Health-related quality of life and survival in liver transplant candidates.

Health-related quality of life (HRQOL) is an important measure of the effects of chronic liver disease in affected patients that helps guide interventions to improve well-being. However, the relationship between HRQOL and survival in liver transplant candidates remains unclear. We examined whether the Physical Component Summary (PCS) and Mental Component Summary (MCS) scores from the Short Form 36 (SF-36) Health Survey were associated with survival in liver transplant candidates. We administered the SF-36 questionnaire (version 2.0) to patients in the Pulmonary Vascular Complications of Liver Disease study, a multicenter prospective cohort of patients evaluated for liver transplantation in 7 academic centers in the United States between 2003 and 2006. Cox proportional hazards models were used with death as the primary outcome and adjustment for liver transplantation as a time-varying covariate. The mean age of the 252 participants was 54 +/- 10 years, 64% were male, and 94% were white. During the 422 person years of follow-up, 147 patients (58%) were listed, 75 patients (30%) underwent transplantation, 49 patients (19%) died, and 3 patients were lost to follow-up. Lower baseline PCS scores were associated with an increased mortality rate despite adjustments for age, gender, Model for End-Stage Liver Disease score, and liver transplantation (P for the trend = 0.0001). The MCS score was not associated with mortality (P for the trend = 0.53). In conclusion, PCS significantly predicts survival in liver transplant candidates, and interventions directed toward improving the physical status may be helpful in improving outcomes in liver transplant candidates.

Chronic lymphocytic leukemia: A study of the changing patterns of the natural history, clinical factors associated with prognosis, and risk of second cancers

A retrospective cohort study was conducted among 1542 patients diagnosed with CLL between 1970 and 2001 at the M. D. Anderson Cancer Center (MDACC). Changes in clinical characteristics and the impact of CLL on life expectancy were assessed across three decades (1970–2001) and the role of clinical factors on prognosis of CLL were evaluated among patients diagnosed between 1985 and 2001 using Kaplan-Meier and Cox proportional hazards method. Among 1485 CLL patients diagnosed from 1970 to 2001, patients in the recent cohort (1985–2001) were diagnosed at a younger age and an earlier stage compared to the earliest cohort (1970–1984). There was a 44% reduction in mortality among patients diagnosed in 1985–1995 compared to those diagnosed in 1970–1984 after adjusting for age, sex and Rai stage among patients who ever received treatment. There was an overall 11 years (5 years for stage 0) loss of life expectancy among 1485 patients compared with the expected life expectancy based on the age-, sex- and race-matched US general population, with a 43% decrease in the 10-year survival rate. Abnormal cytogenetics was associated with shorter progression-free (PF) survival after adjusting for age, sex, Rai stage and beta-2 microglobulin (beta-2M); whereas, older age, abnormal cytogenetics and a higher beta-2M level were adverse predictors for overall survival. No increased risk of second cancer overall was observed, however, patients who received treatment for CLL had an elevated risk of developing AML and HD. Two out of three patients who developed AML were treated with alkylating agents. In conclusion, CLL patients had improved survival over time. The identification of clinical predictors of PF/overall survival has important clinical significance. Close surveillance of the development of second cancer is critical to improve the quality of life of long-term survivors. ^

Response to chemotherapy, recurrence and survival in advanced-stage ovarian, fallopian tube and primary peritoneal cancer patients with non-Ashkenazi Jewish BRCA mutations, compared to those without

