Association of processed red meat and prostate cancer stage in Mexican-Americans: A population based case-control study

Objective: The objective of this study is to investigate the association between processed and unprocessed red meat consumption and prostate cancer (PCa) stage in a homogenous Mexican-American population. Methods: This population-based case-control study had a total of 582 participants (287 cases with histologically confirmed adenocarcinoma of the prostate gland and 295 age and ethnicity-matched controls) that were all residing in the Southeast region of Texas from 1998 to 2006. All questionnaire information was collected using a validated data collection instrument. Statistical Analysis: Descriptive analyses included Student's t-test and Pearson's Chi-square tests. Odds ratios and 95% confidence intervals were calculated to quantify the association between nutritional factors and PCa stage. A multivariable model was used for unconditional logistic regression. Results: After adjusting for relevant covariates, those who consume high amounts of processed red meat have a non-significant increased odds of being diagnosed with localized PCa (OR = 1.60 95% CI: 0.85 - 3.03) and total PCa (OR = 1.43 95% CI: 0.81 - 2.52) but not for advanced PCa (OR = 0.91 95% CI: 1.37 - 2.23). Interestingly, high consumption of carbohydrates shows a significant reduction in the odds of being diagnosed with total PCa and advanced PCa (OR = 0.43 95% CI: 0.24 - 0.77; OR = 0.27 95% CI: 0.10 - 0.71, respectively). However, consuming high amounts of energy from protein and fat was shown to increase the odds of being diagnosed with advanced PCa (OR = 4.62 95% CI: 1.69 - 12.59; OR = 2.61 95% CI: 1.04 - 6.58, respectively). Conclusion: Mexican-Americans who consume high amounts of energy from protein and fat had increased odds of being diagnosed with advanced PCa, while high amounts of carbohydrates reduced the odds of being diagnosed with total and advanced PCa.^

Impact of donor-recipient gender and race mismatching on patient survival in patients with end-stage liver diseases undergoing liver transplantation

Background. End-stage liver disease (ESLD) is an irreversible condition that leads to the imminent complete failure of the liver. Orthotopic liver transplantation (OLT) has been well accepted as the best curative option for patients with ESLD. Despite the progress in liver transplantation, the major limitation nowadays is the discrepancy between donor supply and organ demand. In an effort to alleviate this situation, mismatched donor and recipient gender or race livers are being used. However, the simultaneous impact of donor and recipient gender and race mismatching on patient survival after OLT remains unclear and relatively challenging to surgeons. ^ Objective. To examine the impact of donor and recipient gender and race mismatching on patient survival after OLT using the United Network for Organ Sharing (UNOS) database. ^ Methods. A total of 40,644 recipients who underwent OLT between 2002 and 2011 were included. Kaplan-Meier survival curves and the log-rank tests were used to compare the survival rates among different donor-recipient gender and race combinations. Univariate Cox regression analysis was used to assess the association of donor-recipient gender and race mismatching with patient survival after OLT. Multivariable Cox regression analysis was used to model the simultaneous impact of donor-recipient gender and race mismatching on patient survival after OLT adjusting for a list of other risk factors. Multivariable Cox regression analysis stratifying on recipient hepatitis C virus (HCV) status was also conducted to identify the variables that were differentially associated with patient survival in HCV + and HCV − recipients. ^ Results. In the univariate analysis, compared to male donors to male recipients, female donors to male recipients had a higher risk of patient mortality (HR, 1.122; 95% CI, 1.065–1.183), while in the multivariable analysis, male donors to female recipients experienced an increased mortality rates (adjusted HR, 1.114; 95% CI, 1.048–1.184). Compared to white donors to white recipients, Hispanic donors to black recipients had a higher risk of patient mortality (HR, 1.527; 95% CI, 1.293–1.804) in the univariate analysis, and similar result (adjusted HR, 1.553; 95% CI, 1.314–1.836) was noted in multivariable analysis. After the stratification on recipient HCV status in the multivariable analysis, HCV + mismatched recipients appeared to be at greater risk of mortality than HCV − mismatched recipients. Female donors to female HCV − recipients (adjusted HR, 0.843; 95% CI, 0.769–0.923), and Hispanic HCV + recipients receiving livers from black donors (adjusted HR, 0.758; 95% CI, 0.598–0.960) had a protective effect on patient survival after OLT. ^ Conclusion. Donor-recipient gender and race mismatching adversely affect patient survival after OLT, both independently and after the adjustment for other risk factors. Female recipient HCV status is an important effect modifier in the association between donor-recipient gender combination and patient survival.^

