Consequences and costs of noncompliance with iron chelation therapy in patients with transfusion-dependent thalassemia: a literature review

BACKGROUND: Patients with thalassemia major require iron chelation therapy (ICT) to prevent complications from transfusional iron overload. Deferoxamine is effective, but requires administration as a slow continuous subcutaneous or intravenous infusion five to seven times per week. Deferiprone is a three-times-daily oral iron chelator, but has limited availability in the United States. Deferasirox is a once-daily oral iron chelator that was approved in the United States in 2005 for patients older than 2 years of age with transfusional iron overload. STUDY DESIGN AND METHODS: Published evidence on rates of compliance with ICT and the association between compliance, and the incidence and costs of complications of iron overload, in patients with thalassemia major was reviewed. RESULTS: A total of 18 studies were identified reporting data on compliance with ICT, including 7 that examined deferoxamine only, 6 that examined deferiprone only, and 5 that compared deferoxamine and deferiprone; no studies reporting compliance with deferasirox were identified. In studies of deferoxamine only, estimated mean compliance ranged from 59 to 78 percent. Studies of deferiprone generally reported better compliance, ranging from 79 to 98 percent. Results of comparative studies of deferoxamine and deferiprone suggest that compliance may be better with oral therapy. Numerous studies demonstrate that that poor compliance with ICT results in increased risk of cardiac disease and endocrinopathies, as well as lower survival. Although data on the costs of noncompliance are limited, a recent model-based study estimated the lifetime costs of inadequate compliance with deferoxamine to be $33,142. CONCLUSIONS: Inadequate compliance with ICT in thalassemia major is common and results in substantial morbidity and mortality, as well as increased costs.     

Risk-factor clustering and cardiovascular disease risk in hypertensive patients

BACKGROUND: Patients with hypertension often have other major risk factors for cardiovascular disease (CVD). Little is known, however, about the extent of risk-factor clustering in these patients and its importance in CVD risk and medical-care costs. METHODS: Study subjects were selected from the electronic medical records system of Kaiser Permanente Northwest, a large health maintenance organization, and included all patients aged > or =35 years with hypertension who were free of CVD in 1998. Subjects were stratified into eight risk-factor clusters based on whether or not they also had diabetes, hyperlipidemia, or a high body mass index (BMI). The risk of cardiovascular events was examined in each cluster over 6 years beginning January 1, 1999, using Kaplan-Meier methods and Cox proportional hazards models. Cumulative total medical-care costs (per patient) over 6 years also were examined. RESULTS: A total of 57,573 patients with hypertension who were free of CVD in 1998 were identified; 56% of subjects also had diabetes, hyperlipidemia, or high BMI. In analyses controlling for age, sex, and smoking status, the relative risk of cardiovascular events over 6 years was highest for patients with comorbid diabetes, ranging from 2.07 (95% confidence interval, 1.86-2.30) for those with diabetes only to 2.80 (95% confidence interval, 2.48-3.17) for those with diabetes, hyperlipidemia, and high BMI. Cumulative medical-care costs generally increased with additional risk factors. Comorbid diabetes had the greatest impact on costs over 6 years. CONCLUSIONS: More than 50% of patients with hypertension also had diabetes, hyperlipidemia, or high BMI. Patients with these additional risk factors (especially diabetes) had a substantially higher CVD risk and medical-care costs.     

Economic consequences of failure of initial antibiotic therapy in hospitalized adults with complicated intra-abdominal infections

