Faculty Bibliography

Reducing health disparities is a national public health priority. Latinos represent the largest racial/ethnic minority group in the United States and suffer disproportionately from poor health outcomes, including cardiovascular disease risk. Academic training programs are an opportunity for reducing health disparities, in part by increasing the diversity of the public health workforce and by incorporating training designed to develop a skill set to address health disparities. This article describes the Training and Career Development Program at the UCLA Center for Population Health and Health Disparities: a multilevel, transdisciplinary training program that uses a community-engaged approach to reduce cardiovascular disease risk in two urban Mexican American communities. Results suggest that this program is effective in enhancing the skill sets of traditionally underrepresented students to become health disparities researchers and practitioners.

INTRODUCTION: Electronic medical records represent a new source of longitudinal data on tobacco use. METHODS: Electronic medical records of the U.S. Department of Veterans Affairs were extracted to find patients' tobacco use status in 2009 and at another assessment 12-24 months later. Records from the year prior to the first assessment were used to determine patient demographics and comorbidities. These data were analyzed in 2015. RESULTS: An annual quit rate of 12.0% was observed in 754,504 current tobacco users. Adjusted tobacco use prevalence at follow-up was 3.2% greater with alcohol use disorders at baseline, 1.9% greater with drug use disorders, 3.3% greater with schizophrenia, and lower in patients with cancer, heart disease, and other medical conditions (all differences statistically significant with p<0.05). Annual relapse rates in 412,979 former tobacco users were 29.6% in those who had quit for <1 year, 9.7% in those who had quit for 1-7 years, and 1.9% of those who had quit for >7 years. Among those who had quit for <1 year, adjusted relapse rates were 4.3% greater with alcohol use disorders and 7.2% greater with drug use disorders (statistically significant with p<0.05). CONCLUSIONS: High annual cessation rates may reflect the older age and greater comorbidities of the cohort or the intensive cessation efforts of the U.S. Department of Veterans Affairs. The lower cessation and higher relapse rates in psychiatric and substance use disorders suggest that these groups will need intensive and sustained cessation efforts.

PURPOSE: In 2015, both ASCO and the European Society for Medical Oncology (ESMO) proposed frameworks to quantify the benefit of antineoplastic drugs in the face of rising costs. We applied these frameworks to drugs approved by the US Food and Drug Administration over the past 12 years and examined relationships between costs and benefits. METHODS: We searched FDA.gov for drugs that received initial approval for solid tumors from 2004 to 2015 and calculated the ASCO Net Health Benefit version 2016 (NHB16) and 2015 (NHB15) and the ESMO Magnitude of Clinical Benefit Scale scores for each drug. We calculated descriptive statistics and explored correlations and associations among benefit scores, cost, and independent variables. RESULTS: We identified 55 drug approvals supported by phase II (18.2%) and III (81.8%) trials, with primary outcomes of overall survival (36.4%), progression-free survival (43.6%), or response rate (20.0%). No significant association was found between NHB16 and year of approval ( P = .81), organ system ( P = .20), or trial comparator arm ( P = .17), but trials with progression-free survival outcomes were associated with higher scores ( P = .007). Both NHB15 and Magnitude of Clinical Benefit Scale scores were approximately normally distributed, but only a moderate correlation existed between them ( r = 0.40, P = .006). No correlation between benefit score and cost (NHB16, r = 0.19; ESMO, r = -0.07) was found. Before 2010, two (15.3%) of 13 approved drugs exceeded $500/NHB point x month compared with 10 (25.0%) of 40 drugs subsequently approved. CONCLUSION: Our analysis of the ASCO and ESMO value frameworks illuminates the heterogeneous benefit of new medications and highlights challenges in constructing a unified concept of drug value. Drug benefit does not correlate with cost, and the number of high cost/benefit outliers has increased.

