A comparison of deprivation indices and application to transplant populations.

The choice of deprivation index can influence conclusions drawn regarding the extent of deprivation within a community and the identification of the most deprived communities in the United States. This study aimed to determine the degree of correlation among deprivation indices commonly used to characterize transplant populations. We used a retrospective cohort consisting of adults listed for liver or kidney transplants between 2008 and 2018 to compare 4 deprivation indices: neighborhood deprivation index, social deprivation index (SDI), area deprivation index, and social vulnerability index. Pairwise correlation between deprivation indices by transplant referral regions was measured using Spearman correlations of population-weighted medians and upper quartiles. In total, 52 individual variables were used among the 4 deprivation indices with 25% overlap. For both organs, the correlation between the population-weighted 75th percentile of the deprivation indices by transplant referral region was highest between SDI and social vulnerability index (liver and kidney, 0.93) and lowest between area deprivation index and SDI (liver, 0.19 and kidney, 0.15). The choice of deprivation index affects the applicability of research findings across studies examining the relationship between social risk and clinical outcomes. Appropriate application of these measures to transplant populations requires careful index selection based on the intended use and included variable relevance.

Health care resource utilization and clinical outcomes for adult heart transplant recipients with primary graft dysfunction.

INTRODUCTION: The advent of new technologies to reduce primary graft dysfunction (PGD) and improve outcomes after heart transplantation are costly. Adoption of these technologies requires a better understanding of health care utilization, specifically the costs related to PGD. METHODS: Records were examined from all adult patients who underwent orthotopic heart transplantation (OHT) between July 1, 2013 and July 30, 2019 at a single institution. Total costs were categorized into variable, fixed, direct, and indirect costs. Patient costs from time of transplantation to hospital discharge were transformed with the z-score transformation and modeled in a linear regression model, adjusted for potential confounders and in-hospital mortality. The quintile of patient costs was modeled using a proportional odds model, adjusted for confounders and in-hospital mortality. RESULTS: 359 patients were analyzed, including 142 with PGD and 217 without PGD. PGD was associated with a .42 increase in z-score of total patient costs (95% CI: .22-.62; p < .0001). Additionally, any grade of PGD was associated with a 2.95 increase in odds for a higher cost of transplant (95% CI: 1.94-4.46, p < .0001). These differences were substantially greater when PGD was categorized as severe. Similar results were obtained for fixed, variable, direct, and indirect costs. CONCLUSIONS: PGD after OHT impacts morbidity, mortality, and health care utilization. We found that PGD after OHT results in a significant increase in total patient costs. This increase was substantially higher if the PGD was severe. SUMMARY: Primary graft dysfunction after heart transplantation impacts morbidity, mortality, and health care utilization. PGD after OHT is costly and investments should be made to reduce the burden of PGD after OHT to improve patient outcomes.

Association between Gentrification and Health and Healthcare Utilization.

There is tremendous interest in understanding how neighborhoods impact health by linking extant social and environmental drivers of health (SDOH) data with electronic health record (EHR) data. Studies quantifying such associations often use static neighborhood measures. Little research examines the impact of gentrification-a measure of neighborhood change-on the health of long-term neighborhood residents using EHR data, which may have a more generalizable population than traditional approaches. We quantified associations between gentrification and health and healthcare utilization by linking longitudinal socioeconomic data from the American Community Survey with EHR data across two health systems accessed by long-term residents of Durham County, NC, from 2007 to 2017. Census block group-level neighborhoods were eligible to be gentrified if they had low socioeconomic status relative to the county average. Gentrification was defined using socioeconomic data from 2006 to 2010 and 2011-2015, with the Steinmetz-Wood definition. Multivariable logistic and Poisson regression models estimated associations between gentrification and development of health indicators (cardiovascular disease, hypertension, diabetes, obesity, asthma, depression) or healthcare encounters (emergency department [ED], inpatient, or outpatient). Sensitivity analyses examined two alternative gentrification measures. Of the 99 block groups within the city of Durham, 28 were eligible (N = 10,807; median age = 42; 83% Black; 55% female) and 5 gentrified. Individuals in gentrifying neighborhoods had lower odds of obesity (odds ratio [OR] = 0.89; 95% confidence interval [CI]: 0.81-0.99), higher odds of an ED encounter (OR = 1.10; 95% CI: 1.01-1.20), and lower risk for outpatient encounters (incidence rate ratio = 0.93; 95% CI: 0.87-1.00) compared with non-gentrifying neighborhoods. The association between gentrification and health and healthcare utilization was sensitive to gentrification definition.