Objectives. Previous studies have shown a survival advantage in ovarian cancer patients with Ashkenazi-Jewish (AJ) BRCA founder mutations, compared to sporadic ovarian cancer patients. The purpose of this study was to determine if this association exists in ovarian cancer patients with non-Ashkenazi Jewish BRCA mutations. In addition, we sought to account for possible "survival bias" by minimizing any lead time that may exist between diagnosis and genetic testing. ^ Methods. Patients with stage III/IV ovarian, fallopian tube, or primary peritoneal cancer and a non-Ashkenazi Jewish BRCA1 or 2 mutation, seen for genetic testing January 1996-July 2007, were identified from genetics and institutional databases. Medical records were reviewed for clinical factors, including response to initial chemotherapy. Patients with sporadic (non-hereditary) ovarian, fallopian tube, or primary peritoneal cancer, without family history of breast or ovarian cancer, were compared to similar cases, matched by age, stage, year of diagnosis, and vital status at time interval to BRCA testing. When possible, 2 sporadic patients were matched to each BRCA patient. An additional group of unmatched, sporadic ovarian, fallopian tube and primary peritoneal cancer patients was included for a separate analysis. Progression-free (PFS) & overall survival (OS) were calculated by the Kaplan-Meier method. Multivariate Cox proportional hazards models were calculated for variables of interest. Matched pairs were treated as clusters. Stratified log rank test was used to calculate survival data for matched pairs using paired event times. Fisher's exact test, chi-square, and univariate logistic regression were also used for analysis. ^ Results. Forty five advanced-stage ovarian, fallopian tube and primary peritoneal cancer patients with non-Ashkenazi Jewish (non-AJ) BRCA mutations, 86 sporadic-matched and 414 sporadic-unmatched patients were analyzed. Compared to the sporadic-matched and sporadic-unmatched ovarian cancer patients, non-AJ BRCA mutation carriers had longer PFS (17.9 & 13.8 mos. vs. 32.0 mos., HR 1.76 [95% CI 1.13–2.75] & 2.61 [95% CI 1.70–4.00]). In relation to the sporadic- unmatched patients, non-AJ BRCA patients had greater odds of complete response to initial chemotherapy (OR 2.25 [95% CI 1.17–5.41]) and improved OS (37.6 mos. vs. 101.4 mos., HR 2.64 [95% CI 1.49–4.67]). ^ Conclusions. This study demonstrates a significant survival advantage in advanced-stage ovarian cancer patients with non-AJ BRCA mutations, confirming the previous studies in the Jewish population. Our efforts to account for "survival bias," by matching, will continue with collaborative studies. ^

Survival of gastrointestinal and stromal tumor patients at UT M.D. Anderson Cancer Center

Objective. Gastrointestinal Stromal Tumors (GISTs) are rare mesenchymal tumors of the gastrointestinal (GI) tract with spindled cell, epithelioid, or occasionally pleomorphic morphology. The primary objective of this paper is to describe the demographic and clinical characteristics and survival among GIST patients registered at the University of Texas M.D. Anderson Cancer Center (MDACC). ^ Methods. This cohort study includes 783 consecutive patients diagnosed with GIST from 1995 to 2007. Demographic, clinical and survival information were obtained from the MDACC cancer registry. ^ Statistical Analysis. Kaplan-Meier survival curves, univariate and multivariate Cox proportional hazards analysis were conducted to estimate survival and identify prognostic clinical factors associated with survival. Results. The age at diagnosis of MDACC GIST cases ranged from 17 to 91 with a mean of 57 years and a male-to-female ratio of 1.3:1. The racial distribution was whites 77%, African-Americans 9.5%, Hispanics 9.3% and other races 4.2%. Fifty per cent of the GISTs arose from stomach, 35% small intestine, 7% retroperitoneal space, 6% colorectal and 2% were omentum and mesentery. About half of the tumors were less than 10 cm in size. Fifty eight per cent of the tumors were localized whereas 36% were metastatic. MDACC GIST patients were generally comparable to SEER patients, but, on the average, were 7 years younger than SEER patients and were predominantly whites. ^ Stratification of 783 GIST cases by year of diagnosis based on the introduction of imatinib treatment in 2000 revealed that 60% of the GIST cases were first diagnosed between 2000 and 2007 whereas, 40% were first diagnosed between 1995 and 1999. There was a significant difference between the two cohorts in the distribution of race, GIST symptom, tumor size, tumor site, and stage of the tumor at diagnosis. The 1- and 5-year survival was 93% and 59% in the 1995–2007 cohort. Multivariate Cox regression analysis identified age at diagnosis (p<0.001), female sex (p=0.047), tumor size (p=0.07), multiple cancers (p=0.002), and GIST diagnosed between 2000 and 2007 (p<0.001) were significantly associated with survival. Approximately, 58% of the cases were treated with imatinib whereas 42% did not receive imatinib in 2000–2005 cohort. There was a significant difference in survival between imatinib and non-imatinib groups and in the distribution of tumor size categories, stage of the tumor at diagnosis and cancers before the diagnosis of GIST. The 1- and 5-year survival for imatinib patients was 99% and 73% and was 91% and 63% for non-imatinib patients. Multivariate Cox regression analysis of the 2000–2007 cohort identified, age at diagnosis and tumor stage as possible prognostic factors associated with survival.^

