Faculty Bibliography

Purpose The association between exposure to testosterone replacement therapy (TRT) and prostate cancer risk is controversial. The objective was to examine this association through nationwide, population-based registry data. Methods We performed a nested case-control study in the National Prostate Cancer Register of Sweden, which includes all 38,570 prostate cancer cases diagnosed from 2009 to 2012, and 192,838 age-matched men free of prostate cancer. Multivariable conditional logistic regression was used to examine associations between TRT and risk of prostate cancer (overall, favorable, and aggressive). Results Two hundred eighty-four patients with prostate cancer (1%) and 1,378 control cases (1%) filled prescriptions for TRT. In multivariable analysis, no association was found between TRT and overall prostate cancer risk (odds ratio [OR], 1.03; 95% CI, 0.90 to 1.17). However, patients who received TRT had more favorable-risk prostate cancer (OR, 1.35; 95% CI, 1.16 to 1.56) and a lower risk of aggressive prostate cancer (OR, 0.50; 95% CI, 0.37 to 0.67). The increase in favorable-risk prostate cancer was already observed within the first year of TRT (OR, 1.61; 95% CI, 1.10 to 2.34), whereas the lower risk of aggressive disease was observed after > 1 year of TRT (OR, 0.44; 95% CI, 0.32 to 0.61). After adjusting for previous biopsy findings as an indicator of diagnostic activity, TRT remained significantly associated with more favorable-risk prostate cancer and lower risk of aggressive prostate cancer. Conclusion The early increase in favorable-risk prostate cancer among patients who received TRT suggests a detection bias, whereas the decrease in risk of aggressive prostate cancer is a novel finding that warrants further investigation.

BACKGROUND:Rural settings in Sub-Saharan Africa (SSA) consistently report low participation in non-communicable disease (NCD) treatment programs and poor outcomes. OBJECTIVE:The objective of this study is to assess the impact of the implementation of a patient-centered rural NCD care delivery model called Bridging Income Generation through grouP Integrated Care (BIGPIC). DESIGN/METHODS:The study prospectively tracked participation and health outcomes for participants in a screening event and compared linkage frequencies to a historical comparison group. PARTICIPANTS/METHODS:Rural Kenyan participants attending a voluntary NCD screening event were included within the BIGPIC model of care. INTERVENTIONS/METHODS:The BIGPIC model utilizes a contextualized care delivery model designed to address the unique barriers faced in rural settings. This model emphasizes the following steps: (1) find patients in the community, (2) link to peer/microfinance groups, (3) integrate education, (4) treat in the community, (5) enhance economic sustainability and (6) generate demand for care through incentives. MAIN MEASURES/METHODS:The primary outcome is the linkage frequency, which measures the percentage of patients who return for care after screening positive for either hypertension and/or diabetes. Secondary measures include retention frequencies defined as the percentage of patients remaining engaged in care throughout the 9-month follow-up period and changes in systolic (SBP) and diastolic blood pressure (DBP) and blood sugar over 12 months. KEY RESULTS/RESULTS:Of the 879 individuals who were screened, 14.2 % were confirmed to have hypertension, while only 1.4 % were confirmed to have diabetes. The implementation of a comprehensive microfinance-linked, community-based, group care model resulted in 72.4 % of screen-positive participants returning for subsequent care, of which 70.3 % remained in care through the 12 months of the evaluation period. Patients remaining in care demonstrated a statistically significant mean decline of 21 mmHg in SBP [95 % CI (13.9 to 28.4), P < 0.01] and 5 mmHg drop in DBP [95 % CI (1.4 to 7.6), P < 0.01]. CONCLUSIONS:The implementation of a contextualized care delivery model built around the unique needs of rural SSA participants led to statistically significant improvements in linkage to care and blood pressure reduction.

