Publications

BACKGROUND: There is a paucity of reports evaluating the perioperative risk of noncardiac surgery in patients with hypertrophic cardiomyopathy (HCM).

HYPOTHESIS: The study was undertaken to evaluate the incidence of acute myocardial infarction (MI) and all-cause inhospital mortality following noncardiac surgery in patients with HCM.

METHODS: We searched the National Hospital Discharge Survey database for patients with a diagnosis of HCM who had undergone noncardiac surgery. Cases were matched by age, gender, and year of surgery. Death or acute MI were used as endpoints for analysis.

RESULTS: From 1996 to 2002, 227 patients with HCM were matched with 554 controls (representing national estimates of 25,874 HCM and 50,326 controls patients). Patients with HCM were more likely than controls to have a history of atrial fibrillation (22.7 vs. 10.6%, p < 0.001) and of congestive heart failure (CHF) (24.2 vs. 14.1%, p < 0.001). The in-hospital incidence of death or MI was higher in patients with HCM than in controls (6.7 vs. 2.5%, p < 0.001 for death and 2.2 vs. 0.3%, p < 0.001 for MI). After correcting for age, gender, race, presence of hypertension, diabetes mellitus, history of coronary artery-disease, history of CHF, atrial fibrillation, and ventricular arrhythmias in a multivariate binary logistic regression model, the presence of HCM increased the odds of death by 61% (odds ratio [OR] = 1.61, 95% confidence interval [CI] 1.46-1.77, p < 0.001), and almost tripled the odds of the combined endpoint of death or MI (OR = 2.82, 95% CI 2.59-3.07, p < 0.001).

CONCLUSION: The presence of HCM significantly increases the risk of death and MI associated with noncardiac surgery. Patients with HCM undergoing elective procedures may require more careful preoperative assessment and perioperative monitoring. The impact of the severity of HCM on outcomes of noncardiac surgery needs further study.

Primary and metastatic bone cancers are difficult to eradicate and novel approaches are needed to improve treatment and extend life. As bone cancer grows, osteoclasts, the principal bone-resorbing cells of the body, are recruited to and activated at sites of cancer. In this investigation, we determined if osteoclast lineage cells could function as a cell-based gene delivery system to bone cancers. We used the cytosine deaminase (CD) 5-fluorocytosine (5-FC) enzyme/prodrug system and studied bone marrow and bones from transgenic mice expressing a novel CD gene regulated by the osteoclast tartrate-resistant acid phosphatase (TRAP) gene promoter (Tg/NCD). DsRed2-labeled 2472 sarcoma cells were placed in Tg/NCD osteoclastogenic cultures and treated with 5-FC. 5-FC treatment resulted in profound bystander killing (90%; P < 0.05). The effect of 5-FC treatment on osteoclast lineage cells was most dramatic when administered at the beginning of the 7-day cultures, suggesting that mature osteoclasts are less sensitive to 5-FC. Evaluation of osteoclast-directed bystander killing in vivo revealed dramatic killing of bone cancer with only a modest effect on osteoclast number. Specifically, 5-FC treatment of tumor-bearing Tg/NCD mice or Tg/NCD bone marrow transplanted C3H mice (Tg/NCD-C3H) resulted in 92% and 44% reductions in tumor area, respectively (P < 0.05). Eight of ten 5-FC-treated Tg/NCD mice had complete bone tumor killing and five of six 5-FC-treated Tg/NCD-C3H mice had reduced tumor compared with controls. In addition, Tg/NCD osteoclasts were resistant to 5-FC treatment in vivo, a very important feature, as it identifies osteoclasts as an ideal CD gene delivery system.

BACKGROUND: An increased prevalence of bacteremia caused by methicillin-resistant Staphylococcus aureus (MRSA) with a vancomycin hydrochloride MIC of 2 microg/mL was noted in a population of inpatients undergoing hemodialysis at Baptist Memorial Health Care, Memphis, Tennessee.

OBJECTIVES: The aims of this study were to determine risk factors for infection with MRSA and to assess the differences in clinical and economic outcomes in patients undergoing hemodialysis with MRSA bacteremia with vancomycin MIC 2 microg/mL versus those with MRSA bacteremia with vancomycin MIC < or =0.5 microg/mL and uninfected controls.

