Predictors of response to sequential sunitinib and the impact of prior VEGF-targeted drug washout in patients with metastatic clear-cell renal cell carcinoma.

OBJECTIVE: To identify factors that can be used to identify metastatic clear cell RCC patients more likely to benefit from sequential sunitinib. PATIENTS AND METHODS: We identified patients who failed sorafenib or bevacizumab and subsequently received sunitinib. We looked at objective response rates (ORR), progression-free survival (PFS), and overall survival (OS) to sunitinib in relation to baseline clinical variables. RESULTS: Seventy-one patients received sunitinib sequential therapy. Median duration of follow-up after starting sunitinib was 9.3 months. Median PFS was 5.8 months; median OS was not reached. Significantly higher ORR was seen in patients with normal hemoglobin (25.6%) [defined as >12 gm/dl for female; >13 gm/dl for male]. In addition, a shorter PFS for patients with low hemoglobin, and patients with time from diagnosis to first treatment ≤ 1 year was found. There was a shorter OS for patients ≥ 60 years old, with brain metastasis, low hemoglobin, and time from diagnosis to treatment ≤ 1 year. There was no difference in ORR, PFS, or OS in patients who started sunitinib after or within a 30-day period. CONCLUSIONS: Metastatic clear-cell RCC patients with anemia have less clinical benefit from sequential sunitinib after failure of bevacizumab or sorafenib. Other factors associated with poor outcome include brain metastases, older age, and <1 year between diagnosis and first treatment. Importantly, no difference in outcomes was observed if sequential therapy was initiated within or after 30 days. External validation and prospective evaluation are needed to confirm these findings.

Angiogenesis inhibitor therapies for metastatic renal cell carcinoma: effectiveness, safety and treatment patterns in clinical practice-based on medical chart review.

OBJECTIVE: To assess the effectiveness, safety, and treatment patterns of anti-angiogenic agents in metastatic renal cell carcinoma (mRCC) in tertiary clinical practice settings. PATIENTS AND METHODS: We retrospectively reviewed the medical records in two tertiary oncology centres in the USA for all patients treated while off clinical trials from April 2003 to June 2008 who met the entry criteria and received one or more prescriptions for sunitinib or sorafenib, or one or more intravenous administrations of bevacizumab (off-label) as first-line anti-angiogenic treatment. The objective response rate (ORR) reviewed by independent physicians, adverse events (AEs), and treatment modifications were assessed. RESULTS: Among 144 patients receiving sunitinib (57), sorafenib (62) and bevacizumab (25), the median treatment duration was 10.5, 8.1 and 7.9 months, and the ORR was 37%, 9% and 13%, respectively. The ORR was lower for patients with metastases to bone, brain, lungs or lymph nodes. Common AEs (all grades) for sunitinib were fatigue (53%), diarrhoea (37%); for sorafenib, diarrhoea (50%), fatigue (40%); for bevacizumab, fatigue (40%), nausea (24%). In all, 34 (60%), 51 (82%) and 20 (80%) patients receiving sunitinib, sorafenib and bevacizumab, respectively, discontinued treatment; 10 (18%), 11 (18%) and four (16%) discontinued due to AEs; 21%, 40% and 12% had a dose interruption, and 30%, 35% and 0% had a dose reduction. CONCLUSIONS: Currently available anti-angiogenic agents had considerable effectiveness in clinical practice. However, the response rates appeared to be low in certain subgroups, but sample sizes were small. Patients had significant rates of AEs, many of which led to treatment modifications. The findings from this retrospective study suggest that there is a need for better-tolerated therapies for mRCC.

Treatment of anemia among women with chronic kidney disease in United States outpatient settings.

