Faculty Bibliography

Varied diets are diverse with respect to diet quality, and existing dietary variety indices do not capture this heterogeneity. We developed and evaluated the multidimensional US Healthy Food Diversity (HFD) index, which measures dietary variety, dietary quality and proportionality according to the 2010 Dietary Guidelines for Americans (DGA). In the present study, two 24 h dietary recalls from the 2003-6 National Health and Nutrition Examination Survey (NHANES) were used to estimate the intake of twenty-six food groups and health weights for each food group were informed by the 2010 DGA. The US HFD index can range between 0 (poor) and 1 - 1/n, where n is the number of foods; the score is maximised by consuming a variety of foods in proportions recommended by the 2010 DGA. Energy-adjusted Pearson's correlations were computed between the US HFD index and each food group and the probability of adequacy for fifteen nutrients. Linear regression was run to test whether the index differentiated between subpopulations with differences in dietary quality commonly reported in the literature. The observed mean index score was 0.36, indicating that participants did not consume a variety of healthful foods. The index positively correlated with nutrient-dense foods including whole grains, fruits, orange vegetables and low-fat dairy (r 0.12 to 0.64) and negatively correlated with added sugars and lean meats (r - 0.14 to - 0.23). The index also positively correlated with the mean probability of nutrient adequacy (r 0.41; P< 0.0001) and identified non-smokers, women and older adults as subpopulations with better dietary qualities. The US HFD index may be used to inform national dietary guidance and investigate whether healthful dietary variety promotes weight control.

Immunity and inflammatory pathways are important in the genesis of non-melanoma skin cancers (NMSC). Functional genetic variation in immune modulators has the potential to affect disease etiology. We investigated associations between common variants in two key regulators, MIR146A and RNASEL, and their relation to NMSCs. Using a large population-based case-control study of basal cell (BCC) and squamous cell carcinoma (SCC), we investigated the impact of MIR146A SNP rs2910164 on cancer risk, and interaction with a SNP in one of its putative targets (RNASEL, rs486907). To examine associations between genotype and BCC and SCC, occurrence odds ratios (OR) and 95% confidence intervals (95%CI) were calculated using unconditional logistic regression, accounting for multiple confounding factors. We did not observe an overall change in the odds ratios for SCC or BCC among individuals carrying either of the RNASEL or MIR146A variants compared with those who were wild type at these loci. However, there was a sex-specific association between BCC and MIR146A in women (ORGC = 0.73, [95%CI = 0.52-1.03]; ORCC = 0.29, [95% CI = 0.14-0.61], p-trend<0.001), and a reduction in risk, albeit not statistically significant, associated with RNASEL and SCC in men (ORAG = 0.88, [95%CI = 0.65-1.19]; ORAA = 0.68, [95%CI = 0.43-1.08], p-trend = 0.10). Most striking was the strong interaction between the two genes. Among individuals carrying variant alleles of both rs2910164 and rs486907, we observed inverse relationships with SCC (ORSCC = 0.56, [95%CI = 0.38-0.81], p-interaction = 0.012) and BCC (ORBCC = 0.57, [95%CI = 0.40-0.80], p-interaction = 0.005). Our results suggest that genetic variation in immune and inflammatory regulators may influence susceptibility to NMSC, and novel SNP-SNP interaction for a microRNA and its target. These data suggest that RNASEL, an enzyme involved in RNA turnover, is controlled by miR-146a and may be important in NMSC etiology.

The vast majority of mental illnesses can be conceptualized as developmental disorders of neural interactions within the connectome, or developmental miswiring. The recent maturation of pediatric in vivo brain imaging is bringing the identification of clinically meaningful brain-based biomarkers of developmental disorders within reach. Even more auspicious is the ability to study the evolving connectome throughout life, beginning in utero, which promises to move the field from topological phenomenology to etiological nosology. Here, we scope advances in pediatric imaging of the brain connectome as the field faces the challenge of unraveling developmental miswiring. We highlight promises while also providing a pragmatic review of the many obstacles ahead that must be overcome to significantly impact public health.

Arsenic has wide-ranging effects on human health and there is evidence that it alters the immune response by influencing CD4+/CD8+ T cell ratios, IL-2 cytokine levels, and the expression of immune-response genes. We investigated the impact of in utero environmental arsenic exposure on immune development and function in newborns participating in a pregnancy cohort in New Hampshire, U.S., where arsenic levels have exceeded the current EPA maximum contaminant level of 10mug/L. Our results showed that maternal urinary arsenic concentrations were inversely related to absolute total CD45RA+ CD4+ cord blood CD69+ T cell counts (N=116, p=0.04) and positively associated with CD45RA+ CD69- CD294+ cell counts (p=0.01). In placental samples (N=70), higher in utero urinary arsenic concentrations were positively associated with the expression of IL1beta (p=0.03). These data provide evidence that relatively low-level arsenic exposure in utero may alter the fetal immune system and lead to immune dysregulation.

Nested case-control sampling is a popular design for large epidemiological cohort studies due to its cost effectiveness. A number of methods have been developed for the estimation of the proportional hazards model with nested case-control data; however, the evaluation of modeling assumption is less attended. In this article, we propose a class of goodness-of-fit test statistics for testing the proportional hazards assumption based on nested case-control data. The test statistics are constructed based on asymptotically mean-zero processes derived from Samuelsen's maximum pseudo-likelihood estimation method. In addition, we develop an innovative resampling scheme to approximate the asymptotic distribution of the test statistics while accounting for the dependent sampling scheme of nested case-control design. Numerical studies are conducted to evaluate the performance of our proposed approach, and an application to the Wilms' Tumor Study is given to illustrate the methodology.