Optimal, minimax, and Bayesian two-stage designs in two-dose phase II clinical trials

Background: For most cytotoxic and biologic anti-cancer agents, the response rate of the drug is commonly assumed to be non-decreasing with an increasing dose. However, an increasing dose does not always result in an appreciable increase in the response rate. This may especially be true at high doses for a biologic agent. Therefore, in a phase II trial the investigators may be interested in testing the anti-tumor activity of a drug at more than one (often two) doses, instead of only at the maximum tolerated dose (MTD). This way, when the lower dose appears equally effective, this dose can be recommended for further confirmatory testing in a phase III trial under potential long-term toxicity and cost considerations. A common approach to designing such a phase II trial has been to use an independent (e.g., Simon's two-stage) design at each dose ignoring the prior knowledge about the ordering of the response probabilities at the different doses. However, failure to account for this ordering constraint in estimating the response probabilities may result in an inefficient design. In this dissertation, we developed extensions of Simon's optimal and minimax two-stage designs, including both frequentist and Bayesian methods, for two doses that assume ordered response rates between doses. ^ Methods: Optimal and minimax two-stage designs are proposed for phase II clinical trials in settings where the true response rates at two dose levels are ordered. We borrow strength between doses using isotonic regression and control the joint and/or marginal error probabilities. Bayesian two-stage designs are also proposed under a stochastic ordering constraint. ^ Results: Compared to Simon's designs, when controlling the power and type I error at the same levels, the proposed frequentist and Bayesian designs reduce the maximum and expected sample sizes. Most of the proposed designs also increase the probability of early termination when the true response rates are poor. ^ Conclusion: Proposed frequentist and Bayesian designs are superior to Simon's designs in terms of operating characteristics (expected sample size and probability of early termination, when the response rates are poor) Thus, the proposed designs lead to more cost-efficient and ethical trials, and may consequently improve and expedite the drug discovery process. The proposed designs may be extended to designs of multiple group trials and drug combination trials.^

Effect of insurance status on stage of breast cancer diagnosis

Objective: The purpose of this study is to compare the stages of breast cancer presented between the insured and uninsured patients diagnosed at The Rose, an active non-profit breast healthcare organization to determine if uninsured patients present with more advanced stage breast cancer as compared to their insured counterparts. ^ Study Design: Retrospective cross-sectional study. ^ Methods: The study included 1,265 patients who received breast healthcare services and were diagnosed with breast cancer at The Rose between FY 2007 and FY 2012. 738 of the patients in the study were presumably uninsured since their breast healthcare services were sponsored through various funding sources and they were navigated into treatment through The Rose patient navigation program. We compared breast cancer stages for women who had insurance with those who did not have insurance. The effects of age and race/ethnicity along with the insurance status on the stage of reast cancer diagnosis were also analyzed. We calculated the odds ratio using the contingency tables; and estimated odds ratios (ORs) and 95% confidence intervals (CIs) using ordinal logistic regression by applying multiple imputation method for missing tumor stage data. ^ Results: The ordered logistic regression analysis with ordered tumor stage as dependent variable and uninsured as independent variable gave us an odds ratio of 1.73 (OR=1.73; p-value<0.05; 95% CI: 1.36 - 2.12). ^ Conclusions: Insurance status is a strong predictor of stage of breast cancer diagnosed among women seen at The Rose. Uninsured women seen at The Rose are almost twice as likely to present at a advanced stage of breast cancer as opposed to their insured counterparts.^

Marine Isotope Stage (MIS) 11 results of model data with Community Climate System Model version 3 including the Dynamic Global Vegetation Model (CCSM3-DGVM) in NetCDF format at global and regional scale

The climate of Marine Isotope Stage (MIS) 11, the interglacial roughly 400,000 years ago, is investigated for four time slices, 416, 410, 400, and 394 ka. The overall picture is that MIS 11 was a relatively warm interglacial in comparison to preindustrial, with Northern Hemisphere (NH) summer temperatures early in MIS 11 (416-410 ka) warmer than preindustrial, though winters were cooler. Later in MIS 11, especially around 400 ka, conditions were cooler in the NH summer, mainly in the high latitudes. Climate changes simulated by the models were mainly driven by insolation changes, with the exception of two local feedbacks that amplify climate changes. Here, the NH high latitudes, where reductions in sea ice cover lead to a winter warming early in MIS 11, as well as the tropics, where monsoon changes lead to stronger climate variations than one would expect on the basis of latitudinal mean insolation change alone, are especially prominent. The results support a northward expansion of trees at the expense of grasses in the high northern latitudes early during MIS 11, especially in northern Asia and North America.