AIMS: Women with chronic kidney disease (CKD) are often at risk for anemia. This study examined variations in anemia care and management among women with CKD in outpatient settings in the United States. METHODS: The study utilized National Ambulatory Medical Care Survey (NAMCS) data from 1996 to 2003. Women aged 18 years or older with CKD were included based on ICD-9-CM codes for CKD, anemia, and reason for visit. Anemia-related medications were retrieved using NAMCS drug codes. RESULTS: Approximately 58 million weighted outpatient visits for women with CKD were made. Nearly 14% of these visits were by Hispanic women and 50% visits were by patients aged 65 years or older. Nephrologists accounted for only 15% of CKD patient visits and 51% of these patients had anemia diagnosis. Additionally, 32% of patients were using 5 or more medications. Women with Medicare coverage were 2.6 times more likely (p < .05) to be diagnosed with anemia by a nephrologist and were 2.4 times more likely (p < .05) to receive a prescription to treat anemia than patients seen by non-nephrologists. Hispanic women were 56% less likely (p < or = .05) to use 5 or more medications than non-Hispanic patients. CKD patients with anemia diagnosis were 50% less likely to receive 5 or more medications (p < or = .05). CONCLUSION: This study found many risk factors associated with the diagnosis and treatment of anemia in women with CKD being treated in U.S. outpatient settings. Increased awareness of early treatments for anemia and assessments of patients receiving multiple medications is needed in women with CKD.

Costs associated with cardiovascular events in patients with hypertension in US managed care settings.

Study quantified incremental cost of cardiovascular (CV) events in 6 high-risk and compelling indication subgroups: post-myocardial infarction (MI), diabetes, diabetic nephropathy, elderly, chronic kidney disease, and prior stroke. Based on claims data from privately insured individuals with 2+ hypertension (HTN) diagnoses in 2004-2006, we estimated regression-adjusted per-member-per-month healthcare costs after CVE. Costs were compared between patients with and without a CV events, and before and after CV events in each subgroup. The following CVevents were studied: acute MI, acute coronary syndrome, angina, ventricular arrhythmia, atrial arrhythmia, heart failure, coronary artery disease, left ventricular hypertrophy, stroke, and sinus tachycardia. Of 1,598,890 HTN patients, 510,118 had >/=1 CV event. Compared with controls, healthcare costs among patients with events were significantly greater across all cost components (inpatient, outpatient, and prescription drug). Acute MI and congestive heart failure generally had the largest incremental total healthcare costs. First-quarter post-event costs were attributable to inpatient costs. CV events are costly sequelae of hypertension in high-risk and CI subgroups.

Asthma pharmacotherapy prescribing in the ambulatory population of the United States: evidence of nonadherence to national guidelines and implications for elderly people.

OBJECTIVES: To examine the level of physician adherence to the Expert Panel Report 2 (EPR-2) pharmacotherapy guidelines of the asthma population, specifically in the elderly ambulatory patient population of the United States. DESIGN: Retrospective cross-sectional study using a national survey. SETTING: National Ambulatory Medical Care Survey data of U.S. elderly patients from 1998 through 2004. PARTICIPANTS: The weighted population sample size was 82,020,318 patients. There were 1,540 observations in this study (preweighted sample size) and 96 strata, with 446 population sampling units (PSUs). There were 11,868,340 patients that were elderly, and they accounted for 14.5% of the overall population sampled. MEASUREMENTS: Specific patient demographic variables, physician demographic variables, and information about asthma medications prescribed were extracted from the data set and analyzed. Descriptive statistics for the patient demographic, physician demographic, and asthma pharmacotherapy variables were generated. A series of logistic regression models were created, with the choice of asthma pharmacotherapy agent used as the dependent variable and patient and physician demographic variables as the independent variables. RESULTS: A major finding was that physicians were not adherent to the National Asthma Education and Prevention Program EPR-2 asthma pharmacotherapy guidelines. Another finding was that, although elderly patients (aged >or=65) were exposed to more-stable patterns of care, they were less likely to be prescribed controller medications, long-acting bronchodilators (LABAs), combinations of inhaled corticosteroids and LABAs, and short-acting beta agonists than patients aged 35 to 64. CONCLUSION: A more-concerted effort needs to be undertaken to improve physician adherence to the EPR-2 guidelines, especially in prescribing asthma pharmacotherapy to elderly patients.

Physician adherence to the national asthma prescribing guidelines: evidence from national outpatient survey data in the United States.