BACKGROUND:The 2020 American Heart Association Impact Goal aims to improve cardiovascular health of all Americans by 20% while reducing deaths from cardiovascular disease and stroke by 20%. A large step toward this goal would be to better understand and take advantage of the significant intersection between behavior and biology across the entire life-span. In the proposed FAMILIA studies, we aim to directly address this major knowledge and clinical health gap by implementing an integrated family-centric health promotion intervention and focusing on the intersection of environment and behavior, while understanding the genetic and biologic basis of cardiovascular disease. METHODS:We plan to recruit 600 preschool children and their 600 parents or caregivers from 12-15 Head Start schools in Harlem, NY, and perform a 2:1 (2 intervention/1 control) cluster randomization of the schools. The preschool children will receive our intensive 37-hour educational program as the intervention for 4 months. For the adults, those in the "intervention" group will be randomly assigned to 1 of 2 intervention programs: an "individual-focused" or "peer-to-peer based." The primary outcome in children will be a composite score of knowledge (K), attitudes (A), habits (H), related to body mass index Z score (B), exercise (E), and alimentation (A) (KAH-BEA), using questionnaires and anthropometric measurements. For adults, the primary outcome will be a composite score for behaviors/outcomes related to blood pressure, exercise, weight, alimentation (diet) and tobacco (smoking; Fuster-BEWAT score). Saliva will be collected from the children for SNP genotyping, and blood will be collected from adults for RNA sequencing to identify network models and predictors of primary prevention outcomes. CONCLUSION/CONCLUSIONS:The FAMILIA studies seek to demonstrate that targeting a younger age group (3-5 years) and using a family-based approach may be a critical strategy in promoting cardiovascular health across the life-span.

OBJECTIVE: To describe infant activity at 3 months old and to test the efficacy of a primary care-based child obesity prevention intervention on promoting infant activity in low-income Hispanic families. METHODS: This study was a randomized controlled trial (n = 533) comparing a control group of mother-infant dyads receiving standard prenatal and pediatric primary care with an intervention group receiving "Starting Early," with individual nutrition counseling and nutrition and parenting support groups coordinated with prenatal and pediatric visits. Outcomes included infant activity (tummy time, unrestrained floor time, time in movement-restricting devices). Health literacy was assessed using the Newest Vital Sign. RESULTS: Four hundred fifty-six mothers completed 3-month assessments. Infant activity results were: 82.6% ever practiced tummy time; 32.0% practiced tummy time on the floor; 34.4% reported unrestrained floor time; 56.4% reported >/=1 h/d in movement-restricting devices. Inadequate health literacy was associated with reduced tummy time and unrestrained floor time. The intervention group reported more floor tummy time (OR 2.16, 95% CI 1.44-3.23) and unrestrained floor time (OR 1.69, 95% CI 1.14-2.49) compared to controls. No difference in the time spent in movement-restricting devices was found. CONCLUSIONS: Tummy time and unrestrained floor time were low. Primary care-based obesity prevention programs have potential to promote these activities.

Parathyroid hormone (PTH) is a primary calcium regulatory hormone. Elevated serum PTH concentrations in primary and secondary hyperparathyroidism have been associated with bone disease, hypertension, and in some studies, cardiovascular mortality. Genetic causes of variation in circulating PTH concentrations are incompletely understood. We performed a genome-wide association study of serum PTH concentrations among 29,155 participants of European ancestry from 13 cohort studies (n=22,653 and n=6502 in discovery and replication analyses, respectively). We evaluated the association of single nucleotide polymorphisms (SNPs) with natural log-transformed PTH concentration adjusted for age, sex, season, study site, and principal components of ancestry. We discovered associations of SNPs from five independent regions with serum PTH concentration, including the strongest association with rs6127099 upstream of CYP24A1 (P=4.2 × 10^-53), a gene that encodes the primary catabolic enzyme for 1,25-dihydroxyvitamin D and 25-dihydroxyvitamin D. Each additional copy of the minor allele at this SNP associated with 7% higher serum PTH concentration. The other SNPs associated with serum PTH concentration included rs4074995 within RGS14 (P=6.6 × 10^-17), rs219779 adjacent to CLDN14 (P=3.5 × 10^-16), rs4443100 near RTDR1 (P=8.7 × 10^-9), and rs73186030 near CASR (P=4.8 × 10^-8). Of these five SNPs, rs6127099, rs4074995, and rs219779 replicated. Thus, common genetic variants located near genes involved in vitamin D metabolism and calcium and renal phosphate transport associated with differences in circulating PTH concentrations. Future studies could identify the causal variants at these loci, and the clinical and functional relevance of these variants should be pursued.

