Faculty Bibliography

OBJECTIVE: To examine the use of the Prostate Health Index (phi)* as a continuous variable in multivariable risk assessment for aggressive prostate cancer in a large multicenter US study. MATERIALS AND METHODS: The study population included 728 men with PSA levels of 2-10 ng/mL and negative digital rectal examination enrolled in a prospective, multi-site early detection trial. The primary endpoint was aggressive prostate cancer, defined as biopsy Gleason score >/=7. First, we evaluated whether the addition of phi improves the performance of currently available risk calculators (PCPT and ERSPC). We also designed and internally validated a new phi-based multivariable predictive model, and created a nomogram. RESULTS: Of 728 men undergoing biopsy, 118 (16.2%) had aggressive prostate cancer. Phi predicted the risk of aggressive prostate cancer across the spectrum of values. Adding phi significantly improved the predictive accuracy of the PCPT and ERSPC risk calculators for aggressive disease. A new model was created using age, prior biopsy, prostate volume, PSA, and phi with an AUC of 0.746. The bootstrap-corrected model showed good calibration with observed risk for aggressive prostate cancer and had net benefit on decision curve analysis. CONCLUSION: Using phi as part of multivariable risk assessment leads to a significant improvement in the detection of aggressive prostate cancer, potentially reducing harms from unnecessary prostate biopsy and overdiagnosis

OBJECTIVE:), a measure of average blood glucose level, is associated with the risk of dementia and cognitive impairment. However, the role of glycemic variability or glucose excursions in this association is unclear. We examined the association of glucose peaks in midlife, as determined by the measurement of 1,5-anhydroglucitol (1,5-AG) level, with the risk of dementia and 20-year cognitive decline. RESEARCH DESIGN AND METHODS:. RESULTS:< 0.001). We found no significant associations in persons without diabetes. CONCLUSIONS:Among participants with diabetes, glucose peaks are a risk factor for cognitive decline and dementia. Targeting glucose peaks, in addition to average glycemia, may be an important avenue for prevention.

OBJECTIVE:The Eating Disorder Examination (EDE) was originally developed and validated in primarily white female samples. Since data indicate that eating pathology impacts black youth, elucidating the psychometric appropriateness of the EDE for black youth is crucial. METHODS:A convenience sample was assembled from seven pediatric obesity studies. The EDE was administered to all youth. Confirmatory factor analyses (CFA) were conducted to examine the original four-factor model fit and two alternative factor structures for black and white youth. With acceptable fit, multiple-group CFAs were conducted. For measurement invariant structures, the interactive effects of race with sex, BMIz, adiposity, and age were explored (all significance levels p < .05). RESULTS:For both black and white youth (N = 820; 41% black; 37% male; 6-18 years; BMIz -3.11 to 3.40), the original four-factor EDE structure and alternative eight-item one-factor structure had mixed fit via CFA. However, a seven-item, three-factor structure reflecting Dietary Restraint, Shape/Weight Overvaluation, and Body Dissatisfaction had good fit and held at the level of strict invariance. Girls reported higher factor scores than boys. BMIz and adiposity were positively associated with each subscale. Age was associated with Dietary Restraint and Body Dissatisfaction. The interactional effects between sex, BMIz, and age with race were not significant; however, the interaction between adiposity and race was significant. At higher adiposity, white youth reported greater pathology than black youth. CONCLUSION:An abbreviated seven-item, three-factor version of the EDE captures eating pathology equivalently across black and white youth. Full psychometric testing of the modified EDE factor structure in black youth is warranted.

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.

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.

OBJECTIVE:Dietary protein restriction is recommended for patients with moderate to severe renal insufficiency. Long-term data on the relationship between dietary protein sources and risk for incident kidney disease in individuals with normal kidney function are largely missing. This study aimed to assess the association between dietary protein sources and incident chronic kidney disease (CKD). DESIGN:Prospective cohort. SETTING:Atherosclerosis Risk in Communities study participants from 4 US communities. SUBJECTS:. MAIN OUTCOME MEASURE:; CKD-related hospitalization; CKD-related death; or end-stage renal disease. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression. RESULTS: = 0.03). CONCLUSION:There were varied associations of specific dietary protein sources with risk of incident CKD; with red and processed meat being adversely associated with CKD risk; and nuts, low-fat dairy products, and legumes being protective against the development of CKD.

PURPOSE: Research demonstrates a negative psychosocial impact of infertility among otherwise healthy adults, and distress among adolescents facing the prospect of future infertility due to various medical conditions and treatments that impair reproductive health. Guidelines state that providers should counsel transgender youth about potential infertility and fertility preservation (FP) options prior to initiation of hormone therapy. The purpose of this study was to examine the rates of fertility counseling and utilization of FP among a cohort of adolescents with gender dysphoria seen at a large gender clinic. METHODS: An Institutional Review Board-approved retrospective review of electronic medical records was conducted of all patients with ICD-9/10 codes for gender dysphoria referred to Pediatric Endocrinology for hormone therapy (puberty suppression and/or cross-sex hormones) from January 2014 to August 2016. RESULTS: Seventy-eight patients met inclusion criteria. Five children were prepubertal, no hormone therapy was considered, and they were therefore excluded. Of the remaining 73 patients, 72 had documented fertility counseling prior to initiation of hormone therapy and 2 subjects attempted FP; 45% of subjects mentioned a desire or plan to adopt, and 21% said they had never wanted to have children. CONCLUSIONS: Utilization rates of FP are low among transgender adolescents. More research is needed to understand parenthood goals among transgender youth at different ages and developmental stages and to explore the impact of gender dysphoria on decision-making about FP and parenthood. Discussions about infertility risk, FP, and other family building options should be prioritized in this vulnerable adolescent population.

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.