The Association Between Hearing Loss and Surgical Complications in Older Adults.

OBJECTIVES: In this study, we sought to evaluate whether older patients with hearing loss who underwent surgery were at greater risk of postsurgical complications, increased inpatient length-of-stay (LOS), and hospital readmission. DESIGN: This was a retrospective cohort study of patients receiving surgery at a tertiary medical center. Utilizing electronic health record data from two merged datasets, we identified patients 65 years and older, undergoing major surgery between January 1, 2014 and January 31, 2017, and who had audiometric evaluation before surgery. Patients were classified as having either normal hearing or hearing loss based on pure-tone average in the better ear. A Generalized Estimating Equations approach was used to fit multivariable regression models for outcome variables of interest. RESULTS: Of patients ≥65 years undergoing major surgery in our time frame, a total of 742 surgical procedures were performed on 621 patients with available audiometric data. After adjusting for age, sex, race, and comorbidities, hearing loss was associated with an increase in the odds of developing postoperative complications. Every 10 dB increase in hearing loss was associated with a 14% increase in the odds of developing a postoperative complication (odds ratio = 1.14, 95% confidence interval = 1.01-1.29, p = 0.031). Hearing loss was not significantly associated with increased hospital LOS, 30-day readmission, or 90-day readmission. CONCLUSIONS: Hearing loss was significantly associated with developing postoperative complications in older adults undergoing major surgery. Screening for hearing impairment may be a useful addition to the preoperative assessment and perioperative management of older patients undergoing surgery.

Impact of Hearing Aid Use on Falls and Falls-Related Injury: Results From the Health and Retirement Study.

OBJECTIVES: Falls are considered a significant public health issue and falls risk increases with age. There are many age-related physiologic changes that occur that increase postural instability and the risk for falls (i.e., age-related sensory declines in vision, vestibular, somatosensation, age-related orthopedic changes, and polypharmacy). Hearing loss has been shown to be an independent risk factor for falls. The primary objective of this study was to determine if hearing aid use modified (reduced) the association between self-reported hearing status and falls or falls-related injury. We hypothesized that hearing aid use would reduce the impact of hearing loss on the odds of falling and falls-related injury. If hearing aid users have reduced odds of falling compared with nonhearing aid users, then that would have an important implications for falls prevention healthcare. DESIGN: Data were drawn from the 2004-2016 surveys of the Health and Retirement Study (HRS). A generalized estimating equation approach was used to fit logistic regression models to determine whether or not hearing aid use modifies the odds of falling and falls injury associated with self-reported hearing status. RESULTS: A total of 17,923 individuals were grouped based on a self-reported history of falls. Self-reported hearing status was significantly associated with odds of falling and with falls-related injury when controlling for demographic factors and important health characteristics. Hearing aid use was included as an interaction in the fully-adjusted models and the results showed that there was no difference in the association between hearing aid users and nonusers for either falls or falls-related injury. CONCLUSIONS: The results of the present study show that when examining self-reported hearing status in a longitudinal sample, hearing aid use does not impact the association between self-reported hearing status and the odds of falls or falls-related injury.

A three-tier system for evaluation of organ procurement organizations' willingness to pursue and utilize nonideal donor lungs.