BACKGROUND: The Expert Panel 2 Guidelines for the Diagnosis and Management of Asthma (EPR-2 guidelines) were developed to improve medication prescribing for patients with persistent asthma and to control acute exacerbations of asthma. In addition, these guidelines also encourage physician-provided asthma education. Little is known about prescribing adherence to EPR-2 guidelines. OBJECTIVES: To examine physician adherence to EPR-2 asthma medication prescribing guidelines and determine patient and physician factors associated with prescribing of asthma medications. METHODS: This study was a cross-sectional retrospective analysis of National Ambulatory Medical Care Survey physician visit survey data from 1998 through 2004. Data were extracted on all patients with an International Classification of Diseases, Ninth Revision (ICD-9) code for asthma (493.XX) and reason for visit as asthma. The unit of analysis was individual patient visit. The dependent variables in analyses were specific type of drug class. The independent variables were various patient and physician factors. Logistic regression analysis was used to evaluate study objectives. RESULTS: Asthma patients in 2002 had 3.3 times more odds of being prescribed controller medications compared with asthma patients in 1998. Findings in 2004 were not significant. Elderly patients had 54% less odds of receiving controller medication compared with those in the 35- to 64-year-old age group. Patients in the other race category are 40% as likely to receive controller asthma medication compared with white patients. Physicians in 2002 had 6.3 times more odds of prescribing long-acting beta-agonists compared with those in 1998. Physicians without ownership stake in their practice had 1.9 times more odds of providing asthma education to their patients compared with those who owned their practice. CONCLUSION: Physician prescribing of asthma pharmacotherapy does not adequately comply with EPR-2 treatment guidelines.

Comparison of the Short-Form Survey 12 and the MacNew Heart Disease Health-Related Quality of Life Survey among patients with cardiac disease.

BACKGROUND: Health-related quality of life (HRQL) is an important outcome, especially for chronic diseases with no cure such as cardiovascular diseases. OBJECTIVE: To investigate the comparability of 2 HRQL instruments, the Short Form-12 (SF-12) survey and the MacNew Heart Disease HRQL survey (MacNew) in patients with cardiac diseases. METHODS: A nonexperimental cross-sectional study was conducted in a lipid clinic in the Houston metropolitan area. Patients with a prior cardiac disease were requested to complete the SF-12 and the MacNew scales while waiting to see the physician during their regular clinic visit. Cronbach's alpha values were estimated to evaluate internal consistency. Spearman's correlation was performed to examine the correlation between the SF-12 and the MacNew scale domains. RESULTS: A total of 118 patients were enrolled in this study. High Cronbach's alpha (from 0.89 to 0.94) were observed from all component scores in the MacNew scales. Physical component scores from the SF-12 and from the MacNew were highly correlated (r = 0.74; p < 0.001), as were the mental component score from the SF-12 and the emotional component score from the MacNew (r = 0.68; p < 0.001). CONCLUSIONS: The SF-12 and the MacNew appeared to be strongly correlated to each other for predicting a patient's HRQL in patients with a cardiac disease.

The economic burden associated with SSRI treatment failure in a managed care population.

OBJECTIVE: The objective of this study was to describe the economic burden to managed care associated with failure of selective serotonin reuptake inhibitor (SSRI) therapy in terms of direct medical costs. METHODS: A retrospective analysis of the PharMetrics database, a national managed care medical and pharmacy claims dataset of 1.9 million major depressive disorder patients between January 2003 and June 2005 was conducted. A pre-post comparison of annual medical cost increases following new SSRI treatment was performed and differences in mean cost increases for the SSRI-failure versus non-failure groups were calculated using t-tests and confirmed using multivariate linear regression. RESULTS: The percentage of subjects with likely SSRI treatment failure was 30.7% (n=2,595). The two groups were statistically similar (p>0.05) in age, gender distribution and insurance status. The mean increase in total direct medical costs was $6,489 versus $3,257 for the SSRI treatment failure and non-failure cohorts, respectively. The major components of these cost increases were outpatient cost ($2,579 vs. $1,309) and inpatient cost ($2,862 vs. $1,532), between the SSRI treatment failure and non-failure cohorts, respectively. All differences remained statistically significant at p<0.001, even after controlling for potential confounders. CONCLUSIONS: This descriptive study found that increased costs of major depressive disorder are substantial following the onset of a new SSRI treatment episode and significantly higher among patients with likely SSRI treatment failure.

Prescription refills and healthcare costs associated with topical metronidazole in Medicaid enrolled patients with rosacea.

