Faculty Bibliography

BACKGROUND:and incorporates age, sex, GFR, and urine albumin-creatinine ratio (ACR) to forecast individual risk of kidney failure. Implementing the KFRE in electronic medical records is challenging, however, due to low ACR testing in clinical practice. The aim of this study was to determine, when ACR is missing, whether to impute ACR from protein-to-creatinine ratio (PCR) or dipstick protein for use in the four-variable KFRE, or to use the three-variable KFRE, which does not require ACR. METHODS:were categorized on the basis of the availability of ACR testing within the previous 3 years. For patients missing ACR, we extracted urine PCR and dipstick protein results, comparing the discrimination of the three-variable KFRE (age, sex, GFR) with the four-variable KFRE estimated using imputed ACR from PCR and dipstick protein levels. RESULTS:. The proportion with ACR testing was 19% within the previous 3 years. An additional 2% had an available PCR and 36% had a dipstick protein; the remaining 43% had no form of albuminuria testing. The four-variable KFRE had significantly better discrimination than the three-variable KFRE among patients with ACR testing, PCR testing, and urine dipstick protein levels, even with imputed ACR for the latter two groups. Calibration of the four-variable KFRE was acceptable in each group, but the three-variable equation showed systematic bias in the groups that lacked ACR or PCR testing. CONCLUSIONS:Implementation of the KFRE in electronic medical records should incorporate ACR, even if only imputed from PCR or urine dipstick protein levels.

AIMS/OBJECTIVE:Tens of millions of people worldwide use opiates but little is known about their potential role in causing cardiovascular diseases. We aimed to study the association of long-term opiate use with cardiovascular mortality and whether this association is independent of the known risk factors. METHODS AND RESULTS/RESULTS:In the population-based Golestan Cohort Study-50 045 Iranian participants, 40-75 years, 58% women-we used Cox regression to estimate hazard ratios and 95% confidence intervals (HRs, 95% CIs) for the association of opiate use (at least once a week for a period of 6 months) with cardiovascular mortality, adjusting for potential confounders-i.e. age, sex, education, wealth, residential place, marital status, ethnicity, and tobacco and alcohol use. To show independent association, the models were further adjusted for hypertension, diabetes, waist and hip circumferences, physical activity, fruit/vegetable intake, aspirin and statin use, and history of cardiovascular diseases and cancers. In total, 8487 participants (72.2% men) were opiate users for a median (IQR) of 10 (4-20) years. During 548 940 person-years-median of 11.3 years, >99% success follow-up-3079 cardiovascular deaths occurred, with substantially higher rates in opiate users than non-users (1005 vs. 478 deaths/100 000 person-years). Opiate use was associated with increased cardiovascular mortality, with adjusted HR (95% CI) of 1.63 (1.49-1.79). Overall 10.9% of cardiovascular deaths were attributable to opiate use. The association was independent of the traditional cardiovascular risk factors. CONCLUSION/CONCLUSIONS:Long-term opiate use was associated with an increased cardiovascular mortality independent of the traditional risk factors. Further research, particularly on mechanisms of action, is recommended.

The Collaborative Cohort of Cohorts for COVID-19 Research (C4R) is a national prospective study of adults at risk for coronavirus disease 2019 (COVID-19) comprising 14 established United States (US) prospective cohort studies. For decades, C4R cohorts have collected extensive data on clinical and subclinical diseases and their risk factors, including behavior, cognition, biomarkers, and social determinants of health. C4R will link this pre-COVID phenotyping to information on SARS-CoV-2 infection and acute and post-acute COVID-related illness. C4R is largely population-based, has an age range of 18-108 years, and broadly reflects the racial, ethnic, socioeconomic, and geographic diversity of the US. C4R is ascertaining severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 illness using standardized questionnaires, ascertainment of COVID-related hospitalizations and deaths, and a SARS-CoV-2 serosurvey via dried blood spots. Master protocols leverage existing robust retention rates for telephone and in-person examinations, and high-quality events surveillance. Extensive pre-pandemic data minimize referral, survival, and recall bias. Data are being harmonized with research-quality phenotyping unmatched by clinical and survey-based studies; these will be pooled and shared widely to expedite collaboration and scientific findings. This unique resource will allow evaluation of risk and resilience factors for COVID-19 severity and outcomes, including post-acute sequelae, and assessment of the social and behavioral impact of the pandemic on long-term trajectories of health and aging.