Lungs from "nonideal," but acceptable donors are underutilized; however, organ procurement organization (OPO) metrics do not reflect the extent to which OPO-specific practices contribute to these trends. We developed a comprehensive system to evaluate nonideal lung donor avoidance, or risk aversion among OPOs. Adult donors in the UNOS registry who donated ≥1 organ for transplantation between 2007 and 2018 were included. Nonideal donors had any of age>50, smoking history ≥20 pack-years, PaO2 /FiO2 ratio ≤350, donation after circulatory death, or increased risk status. OPO-level risk aversion in donor pursuit, consent attainment, lung recovery, and transplantation was assessed. Among 83916 donors, 70372 (83.9%) were nonideal. Unadjusted OPO-level rates of nonideal donor pursuit ranged from 81 to 100%. In a three-tier system of overall risk aversion, tier 3 OPOs (least risk-averse) had the highest rates of nonideal donor pursuit, consent attainment, lung recovery, and transplantation. Tier 1 OPOs (most risk-averse) had the lowest rates of donor pursuit, consent attainment, and lung recovery, but higher rates of transplantation compared to tier 2 OPOs (moderately risk-averse). Risk aversion varies among OPOs and across the donation process. OPO evaluations should reflect early donation process stages to best differentiate over- and underperforming OPOs and encourage optimal OPO-specific performance.

Developing and evaluating risk prediction models with panel current status data.

Panel current status data arise frequently in biomedical studies when the occurrence of a particular clinical condition is only examined at several prescheduled visit times. Existing methods for analyzing current status data have largely focused on regression modeling based on commonly used survival models such as the proportional hazards model and the accelerated failure time model. However, these procedures have the limitations of being difficult to implement and performing sub-optimally in relatively small sample sizes. The performance of these procedures is also unclear under model misspecification. In addition, no methods currently exist to evaluate the prediction performance of estimated risk models with panel current status data. In this paper, we propose a simple estimator under a general class of nonparametric transformation (NPT) models by fitting a logistic regression working model and demonstrate that our proposed estimator is consistent for the NPT model parameter up to a scale multiplier. Furthermore, we propose nonparametric estimators for evaluating the prediction performance of the risk score derived from model fitting, which is valid regardless of the adequacy of the fitted model. Extensive simulation results suggest that our proposed estimators perform well in finite samples and the regression parameter estimators outperform existing estimators under various scenarios. We illustrate the proposed procedures using data from the Framingham Offspring Study.

African Americans' discussions about living-donor kidney transplants with family or friends: Who, what, and why not?

BACKGROUND: Although discussions with family or friends can improve access to living-donor kidney transplantation (LDKT), they remain an understudied step in the LDKT process. METHODS: Among 300 African American transplant candidates, we examined how sociodemographic, clinical, LDKT-related, and psychosocial characteristics related to the occurrence of LDKT discussions with family or friends. We also analyzed the relation between discussion occurrence and donor activation on transplant candidates' behalves (at least one donor inquiry or completed donor evaluation in the medical record). We assessed associations of discussion characteristics (context, content, and perceptions) with donor activation among discussants, and we identified discussion barriers among non-discussants. RESULTS: Most candidates (90%) had discussed LDKT. Only family functioning was statistically significantly associated with discussion occurrence. Specifically, family dysfunction was associated with 62% lower odds of discussion than family function. Family functioning, discussion occurrence, and different discussion characteristics were statistically significantly related to donor activation. The most prevalent discussion barrier was never having thought about discussing LDKT. CONCLUSIONS: Family functioning affected the likelihood of discussing LDKT, and family functioning, discussion occurrence, and discussion characteristics were associated with donor activation. Advancing understanding of how family functioning and LDKT discussions affect progression to LDKT may benefit interventions to increase LDKT.

Exploring Factors Associated With Morbidity and Mortality in Patients With Do-Not-Resuscitate Orders: A National Surgical Quality Improvement Program Database Analysis Within Surgical Groups.

