Faculty Bibliography

PURPOSE/OBJECTIVE:The following is a summary of discussion at a U.S. Food and Drug Administration (FDA) public workshop reviewing potential trial designs and endpoints for development of therapies to treat localized prostate cancer. MATERIALS AND METHODS/METHODS:The workshop focused on the challenge that drug and device development for the treatment of localized prostate cancer has been limited by the large trial sizes and lengthy timelines required to demonstrate an improvement in overall survival or metastasis-free survival and by the lack of agreed-upon alternative endpoints. Additionally, evolving treatment paradigms in the management of localized prostate cancer include the widespread use of active surveillance for patients with low- and some intermediate-risk prostate cancer and the availability of advances in imaging and genomics. RESULTS:The workshop addressed issues related to trial design in this setting and discussed several potential novel endpoints such as delay of morbidity due to radiation or prostatectomy, and pathologic endpoints such as Gleason Grade Group upgrade. CONCLUSIONS:The workshop provided an open forum for multi-stakeholder engagement to advance the development of effective treatment options in localized prostate cancer. Full workshop proceedings are available online at https://www.fda.gov/NewsEvents/MeetingsConferencesWorkshops/ucm608328.htm.

BACKGROUND:Hypertension is a major risk factor for cardiovascular disease (CVD), yet treatment and control rates for hypertension are very low in low- and middle-income countries (LMICs). Lack of effective referral networks between different levels of the health system is one factor that threatens the ability to achieve adequate blood pressure control and prevent CVD-related morbidity. Health information technology and peer support are two strategies that have improved care coordination and clinical outcomes for other disease entities in other settings; however, their effectiveness and cost-effectiveness in strengthening referral networks to improve blood pressure control and reduce CVD risk in low-resource settings are unknown. METHODS/DESIGN/METHODS:We will use the PRECEDE-PROCEED framework to conduct transdisciplinary implementation research, focused on strengthening referral networks for hypertension in western Kenya. We will conduct a baseline needs and contextual assessment using a mixed-methods approach, in order to inform a participatory, community-based design process to fully develop a contextually and culturally appropriate intervention model that combines health information technology and peer support. Subsequently, we will conduct a two-arm cluster randomized trial comparing 1) usual care for referrals vs 2) referral networks strengthened with our intervention. The primary outcome will be one-year change in systolic blood pressure. The key secondary clinical outcome will be CVD risk reduction, and the key secondary implementation outcomes will include referral process metrics such as referral appropriateness and completion rates. We will conduct a mediation analysis to evaluate the influence of changes in referral network characteristics on intervention outcomes, a moderation analysis to evaluate the influence of baseline referral network characteristics on the effectiveness of the intervention, as well as a process evaluation using the Saunders framework. Finally, we will analyze the incremental cost-effectiveness of the intervention relative to usual care, in terms of costs per unit decrease in systolic blood pressure, per percentage change in CVD risk score, and per disability-adjusted life year saved. DISCUSSION/CONCLUSIONS:This study will provide evidence for the implementation of innovative strategies for strengthening referral networks to improve hypertension control in LMICs. If effective, it has the potential to be a scalable model for health systems strengthening in other low-resource settings worldwide. TRIAL REGISTRATION/BACKGROUND:Clinicaltrials.gov, NCT03543787 . Registered on 29 June 2018.

OBJECTIVES/OBJECTIVE:To explore: (A) the underlying motivators and barriers to smoking cessation among young Arabic speaking smokers and (B) to examine the suitability and preferences for tobacco cessation interventions (specifically text messages) and study the possibility of enrollment methods for a randomised controlled study using text messages as an intervention for tobacco cessation. DESIGN/METHODS:Qualitative research using focus group discussions and content analysis. SETTINGS/METHODS:Two universities, one of them is the first and foremost comprehensive national university in the United Arab Emirates (UAE). The third setting is the largest hospital in the UAE and the flagship institution for the public health system in the emirate of Abu Dhabi. PARTICIPANTS/METHODS:Six focus group discussions with a total of 57 participants. Forty-seven men and 10 women. Fifty-three of them were current smokers. RESULTS:The analysis of six focus groups was carried out. Main themes arose from the data included: preferences for tobacco cessation interventions and acceptability and feasibility of text messaging as tobacco cessation intervention. Different motives and barriers for quitting smoking including shisha and dokha were explored. CONCLUSION/CONCLUSIONS:Interventions using text messaging for smoking cessation have not been used in the Middle East and they could potentially be effective; however, tailoring and closely examining the content and acceptability of text messages to be used is important before the conduction of trials involving their use. Social media is perceived to be more effective and influential, with a higher level of penetration into communities of young smokers.