OBJECTIVE/UNASSIGNED:To define, illustrate and to follow-up the diagnosis, pathophysiology and treatment of a subset of the known enhanced myometrial vascularity (EMV): its extreme form, associated with cesarean scar pregnancies (CSP) and with some cases pf placenta accreta spectrum being at increased risk of significant bleeding complications. We also aim to provide guidance to the management of such cases. MATERIAL AND METHODS/UNASSIGNED:This is an IRB-approved retrospective observational study of thirteen patients with an extreme form of EMV complicating CSPs. Patient's age, parity, number of cesarean deliveries, initial and time to negative serum hCG levels, primary and secondary diagnoses, blood flow peak systolic velocities, primary and secondary treatments, uterine artery embolization and outcomes were recorded. RESULTS/UNASSIGNED:Gestational ages ranged 6-11 weeks at initial presentation. Initial serum hCG was 20.0-102.48 mIU/L (mean 44.4 mIU/L). Diameter of EMV reached 20-75 mm (mean 46.8 mm). The mean peak systolic velocity (PSV) was 84.2 cm/s (range 46.7-118.0). Primary treatments were: systemic methotrexate (MTX) alone; D&C alone; MTX and D&C; local and systemic intra-gestational MTX injection; double cervical ripening balloon with systemic MTX; misoprostol and D&C; emergent UAE. UAE and hysterectomy were the two main secondary treatments in 10 women except 1 having a D&C after UAE, and in 1 the lesion regressed without secondary treatment. Mean time to nonpregnant hCG levels was 21-122 days (mean 67.2). Mean follow-up was 110.2 days (range 26-160). Ten women were treated with UAE, 6 had one, 3 had two embolizations. Two women had hysterectomies, one of these for persistent bleeding. Based upon the common denominators of the clinical and the US pictures, our definition of extreme EMV is sustained form of EMV associated with treated or untreated CSP, with peak systolic velocities of blood flow over 50 cm/s, slow return or plateauing serum hCG, with or without clinically significant vaginal bleeding, unresponsive to initial or secondary treatment requiring uterine artery embolization or hysterectomy. CONCLUSION/UNASSIGNED:differs following the normal regression of the physiologically re-modelled, dilated vascular bed from the faulty "disrepair" of the vessel wall in in treated or untreated CSPs. The "threatening" appearance of the above EMVs warranted the term "extreme", creating their separate new sub-category." Extreme forms of CSP-related EMV pose significant diagnostic and management challenges. Prompt recognition and intervention, the proactive use of UAE, can maximize the outcome of women affected by this "extreme" form of EMV enabling to preserve reproductive potential. Obstetricians, gynecologists and interventional radiologists should be aware of this form of severe vascular complication.

Best practice standards for measuring analyte levels in saliva recommend that all biospecimens be tested in replicate with mean concentrations used in statistical analyses. This approach prioritizes minimizing laboratory-based measurement error but, in the process, expends considerable resources. We explore the possibility that, due to advances in salivary assay precision, the contribution of laboratory-based measurement error in salivary analyte data is very small relative to more important and meaningful variability in analyte levels across biological replicates (i.e., between different specimens). To evaluate this possibility, we examine the utility of the repeatability intra-class correlation (rICC) as an additional index of salivary analyte data precision. Using randomly selected subsamples (Ns=200 and 60) of salivary analyte data collected as part of a larger epidemiologic study, we compute the rICCs for seven commonly assayed salivary measures in biobehavioral research - cortisol, alpha-amylase, c-reactive protein, interlekin-6, uric acid, secretory immunoglobulin A, and testosterone. We assess the sensitivity of rICC estimates to assay type and the unique distributions of the underlying analyte data. We also use simulations to examine the bias, precision, and coverage probability of rICC estimates calculated for small to large sample sizes. For each analyte, the rICCs revealed that less than 5% of variation in analyte levels was attributable to laboratory-based measurement error. rICC estimates were similar across all analytes despite differences in analyte levels, average intra-assay coefficients of variation, and in the distributional properties of the data. Guidelines for calculating rICC are provided to enable investigators and laboratory staff to apply this metric and more accurately quantify, and communicate, the magnitude of laboratory-based measurement error in their data. By helping investigators scale measurement error relative to more scientifically meaningful variability between biological replicates, the application of the rICC has the potential to influence research strategies and tactics such that resources (e.g., finances, effort, number/volume of biospecimens) are allocated more efficiently and effectively.

