers, and HPV vaccines in a working, uninsured clinic population. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr B91.

Abstract African American Hereditary Prostate Cancer Study (AAHPC) was developed as a national collaboration to explore the role of genetics in the causation of hereditary prostate cancer (HPC) in African American (AA) men. AAHPC is in partnership with the International Consortium for Prostate Cancer Genetics (ICPCG), which conducts collaborative studies of HPC genetics in multiplex families. As part of an ICPCG sequencing study of 539 affected individuals from 366 HPC pedigrees, we performed whole exome sequencing in 21 ICPCG AA families, of which there were 14 AAHPC affected men from 11 pedigrees. The combined ICPCG AA cohort consisted of N=26 affected members. Post-variant calling quality control (QC) was implemented using Golden Helix SVS 8 software with filters set for removal of variants with Read Depth < 10, Quality Score < 20, Quality Score: Read Depth Ratio < 0.5, Call Rate < 0.75. Variants were additionally filtered by MAF based on the NHLBI ESP650051-V2 exomes variant frequencies for the AA population using a MAF threshold of 5%. Following QC, 176/299 SNVs and 20/39 INDELs remained for further analysis. In these analyses, we focused on 13 known cancer genes (MSR1, AR, BRCA1, BRCA2, BTNL2, EPHB2, CDH1, RNASEL, ELAC2, HOXB13, CHEK2, TP53 and NBN). Three sequenced families had > 1 affected members sequenced (2 or 3 per family) and the remaining 18 families had one member sequenced. Under the dominant model, our preliminary results show that no rare variants in the 13 candidate genes were found in 3/3 affecteds in two families. Rare SNVs in seven candidate genes (AR, CDH1, ELAC2, HOXB13, RNASEL, BRCA2 and EPHB2) were found in 2/3 affecteds for two families and 2/2 affecteds in one family. Several of the remaining 18 affected men (1 sequenced per pedigree) shared the same rare SNV in these candidate genes. For INDELs, rare variants in three candidate genes were found in pedigrees with ≥ 2 affecteds. Several of the remaining 18 affected men (one sequenced per pedigree) shared the same rare INDEL. Additional QC is underway to validate these variants and bioinformatic analyses are being used to predict effects of the variants in an effort to unravel the complex genetic heterogeneity of HPC in AA. Citation Format: Cheryl D. Cropp, Shannon K. McDonnell, Sumit Middha, Melissa DeRycke, Danielle M. Karyadi, Daniel Schaid, Stephen N. Thibodeau, William B. Isaacs, Elaine A. Ostrander, Janet Stanford, Kathleen A. Cooney, Joan E. Bailey-Wilson, John D. Carpten. Rare variant discovery in known cancer genes from whole-exome sequencingof African American hereditary prostate cancer families. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr B40.

Abstract Background: Recent studies have indicated that vaccination can protect against cancer development. One key aspect of developing vaccines is circumventing peripheral tolerance by identifying subdominant epitopes that are unique to the deregulated tumor microenvironment. While existing subdominant epitope vaccines are showing efficacy in preventing cancer, these vaccines are applicable only for subsets of patients with specific HLA subtypes. Therefore, we recently developed a degenerate HER2 subdominant epitope-based vaccine that should be useful in approximately 85% of all patients. The vaccine consists of a pool of four HLA-DR-restricted 15-amino acid epitopes (p59, p88, p422, and p885) that are naturally processed and are designed to elicit helper T cell immunity, the cornerstone of immune surveillance. Here we present Phase I trial results of this multi-peptide HER2 vaccine. Methods: Eligible women had HER2+ breast cancer (Stages II-III) and had completed standard treatment (i.e. surgery, chemotherapy, and trastuzumab) at least 90 days prior to enrollment and were rendered disease free. Vaccine included the above epitope pool along with adjuvant GM-CSF. Patients were vaccinated six times over six months and were monitored for toxicity at each visit. Peripheral blood samples were collected for immune responses evaluating for T cell and antibody immunity. Endpoints were safety and immunogenicity leading to the development CD4 helper T cells that recognized naturally-processed HER2. Results: Twenty-two subjects (age 33 to 69 years) were enrolled. At the present analysis, 21 have completed all 6 vaccination cycles; one patient withdrew after developing a grade 1 injection site reaction during the first vaccination cycle. Twenty patients have had LVEF measured after vaccination; only 2 patients had an LVEF drop of 10% or more but remained in the normal LEVF range. One severe toxicity was reported: a grade 3 INR increase considered unrelated to treatment. Mild to moderate (grade 1-2) toxicities included injection site reactions, fatigue, and white blood cell count decreases. All patients were alive at analysis and only one experienced a recurrence (median follow-up 507 days, range 22 – 844). Twenty patients have had immune response assessments. Vaccine induced T cell immunity was observed in 94% of patients to p59, in 94% of patients to p88, in 82% of patients to p422, and in 74% of patients to p885. Importantly, T cell immunity to naturally processed HER2 proteins occurred in 94% of patients. The mean number of T cells specific for each peptide, post vaccination, ranged from 349–528 T cells per million peripheral blood mononuclear cells (PBMCs). The mean number of T cells specific for whole HER2 protein was 783 T cells per million PBMCs compared to a mean of 898 T cells/million PBMCs specific for the foreign tetanus toxin. In contrast to T cell responses, modestly increased antibody immunity to HER2 occurred in 35% of patients, consistent with the T cell-inducing design of the vaccine. Conclusion: Our results show that it is possible to develop vaccines with broad HLA coverage that circumvent natural tolerance and induce tumor antigen-specific immunity in the vast majority of patients. Citation Format: Knutson KL, Kalli KR, Block MS, Hobday TJ, Padley DJ, Erskine CL, Dockter T, Suman VJ, Wilson G, Degnim AC. Robust generation of T cell immunity to HER2 in HER2+ breast cancer patients with a degenerate subdominant HLA-DR epitope vaccine. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-11-02.

