Citations

The US Centers for Disease Control and Prevention (CDC) recommend human immunodeficiency virus (HIV) screening for all persons aged 13 to 64 years who present to a health care provider. We sought to improve adherence to the CDC guidelines on the Internal Medicine Resident Hospital Service. We surveyed residents about the CDC guidelines, sent email reminders, provided education, and engaged them in friendly competition. Credit for guideline adherence was awarded if an offer of HIV screening was documented at admission, if a screening test was performed, or if a notation in the resident sign out sheet indicated why screening was not performed. We examined HIV screening of a postintervention group of patients admitted between August 8, 2012, and June 30, 2013, and compared them to a preintervention group admitted between August 1, 2011, and June 30, 2012. Postintervention offers of HIV screening increased significantly (7.9% [44/559] vs 55.5% [300/541]; P<.001), as did documentation of residents' contemplation of screening (8.9% [50/559] vs 67.5% [365/541]; P<.001). A significantly higher proportion of HIV screening tests was ordered postintervention (7.7% [43/559] vs 44.4% [240/541]; P<.001). Monthly HIV screening documentation ranged from 0% (0/53) to 17% (9/53) preintervention, whereas it ranged from 30.6% (11/36) to 100% (62/62) postintervention. HIV screening adherence can be improved through resident education, friendly competition, and system reminders. Barriers to achieving sustained adherence to the CDC guidelines include a heterogeneous patient population and provider discomfort with the subject.

Rationale: Coronary endothelial dysfunction (ED)—an early marker of atherosclerosis—increases the risk of cardiovascular events. Objective: We tested the hypothesis that cholesterol efflux capacity and high-density lipoprotein (HDL) particle concentration predict coronary ED better than HDL-cholesterol (HDL-C). Methods and Results: We studied 80 subjects with nonobstructive (<30% stenosis) coronary artery disease. ED was defined as <50% change in coronary blood flow in response to intracoronary infusions of acetylcholine during diagnostic coronary angiography. Cholesterol efflux capacity and HDL particle concentration (HDL-P IMA ) were assessed with validated assays. Cholesterol efflux capacity and HDL-P IMA were both strong, inverse predictors of ED ( P <0.001 and 0.005, respectively). In contrast, HDL-C and other traditional lipid risk factors did not differ significantly between control and ED subjects. Large HDL particles were markedly decreased in ED subjects (33%; P =0.005). After correction for HDL-C, both efflux capacity and HDL-P IMA remained significant predictors of ED status. HDL-P IMA explained cholesterol efflux capacity more effectively than HDL-C ( r =0.54 and 0.36, respectively). The efflux capacities of isolated HDL and serum HDL correlated strongly ( r =0.49). Conclusions: Cholesterol efflux capacity and HDL-P IMA are reduced in subjects with coronary ED, independently of HDL-C. Alterations in HDL-P IMA and HDL itself account for a much larger fraction of the variation in cholesterol efflux capacity than does HDL-C. A selective decrease in large HDL particles may contribute to impaired cholesterol efflux capacity in ED subjects. These observations support a role for HDL size, concentration, and function as markers—and perhaps mediators—of coronary atherosclerosis in humans.

Abstract The addition of trastuzumab to chemotherapy extends survival among patients with HER2+ breast cancer. Prior work showed that trastuzumab and chemotherapy augments HER2 extracellular domain (ECD)-specific antibodies. The current study investigated whether combination therapy induced immune responses beyond HER2-ECD and, importantly, whether those immune responses were associated with survival. Pretreatment and posttreatment sera were obtained from 48 women with metastatic HER2+ breast cancer on NCCTG (now Alliance for Clinical Trials in Oncology) studies, N0337 and N983252. IgG to HER2 intracellular domain (ICD), HER2-ECD, p53, IGFBP2, CEA, and tetanus toxoid were examined. Sera from 25 age-matched controls and 26 surgically resected HER2+ patients were also examined. Prior to therapy, some patients with metastatic disease had elevated antibodies to IGFBP2, p53, HER2-ICD, HER2-ECD, and CEA, but not to tetanus toxin, relative to controls and surgically resected patients. Treatment augmented antibody responses to HER2-ICD in 69% of metastatic patients, which was highly associated with improved progression-free survival (PFS; HR = 0.5, P = 0.0042) and overall survival (OS; HR = 0.7, P = 0.038). Augmented antibody responses to HER2-ICD also correlated (P = 0.03) with increased antibody responses to CEA, IGFBP2, and p53, indicating that treatment induces epitope spreading. Paradoxically, patients who already had high preexisting immunity to HER2-ICD did not respond to therapy with increased antibodies to HER2-ICD and demonstrated poorer PFS (HR = 1.6, P &lt; 0.0001) and OS (HR = 1.4, P = 0.0006). Overall, the findings further demonstrate the importance of the adaptive immune system in the efficacy of trastuzumab-containing regimens. Cancer Res; 76(13); 3702–10. ©2016 AACR.

Abstract Identifying genetic variants with pleiotropic associations can uncover common pathways influencing multiple cancers. We took a two-stage approach to conduct genome-wide association studies for lung, ovary, breast, prostate, and colorectal cancer from the GAME-ON/GECCO Network (61,851 cases, 61,820 controls) to identify pleiotropic loci. Findings were replicated in independent association studies (55,789 cases, 330,490 controls). We identified a novel pleiotropic association at 1q22 involving breast and lung squamous cell carcinoma, with eQTL analysis showing an association with ADAM15/THBS3 gene expression in lung. We also identified a known breast cancer locus CASP8/ALS2CR12 associated with prostate cancer, a known cancer locus at CDKN2B-AS1 with different variants associated with lung adenocarcinoma and prostate cancer, and confirmed the associations of a breast BRCA2 locus with lung and serous ovarian cancer. This is the largest study to date examining pleiotropy across multiple cancer-associated loci, identifying common mechanisms of cancer development and progression. Cancer Res; 76(17); 5103–14. ©2016 AACR.

Purpose The authors performed a review of 30 Accelerating Change in Medical Education full grant submissions and an analysis of the health systems science (HSS)-related curricula at the 11 grant recipient schools to develop a potential comprehensive HSS curricular framework with domains and subcategories. Method In phase 1, to identify domains, grant submissions were analyzed and coded using constant comparative analysis. In phase 2, a detailed review of all existing and planned syllabi and curriculum documents at the grantee schools was performed, and content in the core curricular domains was coded into subcategories. The lead investigators reviewed and discussed drafts of the categorization scheme, collapsed and combined domains and subcategories, and resolved disagreements via group discussion. Results Analysis yielded three types of domains: core, cross-cutting, and linking. Core domains included health care structures and processes; health care policy, economics, and management; clinical informatics and health information technology; population and public health; value-based care; and health system improvement. Cross-cutting domains included leadership and change agency; teamwork and interprofessional education; evidence-based medicine and practice; professionalism and ethics; and scholarship. One linking domain was identified: systems thinking. Conclusions This broad framework aims to build on the traditional definition of systems-based practice and highlight the need for medical and other health professions schools to better align education programs with the anticipated needs of the systems in which students will practice. HSS will require a critical investigation into existing curricula to determine the most efficient methods for integration with the basic and clinical sciences.

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.