Geographic variation in the utilization and survival associated with oxaliplatin chemotherapy in patients with stage III colon cancer

Background: Overall objectives of this dissertation are to examine the geographic variation and socio-demographic disparities (by age, race and gender) in the utilization and survival of newly FDA-approved chemotherapy agents (Oxaliplatin-containing regimens) as well as to determine the cost-effectiveness of Oxaliplatin in a large nationwide and population-based cohort of Medicare patients with resected stage-III colon cancer. Methods: A retrospective cohort of 7,654 Medicare patients was identified from the Surveillance, Epidemiology and End Results – Medicare linked database. Multiple logistic regression was performed to examine the relationship between receipt of Oxaliplatin-containing chemotherapy and geographic regions while adjusting for other patient characteristics. Cox proportional hazard model was used to estimate the effect of Oxaliplatin-containing chemotherapy on the survival variation across regions using 2004-2005 data. Propensity score adjustments were also made to control for potential bias related to non-random allocation of the treatment group. We used Kaplan-Meier sample average estimator to calculate the cost of disease after cancer-specific surgery to death, loss-to follow-up or censorship. Results: Only 51% of the stage-III patients received adjuvant chemotherapy within three to six months of colon-cancer specific surgery. Patients in the rural regions were approximately 30% less likely to receive Oxaliplatin chemotherapy than those residing in a big metro region (OR=0.69, p=0.033). The hazard ratio for patients residing in metro region was comparable to those residing in big metro region (HR: 1.05, 95% CI: 0.49-2.28). Patients who received Oxalipaltin chemotherapy were 33% less likely to die than those received 5-FU only chemotherapy (adjusted HR=0.67, 95% CI: 0.41-1.11). KMSA-adjusted mean payments were almost 2.5 times higher in the Oxaliplatin-containing group compared to 5-FU only group ($45,378 versus $17,856). When compared to no chemotherapy group, ICER of 5-FU based regimen was $12,767 per LYG, and ICER of Oxaliplatin-chemotherapy was $60,863 per LYG. Oxaliplatin was found economically dominated by 5-FU only chemotherapy in this study population. Conclusion: Chemotherapy use varies across geographic regions. We also observed considerable survival differences across geographic regions; the difference remained even after adjusting for socio-demographic characteristics. The cost-effectiveness of Oxaliplatin in Medicare patients may be over-estimated in the clinical trials. Our study found 5-FU only chemotherapy cost-effective in adjuvant settings in patients with stage-III colon cancer.^

The prognostic significance of sialyl-Tn antigen in women treated with adjuvant chemotherapy for breast cancer

