Adjuvant chemotherapy for stage III colon cancer: relative dose intensity and survival among veterans.

BACKGROUND: Given the paucity of information on dose intensity, the objective of this study is to describe the use of adjuvant chemotherapy for stage III colon cancer, focusing on relative dose intensity (RDI), overall survival (OS) and disease-free survival (DFS). METHODS: Retrospective cohort of 367 patients diagnosed with stage III colon cancer in 2003-2008 and treated at 19 VA medical centers. Kaplan-Meier curves summarize 5-year OS and 3-year DFS by chemotherapy regimen and RDI, and multivariable Cox proportional hazards regression was used to model these associations. RESULTS: 5-fluorouracil/leucovorin (FU/LV) was the most commonly initiated regimen in 2003 (94.4%) and 2004 (62.7%); in 2005-2008, a majority of patients (60%-74%) was started on an oxaliplatin-based regimen. Median RDI was 82.3%. Receipt of >70% RDI was associated with better 5-year OS (p < 0.001) and 3-year DFS (P = 0.009) than was receipt of ≤70% RDI, with 5-year OS rates of 66.3% and 50.5%, respectively and 3-year DFS rates of 66.1% and 52.7%, respectively. In the multivariable analysis of 5-year OS, oxaliplatin + 5-FU/LV (versus 5-FU/LV) (HR = 0.55; 95% CI = 0.34-0.91), >70% RDI at the first year (HR = 0.58; 95% CI = 0.37-0.89) and married status (HR = 0.66; 95% CI = 0.45-0.97) were associated with significantly decreased risk of death, while age ≥75 (versus 55-64) (HR = 2.06; 95% CI = 1.25-3.40), Charlson Comorbidity Index (HR = 1.17; 95% CI = 1.06-1.30), T4 tumor status (versus T1/T2) (HR = 5.88; 95% CI = 2.69-12.9), N2 node status (HR = 1.68; 95% CI = 1.12-2.50) and bowel obstruction (HR = 2.32, 95% CI = 1.36-3.95) were associated with significantly increased risk. Similar associations were observed for DFS. CONCLUSION: Patients with stage III colon cancer who received >70% RDI had improved 5-year OS. The association between RDI and survival needs to be examined in studies of adjuvant chemotherapy for colon cancer outside of the VA.

Evaluation of Clostridium difficile-associated diarrhea with a drug formulary change in preferred fluoroquinolones.

BACKGROUND: Recent publications report that gatifloxacin might be associated with a greater incidence of Clostridium difficile-associated diarrhea (C. difficile, CDAD) than are other fluoroquinolones. We performed a drug use evaluation to examine this issue after adding gatifloxacin to the formulary and changing from levofloxacin to gatifloxacin as the preferred oral fluoroquinolone in 10 Department of Veterans Affairs (VA) medical centers in the northeastern United States. OBJECTIVES: To estimate (1) the overall incidence of CDAD before and after the change from levofloxacin to gatifloxacin as the preferred oral fluoroquinolone and (2) the incidence rates for ciprofloxacin, levofloxacin, and gatifloxacin separately. METHODS: Using the VA's Pharmacy Benefits Management database, the total number of days of antibiotic therapy was determined for all inpatients and outpatients of the 10 medical centers who filled at least 1 antibiotic prescription between July 1, 2003, and June 30, 2004. This time frame was chosen because it included 6 months before and 6 months after the change in the preferred oral fluoroquinolone from levofloxacin to gatifloxacin for the VA health system on January 1, 2004. For the same study period and medical centers, the electronic medical records of all inpatients and outpatients with an entry for a positive C. difficile toxin were reviewed. Positive toxins that occurred within 6 weeks of a previous positive result in the same patient were excluded. Exact Poisson tests were used to compare the incidence rates of CDAD (number of CDAD cases per 1,000 days of antibiotic treatment) for antibiotics overall, the fluoroquinolones as a group, non-fluoroquinolone antibiotics, and the individual fluoroquinolones, com-paring the 6-month time periods before (pre-change) versus after (post-change) the addition of gatifloxacin as the preferred oral fluoroquinolone. RESULTS: Of 505 cases of CDAD in the 12-month study period, 413 (81.7%) were associated with antibiotic use in the previous 6 weeks. Among anti-biotic users, incidence rates of CDAD were 166 per 72,114 days of antibiotic therapy in the pre-change period (2.3 cases per 1,000 days of antibiotics) versus 247 per 72,354 days in the post-change period (3.4 cases per 1,000 days of antibiotics, P < 0.001). Fluoroquinolones accounted for 54.8% of the CDAD cases in the pre-change period and 67.2% in the post-change period, representing a 22.6% relative increase in the percentage of CDAD cases that were associated with fluoroquinolone use. The CDAD incidence rates per 1,000 days of fluoroquinolone therapy were 3.7 in the pre-change period versus 7.0 in the post-change period (P < 0.001). Among fluoroqui-nolone users, gatifloxacin accounted for none of the cases of CDAD in the pre-change period when it was nonformulary and 65.1% of the cases in the post-change period, for an incidence rate of 7.6 (108 per 14,239 days). The CDAD incidence rates per 1,000 antibiotic days for patients treated with ciprofloxacin were 4.6 (24 per 5,260 days) in the pre-change period and 7.4 (40 per 5,429 days) in the post-change period, a nonsignificant trend (P = 0.079). The incidence rate of CDAD for levofloxacin increased significantly from 3.9 (75 per 19,417 days) in the pre-change period to 10.7 (44 per 4,108 days) in the post-change period (P < 0.001). The incidence rates of CDAD in the post-change period did not differ significantly for ciprofloxacin, levofloxacin, and gatifloxacin (P = 0.119). CONCLUSIONS: There was an increase in the incidence of CDAD among all antibiotic users and fluoroquinolone users, but not among users of non-fluoroquinolone antibiotics, in the period following the formulary change from levofloxacin to gatifloxacin as the preferred fluoroquinolone. However, rates of CDAD among the 3 fluoroquinolone antibiotics in the post-change period were not significantly different, and levofloxacin was the only fluoroquinolone that was associated with a significant increase in the rate of CDAD between the pre-change and post-change periods. These findings suggest that the increase in the CDAD incidence rate was probably not attributable to the addition of gatifloxacin to the formulary.