Introduction: Many new markers are now available as an aid for decisions about prostate biopsy for men without prostate cancer, and/or to improve risk stratification for men with newly diagnosed prostate cancer. Methods: A literature review was performed on currently available markers for use in decisions about prostate biopsy and initial prostate cancer treatment. Results: Although total prostate-specific antigen cutoffs were traditionally used for biopsy decisions, PSA elevations are not specific. Repeating the PSA test, and adjusting for factors like age, prostate volume and changes over time can increase specificity for biopsy decisions. The Prostate Health Index (phi) and 4K Score are new PSA-based markers that can be offered as second-line tests to decide on initial or repeat prostate biopsy. The PCA3 urine test and ConfirmMDx tissue test are additional options for repeat biopsy decisions. For men with newly diagnosed prostate cancer, genomic tests are available to refine risk classification and may influence treatment decisions. Conclusions: Numerous secondary testing options are now available that can be offered to patients deciding whether to undergo prostate biopsy and those with newly diagnosed prostate cancer.

Lab-based experimental studies with humans and in animal models demonstrate that the relation between glucocorticoid (GC) levels and performance on measures of higher-order cognitive ability such as executive function (EF) is best described by an inverted U-shape curve. Moderate levels of GCs (cortisol/corticosterone) are associated with comparatively better performance relative to GC levels that are particularly high or low. Although findings from experimental studies are definitive and have high internal validity, the external validity of this association as an aspect of children's development is unknown. Here we analyze data from the Family Life Project (N=1292), a prospective longitudinal sample of children and families in predominantly low-income and rural communities followed longitudinally from infancy through age 60 months. Consistent with the prior experimental literature, we found evidence of an inverted-U relation. For children with relatively low cortisol levels, on average, between the ages 7, 15, 24, and 48 months, those illustrating moderate fluctuations in their cortisol levels over this span tended to show subsequently better EF performance at 60 months, than did children with either highly stable or highly variable temporal profiles. This curvilinear function did not extend to children whose cortisol levels were high, on average. These children tended to show lower EF performance, irrespective the stability of their cortisol levels over time.

BACKGROUND:receptor antagonist icatibant is approved for treatment of attacks of hereditary angioedema. Icatibant has been reported to decrease time-to-resolution of angiotensin-converting enzyme (ACE) inhibitor-associated angioedema in 1 study of European patients. OBJECTIVE:receptor antagonist would shorten time-to-resolution from ACE inhibitor-associated angioedema. METHODS:Patients with ACE inhibitor-associated angioedema (defined as swelling of lips, tongue, pharynx, or face during ACE inhibitor use and no swelling in the absence of ACE inhibitor use) were enrolled at Vanderbilt University Medical Center from October 2007 through September 2015 and at Massachusetts General Hospital in 2012. C1 inhibitor deficiency and patients with bowel edema only were excluded. Patients were randomized within 6 hours of presentation to subcutaneous icatibant 30 mg or placebo at 0 and 6 hours later. Patients assessed severity of swelling using a visual analog scale serially following study drug administration or until discharge. RESULTS:Thirty-three patients were randomized and 31 received treatment, with 13 receiving icatibant and 18 receiving placebo. One patient randomized to icatibant did not complete the visual analog scale and was excluded from analyses. Two-thirds of patients were black and two-thirds were women. Time-to-resolution of symptoms was similar in placebo and icatibant treatment groups (P = .19 for the primary symptom and P > .16 for individual symptoms of face, lip, tongue, or eyelid swelling). Frequency of administration of H1 and H2 blockers, corticosteroids, and epinephrine was similar in the 2 treatment groups. Time-to-resolution of symptoms was similar in black and white patients. CONCLUSIONS:receptor antagonist in ACE inhibitor-associated angioedema.