Background and purpose. Sialyl-Tn(STn) represents an aberrantly glycosylated mucin epitope which is expressed in breast cancer and other adenocarcinomas and is an important target for the development of novel immunotherapeutic approaches. It is a marker of adverse prognosis in colon and ovarian cancer, but information about its prognostic impact in breast cancer is limited. The primary aim of the present study was to investigate the influence of STn expression on outcome of invasive breast cancer in 207 women who received anthracyline-containing adjuvant chemotherapy in a prospective clinical trial.^ Methods. Expression of STn was determined by an immunohistochemical procedure using the B72.3 monoclonal antibody. The extent of staining was determined by two observers using a 0 through 4 point scale, with 0 representing $<$5% of cells staining; 1: 5-25%; 2: 26-50%; 3: 51-75%; and 4: $>$75%. Intraobserver and interobserver agreement was.78-.92 (kappa). Kaplan-Meier and Cox proportional regression survival analyses were used to compare STn-negative and STn-positive patients.^ Results. Forty-eight (23%) of the 207 specimens demonstrated positive staining of STn. With a median follow-up of five years, STn-positivity was associated with a higher 5-year recurrence-free survival time than STn-negativity (67% vs. 80%, respectively; p = 0.03). STn expression was significantly associated with menopausal status (p = 0.04) but not other conventional prognostic markers. The risk of breast cancer recurrence and death was assessed by multivariate Cox regression analyses with adjustment for lymph node status, tumor size, menopausal status, hormone receptor status, nuclear grade, S-phase fraction and ploidy. In the final multivariate model for recurrence-free survival, the three factors that showed prognostic significance were: lymph node status (hazard ratio (HR) 3.04, 95% confidence interval (CI) 1.08-8.49), STn expression (HR 2.02, 95% CI 1.09-3.73), and tumor size (HR 1.96, 95% CI 1.05-3.64). STn was also associated with worse overall survival (HR 2.16, 95% CI 0.95-4.92) in multivariate analysis.^ Conclusion. STn antigen was shown to be a predictor of poor outcome in breast cancer. This tumor-associated antigen may be a valuable marker for identifying individuals at high risk of developing recurrent disease who may benefit from adjuvant therapy targeted at STn following definitive local therapy. Further study is needed to clarify the biologic and prognostic role of STn in breast cancer. ^

Analysis of prognostic factors for the development of metastases and survival in renal cell carcinoma patients

Introduction and objective. A number of prognostic factors have been reported for predicting survival in patients with renal cell carcinoma. Yet few studies have analyzed the effects of those factors at different stages of the disease process. In this study, different stages of disease progression starting from nephrectomy to metastasis, from metastasis to death, and from evaluation to death were evaluated. ^ Methods. In this retrospective follow-up study, records of 97 deceased renal cell carcinoma (RCC) patients were reviewed between September 2006 to October 2006. Patients with TNM Stage IV disease before nephrectomy or with cancer diagnoses other than RCC were excluded leaving 64 records for analysis. Patient TNM staging, Furhman Grade, age, tumor size, tumor volume, histology and patient gender were analyzed in relation to time to metastases. Time from nephrectomy to metastasis, TNM staging, Furhman Grade, age, tumor size, tumor volume, histology and patient gender were tested for significance in relation to time from metastases to death. Finally, analysis of laboratory values at time of evaluation, Eastern Cooperative Oncology Group performance status (ECOG), UCLA Integrated Staging System (UISS), time from nephrectomy to metastasis, TNM staging, Furhman Grade, age, tumor size, tumor volume, histology and patient gender were tested for significance in relation to time from evaluation to death. Linear regression and Cox Proportional Hazard (univariate and multivariate) was used for testing significance. Kaplan-Meier Log-Rank test was used to detect any significance between groups at various endpoints. ^ Results. Compared to negative lymph nodes at time of nephrectomy, a single positive lymph node had significantly shorter time to metastasis (p<0.0001). Compared to other histological types, clear cell histology had significant metastasis free survival (p=0.003). Clear cell histology compared to other types (p=0.0002 univariate, p=0.038 multivariate) and time to metastasis with log conversion (p=0.028) significantly affected time from metastasis to death. A greater than one year and greater than two year metastasis free interval, compared to patients that had metastasis before one and two years, had statistically significant survival benefit (p=0.004 and p=0.0318). Time from evaluation to death was affected by greater than one year metastasis free interval (p=0.0459), alcohol consumption (p=0.044), LDH (p=0.006), ECOG performance status (p<0.001), and hemoglobin level (p=0.0092). The UISS risk stratified the patient population in a statistically significant manner for survival (p=0.001). No other factors were found to be significant. ^ Conclusion. Clear cell histology is predictive for both time to metastasis and metastasis to death. Nodal status at time of nephrectomy may predict risk of metastasis. The time interval to metastasis significantly predicts time from metastasis to death and time from evaluation to death. ECOG performance status, and hemoglobin levels predicts survival outcome at evaluation. Finally, UISS appropriately stratifies risk in our population. ^