BACKGROUND: Anesthesiologists caring for patients with do-not-resuscitate (DNR) orders may have ethical concerns because of their resuscitative wishes and may have clinical concerns because of their known increased risk of morbidity/mortality. Patient heterogeneity and/or emphasis on mortality outcomes make previous studies among patients with DNR orders difficult to interpret. We sought to explore factors associated with morbidity and mortality among patients with DNR orders, which were stratified by surgical subgroups. METHODS: Exploratory retrospective cohort study in adult patients undergoing prespecified colorectal, vascular, and orthopedic surgeries was performed using the American College of Surgeons National Surgical Quality Improvement Program Participant Use File data from 2010 to 2013. Among patients with preoperative DNR orders (ie, active DNR order written in the patient's chart before surgery), factors associated with 30-day mortality, increased length of stay, and inpatient death were determined via penalized regression. Unadjusted and adjusted estimates for selected variables are presented. RESULTS: After selection as above, 211,420 patients underwent prespecified procedures, and of those, 2755 (1.3%) had pre-existing DNR orders and met above selection to address morbidity/mortality aims. By specialty, of these patients with a preoperative DNR, 1149 underwent colorectal, 870 vascular, and 736 orthopedic surgery. Across groups, 36.2% were male and had a mean age 79.9 years (range 21-90). The 30-day mortality was 15.4%-27.2% and median length of stay was 6-12 days. Death at discharge was 7.0%, 13.1%, and 23.0% in orthopedics, vascular, and colorectal patients with a DNR, respectively. The strongest factors associated with increased odds of 30-day mortality were preoperative septic shock in colorectal patients, preoperative ascites in vascular patients, and any requirement of mechanical ventilation at admission in orthopedic patients. CONCLUSIONS: In patients with DNR orders undergoing common surgical procedures, the association of characteristics with morbidity and mortality varies in both direction and magnitude. The DNR order itself should not be the defining measure of risk.

Psychosocial determinants of cardiovascular events among black Americans with chronic kidney disease or associated risk factors in the Jackson heart study.

BACKGROUND: Individuals with chronic kidney disease (CKD), hypertension (HTN), or diabetes mellitus (DM) are at increased risk for cardiovascular disease (CVD). The extent to which psychosocial factors are associated with increased CVD risk within these individuals is unclear. Black individuals experience a high degree of psychosocial stressors due to socioeconomic factors, environment, racism, and discrimination. We examined the association between psychosocial factors and risk of CVD events among Black men and women with CKD and CKD risk factors in the Jackson Heart Study. METHODS AND RESULTS: We identified 1919 participants with prevalent CKD or CKD risk factors at baseline. We used rotated principal component analysis - a form of unsupervised machine learning that may identify constructs not intuitively identified by a person - to describe five groups of psychosocial components (including negative moods, religiosity, discrimination, negative outlooks, and negative coping resources) based on a battery of questionnaires. Multiple imputation by chained equation (MICE) was used to impute missing covariate data. Cox models were used to quantify the association between psychosocial components and incident CVD, defined as a fatal coronary heart disease event, myocardial infarction, cardiac procedure (angiography or revascularization procedure), or stroke. Of the 929 participants in the analysis, 67% were female, 28% were current/former smokers with mean age of 56 years and mean BMI of 33 kg/m2. Over a median follow-up of 8 years, 6% had an incident CVD event. In multivariable models, each standard deviation (SD) increase in the religiosity component was associated with an increased hazard for CVD event (hazard ratio [HR] = 1.52, 95% CI: 1.09-2.13). CONCLUSIONS: Religiosity was associated with CVD among participants with prevalent CKD or CKD risk factors. Studies to better understand the mechanisms of this relationship are needed.

Associations of perceived information adequacy and knowledge with pursuit of live donor kidney transplants and living donor inquiries among African American transplant candidates.

