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.

Importance: A neurophysiologic signature of the melanopsin-mediated persistent constriction phase of the pupillary light reflex may represent a surrogate biomarker for the integrity of the retinohypothalamic tract, with potential utility for investigating alterations in homeostatic mechanisms associated with brain disorders and implications for identifying new treatments. Objective: To characterize abnormalities of retinal architecture in patients with multiple sclerosis (MS) and corresponding alterations in the melanopsin-mediated sustained pupillary constriction response. Design, Setting, and Participants: The case-control study was an experimental assessment of various stimulus-induced pupillary response characteristics and was conducted at a university clinical center for MS from September 6, 2012, to February 2015. Twenty-four patients with MS (48 eyes) and 15 individuals serving as controls (30 eyes) participated. The melanopsin-mediated, sustained pupillary constriction phase response following cessation of a blue light stimulus was compared with the photoreceptor-mediated pupillary constriction phase response following cessation of a red light stimulus. Optical coherence tomography was used to characterize the association between pupillary response characteristics and alterations in retinal architecture, specifically, the thickness of the retinal ganglion cell layer and inner plexiform layer (GCL + IPL). Main Outcomes and Measures: Association of pupillary response characteristics with alterations in retinal architecture. Results: Of 24 patients with MS included in the analysis, 17 were women (71%); mean (SD) age was 47 (11) years. Compared with eyes from individuals with MS who had normal optical coherence tomography-derived measures of retinal GCL + IPL thickness, eyes of patients who had GCL + IPL thickness reductions to less than the first percentile exhibited a correspondingly significant attenuation of the melanopsin-mediated sustained pupillary response (mean [SD] pupillary diameter ratios at a point in time, 0.18 [0.1] vs 0.33 [0.09]; P < .001, generalized estimating equation models accounting for age and within-patient intereye correlations). Conclusions and Relevance: In this case-control study, attenuation of the melanopsin-mediated sustained pupillary constriction response was significantly associated with thinning of the GCL + IPL sector of the retina in the eyes of patients with MS, particularly those with a history of acute optic neuritis. Melanopsin-containing ganglion cells in the retina represent, at least in part, the composition of the retinohypothalamic tract. As such, our findings may signify the ability to elucidate a putative surrogate neurophysiologic signature that correlates with a constellation of homeostatic mechanisms in both health and illness.

OBJECTIVES:This study sought to evaluate the association of physical activity with chronic myocardial damage, assessed by elevated high-sensitivity cardiac troponin T (hs-cTnT), in individuals with and without obesity. BACKGROUND:Physical activity is associated with reduced risk of heart failure (HF), particularly among obese people. The role of chronic myocardial damage in this association is uncertain. METHODS:. Physical activity was categorized per American Heart Association guidelines as recommended, intermediate, or poor. We evaluated cross-sectional associations of physical activity and obesity with elevated hs-cTnT (≥14 ng/l). In prospective analyses, we quantified the association of elevated hs-cTnT with HF risk within cross-categories of baseline physical activity and obesity. RESULTS:People with poor physical activity were more likely to have elevated hs-cTnT than those with recommended levels (odds ratio [OR]: 1.39; 95% confidence interval [CI]: 1.15 to 1.68). In cross-categories of physical activity and obesity, using the non-obese/recommended activity group as the reference, individuals with obesity and poor activity were most likely to have elevated hs-cTnT (OR: 2.46; 95% CI: 1.91 to 3.19), whereas the obese/recommended activity group had a weaker association (OR: 1.68; 95% CI: 1.28 to 2.21; p < 0.001 for interaction between physical activity and obesity). In prospective analyses, elevated hs-cTnT was strongly associated (p < 0.001) with incident HF in all obesity/physical activity cross-categories (p > 0.20 for interaction). CONCLUSIONS:Physical activity is inversely associated with chronic subclinical myocardial damage. Physical activity might lessen the association between obesity and subclinical myocardial damage, which could represent a mechanism by which physical activity reduces HF risk.

Older patients with ESRD who receive a kidney transplant (KT) may develop post-KT dementia and Alzheimer's disease (AD) associated with their long-standing kidney disease and/or neurotoxic immunosuppressant agents. To investigate this possibility, we studied 40,918 older (aged ≥55 years) KT recipients (January 1, 1999 to December 31, 2011) linked to Medicare claims through the US Renal Data System. We estimated dementia and AD risk (cumulative incidence) and studied factors associated with these sequelae using competing risks models. We estimated the risk of death-censored graft loss and mortality after developing dementia or the AD subtype of dementia, separately, using adjusted Cox proportional hazards models. Older recipients had a 10-year dementia risk ranging from 5.1% for recipients aged 55-60 years to 17.0% for recipients aged ≥75 years; 10-year AD risk ranged from 1.0% to 6.7%, respectively. The strongest predictors for dementia and AD were older recipient age and pretransplant diabetes. The 10-year graft loss risk was 28.8% for those who did not develop dementia and 43.1% for those who did, and the corresponding mortality risks were 55.7% and 89.9%, respectively. Older recipients with dementia had a 1.52-fold (95% confidence interval, 1.39 to 1.68) increased risk of graft loss and a 2.38-fold (95% confidence interval, 2.26 to 2.49) increased risk of mortality. We observed similar results for AD. We conclude that older KT recipients have a high risk of post-KT dementia and AD, and these sequelae associate with a profound effect on patient and graft survival.