Matrix metalloproteinase-1 as a prognosticator in malignant glioma

The overall purpose of this study was to assess the relationship between the promoter region polymorphism (-2607 1G/2G) of matrix metalloproteinase-1 (MMP-1) polymorphism and outcome in brain tumor patients diagnosed with a primary brain tumor between 1994 and 2000 at The University of Texas M. D. Anderson Cancer Center. The MMP-1 polymorphism was genotyped for all brain tumor patients who participated in the Family Brain Tumor Study and for whom blood samples were available. Relevant covariates were abstracted from medical records for all cases from the original protocol, including information on demographics, tumor histology, therapy and outcome was obtained. The hypothesis was that brain tumor patients with the 2G allele have a poorer prognosis and shorter survival than brain tumor patients with the 1G allele. ^ Experimental Design: Genetic variants for the MMP-1 enzyme were determined by a polymerase chain reaction-restriction fragment length polymorphism assay. Comparison was made between the overall survival for cases with the 2G polymorphism and overall survival for cases with the 1G polymorphism using multivariable Cox Proportional-Hazard analysis, controlling for age, sex, Karnofsky Performance Scale (KPS), extent of surgery, tumor histology and treatment received. Kaplan-Meier and Cox Proportional-Hazard analyses were utilized to assess if the MMP-1 polymorphisms were related to overall survival. Results: Overall survival was not statistically significantly different between the 2G allele brain tumor patients and the 1G allele patients and there was no statistically significant difference between tumor types. ^ Conclusions: No association was found between MMP-1 polymorphisms and survival in patients with malignant gliomas. ^

Genetic variations in the PI3K-AKT-mTOR pathway and bladder cancer susceptibility and clinical outcomes

Bladder cancer is the fourth most common cancer in men in the United States. There is compelling evidence supporting that genetic variations contribute to the risk and outcomes of bladder cancer. The PI3K-AKT-mTOR pathway is a major cellular pathway involved in proliferation, invasion, inflammation, tumorigenesis, and drug response. Somatic aberrations of PI3K-AKT-mTOR pathway are frequent events in several cancers including bladder cancer; however, no studies have investigated the role of germline genetic variations in this pathway in bladder cancer. In this project, we used a large case control study to evaluate the associations of a comprehensive catalogue of SNPs in this pathway with bladder cancer risk and outcomes. Three SNPs in RAPTOR were significantly associated with susceptibility: rs11653499 (OR: 1.79, 95%CI: 1.24–2.60), rs7211818 (OR: 2.13, 95%CI: 1.35–3.36), and rs7212142 (OR: 1.57, 95%CI: 1.19–2.07). Two haplotypes constructed from these 3 SNPs were also associated with bladder cancer risk. In combined analysis, a significant trend was observed for increased risk with an increase in the number of unfavorable genotypes (P for trend<0.001). Classification and regression tree analysis identified potential gene-environment interactions between RPS6KA5 rs11653499 and smoking. In superficial bladder cancer, we found that PTEN rs1234219 and rs11202600, TSC1 rs7040593, RAPTOR rs901065, and PIK3R1 rs251404 were significantly associated with recurrence in patients receiving BCG. In muscle invasive and metastatic bladder cancer, AKT2 rs3730050, PIK3R1 rs10515074, and RAPTOR rs9906827 were associated with survival. Survival tree analysis revealed potential gene-gene interactions: patients carrying the unfavorable genotypes of PTEN rs1234219 and TSC1 rs704059 exhibited a 5.24-fold (95% CI: 2.44–11.24) increased risk of recurrence. In combined analysis, with the increasing number of unfavorable genotypes, there was a significant trend of higher risk of recurrence and death (P for trend<0.001) in Cox proportional hazard regression analysis, and shorter event (recurrence and death) free survival in Kaplan-Meier estimates (P log rank<0.001). This study strongly suggests that genetic variations in PI3K-AKT-mTOR pathway play an important role in bladder cancer development. The identified SNPs, if validated in further studies, may become valuable biomarkers in assessing an individual's cancer risk, predicting prognosis and treatment response, and facilitating physicians to make individualized treatment decisions. ^