BACKGROUND: Refill adherence to medications and healthcare costs are important factors to consider while making informed decisions regarding the treatment of rosacea patients. OBJECTIVE: The objective of this study was to examine predictors of number of refills related to topical metronidazole and total healthcare costs in rosacea patients. METHODS: This study utilized a longitudinal cohort design and followed rosacea patients enrolled in North Carolina Medicaid and who were prescribed at least one study medication (topical metronidazole, adapalene, azelaic acid, permethrin, and sulfacetamide). Patients' demographic characteristics, number of metronidazole refills, and different components of healthcare costs were examined. RESULTS: Out of the total 2587 rosacea patients, the majority (approximately 69%, n=1771) had one or more prescriptions for topical metronidazole. Most of the patients in this study were white (73%). After controlling for other variables, increasing age was associated with a higher number of metronidazole refills and healthcare costs (both p<0.001). Compared with white patients, African American patients had a significantly lower number of metronidazole refills (p<0.001). Compared with white patients, African American patients and 'other' races were associated with an 8.6% and 10.3% decrease in total healthcare costs respectively (both p<0.001). An increase in the number of metronidazole refills was not associated with an increase in healthcare costs. CONCLUSION: Patients' race is significantly associated with the number of topical metronidazole refills. Patients' healthcare costs increased with increasing age and charges paid for prescriptions. Topical metronidazole seems to be an economically feasible treatment option for Medicaid-enrolled patients with rosacea.

Depressive symptomatology, medication persistence, and associated healthcare costs in older adults with glaucoma.

PURPOSE: Depressive symptoms may impact patients' medication use behavior and utilization of healthcare services. This study examined association between depressive symptoms and Glaucoma medication-related persistence and predictors of associated healthcare charges in older adults with primary open angle Glaucoma. METHODS: This study used a retrospective cohort of older adults with primary open angle Glaucoma who completed health status assessment, used Glaucoma medications, and were enrolled in a Medicare Health Maintenance Organization. Baseline assessment surveyed patients on demographics, healthcare service utilization in year before enrollment, lifestyle, and quality of life. Demographic, clinical, and utilization-related economic variables were retrieved from administrative claims database of patients' Health Maintenance Organization. Survival techniques were used to measure time to discontinuation (persistence) and Center for Epidemiologic Studies Depression Scale a 20-item self-reporting scale assessed depressive symptomatology on a range of 0 to 60. Associations were examined using mixed-model regression approach. Sensitivity analysis that considered log-transformed and untransformed specifications of cost variable tested model appropriateness. RESULTS: In total 268 patients were followed for 2 years (N=536). After controlling for potential confounders and temporal effects, depressive symptomatology was associated with decreased Glaucoma medication-related persistence (P<0.005). Patients who lived alone and had cardiovascular disease showed higher odds of experiencing depressive symptoms (P<0.005). Healthcare charges increased with number of comorbidities and prescriptions (P<0.005). CONCLUSIONS: Presence of depressive symptoms in patients lead to poor Glaucoma medication use behavior. Healthcare expenditures increased for patients with increase in comorbidities. Plan enrollees' risk assessment offers advantage of improving health outcomes and reduces healthcare utilization.

The controversy surrounding OxyContin abuse: issues and solutions.

This paper overviews the controversies surrounding the abuse of prescription analgesic OxyContin((R)) (oxycodone hydrochloride; Purdue Pharma, Stamford, CT, USA). It discusses solutions to this medication-related issue, which has been touted as reaching epidemic proportions. Relevant literature from 1990 to 2004 was identified through a MEDLINE search, and a thorough internet-based search was conducted to obtain the latest updates and government reports. OxyContin became popular as a street drug through its ability to induce a quick heroin-like euphoria. The media hype surrounding OxyContin abuse and the "black box" warning on its label may have added to the abuse and diversion. The US Food and Drug Administration took steps by writing letters to Purdue Pharma, the manufacturers of OxyContin. Purdue Pharma developed a database to identify OxyContin abusers throughout the nation and also launched campaigns to educate patients through the internet. Further suggestions to managing the abuse of OxyContin include: community pharmacists' assessment of behavioral risk factors that could lead to patient medication abuse; medication abuse risk management courses for physicians; development of a national database linking all pharmacies specifically designed to identify abusers; and tamper-resistant prescription pads for controlled substances, which seems the most plausible and immediate solution to this problem.