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.

AbstractObjectiveDisparities in tobacco use persist despite successful policies reducing use within the United States. In particular, the prevalence of tobacco use in rural and certain minority communities is significantly higher compared to that of their counterparts. In this work, we examine the impact of rurality, mental health, and racial discrimination on tobacco use.MethodsData come from the 2003 California Health Interview Survey (n = 42,044). Modified Poisson regression models were adjusted for age, sex, race/ethnicity, birth origin, education, income, insurance, and marital status.ResultsCompared to urban residents, rural residents had a significantly higher risk for smoking after adjustment (RR = 1.10, 95% CI: 1.01‐1.19). Those who reported having experienced racial discrimination also had a significantly greater risk for smoking compared to those who did not (RR = 1.17, 95% CI: 1.07‐1.27). Additionally, those who reported higher stress had a significantly greater risk for smoking (RR = 1.61, 95% CI: 1.07‐1.67). There was evidence of interaction between rurality and race/ethnicity, and rurality and gender (P < .05).ConclusionResiding in rural areas was associated with an increased risk for smoking, above and beyond sociodemographics. There were no significant differences across rural‐urban environments for the relationship between stress and tobacco use—an indication that the impact of stress and discrimination is not buffered or exacerbated by environmental characteristics potentially found in either location. Mechanisms that explain rural‐urban tobacco use disparities need to be explored, and smoking cessation programs and policies should be tailored to target these factors within rural communities.

Abstract Background Shoulder pain resulting from subacromial impingement syndrome (SAIS) is a common problem with a relatively poor response to treatment. There is little research exploring physical therapists' perspectives on the management of the syndrome. Objectives The study objective was to investigate physical therapists' perceptions and experiences regarding the use of exercise in the treatment of patients with SAIS. Design This was a qualitative focus group study. Methods Three 60- to 90-minute focus group sessions containing 6 to 8 experienced musculoskeletal physical therapists (total number=20) were conducted. Thematic content analysis was used to analyze transcripts and develop core themes and categories. Results Exercise was seen as key in the management of SAIS. The overarching theme was the need to “gain buy-in to exercise” at an early stage. The main subtheme was patient education. Therapists identified the need to use education about SAIS etiology to foster buy-in and “sell” self-management through exercise to the patient. They consistently mentioned achieving education and buy-in using visual tools, postural advice, and sometimes a “quick fix” of pain control. Furthermore, experienced practitioners reported including educational interventions much earlier in treatment than when they first qualified. Therapists emphasized the need for individually tailored exercises, including: scapular stabilization; rotator cuff, lower trapezius, and serratus anterior muscle strengthening; and anterior shoulder and pectoralis minor muscle stretching. Quality of exercise performance was deemed more important than the number of repetitions that the patients performed. Limitations Expanding the geographical area over which the focus groups were conducted and including therapists with less than 5 years of postgraduate experience may have strengthened the findings of this study. Conclusion Experienced musculoskeletal physical therapists believe that exercise is central in treating patients with SAIS and that gaining patient buy-in to its importance, patient education, promoting self-management, and postural advice are central to the successful treatment of people with SAIS.