The role of cardiovascular comorbidities in ovarian cancer survival

Objective. One facet of cancer care that often goes ignored is comorbidities, or diseases that exist in concert with cancer. Comorbid conditions may affect survival by influencing treatment decisions and prognosis. The purpose of this secondary data analysis was to identify whether a history of cardiovascular comorbidities among ovarian cancer patients influenced survival time at the University of Texas M. D. Anderson Cancer Center. The parent study, Project Peace, has a longitudinal design with an embedded randomized efficacy study which seeks to improve detection of depressive disorders in ovarian, peritoneal, and fallopian tube cancers. ^ Methods. Survival time was calculated for the 249 ovarian cancer patients abstracted by Project Peace staff. Cardiovascular comorbidities were documented as present, based upon information from medical records in addition to self reported comorbidities in a baseline study questionnaire. Kaplan-Meier survival curves were used to compare survival time among patients with a presence or absence of particular cardiovascular comorbidities. Cox Regression proportional models accounted for multivariable factors such as age, staging, family history of cardiovascular comorbidities, and treatment. ^ Results. Among our patient population, there was a statistically significant relationship between shorter survival time and a history of thrombosis, pericardial disease/tamponade, or COPD/pulmonary hypertension. Ovarian cancer patients with a history of thrombosis lived approximately half as long as patients without thrombosis (58.06 months vs. 121.55 months; p=.001). In addition, patients who suffered from pericardial disease/tamponade had poorer survival than those without a history of pericardial disease/tamponade (48 months vs. 80.07 months; p=.002). Ovarian cancer patients with a history of COPD or pulmonary hypertension had a median survival of 60.2 months, while the median survival for patients without these comorbidities was 80.2 months (p=.014). ^ Conclusion. Especially because of its relatively lower survival rate, greater emphasis needs to be placed on the potential influence of cardiovascular comorbid conditions in ovarian cancer.^

Racial/ethnic disparities in colorectal cancer screening and survival in a large nationwide population-based cohort