METHODS: This retrospective case-control study was conducted at Baptist Memorial Health Care. The study population (inpatients undergoing hemodialysis for MRSA bacteremia with vancomycin MIC 2 microg/mL [high-MIC group], MIC < or = 0.5 microg/mL [low-MIC group], and uninfected controls) was identified. Risk factors and clinical and economic outcomes (costs of hospitalization, nursing, and pharmacy) were determined and compared using univariate and multivariate statistics.

RESULTS: Fifty patients with MRSA bacteremia undergoing hemodialysis were identified during the study period (high-MIC group, 17 [11 women, 6 men; mean (SD) age, 60 (17) years]; low-MIC group, 33 [23 women, 10 men; mean (SD) age, 62 (14) years]) and matched with 100 uninfected controls (57 men, 43 women; mean [SD] age, 63 [15] years). Risk factors for MRSA bacteremia found to be associated with high MIC included female sex, higher body mass index (1-point increments), recent surgery, and a history of cardiovascular disease (P < 0.05, P < 0.046, P = 0.04, and P = 0.028, respectively) (multivariate analysis). In the outcomes analysis, mortality was significantly higher in the high-MIC group compared with those in the low-MIC and control groups (35% vs 24% and 15%, respectively; P = 0.022). Total mean (SD) hospitalization costs were significantly higher in the high-MIC group compared with those in the low-MIC group and controls (US $47,624 [$80,534] vs $26,792 [$25,167] and $13,185 [$15,568], respectively; P < 0.001). Nursing costs were almost 6-fold higher in both infected groups compared with those in controls. Pharmacy costs in the low- and high-MIC groups were 3- to 6-fold higher, respectively, compared with those in controls.

CONCLUSIONS: Surgery within the previous 6 months and intensive care unit admission were identified as significant risk factors for patients with MRSA bacteremia with a vancomycin MIC 2 microg/mL undergoing hemodialysis. These patients experienced a longer mean hospital length of stay and increased hospital costs compared with patients with MRSA bacteremia with a vancomycin MIC < or =0.5 microg/mL and uninfected controls.

BACKGROUND: Inadequate antimicrobial treatment is an independent determinant of hospital mortality, and fungal bloodstream infections are among the types of infection with the highest rates of inappropriate initial treatment. Because of significant potential for reducing high mortality rates, we sought to assess the impact of delayed treatment across multiple study sites. The goals our analyses were to establish the frequency and duration of delayed antifungal treatment and to evaluate the relationship between treatment delay and mortality.

METHODS: We conducted a retrospective cohort study of patients with candidemia from 4 medical centers who were prescribed fluconazole. Time to initiation of fluconazole therapy was calculated by subtracting the date on which fluconazole therapy was initiated from the culture date of the first blood sample positive for yeast.

RESULTS: A total of 230 patients (51% male; mean age +/- standard deviation, 56 +/- 17 years) were identified; 192 of these had not been given prior treatment with fluconazole. Patients most commonly had nonsurgical hospital admission (162 patients [70%]) with a central line catheter (193 [84%]), diabetes (68 [30%]), or cancer (54 [24%]). Candida species causing infection included Candida albicans (129 patients [56%]), Candida glabrata (38 [16%]), Candida parapsilosis (25 [11%]), or Candida tropicalis (15 [7%]). The number of days to the initiation of antifungal treatment was 0 (92 patients [40%]), 1 (38 [17%]), 2 (33 [14%]) or > or = 3 (29 [12%]). Mortality rates were lowest for patients who began therapy on day 0 (14 patients [15%]) followed by patients who began on day 1 (9 [24%]), day 2 (12 [37%]), or day > or = 3 (12 [41%]) (P = .0009 for trend). Multivariate logistic regression was used to calculate independent predictors of mortality, which include increased time until fluconazole initiation (odds ratio, 1.42; P < .05) and Acute Physiology and Chronic Health Evaluation II score (1-point increments; odds ratio, 1.13; P < .05).

CONCLUSION: A delay in the initiation of fluconazole therapy in hospitalized patients with candidemia significantly impacted mortality. New methods to avoid delays in appropriate antifungal therapy, such as rapid diagnostic tests or identification of unique risk factors, are needed.