Is lower 30-day mortality posthospital admission among blacks unique to the Veterans Affairs health care system?

BACKGROUND: Several studies have reported lower risk-adjusted mortality for blacks than whites within the Veterans Affairs (VA) health care system, particularly for those age 65 and older. This finding may be a result of the VA's integrated health care system, which reduces barriers to care through subsidized comprehensive health care services. However, no studies have directly compared racial differences in mortality within 30 days of hospitalization between the VA and non-VA facilities in the US health care system. OBJECTIVE: To compare risk-adjusted 30-day mortality for black and white males after hospital admission to VA and non-VA hospitals, with separate comparisons for patients younger than age 65 and those age 65 and older. RESEARCH DESIGN: Retrospective observational study using hospital claims data from the national VA system and all non-VA hospitals in Pennsylvania and California. SUBJECTS: A total of 369,155 VA and 1,509,891 non-VA hospitalizations for a principal diagnosis of pneumonia, congestive heart failure, gastrointestinal bleeding, hip fracture, stroke, or acute myocardial infarction between 1996 and 2001. MEASURES: Mortality within 30 days of hospital admission. RESULTS: Among those under age 65, blacks in VA and non-VA hospitals had similar odds ratios of 30-day mortality relative to whites for gastrointestinal bleeding, hip fracture, stroke, and acute myocardial infarction. Among those age 65 and older, blacks in both VA and non-VA hospitals had significantly reduced odds of 30-day mortality compared with whites for all conditions except pneumonia in the VA. The differences in mortality by race are remarkably similar in VA and non-VA settings. CONCLUSIONS: These findings suggest that factors associated with better short-term outcomes for blacks are not unique to the VA.

Influence of DHEA administration on 24-hour cortisol concentrations.

DHEA is marketed and readily available as a daily nutritional supplement to counteract the effects of aging. The effect of DHEA administration on 24-hour plasma cortisol profiles has not been investigated. In this single-blind placebo-controlled crossover study, the effect of DHEA administration on cortisol concentrations was evaluated in healthy older women and men. Once each morning, subjects took either placebo (Days 1 to 7, and 23 to 29) or oral DHEA 200 mg (Days 8 to 22: doses 1 to 15). Twenty-four hour DHEA and cortisol concentrations were measured on Day 1 (placebo), Day 8 (DHEA dose 1), Day 15 (DHEA dose 8), Day 22 (DHEA dose 15), and Day 29 (placebo washout dose 7). DHEA administration resulted in a decrease in plasma cortisol concentrations (mean, peak, and/or AUC) in healthy older women and men. The cortisol-lowering effect of DHEA was more pronounced in women than in men in our study; pairwise differences in concentrations between days showed that relative to Day 1, cortisol was lower on Days 15, 22, and 29 in women (p = 0.0001) and on Day 15 in men (p = 0.002). The mechanism by which DHEA lowers plasma cortisol concentrations merits further investigation.