OBJECTIVE: To explore and identify factors that influence physicians' decisions while monitoring patients with prostate cancer on active surveillance (AS). SUBJECTS AND METHODS: A purposive sampling strategy was used to identify physicians treating prostate cancer from diverse clinical backgrounds and geographic areas across the USA. We conducted 24 in-depth interviews from July to December 2015, until thematic saturation was reached. The Applied Thematic Analysis framework was used to guide data collection and analysis. Interview transcripts were reviewed and coded independently by two researchers. Matrix analysis and NVivo software were used for organization and further analysis. RESULTS: Eight key themes emerged to explain variation in AS monitoring: (i) physician comfort with AS; (ii) protocol selection; (iii) beliefs about the utility and quality of testing; (iv) years of experience and exposure to AS during training; (v) concerns about inflicting 'harm'; (vi) patient characteristics; (vii) patient preferences; and (viii) financial incentives. CONCLUSION: These qualitative data reveal which factors influence physicians who manage patients on AS. There is tension between providing standardized care while also considering individual patients' needs and health status. Additional education on AS is needed during urology training and continuing medical education. Future research is needed to empirically understand whether any specific protocol is superior to tailored, individualized care.

BACKGROUND: Annexin A5 (A5) is a potent anticoagulant protein that shields anionic phospholipids from availability for coagulation reactions. Previous studies showed that antibodies from patients with antiphospholipid (aPL) syndrome (APS) interfere with A5 crystallization and anticoagulant activity. OBJECTIVE: The purpose of this study was to investigate whether reduction of the Annexin A5 Anticoagulant Ratio (A5R) assay (i.e. 'A5 resistance') is associated with adverse clinical events in aPL antibody-positive patients. PATIENTS/METHODS: In an initial discovery phase group of 679 patient samples from a 'real world' tertiary care hospital population who were tested for A5R. This was followed by a validation phase cohort of 71 asymptomatic patients with aPL antibodies and no prior history for an adverse clinical event whose baseline samples were tested for A5R then subsequently observed for up to 4 years. RESULTS: In the discovery phase group, we found a reduction of A5R in aPL antibody-positive patients with thrombosis and/or pregnancy complications compared to aPL antibody-negative patients and controls. In addition, reduced A5R values in both the discovery and validation phase cohorts correlated with the extent of multipositivity for standard APS tests, which has also been shown to be associated with risk for adverse clinical outcomes. CONCLUSION: Reduction of A5R levels was associated with a multipositivity profile in aPL antibody-positive patients within both groups and with the development of adverse clinical events

ISSUES: Mobile phone use has increased dramatically and concurrent with rapid developments in mobile phone-based health interventions. The integration of text messaging interventions promises to optimise the delivery of care for persons with substance dependence with minimal disruption to clinical workflows. We conducted a systematic review to assess the acceptability, feasibility and clinical impact of text messaging interventions for persons with illicit drug and alcohol dependence. APPROACH: Studies were required to evaluate the use of text messaging as an intervention for persons who met Diagnostic and Statistical Manual of Mental Disorders, 4th edition criterion for a diagnosis of illicit drug and/or alcohol dependence. Authors searched for articles published to date in MEDLINE (pubmed.gov), the Cochrane Library, EMBASE, CINAHL, Google Scholar and PsychINFO. KEY FINDINGS: Eleven articles met the search criteria for this review and support the acceptability and feasibility of text messaging interventions for addressing illicit drug and alcohol dependence. Most studies demonstrated improved clinical outcomes, medication adherence and engagement with peer support groups. Text messaging interventions also intervened on multiple therapeutic targets such as appointment attendance, motivation, self-efficacy, relapse prevention and social support. IMPLICATIONS: Suggestions for future research are described, including intervention design features, clinician contact, privacy measures and integration of behaviour change theories. CONCLUSION: Text messaging interventions offer a feasible platform to address a range of substances (i.e. alcohol, methamphetamine, heroin and alcohol), and there is increasing evidence supporting further larger-scale studies. [Tofighi B, Nicholson JM, McNeely J, Muench F, Lee JD. Mobile phone messaging for illicit drug and alcohol dependence: A systematic review of the literature. Drug Alcohol Rev 2017;00:000-000].