Low levels of engagement in implementation science (IS) among health researchers is a multifaceted issue. With the aim of guiding efforts to increase engagement in IS research, we sought to identify barriers to engagement in IS within the health research community. We performed an online survey of health researchers in the United States in 2018. Basic science researchers were excluded from the sample. IS engagement was measured by self-reported conduct of or collaboration on an IS study in the past 5 years. Potential barriers tested were (a) knowledge and awareness of IS, (b) attitudes about IS research, (c) career benefits of IS, (d) research community support, and (e) research leadership support. We performed simple logistic regressions and tested multivariable logistic regression models of researcher characteristics and potential barriers as predictors of IS engagement. Of the 1,767 health researchers, 49.7% indicated they engaged in an implementation study. Being able to define IS (aOR 3.42, 95%CI 2.68-4.36, p < .001) and having attended IS training (aOR 3.77, 95%CI 2.96-4.81, p < .001) were associated with engaging in IS research. Among other potential barriers tested, perceptions that engaging in IS would not be good for their career (aOR 0.29, 95%CI 0.2-0.41, p < .001) was strongly associated with decreased engagement in IS research. Efforts to increase researcher familiarity with IS methods and foster support for IS within research communities, along with decreasing barriers to funding and publishing, are likely to be most effective for increasing engagement in IS research.

Background/UNASSIGNED:The viral entry of SARS-CoV-2 requires host-expressed TMPRSS2 to facilitate the viral spike (S) protein priming. Objectives/UNASSIGNED:. Methods/UNASSIGNED:This study is nested within the Personalized Prevention of Colorectal Cancer Trial (PPCCT), a double-blind 2×2 factorial randomized controlled trial, which enrolled 250 participants from Vanderbilt University Medical Center. Target doses for both Mg and placebo arms were personalized. Results/UNASSIGNED:value=0.088). Conclusion/UNASSIGNED:genotype.

Neighborhood deprivation plays an important role in childhood health and development, but defining the appropriate neighborhood definition presents theoretical as well as practical challenges. Few studies have compared neighborhood definitions outside of highly urbanized settings. The purpose of the current study was to evaluate how various administrative and ego-centric neighborhood definitions may impact measured exposure to deprivation across the urban-rural continuum. We do so using the Family Life Project, a prospective longitudinal population-based sample of families living in North Carolina and Pennsylvania (USA), which also sets the stage for future investigations of neighborhood impacts on childhood health and development. To measure neighborhood deprivation, a standardized index of socioeconomic deprivation was calculated using data from the 2007-2011 American Community Survey. Families' residential addresses when children were 2 months of age (n=1036) were geocoded and overlaid onto a deprivation index layer created at the census block group level to construct multiple administrative and ego-centric neighborhood definitions. Friedman tests were used to compare distributions of neighborhood deprivation across these neighborhood definitions within urbanized areas, urban clusters, and rural areas. Results indicated differences in urbanized areas (Chisquare= 897.75, P<0.001) and urban clusters (Chi-square=687.83, P<0.001), but not in rural areas (Chi-square=13.52, P=0.332). Findings imply that in urban areas, choice of neighborhood definition impacts measured exposure to neighborhood deprivation. Although exposure to neighborhood deprivation appears to be less sensitive to neighborhood definition in rural areas, researchers should apply theoretical reasoning to choose appropriate definitions of children's neighborhood.