Faculty Bibliography

Background: Melanoma cases may exist in pancreatic cancer kindreds, while there is increased risk of pancreatic cancer in familial melanoma. The two cancers may share genetic susceptibility variants in common. Methods: Three dbGaP-deposited GWAS datasets (MD Anderson melanoma, PanScan 1, and PanScan 2 for pancreatic cancer) were used. Thirty-seven melanoma susceptibility variants in 22 genomic regions from published GWAS, plus melanoma-related genes and pathways were examined for pancreatic cancer risk in the PanScan datasets. Conversely, nine known pancreatic cancer susceptibility variants were examined for melanoma risk in the MD Anderson dataset. Results: In the PanScan data, initial associations were found with melanoma susceptibility variants in NCOA6 (rs4911442) (OR=1.32, 95% CI 1.03-1.70, p=0.03), YWHAZP5 (rs17119461) (OR=2.62, 95% CI 1.08-6.35, p=0.03), and YWHAZP5 (rs17119490) (OR=2.62, 95% CI 1.08-6.34, p=0.03), TYRP1 (p=0.04), and IFNA13 (p=0.04). In the melanoma dataset, two pancreatic cancer susceptibility variants were associated: NR5A2 (rs12029406) (OR=1.39, 95% CI 1.01-1.92, p=0.04) and CLPTM1L-TERT (rs401681) (OR=1.16, 95% CI 1.01-1.34, p=0.04). None of these associations remained significant after correcting for multiple comparisons. Conclusion: Reported variants of melanoma genes and pathways do not play a role in pancreatic cancer predisposition. Reciprocally, pancreatic cancer susceptibility variants are not associated with melanoma risk. Impact: Known melanoma-related genes and pathways, as well as GWAS-derived susceptibility variants of melanoma and pancreatic cancer, do not explain the shared genetic etiology of these two cancers.

OBJECTIVE: To evaluate the effects of intravenous (IV) golimumab 2 mg/kg + methotrexate (MTX) on patient-reported measures of health-related quality of life (HRQOL) in patients with active rheumatoid arthritis (RA) despite prior MTX therapy. METHODS: In this randomized, multicenter, double-blind, placebo-controlled, phase III trial, adults with RA were randomly assigned to receive IV placebo (n = 197) or golimumab 2 mg/kg (n = 395) infusions at Week 0, Week 4, and every 8 weeks thereafter. All patients continued stable oral MTX (15-25 mg/wk). HRQOL assessments included Health Assessment Questionnaire-Disability Index (HAQ-DI; physical function), Medical Outcomes Study Short Form-36 questionnaire physical/mental component summary (SF-36 PCS/MCS) scores, EQ-5D assessment of current health state, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) questionnaire, and disease effect on productivity [10-cm visual analog scale (VAS)]. RESULTS: Mean HAQ-DI improvements from baseline were significantly greater with golimumab + MTX than placebo + MTX at Week 14 and Week 24 (p < 0.001). Significantly greater improvements in all 8 individual SF-36 subscores and both the SF-36 PCS and MCS scores (p < 0.001) also accompanied golimumab + MTX therapy. Improved EQ-5D and EQ-5D VAS (p < 0.001) and FACIT-Fatigue (p < 0.001) scores were also observed for golimumab + MTX-treated patients at Week 12, Week 16, and Week 24, and greater proportions of golimumab + MTX-treated patients had clinically meaningful improvements in these measures. Greater reductions in disease effect on productivity were observed with golimumab + MTX versus placebo + MTX at Week 24 (p < 0.001). Improvements in physical function, HRQOL, fatigue, and productivity significantly correlated with disease activity improvement. CONCLUSION: In active RA, IV golimumab + MTX significantly improved physical function, HRQOL, fatigue, and productivity using multiple measurement tools; all correlated with improvements in disease activity (NCT00973479, EudraCT 2008-006064-11).

Given the disproportionately high rates of obesity-related morbidity among low-income, ethnic minority youth, obesity prevention in this population is critical. Prior efforts to curb childhood obesity have had limited public health impact. The present study evaluates an innovative approach to obesity prevention by promoting foundational parenting and child behavioral regulation. This pre-post intervention study evaluated an enhanced version of ParentCorps with 91 families of pre-Kindergarten students in low-income, urban communities. Assessments included tests of knowledge and parent report. Consistent with findings from two randomized controlled trials of ParentCorps, parent knowledge and use of foundational parenting practices increased and child behavior problems decreased. Child nutrition knowledge and physical activity increased and television watching decreased; for boys, sleep problems decreased. Comparable benefits occurred for children at high risk for obesity based on child dysregulation, child overweight, and parent overweight. Results support a "whole child," family-centered approach to health promotion in early childhood.

OBJECTIVES: Despite the increased focus on health care consumers' active choice, not enough is known about how to best facilitate the choice process. We sought to assess methods of improving this process for vulnerable consumers in the United States by testing alternatives that emphasize insights from behavioral economics, or 'nudges'. METHODS: We performed a hypothetical choice experiment where subjects were randomized to one of five experimental conditions and asked to choose a health center (location where they would receive all their care). The conditions presented the same information about health centers in different ways, including graphically as a chart, via written summary and using behavioral economics, 'nudging' consumers toward particular choices. We hypothesized that these 'nudges' might help simplify the choice process. Our primary outcomes focused on the health center chosen and whether consumers were willing to accept 'nudges'. RESULTS: We found that consumer choice was influenced by the method of presentation and the majority of consumers accepted the health center they were 'nudged' towards. CONCLUSIONS: Consumers were accepting of choices grounded in insights from behavioral economics and further consideration should be given to their role in patient choice.

OBJECTIVE: To describe a novel neurophysiologic signature of the retinal ganglion cell and to elucidate its relationship to abnormalities in validated structural and functional measures of the visual system. METHODS: We used multifocal electroretinogram-generated optic nerve head component (ONHC) responses from normal subjects (n = 18), patients with multiple sclerosis (MS) (n = 18), and those with glaucoma (n = 3). We then characterized the relationship between ONHC response abnormalities and performance on low-contrast visual acuity, multifocal visual-evoked potential-induced cortical responses, and average and quadrant retinal nerve fiber layer (RNFL) thicknesses, as measured by spectral-domain optical coherence tomography. RESULTS: Compared with the eyes of normal subjects, the eyes of patients with MS exhibited an increased number of abnormal or absent ONHC responses (p < 0.0001). For every 7-letter reduction in low-contrast letter acuity, there were corresponding 4.6 abnormal ONHC responses at 2.5% contrast (p < 0.0001) and 6.6 abnormalities at the 1.25% contrast level (p < 0.0001). Regarding average RNFL thickness, for each 10-mum thickness reduction, we correspondingly observed 6.8 abnormal ONHC responses (p = 0.0002). The most robust association was between RNFL thinning in the temporal quadrant and ONHC response abnormalities (p < 0.0001). CONCLUSION: Further characterization of ONHC abnormalities (those that are reversible and irreversible) may contribute to the development of novel neurotherapeutic strategies aimed at achieving neuroprotective, and perhaps even neurorestorative, effects in disorders that target the CNS in general, and MS in particular.