BACKGROUND: Initial antibiotic therapy in hospitalized adults with complicated intra-abdominal infection (cIAI) usually is empiric. We explored the economic consequences of failure of such therapy in this patient population. METHODS: Using a large U.S. multi-institutional database, we identified all hospitalized adults admitted between April 1, 2003, and March 31, 2004; who had any cIAI; underwent laparotomy, laparoscopy, or percutaneous drainage of an intra-abdominal abscess ("surgery"); and received intravenous (IV) antibiotics. Initial therapy was characterized in terms of all IV antibiotics received, on the day of or one day before initial surgery. Antibiotic failure was designated on the basis of the need for reoperation or receipt of other IV antibiotics postoperatively. Switches to narrower spectrum agents and changes in regimen prior to discharge with no other evidence of clinical failure were not counted as antibiotic failures. Using multivariable linear regression, duration of IV antibiotic therapy, hospital length of stay, and total inpatient charges were compared between patients who did and did not fail initial therapy. Mortality was compared using multivariable logistic regression. RESULTS: Among 6,056 patients who met the study entrance criteria, 22.4% failed initial antibiotic therapy. Patients who failed received an additional 5.6 days of IV antibiotic therapy (10.4 total days [95% confidence interval 10.1, 10.8] days vs. 4.8 total days [4.8, 4.9] for those not failing), were hospitalized an additional 4.6 days (11.6 total days [11.3, 11.9] vs. 6.9 total days [6.8, 7.0], respectively), and incurred $6,368 in additional inpatient charges ($16,520 [$16,131, $16,919] vs. $10,152 [$10,027, $10,280]) (all, p < 0.01). They also were more likely to die in the hospital (9.5% vs. 1.3%; multivariable odds ratio 3.58 [95% confidence interval 2.53, 5.06]). CONCLUSIONS: Failure of initial IV antibiotic therapy in hospitalized adults with cIAIs is associated with longer hospitalization, higher hospital charges, and a higher mortality rate.     

Retrospective study of the effect of skeletal complications on total medical care costs in patients with bone metastases of breast cancer seen in typical clinical practice

Intravenous bisphosphonates are effective in reducing the incidence of skeletal-related events (SREs) in women with bone metastases of breast cancer. The cost-effectiveness of such therapy depends in part on the potential cost savings achieved by preventing these events. However, estimates of the costs of SREs in women with bone metastases of breast cancer in typical US clinical practice are unavailable. The purpose of this study was to estimate the treatment costs of clinically significant SREs and the impact of these events on total medical care costs in patients with bone metastases of breast cancer. Data were gathered from a large US health insurance claims database. Patients with bone metastases of breast cancer who experienced one or more clinically significant SREs in typical clinical practice were matched to similar patients without SREs based on propensity scores. Kaplan-Meier estimated total medical care costs were compared over 60 months for propensity-matched samples of patients with SREs and without SREs. We identified 617 patients with breast cancer and bone metastases, including 321 (52%) with > or = 1 clinically significant SRE. After matching, there were 201 patients each in the SRE and no-SRE groups, with mean follow-up of 13.8 and 11.0 months, respectively. In the SRE group, costs of treatment of SREs were $13,940 (95% CI, $11,240-$16,856) per patient. Total medical care costs were $48,173 (95% CI, $19,068-$77,684) greater in SRE versus no-SRE patients (P = 0.001). The costs of clinically significant SREs in patients with breast cancer and bone metastases seen in typical clinical practice are substantial. Treatments that reduce the incidence of SREs, such as intravenous bisphosphonates, should reduce these costs.     

Risk of chronic kidney disease in hypertensive patients with other metabolic conditions

Using a retrospective cohort design and electronic medical records, we examined chronic kidney disease (CKD) risk over a 6-year period among hypertensive patients in relation to the presence of diabetes, hyperlipidaemia and/or high body mass index. After adjusting for age, sex, smoking status and baseline glomerular filtration rate (GFR), hypertensive patients without other metabolic risk factors had a relative risk of CKD (versus normotensive patients) of 2.0 (95% CI 1.8-2.2); hypertensive patients with other metabolic conditions had adjusted relative risks ranging from 2.4 to 2.6 for those without comorbid diabetes, and from 3.3 to 5.5 for those with comorbid diabetes. Our study thus confirms prior research demonstrating elevated CKD risk in hypertensive patients, and suggests that this risk varies substantially in relation to other metabolic conditions, especially diabetes.