Background. Colorectal cancer (CRC) is the third most commonly diagnosed cancer (excluding skin cancer) in both men and women in the United States, with an estimated 148,810 new cases and 49,960 deaths in 2008 (1). Racial/ethnic disparities have been reported across the CRC care continuum. Studies have documented racial/ethnic disparities in CRC screening (2-9), but only a few studies have looked at these differences in CRC screening over time (9-11). No studies have compared these trends in a population with CRC and without cancer. Additionally, although there is evidence suggesting that hospital factors (e.g. teaching hospital status and NCI designation) are associated with CRC survival (12-16), no studies have sought to explain the racial/ethnic differences in survival by looking at differences in socio-demographics, tumor characteristics, screening, co-morbidities, treatment, as well as hospital characteristics. ^ Objectives and Methods. The overall goals of this dissertation were to describe the patterns and trends of racial/ethnic disparities in CRC screening (i.e. fecal occult blood test (FOBT), sigmoidoscopy (SIG) and colonoscopy (COL)) and to determine if racial/ethnic disparities in CRC survival are explained by differences in socio-demographic, tumor characteristics, screening, co-morbidities, treatment, and hospital factors. These goals were accomplished in a two-paper format.^ In Paper 1, "Racial/Ethnic Disparities and Trends in Colorectal Cancer Screening in Medicare Beneficiaries with Colorectal Cancer and without Cancer in SEER Areas, 1992-2002", the study population consisted of 50,186 Medicare beneficiaries diagnosed with CRC from 1992 to 2002 and 62,917 Medicare beneficiaries without cancer during the same time period. Both cohorts were aged 67 to 89 years and resided in 16 Surveillance, Epidemiology and End Results (SEER) regions of the United States. Screening procedures between 6 months and 3 years prior to the date of diagnosis for CRC patients and prior to the index date for persons without cancer were identified in Medicare claims. The crude and age-gender-adjusted percentages and odds ratios of receiving FOBT, SIG, or COL were calculated. Multivariable logistic regression was used to assess race/ethnicity on the odds of receiving CRC screening over time.^ Paper 2, "Racial/Ethnic Disparities in Colorectal Cancer Survival: To what extent are racial/ethnic disparities in survival explained by racial differences in socio-demographics, screening, co-morbidities, treatment, tumor or hospital characteristics", included a cohort of 50,186 Medicare beneficiaries diagnosed with CRC from 1992 to 2002 and residing in 16 SEER regions of the United States which were identified in the SEER-Medicare linked database. Survival was estimated using the Kaplan-Meier method. Cox proportional hazard modeling was used to estimate hazard ratios (HR) of mortality and 95% confidence intervals (95% CI).^ Results. The screening analysis demonstrated racial/ethnic disparities in screening over time among the cohort without cancer. From 1992 to 1995, Blacks and Hispanics were less likely than Whites to receive FOBT (OR=0.75, 95% CI: 0.65-0.87; OR=0.50, 95% CI: 0.34-0.72, respectively) but their odds of screening increased from 2000 to 2002 (OR=0.79, 95% CI: 0.72-0.85; OR=0.67, 95% CI: 0.54-0.75, respectively). Blacks and Hispanics were less likely than Whites to receive SIG from 1992 to 1995 (OR=0.75, 95% CI: 0.57-0.98; OR=0.29, 95% CI: 0.12-0.71, respectively), but their odds of screening increased from 2000 to 2002 (OR=0.79, 95% CI: 0.68-0.93; OR=0.50, 95% CI: 0.35-0.72, respectively).^ The survival analysis showed that Blacks had worse CRC-specific survival than Whites (HR: 1.33, 95% CI: 1.23-1.44), but this was reduced for stages I-III disease after full adjustment for socio-demographic, tumor characteristics, screening, co-morbidities, treatment and hospital characteristics (aHR=1.24, 95% CI: 1.14-1.35). Socioeconomic status, tumor characteristics, treatment and co-morbidities contributed to the reduction in hazard ratios between Blacks and Whites with stage I-III disease. Asians had better survival than Whites before (HR: 0.73, 95% CI: 0.64-0.82) and after (aHR: 0.80, 95% CI: 0.70-0.92) adjusting for all predictors for stage I-III disease. For stage IV, both Asians and Hispanics had better survival than Whites, and after full adjustment, survival improved (aHR=0.73, 95% CI: 0.63-0.84; aHR=0.74, 95% CI: 0.61-0.92, respectively).^ Conclusion. Screening disparities remain between Blacks and Whites, and Hispanics and Whites, but have decreased in recent years. Future studies should explore other factors that may contribute to screening disparities, such as physician recommendations and language/cultural barriers in this and younger populations.^ There were substantial racial/ethnic differences in CRC survival among older Whites, Blacks, Asians and Hispanics. Co-morbidities, SES, tumor characteristics, treatment and other predictor variables contributed to, but did not fully explain the CRC survival differences between Blacks and Whites. Future research should examine the role of quality of care, particularly the benefit of treatment and post-treatment surveillance, in racial disparities in survival.^

Racial differences in heart failure with preserved ejection fraction in the ambulatory heart failure population