BACKGROUND/OBJECTIVES: Obesity has been declared a 21st century pandemic by WHO. Yet surveys reveal physicians-in-training are uncomfortable managing obesity. One major barrier is the lack of residency education on obesity management. This study incorporates an obesity-specific didactic curriculum into an internal medicine (IM) residency programme and assesses its impact on residents' knowledge, attitudes, practice behaviours, and clinical outcomes in patients with obesity. METHODS: The intervention consisted of four, 1 h, obesity-specific lectures in the University of Florida Resident Noon Conference. Lectures were taught by multidisciplinary experts and offered to 75 IM residents every 2 weeks from 5 November 2010 to 17 December 2010. Impact on IM residents' knowledge and attitudes was assessed by a pre- and post-intervention Obesity Awareness Questionnaire (OAQ). IM residents' clinical performance was assessed by chart reviews of 238 patients with body mass index >25 kg/m(2) in residents' clinics 4 months pre- and 6 months post-intervention for three clinical outcomes and seven practice behaviours on obesity management. Pre- and post-intervention outcomes were compared via paired t tests (quantitative data) or McNemar's test (binary data). RESULTS: Mean lecture attendance was 25/75 residents (33%) per lecture. Survey response was 67/75 residents (89%) pre-OAQ and 63/75 residents (84%) post-OAQ. While most attitudes remained unchanged, IM residents gained significant confidence in exercise counselling, safety of bariatric surgery, and patients' weight loss potential; they were more likely to address obesity in the plan and referrals to bariatric surgery. Clinical outcomes and IM residents' knowledge demonstrated no improvement. CONCLUSIONS: Our brief lecture-based curriculum has the potential to improve IM residents' attitudes and practice behaviours towards obesity. The lack of improvement in clinical outcomes and resident knowledge prompts the need for multimodal, longitudinal curricula with experiential application of obesity medicine.

OBJECTIVE: To characterise the trends in the left ventricular assist device (LVAD) implantation rates and outcomes between 2004 and 2011 in the Medicare population. Since the approval of the HeartMate II in 2008, the use of LVADs has steadily climbed. Given the increase in LVAD use, issues around discharge disposition, post-implant hospitalisations and costs require further understanding. METHODS: We examined LVAD implantation rates and short-term and long-term outcomes among Medicare fee-for-service beneficiaries hospitalised for LVAD implantation. We also conducted analyses among survivors 1-year post-discharge to examine rehospitalisation rates. Lastly, we reported Centers for Medicare & Medicaid Services (CMS) payments for both index hospitalisation and rehospitalisations 1 year post-discharge. RESULTS: A total of 2152 LVAD implantations were performed with numbers increasing from 107 in 2004 to 612 in 2011. The 30-day mortality rate decreased from 52% to 9%, and 1-year mortality rate decreased from 69% to 31%. We observed no change in overall length of stay, but post-procedure length of stay increased. We also found an increase in home discharge dispositions from 26% to 53%. Between 2004 and 2010, the rehospitalisation rate increased and the number of hospital days decreased. The adjusted CMS payment for the index hospitalisation increased from $188 789 to $225 697 over time but decreased for rehospitalisation from $60 647 to $53 630. CONCLUSIONS: LVAD implantations increased over time. We found decreasing 30-day and 1-year mortality rates and increasing home discharge disposition. The proportion of patients rehospitalised among 1-year survivors remained high with increasing index hospitalisation cost, but decreasing post-implantation costs over time.

OBJECTIVE/BACKGROUND: This study aims to determine why patients with migraine present to an emergency department (ED). While migraine accounts for over 800,000 ED visits annually, no prospectively gathered data characterize patients' reasons for presenting to an ED. METHODS: We prospectively interviewed 309 consecutive patients presenting to an urban ED for headache. Patients were asked 100 closed-ended questions regarding sociodemographics, headache history, and current headache attack. We performed descriptive analyses on patients fulfilling International Classification of Headache Disorders 2 migraine criteria. RESULTS: Of 186 patients who met migraine criteria, 77% (95% confidence interval [CI]: 71, 83%) had a primary care provider (PCP), 87% (95% CI: 82, 92%) had medical insurance, and 83% (95% CI: 77, 88%) had drug coverage. Fifty-three percent (95% CI: 46, 60%) reported that they previously visited a doctor for headache. Fifty-five percent (95% CI: 48, 62%) previously received a migraine diagnosis. Twenty-two percent (95% CI: 16, 28%) sought medical care for the current headache prior to ED presentation. Fifty-five percent (95% CI: 48, 63%) took abortive medication for migraine on the day of the ED visit. Median headache duration was 24 hours (IQR: 12-72). Forty-nine percent (95% CI: 42, 57%) screened positive for depression. The most common reason for visiting the ED was a perceived emergency condition or referral by a physician (33.3% [95% CI: 27, 40%]). Other commonly cited reasons related to access to care. CONCLUSIONS: Most migraineurs presenting to the ED have a PCP and health insurance. ED visits commonly result from an inability to access care elsewhere and because patients consider pain to be an emergency condition. Missed opportunities for diagnosis and treatment likely contribute to ED visits.