Publications

Depression is a highly prevalent condition that results in substantial functional impairment. Advocates have attempted in recent years to make the 'business case' for investing in quality improvement efforts in depression care, particularly in primary care settings. The business case suggests that the costs of depression treatment may be offset by gains in worker productivity and/or reductions in other healthcare spending. In this paper, we review the evidence in support of this argument for improving the quality of depression treatment. We examined the impact of depression on two of the primary drivers of the societal burden of depression: healthcare utilisation and worker productivity. Depression leads to higher healthcare utilisation and spending, most of which is not the result of depression treatment costs. Depression is also a leading cause of absenteeism and reduced productivity at work. It is clear that the economic burden of depression is substantial; however, critical gaps in the literature remain and need to be addressed. For instance, we do not know the economic burden of untreated and/or inappropriately treated versus appropriately treated depression. There remain considerable problems with access to and quality of depression treatment. Progress has been made in terms of access to care, but quality of care is seldom consistent with national treatment guidelines. A wide range of effective treatments and care programmes for depression are available, yet rigorously tested clinical models to improve depression care have not been widely adopted by healthcare systems. Barriers to improving depression care exist at the patient, healthcare provider, practice, plan and purchaser levels, and may be both economic and non-economic. Studies evaluating interventions to improve the quality of depression treatment have found that the cost per QALY associated with improved depression care ranges from a low of 2519 US dollars to a high of 49,500 US dollars. We conclude from our review of the literature that effective treatment of depression is cost effective, but that evidence of a medical or productivity cost offset for depression treatment remains equivocal, and this points to the need for further research in this area.

INTRODUCTION: Based on Infectious Diseases Society of America (IDSA) guidelines, inappropriate fluconazole therapy in patients with candidemia is defined as an empiric dose <6 mg/kg/d, <12 mg/kg/d after Candida glabrata identification, or continued fluconazole use after identification of Candida krusei. However, the extent to which inappropriate antifungal therapy is due to improper dosing or drug selection has not been well investigated. The objectives of this study were to assess the incidence of inappropriate fluconazole therapy in patients with candidemia and to identify variables associated with inappropriate therapy.

METHODS: Retrospective cohort study from four medical centers of hospitalized patients with candidemia prescribed fluconazole. Appropriateness of fluconazole dosages (adjusted for renal dysfunction) was assessed at the time of symptom onset and after Candida identification.

RESULTS: Patients (206) were identified. Sixty-one of 112 (55%) patients who were given empiric therapy received an initial dose of fluconazole <6 mg/kg. After identification of the Candida species, 97 of 206 (47%) patients received inadequate fluconazole therapy based on IDSA guideline recommendations due to a fluconazole dose <12 mg/kg after isolation of C. glabrata (12%), continued use of fluconazole after isolation of C. krusei (3%), or a dose <6 mg/kg for all other Candida species (32%). Using multivariate logistic regression, increased weight in 1-kg increments (OR: 1.02; p = 0.0142) and a creatinine clearance (CRCL) >50 ml/minute (OR: 3.17; p = 0.0003) were associated with increased risk of inadequate fluconazole therapy.

CONCLUSION: A high prevalence of suboptimal dosing of fluconazole given empirically or after Candida species identification was documented. Increased weight and CRCL were significant predictors of inadequate fluconazole doses.

BACKGROUND: Nonadherence to prescription drugs results in poorer control of chronic health conditions. Because of significant racial/ethnic disparities in the control of many chronic diseases, differences in the rates of and reasons for medication nonadherence should be studied.

OBJECTIVES: 1) To determine whether rates of and reasons for medication nonadherence vary by race/ethnicity among seniors; and 2) to evaluate whether any association between race/ethnicity and nonadherence is moderated by prescription coverage and income.

DESIGN/SETTING: Cross-sectional national survey, 2003.

PATIENTS: Medicare beneficiaries > or = 65 years of age, who reported their race/ethnicity as white, black, or Hispanic, and who reported taking at least 1 medication (n = 14,829).

MAIN OUTCOME MEASURES: Self-reported nonadherence (caused by cost, self-assessed need, or experiences/side effects) during the last 12 months.

RESULTS: Blacks and Hispanics were more likely than whites to report cost-related nonadherence (35.1%, 36.5%, and 26.7%, respectively, p < .001). There were no racial/ethnic differences in nonadherence caused by experiences or self-assessed need. In analyses controlling for age, gender, number of chronic conditions and medications, education, and presence and type of prescription drug coverage, blacks (odds ratio [OR] 1.38; 95% confidence interval [CI] 1.08-1.78) and Hispanics (1.35; 1.02-1.78) remained more likely to report cost-related nonadherence compared to whites. When income was added to the model, the relationship between cost-related nonadherence and race/ethnicity was no longer statistically significant (p = .12).

CONCLUSIONS: Racial/ethnic disparities in medication nonadherence exist among seniors, and are related to cost concerns, and not to differences in experiences or self-assessed need. Considering the importance of medication adherence in controlling chronic diseases, affordability of prescriptions should be explicitly addressed to reduce racial/ethnic disparities.

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.