We studied associations between perceived adequacy of live donor kidney transplant (LDKT) information or knowledge with pursuit of LDKT or receipt of live donor inquiries among 300 African American kidney transplant candidates. Participants reported via questionnaire how informed or knowledgeable they felt regarding LDKT. Participants also reported their pursuit of LDKT, categorized as "low" (no discussion with family or friends about LDKT and no identified donor), "intermediate" (discussed LDKT with family but no identified donor) or "high" (discussed LDKT with family and identified a potential donor). We reviewed participants' electronic health records to identify potential donors' transplant center inquiries on participants' behalves. A minority of participants reported they felt "very" or "extremely" well informed about LDKT (39%) or had "a great deal" of LDKT knowledge (38%). Participants perceiving themselves as "very" or "extremely" (vs "not" or "slightly") well informed about LDKT had statistically significantly greater odds of intermediate or high (vs low) pursuit of LDKT (odds ratio [95% confidence interval] 2.71 [1.02-7.17]). Perceived LDKT knowledge was not associated with pursuit of LDKT. Neither perceived information adequacy nor knowledge was associated with living donor inquiries. Efforts to better understand the role of education in the pursuit of LDKT among African American transplant candidates are needed.

Adding the Team into T1 Translational Research: A Case Study of Multidisciplinary Team Science in the Evaluation of Biomarkers of Prostate Cancer Risk and Prognosis.

BACKGROUND: Given translational research challenges, multidisciplinary team science is promoted to increase the likelihood of moving from discovery to health effect. We present a case study documenting the utility of multidisciplinary team science in prostate cancer tissue biomarker validation. METHODS: We used primary data generated by a team consisting of a pathologist, cancer biologists, a biostatistician, and epidemiologists. We examined their contributions by phase of biomarker evaluation to identify when, through the practice of team science, threats to internal validity were recognized and solved. Next, we quantified the extent of bias avoided in evaluating the association of Ki67 (immunohistochemistry), stromal cell telomere length (fluorescence in situ hybridization), and microRNA (miRNA) (miR-21, miR-141, miR-221; quantitative RT-PCR) with prostate cancer risk or recurrence in nested case-control studies. RESULTS: Threats to validity were tissue storage time (Ki67, miRNA) and laboratory equipment maintenance (telomeres). Solutions were all in the data analysis phase and involved using tissue storage-time specific cutpoints and/or batch-specific cutpoints. Bias in the regression coefficient for quantiles of each biomarker ranged from 24% to 423%, and the coefficient for the test for trend ranged from 15% to 910%. The interpretation of the associations changed as follows: Ki67, null to positive; stromal cell telomere length, null to positive; miR-21 and miR-141 remained null; miR-221, weak to moderate inverse. CONCLUSIONS: In this case study, we documented the inferential benefits of multidisciplinary team science when the team's collaboration and coordination led to the identification of threats to validity and the implementation of appropriate solutions.

The Impact of Ergonomics on Recruitment to Surgical Fields: A Multi-Institutional Survey Study.

BACKGROUND: Awareness of ergonomics in surgery is growing, but whether musculoskeletal (MSK) injuries in surgery influence trainee career choices remains unknown. This study aimed to characterize medical students' MSK pain during surgical rotations and determine whether ergonomics influence student interest in surgical fields. METHODS: An online survey was administered to medical students in North Carolina. Students were asked about specialty interest, MSK pain on surgical rotations, and deterrents from surgical fields. Students were exposed to literature about ergonomics in surgery then queried again about relative specialty interest (medical versus surgical). Differences in specialty interest before and after the exposure were compared using a Wilcoxon signed-rank test. RESULTS: Of 243 participants, 44.0% were interested in pursuing a surgical specialty. Overall, 75.3% reported MSK pain during their surgical rotation, with the average daily pain score highest during surgery rotations compared to all other clinical rotations. The worst pain was reported in the feet and low back while "standing in the operating room" (81.2%) or "retracting" (59.4%). Among students initially interested in surgery but whose interest changed to a medical specialty during medical school, "physical demands of the field" was a common deterrent (36.4%). After exposure to literature regarding the incidence of MSK injuries in surgery, student interest in surgical fields on a 10-point scale significantly decreased (average -0.5 points; P < 0.01). CONCLUSIONS: High incidence of MSK injury among surgeons may be one factor deterring medical students from surgical careers. Ergonomic interventions may be important both to improve surgeon longevity and maintain the surgical workforce.