BACKGROUND: In 2012 The Joint Commission implemented new Tobacco Treatment (TOB) performance measures for hospitals. A study evaluated the impact of a hospital-based electronic health record (EHR) intervention on adherence to the revised TOB measures. METHODS: The study was conducted in two acute care hospitals in New York City. Data abstracted from the EHR were analyzed retrospectively from 4,871 smokers discharged between December 2012 and March 2015 to evaluate the impact of two interventions: an order set to prompt clinicians to prescribe pharmacotherapy and a nurse-delivered counseling module that automatically populated the nursing care plan for all smokers. The study estimated the relative odds of a patient being prescribed medication and/or receiving smoking cessation counseling in the intervention period compared to the baseline time period. RESULTS: There was a modest increase in medication orders (odds ratio [OR], 1.35). In contrast, rates of counseling increased 10-fold (OR, 10.54). Patients admitted through surgery were less likely to receive both counseling and medication compared with the medicine service. CONCLUSION: Hospitalization presents an important opportunity to engage smokers in treatment for primary and secondary prevention of tobacco-related illnesses. EHRs can be leveraged to facilitate integration of TOB measure requirements into routine inpatient care; however, the smaller effect on prescribing patterns suggests limitations in this approach alone in changing clinician behavior to meet this measure. The success of the nurse-focused EHR-driven intervention suggests an effective tool for integrating the cessation counseling component of the new measures and the importance of nursing's role in achieving the Joint Commission measure targets.

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

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.

OBJECTIVE: To determine whether patient-specific 3D printed renal tumor models change pre-operative planning decisions made by urological surgeons in preparation for complex renal mass surgical procedures. MATERIALS AND METHODS: From our ongoing IRB approved study on renal neoplasms, ten renal mass cases were retrospectively selected based on Nephrometry Score greater than 5 (range 6-10). A 3D post-contrast fat-suppressed gradient-echo T1-weighted sequence was used to generate 3D printed models. The cases were evaluated by three experienced urologic oncology surgeons in a randomized fashion using (1) imaging data on PACS alone and (2) 3D printed model in addition to the imaging data. A questionnaire regarding surgical approach and planning was administered. The presumed pre-operative approaches with and without the model were compared. Any change between the presumed approaches and the actual surgical intervention was recorded. RESULTS: There was a change in planned approach with the 3D printed model for all ten cases with the largest impact seen regarding decisions on transperitoneal or retroperitoneal approach and clamping, with changes seen in 30%-50% of cases. Mean parenchymal volume loss for the operated kidney was 21.4%. Volume losses >20% were associated with increased ischemia times and surgeons tended to report a different approach with the use of the 3D model compared to that with imaging alone in these cases. The 3D printed models helped increase confidence regarding the chosen operative procedure in all cases. CONCLUSIONS: Pre-operative physical 3D models created from MRI data may influence surgical planning for complex kidney cancer.

The King-Devick (K-D) test of rapid number naming is a visual performance measure that captures saccadic eye movements. Patients with multiple sclerosis (MS) have slowed K-D test times associated with neurologic disability and reduced quality of life. We assessed eye movements during the K-D test to identify characteristics associated with slowed times. Participants performed a computerized K-D test with video-oculography. The 25-Item National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25) and its 10-Item Neuro-Ophthalmic Supplement measured vision-specific quality of life (VSQOL). Among 25 participants with MS (age 37 +/- 10 years, range 20-59) and 42 controls (age 33 +/- 9 years, range 19-54), MS was associated with significantly longer (worse) K-D times (58.2 +/- 19.8 vs. 43.8 +/- 8.6 s, P = 0.001, linear regression models, accounting for age). In MS, test times were slower among patients with higher (worse) Expanded Disability Status Scale scores (P = 0.01). Average inter-saccadic intervals (ISI) were significantly longer in MS participants compared to controls (362 +/- 103 vs. 286 +/- 50 ms, P = 0.001), and were highly associated with prolonged K-D times in MS (P = 0.006). MS participants generated greater numbers of saccades (P = 0.007). VSQOL scores were reduced in MS patients with longer (worse) K-D times (P = 0.04-0.001) and longer ISI (P = 0.002-0.001). Patients with MS have slowed K-D times that may be attributable to prolonged ISI and greater numbers of saccades. The K-D test and its requisite eye movements capture VSQOL and make rapid number naming a strong candidate efferent visual performance measure in MS.

Numerous epidemiological accounts suggest that waterpipe smoking (aka hookah, shisha, narghile) has become a global phenomenon, especially among youth. The alarming spread of waterpipe and accumulating evidence of its addictive and harmful effects represent a new threat in the global fight to limit tobacco-related morbidity and mortality. In response to waterpipe's alarming trends, major public health and tobacco control organisations have started or are considering systematic collection of data about waterpipe smoking to monitor its trends and assess its harmful effects in different societies. Such plans require coordination and agreement on epidemiological measurement tools that reflect the uniqueness of this tobacco use method, and at the same time allow comparison of waterpipe trends across time and place, and with other tobacco use methods. We started a decade ago our work to develop standardised measures and definitions for the assessment of waterpipe smoking in epidemiological studies. In this communication, we try to expand and update these assessment tools in light of our increased knowledge and understanding of waterpipe use patterns, its context and marketing, as well as the need for evidence-guided policies and regulations to curb its spread. We have assembled for this purpose a group of leading waterpipe researchers worldwide, and worked through an iterative process to develop the suggested instruments and definitions based on what we know currently about the waterpipe epidemic. While the suggested measures are by no means comprehensive, we hope that they can provide the building blocks for standard and comparable surveillance of waterpipe smoking globally.