Background/Purpose: Parent anxiety can affect infant experiences of procedural pain. However, little is known about other parent psychological factors associated with parent anxiety related to infant/toddler cleft and craniofacial surgery, and to what degree preoperative parent anxiety affects infant/toddler experiences of postoperative pain. Objectives 1. To identify psychological factors associated with preoperative anxiety for parents with young infants/toddlers undergoing craniofacial surgery 2. To determine whether preoperative parent anxiety is associated with infant/toddler postoperative pain Methods/Description: This was a prospective cohort study of all patients undergoing primary cleft and craniofacial surgery at a tertiary care medical center. Seventy-one consecutive parents of infants/toddlers 2-18 months were recruited for this study. Preoperative parent assessment included: anxiety (Hospital Anxiety and Depression Scale [HADS]), coping (Brief COPE), Parent Health Locus of Control scale, de novo self-efficacy around child pain, and pain knowledge. Sociodemographic data included child's age, gender; previous surgery, NICU or feeding tube; and parent age, gender, socioeconomic status, and race. Subsequent nurse-assessed child pain scores were collected for patients admitted postoperatively. Analyses included hierarchical multivariable logistic and linear regression models. Results: Parents (n=71, 90% female) of young children (mean age 6.6 mo) undergoing cleft lip/palate (n=59) or cranial vault repair (n=13) were enrolled. Only maladaptive coping (OR 1.3, p<0.01, 95% CI 1.1, 1.6), low pain management parent self-efficacy (OR 2.4, p<0.01, 95% CI 1.3, 4.5), and external locus of control (1.74, p 0.024, 95% CI 11, 2.9) were associated with high anxiety on bivariable analysis. In the final model, odds of parent preoperative anxiety was associated with differences in maladaptive coping score (aOR). Moderate/severe preoperative parental anxiety (HADS>10) was correlated with significantly higher child mean hospital pain scores in families of children undergoing cleft lip repair (1.87 point on 0-10 scale, 95% CI.42, 3.70, p =0.045). Conclusions: Infants/toddlers undergoing cleft and craniofacial surgery with highly anxious parents prior to surgery are at greater risk for higher hospital pain. Coping and self-efficacy are modifiable factors that contribute to parent anxiety before and during hospitalization and may be targets for intervention. Health locus of control could be incorporated into preoperative screening for vulnerable families

PURPOSE OF REVIEW/OBJECTIVE:This article intends to review biomarkers derived from blood, urine, and tissue that can aid in the diagnosis of prostate cancer (PCa). RECENT FINDINGS/RESULTS:PCa screening requires tools that complement prostate-specific antigen (PSA) with a higher specificity for clinically significant disease. Novel blood biomarkers, such as the Prostate Health Index (phi) and 4Kscore, utilize isoforms of PSA to more accurately predict high-grade PCa than traditional tools such as PSA and the percentage free-to-total PSA. Several gene products associated with PCa can be detected in the urine through commercially available assays. PCa antigen 3 (PCA3), though approved for repeat biopsy decisions, appears inferior to other biomarkers such as phi for identifying aggressive disease. However, combinations of PCA3 with other urine assays have shown promising results. One tissue-based hypermethylation test, named ConfirmMDx, can also be used to determine the need for repeat biopsy in men with a prior negative biopsy. SUMMARY/CONCLUSIONS:Several biomarkers have been developed to aid in the screening and diagnosis of PCa. Such tests are often indicated in men with moderately elevated PSA or history of a prior negative biopsy. Their use facilitates reduction of unnecessary biopsies without sacrificing the early diagnosis of clinically significant PCa.

OBJECTIVE: Hispanic parents in the United States are disproportionately affected by low health literacy and limited English proficiency (LEP). We examined associations between health literacy, LEP, and liquid medication dosing errors in Hispanic parents. METHODS: Cross-sectional analysis of data from a multisite randomized controlled experiment to identify best practices for the labeling/dosing of pediatric liquid medications (SAFE Rx for Kids study); 3 urban pediatric clinics. Analyses were limited to Hispanic parents of children aged 20% dose deviation. Predictor variables included health literacy (Newest Vital Sign) (limited = 0-3; adequate = 4-6) and LEP (speaks English less than "very well"). RESULTS: A total of 83.1% made dosing errors (mean [SD] errors per parent = 2.2 [1.9]). Parents with limited health literacy and LEP had the greatest odds of making a dosing error compared to parents with adequate health literacy who were English proficient (trials with errors per parent = 28.8 vs 12.9%; adjusted odds ratio = 2.2 [95% confidence interval 1.7-2.8]). Parents with limited health literacy who were English proficient were also more likely to make errors (trials with errors per parent = 18.8%; adjusted odds ratio = 1.4 [95% confidence interval 1.1-1.9]). CONCLUSIONS: Dosing errors are common among Hispanic parents; those with both LEP and limited health literacy are at particular risk. Further study is needed to examine how the redesign of medication labels and dosing tools could reduce literacy- and language-associated disparities in dosing errors.