Validation of the American College of Surgeons National Surgical Quality Improvement Program Risk Model for Patients Undergoing Panniculectomy.

Panniculectomy procedures have been reported to significantly improve quality of life, increase mobility, and improve hygiene in patients with a significant pannus formation. The primary aims of this study were to determine which preoperative risk factors may be used to differentiate postoperative complication rate among patient cohorts and to validate utilization of the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) risk calculator in patients undergoing panniculectomies. METHODS: This retrospective study included all patients who underwent a panniculectomy procedure at our institution from 2005 to 2016. Baseline characteristics, preoperative risk factors, medical comorbidities, and postoperative complications were collected via retrospective chart review. RESULTS: Two hundred sixty-four patients who underwent a panniculectomy were identified. The odds ratios of any postoperative complication were 8.26, 7.76, and 16.6 for patients with classes 1, 2, and 3 obesity, respectively (P < 0.05). Statistical modeling was utilized to evaluate the predictive performance of the ACS-NSQIP Surgical Risk Calculator. We calculated the C-statistic for the ACS-NSQIP model to be only 0.61, indicating that although the model is associated with the risk of complication, it does not have a strong predictive value for this particular procedure. DISCUSSION: This study is one of the first to characterize postoperative complication rate based on extremum of body mass index for panniculectomy patients. Our results show that the utilization of the ACS-NSQIP Risk Calculator in this particular patient population underestimates the complication risk as a whole, which may necessitate the future development of a separate risk assessment model for this procedure.

Current or recent smoking is associated with more variable telomere length in prostate stromal cells and prostate cancer cells.

BACKGROUND: Current and recent smoking have been associated with a greater risk of prostate cancer recurrence and mortality, though the underlying mechanism is unknown. METHODS: To determine if telomere shortening, which has been associated with poor outcomes, may be a potential underlying mechanism, we prospectively evaluated the association between smoking status and telomere length in 567 participants in the Health Professionals Follow-up Study, who were surgically treated for prostate cancer. Using tissue microarrays (TMA), we measured telomere length in cancer and benign tissue, specifically stromal cells in the same TMA spot using a telomere-specific fluorescence in situ hybridization assay. Smoking status was collected via questionnaire 2-years before diagnosis. Adjusting for age, pathologic stage and grade, the median and standard deviation of the per-cell telomere signals were determined for each man for stromal cells and cancer cells by smoking categories. In sub-analyses, we restricted to men without major co-morbidities diagnosed before prostate cancer. RESULTS: Overall, there were no associations between smoking status and telomere length or variability in stromal cells or cancer cells. However, among men without comorbidities, current smokers and former smokers who quit <10 years ago had the most variable telomere length in stromal cells (29.3% more variable than never smokers; P-trend = 0.0005) and in cancer cells (27.7% more variable than never smokers; P-trend = 0.05). Among men without comorbidities, mean telomere length did not differ by smoking status in stromal cells or cancer cells. CONCLUSION: Telomere variability in prostate cells may be one mechanism through which smoking influences poor prostate cancer outcomes.

Prevalence estimation when disease status is verified only among test positives: Applications in HIV screening programs.