BACKGROUND:Evidence-based therapy for heart failure remains underutilized at hospital discharge, particularly for patients with heart failure who are hospitalized for another cause. We developed clinical decision support (CDS) to recommend an angiotensin converting enzyme (ACE) inhibitor during hospitalization to promote its continuation at discharge. The CDS was designed to be implemented in both interruptive and non-interruptive versions. OBJECTIVES/OBJECTIVE:To compare the effectiveness and implementation of interruptive and non-interruptive versions of a CDS to improve care for heart failure. METHODS:Hospitalizations of patients with reduced ejection fraction were pseudo-randomized to deliver interruptive or non-interruptive CDS alerts to providers based on even or odd medical record number. We compared discharge utilization of an ACE inhibitor or angiotensin receptor blocker (ARB) for these two implementation approaches. We also assessed adoption and implementation fidelity of the CDS. RESULTS:percentile) of 14 (5,32) alerts were triggered per hospitalization. CONCLUSIONS:A CDS implemented as an interruptive alert was associated with improved quality of care for heart failure. Whether the potential benefits of CDS in improving cardiovascular care were worth the high burden of interruptive alerts deserves further consideration. CLINICALTRIALS. GOV IDENTIFIER/UNASSIGNED:NCT02858674.

BACKGROUND:The incidence of cardiovascular (CV) risk factors is increasing globally, with a disproportionate burden in the low and low-middle income countries (L/LMICs). Peer support, as a low-cost lifestyle intervention, has succeeded in managing chronic illness. For global CV risk reduction, limited data exists in LMICs. AIM/OBJECTIVE:The GHP-CHANGE was designed as a community-based randomized trial to test the effectiveness of peer support strategy for CV risk reduction in the island of Grenada, a LMIC. METHODS:We recruited 402 adults from the Grenada Heart Project (GHP) Cohort Study of 2827 subjects with at least two CV risk factors. Subjects were randomized in a 1:1 fashion to a peer-group based intervention group (n = 206) or a self-management control group (n = 196) for 12 months. The primary outcome was the change from baseline in a composite score related to Blood pressure, Exercise, Weight, Alimentation and Tobacco (FBS, Fuster-BEWAT Score), ranging from 0 to 15 (ideal health = 15). Linear mixed-effects models were used to test for intervention effects. RESULTS:Participants mean age was 51.4 years (SD 14.5) years, two-thirds were female, and baseline mean FBS was 8.9 (SD 2.6) and 8.5 (SD 2.6) in the intervention and control group, respectively (P = .152). At post intervention, the mean FBS was higher in the intervention group compared to the control group [9.1 (SD 2.7) vs 8.5 (SD 2.6), P = .028]. When balancing baseline health profile, the between-group difference (intervention vs. control) in the change of FBS was 0.31 points (95% CI: -0.12 to 0.75; P = .154). CONCLUSIONS:The GHP-CHANGE trial showed that a peer-support lifestyle intervention program was feasible; however, it did not demonstrate a significant improvement in the FBS as compared to the control group. Further studies should assess the effects of low-cost lifestyle interventions in LMICs.

Background Little is known regarding use of cardiac therapies and clinical outcomes among older myocardial infarction (MI) patients with cognitive impairment. Methods and Results Patients ≥65 years old with MI in the NCDR (National Cardiovascular Data Registry) Chest Pain-MI Registry between January 2015 and December 2016 were categorized by presence and degree of chart-documented cognitive impairment. We evaluated whether cognitive impairment was associated with all-cause in-hospital mortality after adjusting for known prognosticators. Among 43 812 ST-segment-elevation myocardial infarction (STEMI) patients, 3.9% had mild and 2.0% had moderate/severe cognitive impairment; among 90 904 non-ST-segment-elevation myocardial infarction (NSTEMI patients, 5.7% had mild and 2.6% had moderate/severe cognitive impairment. A statistically significant but numerically small difference in the use of primary percutaneous coronary intervention was observed between patients with STEMI with and without cognitive impairment (none, 92.1% versus mild, 92.8% versus moderate/severe, 90.4%; P=0.03); use of fibrinolysis was lower among patients with cognitive impairment (none, 40.9% versus mild, 27.4% versus moderate/severe, 24.2%; P<0.001). Compared with NSTEMI patients without cognitive impairment, rates of angiography, percutaneous coronary intervention, and coronary artery bypass grafting were significantly lower among patients with NSTEMI with mild (41%, 45%, and 70% lower, respectively) and moderate/severe cognitive impairment (71%, 74%, and 93% lower, respectively). After adjustment, compared with no cognitive impairment, presence of moderate/severe (STEMI: odds ratio, 2.2, 95% CI, 1.8-2.7; NSTEMI: odds ratio, 1.7, 95% CI, 1.4-2.0) and mild cognitive impairment (STEMI: OR, 1.3, 95% CI, 1.1-1.5; NSTEMI: odds ratio, 1.3, 95% CI, 1.2-1.5) was associated with higher in-hospital mortality. Conclusions Patients with NSTEMI with cognitive impairment are substantially less likely to receive invasive cardiac care, while patients with STEMI with cognitive impairment receive similar primary percutaneous coronary intervention but less fibrinolysis. Presence and degree of cognitive impairment was independently associated with increased in-hospital mortality. Approaching clinical decision making for older patients with MI with cognitive impairment requires further study.