PURPOSE: Racial disparities have been reported in the care and outcome of cancer patients. We evaluated whether race would influence the cost and outcomes of inpatient neutropenic cancer patients in a multicenter study from a large health care system in the southern United States.

METHODS: Data was collected on all cancer inpatients with a diagnosis code for neutropenia in a 16-hospital system between October 1, 2002, and September 30, 2003. Demographics, treatment outcomes, and costs were compared between white and minority patients. A P value less than .05 was considered statistically significant.

RESULTS: Two hundred seventy-nine cancer patients (0.29% of all admits) had a diagnosis of neutropenia. Demographics were similar between white and minority patients. However, minorities were more likely to be younger than whites (P = .002). With regards to outcomes, length of stay (LOS), LOS in the intensive care unit, and discharge status were not statistically different. Total hospital, medication, laboratory, radiation, surgery, and respiratory costs were also similar (P > .05), although minorities were less likely to receive myeloid colony-stimulating factors (P = .032) and more likely to have higher nursing care costs (P = .048).

CONCLUSION: In light of the escalating reports of racial disparities in cancer care, these minimal differences are encouraging.

This study estimates how out-of-pocket drug costs could change for vulnerable populations (racial and ethnic minorities, the near-poor, and seniors with a greater burden of chronic conditions) who qualify for the standard Medicare drug benefit. Although the new benefit might be associated with modest-to-moderate declines in out-of-pocket spending for seniors who do not qualify for subsidies, the savings might not be shared equitably and therefore might not reduce financial barriers to medication use for these populations.

The Department of Veterans Affairs (VA) Pharmacy Benefits Management Strategic Healthcare Group (VA PBM) oversees the formulary for the entire VA system, which serves more than 4 million veterans and provides more than 108 million prescriptions per year. Since its establishment in 1995, the VA PBM has managed pharmaceuticals and pharmaceutical-related policies, including drug safety and efficacy evaluations, pharmacologic management algorithms, and criteria for drug use. These evidence-based practices promote, optimize, and assist VA providers with the safe and appropriate use of pharmaceuticals while allowing for formulary decisions that can result in substantial cost savings. The VA PBM also has utilized various contracting techniques to standardize generic agents as well as specific drugs and drug classes (eg, antihistamines, angiotensin-converting enzyme inhibitors, alpha-blockers, and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors [statins]). These methods have enabled the VA to save approximately dollar 1.5 billion since 1996 even as drug expenditures continued to rise from roughly dollar 1 billion in fiscal year (FY) 1996 to more than dollar 3 billion in FY 2003. Furthermore, the VA PBM has established an outcomes research section to undertake quality-improvement and safety initiatives that ultimately monitor and determine the clinical impact of formulary decisions on the VA system nationwide. The experiences of this pharmacy benefits program, including clinical and contracting processes/procedures and their impact on the VA healthcare system, are described.

The perioperative risk of noncardiac surgery in patients with aortic stenosis (AS) remains ill-defined, and the few studies published have reported conflicting results. A sample of patients from the National Hospital Discharge Survey database diagnosed with AS who underwent any noncardiac surgical procedure was searched. Patients who underwent any cardiac surgery were excluded. Patients with AS were matched by decile of age and surgical risk for twice as many controls. A discharge diagnosis of acute myocardial infarction (AMI) and death was used as the end points for analysis. From 1996 to 2002, 5,149 patients with a diagnosis of AS had undergone noncardiac surgery and were matched with 10,284 controls. The incidence of AMI was greater in patients with AS than in controls (3.86% vs 2.03%, p <0.001). After correcting for gender and the presence of coronary artery disease, hypertension, and diabetes mellitus in a multivariate logistic regression model, the presence of AS was associated with an increased likelihood of AMI (odds ratio 1.55, 95% confidence interval 1.27 to 1.90, p <0.001). There was no significantly increased risk for death in patients with AS versus controls. In the era of more intense perioperative medical management of patients who undergo noncardiac surgery, the presence of AS increases the risk for perioperative AMI but not overall mortality. The impact of the actual severity of AS on outcomes with noncardiac surgery needs further study.