The first goal of the United Nations' 90-90-90 HIV/AIDS elimination strategy is to ensure that, by 2020, 90% of HIV-positive people know their HIV status. Estimating the prevalence of HIV among people eligible for screening allows assessment of the number of additional cases that might be diagnosed through continued screening efforts in this group. Here, we present methods for estimating prevalence when HIV status is verified by a gold standard only among those who test positive on an initial, imperfect screening test with known sensitivity and specificity. We develop maximum likelihood estimators and asymptotic confidence intervals for use in 2 scenarios: when the total number of test negatives is known (Scenario 1) and unknown (Scenario 2). We derive Bayesian prevalence estimators to account for non-negligible uncertainty in previous estimates of the sensitivity and specificity. The Scenario 1 estimator consistently outperformed the Scenario 2 estimator in simulations, demonstrating the use of recording the number of test negatives in public health screening programs. For less accurate tests (sensitivity and specificity < 90%), the performance of the 2 estimators was comparable, suggesting that, under these circumstances, prevalence can still be estimated with adequate precision when the number of test negatives is unknown. However, use of the Bayesian approach to account for uncertainty in the sensitivity and specificity is especially recommended for the Scenario 2 estimator, which was particularly sensitive to misspecification of these values. R code for implementing these methods is available at hsph.harvard.edu/donna-spiegelman/software.

The effect of risk factor misclassification on the partial population attributable risk.

The partial population attributable risk (pPAR) is used to quantify the population-level impact of preventive interventions in a multifactorial disease setting. In this paper, we consider the effect of nondifferential risk factor misclassification on the direction and magnitude of bias of pPAR estimands and related quantities. We found that the bias in the uncorrected pPAR depends nonlinearly and nonmonotonically on the sensitivities, specificities, relative risks, and joint prevalence of the exposure of interest and background risk factors, as well as the associations between these factors. The bias in the uncorrected pPAR is most dependent on the sensitivity of the exposure. The magnitude of bias varies over a large range, and in a small region of the parameter space determining the pPAR, the direction of bias is away from the null. In contrast, the crude PAR can only be unbiased or biased towards the null by risk factor misclassification. The semiadjusted PAR is calculated using the formula for the crude PAR but plugs in the multivariate-adjusted relative risk. Because the crude and semiadjusted PARs continue to be used in public health research, we also investigated the magnitude and direction of the bias that may arise when using these formulae instead of the pPAR. These PAR estimators and their uncorrected counterparts were calculated in a study of risk factors for colorectal cancer in the Health Professionals Follow-up Study, where it was found that because of misclassification, the pPAR for low folate intake was overestimated with a relative bias of 48%, when red meat and alcohol intake were treated as misclassified risk factors that are not modified, and when red meat was treated as the modifiable risk factor, the estimated value of the pPAR went from 14% to 60%, further illustrating the extent to which misclassification can bias estimates of the pPAR.

Children with appendicitis on the US-Mexico border have socioeconomic challenges and are best served by a freestanding children's hospital.

INTRODUCTION: The US-Mexico border is medically underserved. Recent political changes may render this population even more vulnerable. We hypothesized that children on the border present with high rates of perforated appendicitis due to socioeconomic barriers. METHODS: A prospective survey was administered to children presenting with appendicitis in El Paso, Texas. Primary outcomes were rate of perforation and reason for diagnostic delay. We evaluated the association between demographics, potential barriers to care, risk of perforation and risk of misdiagnosis using logistic regression. p < 0.05 was considered significant. RESULTS: 98 patients participated from October 2016 to February 2017. 96 patients (98%) were Hispanic and 81 (82%) had Medicaid or were uninsured. 11 patients (11%) resided in Mexico or Guatemala. Patients were less likely to receive a CT and more likely to receive an ultrasound if they presented to a freestanding children's hospital (p = 0.01). 37 patients (38%) presented with perforation, of which 19 (52%) were the result of practitioner misdiagnosis. Patients who presented to a freestanding children's hospital were less likely to be misdiagnosed than patients presenting to other facilities (p = 0.05). Children who underwent surgery in a freestanding children's hospital had the shortest length of stay after adjusting for perforation status and potential confounders (p < 0.01). CONCLUSION: Children with low socioeconomic status did not have difficulty accessing care on the USA-Mexico border, but they were commonly misdiagnosed. Children were less likely to receive a CT, more likely to be correctly diagnosed and length of stay was shorter when patients presented to a freestanding children's hospital.