The metabolome of World Trade Center (WTC) particulate matter (PM) exposure has yet to be fully defined and may yield information that will further define bioactive pathways relevant to lung injury. A subset of Fire Department of New York firefighters demonstrated resistance to subsequent loss of lung function. We intend to characterize the metabolome of never smoking WTC-exposed firefighters, stratified by resistance to WTC-Lung Injury (WTC-LI) to determine metabolite pathways significant in subjects resistant to the loss of lung function. The global serum metabolome was determined in those resistant to WTC-LI and controls (n = 15 in each). Metabolites most important to class separation (top 5% by Random Forest (RF) of 594 qualified metabolites) included elevated amino acid and long-chain fatty acid metabolites, and reduced hexose monophosphate shunt metabolites in the resistant cohort. RF using the refined metabolic profile was able to classify cases and controls with an estimated success rate of 93.3%, and performed similarly upon cross-validation. Agglomerative hierarchical clustering identified potential influential pathways of resistance to the development of WTC-LI. These pathways represent potential therapeutic targets and warrant further research.

PURPOSE OF REVIEW/OBJECTIVE:This article summarizes the current state of underrepresented minorities (URM) and women within urology. Specific strategies to promote the recruitment and retention of URM and women within urology are discussed. RECENT FINDINGS/RESULTS:Minorities and women remain underrepresented within urology, a disparity that has roots as early as medical school and persists throughout residency and practice. This is likely due to implicit and explicit bias, lack of role models, and persistent disparities in compensation and promotion. Strategies to improve recruitment and retention of these individuals should focus on increasing early exposure to urology, opportunities for mentorship, and support in professional development. Creation of a supportive institutional culture, consideration of alternative career advancement paths, and intentional diversity-focused recruitment efforts are also critical. Successful recruitment and retention of URM and women in urology requires specific, directed efforts to increase opportunities for exposure, mentorship, and career promotion at a programmatic, institutional, and national level.

BACKGROUND:Adherence to healthy dietary patterns, measured by the Healthy Eating Index (HEI), Alternative Healthy Eating Index (AHEI), and alternate Mediterranean diet (aMed) scores, is associated with a reduced risk of cardiovascular disease. The association between these scores and chronic kidney disease (CKD) is undetermined. OBJECTIVE:We aimed to estimate the association between the HEI, AHEI, and aMed scores and risk of incident CKD. METHODS:We conducted a prospective analysis in 12,155 participants aged 45-64 y from the Atherosclerosis Risk in Communities (ARIC) Study. We calculated HEI-2015, AHEI-2010, and aMed scores for each participant and categorized them into quintiles of each dietary score. Incident CKD was defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2 accompanied by ≥25% decline in estimated glomerular filtration rate, a kidney disease-related hospitalization or death, or end-stage renal disease. We used cause-specific hazard models to estimate risk of CKD from the quintile of the dietary score through to 31 December 2017. RESULTS:There were 3980 cases of incident CKD over a median follow-up of 24 y. Participants who had higher adherence to the HEI-2015, AHEI-2010, and aMed scores were more likely to be female, have higher educational attainment, higher income level, be nonsmokers, more physically active, and diabetic compared with participants who scored lower. All 3 dietary scores were associated with lower CKD risk (P-trend < 0.001). Participants who were in the highest quintile of HEI-2015 score had a 17% lower risk of CKD (HR: 0.83; 95% CI: 0.74, 0.92) compared with participants in the lowest quintile. Those in quintile 5 of AHEI-2010 and aMed scores, respectively, had a 20% and 13% lower risk of CKD compared with those in quintile 1. CONCLUSION:Higher adherence to healthy dietary patterns during middle age was associated with lower risk of CKD.

Some food parenting practices (FPPs) are associated with obesogenic dietary intake in non-Hispanic youth, but studies in Hispanics/Latinos are limited. We examined how FPPs relate to obesogenic dietary intake using cross-sectional data from 1214 Hispanic/Latino 8-16-year-olds and their parents/caregivers in the Hispanic Community Children's Health Study/Study of Latino Youth (SOL Youth). Diet was assessed with 2 24-h dietary recalls. Obesogenic items were snack foods, sweets, and high-sugar beverages. Three FPPs (Rules and Limits, Monitoring, and Pressure to Eat) derived from the Parenting strategies for Eating and Activity Scale (PEAS) were assessed. K-means cluster analysis identified 5 groups of parents with similar FPP scores. Survey-weighted multiple logistic regression examined associations of cluster membership with diet. Parents in the controlling (high scores for all FPPs) vs. indulgent (low scores for all FPPs) cluster had a 1.75 (95% CI: 1.02, 3.03) times higher odds of having children with high obesogenic dietary intake. Among parents of 12-16-year-olds, membership in the pressuring (high Pressure to Eat, low Rules and Limits and Monitoring scores) vs. indulgent cluster was associated with a 2.96 (95% CI: 1.51, 5.80) times greater odds of high obesogenic dietary intake. All other associations were null. Future longitudinal examinations of FPPs are needed to determine temporal associations with obesogenic dietary intake in Hispanic/Latino youth.