Racial differences in heart failure with preserved ejection fraction (HFpEF) have rarely been studied in an ambulatory, financially "equal access" cohort, although the majority of such patients are treated as outpatients. ^ Retrospective data was collected from 2,526 patients (2,240 Whites, 286 African American) with HFpEF treated at 153 VA clinics, as part of the VA External Peer Review Program (EPRP) between October 2000 and September 2002. Kaplan Meier curves (stratified by race) were created for time to first heart failure (HF) hospitalization, all cause hospitalization and death and Cox proportional multivariate regression models were constructed to evaluate the effect of race on these outcomes. ^ African American patients were younger (67.7 ± 11.3 vs. 71.2 ± 9.8 years; p < 0.001), had lower prevalence of atrial fibrillation (24.5 % vs. 37%; p <0.001), chronic obstructive pulmonary disease (23.4 % vs. 36.9%, p <0.001), but had higher blood pressure (systolic blood pressure > 120 mm Hg 77.6% vs. 67.8%; p < 0.01), glomerular filtration rate (67.9 ± 31.0 vs. 61.6 ± 22.6 mL/min/1.73 m2; p < 0.001), anemia (56.6% vs. 41.7%; p <0.001) as compared to whites. African Americans were found to have higher risk adjusted rate of HF hospitalization (HR 1.52, 95% CI 1.1 - 2.11; p = 0.01), with no difference in risk-adjusted all cause hospitalization (p = 0.80) and death (p= 0.21). ^ In a financially "equal access" setting of the VA, among ambulatory patients with HFpEF, African Americans have similar rates of mortality and all cause hospitalization but have an increased risk of HF hospitalizations compared to whites.^

The influence of antibacterial susceptibility and pharmacodynamics on the therapeutic response of infection

This prospective cohort study estimated how antibacterial resistance affected the time until clinical response. Relative rates of improvement and cure were estimated by proportional-hazards regression for 391 patients with culture-confirmed bacterial keratitis who had the ciprofloxacin minimal inhibitory concentration (MIC) measured of the principal corneal isolate and who were treated with ciprofloxacin 0.3% solution or ointment. After adjusting for age and hypopyon status and stratifying by ulcer size, clinic, and ciprofloxacin formulation, the summary rate of clinical improvement with ciprofloxacin therapy was reduced by 42% (95% confidence limits [CL], 3%, 65%) among patients whose corneal isolate's ciprofloxacin MIC exceeded 1.0 μg/mL compared to those with more sensitive isolates. The summary rate of resolution to improvement and cure was reduced by 36% (95% CL, 11%, 53%) among corneal infections having a higher ciprofloxacin MIC. Rate ratios were modified by the size of the presenting corneal ulceration; for ulcer diameters of 4 mm or less and of more than 4 mm, improvement rate ratios were 0.56 (95% CL, 0.31, 1.02) and 0.65 (95% CL, 0.23, 1.80), respectively; resolution rate ratios were 0.63 (95% CL, 0.44, 0.91) and 0.67 (95% CL, 0.32, 1.39), respectively. Sensitivity analysis showed that the summary improvement rate ratio could be maximally overestimated by 24% (95% CL, −29%, 114%) because of informative censoring or by 33% (95% CL, −21%, 126%) from loss to follow up. Based on reported corneal pharmacokinetics of topical ciprofloxacin, the probability of clinical improvement was 90% or more if the ratio of the achievable corneal ciprofloxacin concentration to the corneal isolate's ciprofloxacin MIC was above 8 or the ratio of the area under the 24-hour corneal concentration curve to the ciprofloxacin MIC was greater than 151. This study suggests that corneal infections by bacteria having a higher ciprofloxacin MIC respond more slowly to ciprofloxacin treatment than those with a lower MIC. While the rate of clinical resolution is affected by patient age and clinical severity, antimicrobial susceptibility testing of corneal cultures can indicate the relative effectiveness of antibacterial therapy. A pharmacodynamic approach to treating bacterial keratitis offers the prospect of optimal antimicrobial selection and modification. ^