Differential long-term stability of microRNAs and RNU6B snRNA in 12-20 year old archived formalin-fixed paraffin-embedded specimens.

BACKGROUND: The quantitative analysis of microRNA (miRNA) gene expression in archived formalin-fixed, paraffin embedded (FFPE) tissues has been instrumental to identifying their potential roles in cancer biology, diagnosis, and prognosis. However, it remains unclear whether miRNAs remain stable in FFPE tissues stored for long periods of time. METHODS: Here we report Taqman real-time RT-PCR quantification of miR-21, miR-141, miR-221, and RNU6B small nuclear RNA (snRNA) levels from 92 radical prostatectomy specimens stored for 12-20 years in FFPE blocks. The relative stability of each transcript over time was assessed using general linear models. The correlation between transcript quantities, sample age, and RNA integrity number (RIN) were determined utilizing Spearman rank correlation. RESULTS: All transcript levels linearly decreased with sample age, demonstrating a clear loss of miRNA stability and RNU6B snRNA stability over time. The most rapid rates of degradation were observed for RNU6B and miR-21, while miR-141 and miR-221 were more stable. RNA quality was not correlated with sample age or with miR-21, miR-221, or RNU6B snRNA levels. Conversely, miR-141 levels increased with RNA quality. CONCLUSIONS: MiRNA and snRNA levels gradually decreased over an eight year period in FFPE tissue blocks. Sample age was the most consistent feature associated with miRNA stability. The reference snRNA, RUN6B, was more rapidly degraded when compared to miR-141 and miR-221 miRNAs. Various miRNAs demonstrated differential rates of degradation. Quantitative miRNA studies from long-term archived FFPE tissues may therefore benefit from epidemiologic study design or statistical analysis methods that take into account differential storage-dependent transcript degradation.

Prostate stromal cell telomere shortening is associated with risk of prostate cancer in the placebo arm of the Prostate Cancer Prevention Trial.

BACKGROUND: Telomeres are repetitive nucleoproteins that help maintain chromosomal stability by inhibiting exonucleolytic degradation, prohibiting inappropriate homologous recombination, and preventing chromosomal fusions by suppressing double-strand break signals. We recently observed that men treated for clinically localized prostate cancer with shorter telomeres in their cancer-associated stromal cells, in combination with greater variation in cancer cell telomere lengths, were significantly more likely to progress to distant metastases, and die from their disease. Here, we hypothesized that shorter stromal cell telomere length would be associated with prostate cancer risk at time of biopsy. METHODS: Telomere-specific fluorescence in situ hybridization (FISH) analysis was performed in normal-appearing stromal, basal epithelial, and luminal epithelial cells in biopsies from men randomized to the placebo arm of the Prostate Cancer Prevention Trial. Prostate cancer cases (N = 32) were either detected on a biopsy performed for cause or at the end of the study per trial protocol, and controls (N = 50), defined as negative for cancer on an end-of-study biopsy performed per trial protocol (e.g., irrespective of indication), were sampled. Logistic regression was used to estimate the association between mean telomere length of the particular cell populations, cell-to-cell telomere length variability, and risk of prostate cancer. RESULTS: Men with short stromal cell telomere lengths (below median) had 2.66 (95% CI 1.04-3.06; P = 0.04) times the odds of prostate cancer compared with men who had longer lengths (at or above median). Conversely, we did not observe statistically significant associations for short telomere lengths in normal-appearing basal (OR = 2.15, 95% CI 0.86-5.39; P= 0 .10) or luminal (OR = 1.15, 95% CI 0.47-2.80; P = 0.77) cells. CONCLUSIONS: These findings suggest that telomere shortening in normal stromal cells is associated with prostate cancer risk. It is essential to extend and validate these findings, while also identifying the cellular milieu that comprises the subset of cells with short telomeres within the prostate tumor microenvironment.