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Valproic acid (VPA) is an established drug in the long-term therapy of seizure disorders. Recently, VPA has been associated with anticancer activity, an effect thought to be mediated through the inhibition of cellular histone deacetylase 1. We investigated the effect of various doses of VPA (0, 1.2, and 5.0 mmol/L) administered either acutely or chronically on histone acetylation, p21 gene expression, androgen receptor expression, prostate-specific antigen (PSA) expression, and cell survival and proliferation in prostate cancer cell lines. We also studied the effect of chronic VPA on tumor xenograft growth in vivo. Our results show that acute treatment (3 days) VPA can increase net histone H3 acetylation and up-regulate p21, AR, and cytosolic PSA expression. Interestingly, the effects on AR and PSA are reversed with chronic teatment. In addition, acute VPA reduces cell survival but has no effect on the subsequent proliferation of surviving cells following drug withdrawal. However, when VPA is chronically administered (10-14 days) to prostate cancer cells, even lower doses of VPA result in marked decreases in the net proliferation rate, correlating with increased caspase-2 and caspase-3 activation. These effects are evident in both androgen receptor-positive (LNCaP and C4-2) and androgen receptor-negative (DU145 and PC3) prostate cancer cells. Moreover, chronic VPA treatment results in statistically significant reduction of tumor xenograft growth in vivo. We conclude that acute treatment has nominal effects on prostate cancer cell survival and proliferation, but chronic VPA results in profound decreases in proliferation, independently of androgen regulation. (Cancer Res 2006; 66(14): 7237-44)

Supplementary Figure 2 from Chronic Administration of Valproic Acid Inhibits Prostate Cancer Cell Growth In vitro and In vivo

Supplementary Figure 3 from Chronic Administration of Valproic Acid Inhibits Prostate Cancer Cell Growth In vitro and In vivo

Supplementary Figure 1 from Chronic Administration of Valproic Acid Inhibits Prostate Cancer Cell Growth In vitro and In vivo

Supplementary Figure 4 from Chronic Administration of Valproic Acid Inhibits Prostate Cancer Cell Growth In vitro and In vivo

AIM To quantify the wider impacts of increased graft survival on the size of the kidney transplant waitlist and health and economic outcomes. MATERIALS AND METHODS The analysis employed known steady-state solutions to a double-queueing system as well as simulations of this system. Baseline input parameters were sourced from the Organ Procurement and Transplant Network and the United States Renal Data System. Three increased graft survival scenarios were modeled: decreases in repeat transplant candidates joining the waitlist of 25%, 50%, and 100%. RESULTS Under the three scenarios, we estimated that the US waitlist size would decrease from 91,822 to 85,461 (6.9% decrease), 80,073 (12.8% decrease), and 69,340 (24.4% decrease), respectively. Patient outcomes improved, with lifetime quality-adjusted life years (QALYs) for a 1-year cohort of transplant recipients increasing by 10,010, 16,888, and 43,345 over the three scenarios. Discounted lifetime costs for the cohort in the new steady state were lower by $1.6 billion, $2.3 billion, and $9.0 billion for each scenario, respectively. Spillover impacts (i.e. benefits that accrued beyond the patients who directly experienced increased graft survival) accounted for 41-48% of the QALY gains and ranged from cost increases of 3.3% to decreases of 5.5%. LIMITATIONS The model is a simplification of reality and does not account for the full degree of patient heterogeneity occurring in the real world. Health economic outcomes are extrapolated based on the assumption that the median patient is representative of the overall population. CONCLUSIONS Increasing graft survival reduces demand from repeat transplants candidates, allowing additional candidates to receive transplants. These spillover impacts decrease waitlist size and shorten wait times, leading to improvements in graft and patient survival as well as quality-of-life. Cost-effectiveness analyses of treatments that increase kidney graft survival should incorporate spillover benefits that accrue beyond the direct recipient of an intervention.

The relation between elevated lipoprotein(a) and total atherosclerotic cardiovascular disease (ASCVD) residual risk in persons with known cardiovascular disease on statin therapy is not well-established. We examined first and total recurrent ASCVD event risk in statin-treated adults with prior ASCVD. We studied 3,359 adults (mean age 63.6 years, 85.1% male) with prior ASCVD on statin therapy from the AIM-HIGH clinical trial cohort. The first and total ASCVD event rates were calculated by lipoprotein(a) [Lp(a)] categories. Cox regression and Prentice, Williams and Peterson (PWP) models provided hazard ratios (HRs) for ASCVD events over a mean follow-up of 3.3 years, adjusted for age, gender, trial treatment, LDL-C, and other risk factors. A total of 747 events occurred during follow-up, among which 544 were first events. First and total ASCVD event rates were greater with higher Lp(a) levels. Compared with Lp(a)

Background: The relation between elevated lipoprotein(a) [Lp(a)] and future atherosclerotic cardiovascular disease (ASCVD) in those with vs. without diabetes mellitus (DM) but known cardiovascular disease (CVD) is not clear. We examined recurrent ASCVD event risk by DM status in persons with known CVD on statin therapy. Methods: We studied 1,354 patients with and 2,005 patients without DM, all with prior CVD on statin therapy in the AIM-HIGH cohort. First and total recurrent ASCVD event rates were calculated by Lp(a) levels and the PWP model provided hazard ratios (HRs) for events over a mean follow-up of 3.3 years, adjusted for age, sex, trial treatment, LDL-C, and other risk factors. Results: ASCVD event rates (per 1000 person years) increased with Lp(a) levels ranging from Conclusions: Higher Lp(a) levels predict residual ASCVD risk. However, ASCVD event risk may occur at lower levels of Lp(a) in those with vs. without DM. Future investigations in larger cohorts are needed to confirm these findings. Disclosure Y. Zhao: None. J.C. Sung: Employee; Self; Novartis Pharmaceuticals Corporation. A. Browne: Employee; Self; Novartis Pharmaceuticals Corporation. N.D. Wong: Advisory Panel; Self; Esperion Therapeutics, Inc. Research Support; Self; Amarin Corporation, Amgen, Boehringer Ingelheim Pharmaceuticals, Inc., Novartis AG, Novo Nordisk Inc. Speaker’s Bureau; Self; Amarin Corporation, Sanofi.

In metastatic castration-resistant prostate cancer (mCRPC), optimal treatment sequences are unknown. We assessed second-line taxane (TT) versus androgen receptor-targeted therapy (ART), after initial ART failure, in United States oncology community practices.Using electronic medical records, patients with mCRPC receiving first-line ART and second-line therapy (TT, ART) were identified. Response and overall survival (OS) were evaluated from second-line therapy initiation. Multivariate analyses were adjusted for year, age, metastases, opioid use, prostate-specific antigen (PSA), hemoglobin, alkaline phosphatase, and albumin levels.Of 546 patients receiving first-line ART, 206 and 340 received second-line TT and ART. Compared with patients receiving second-line ART, patients receiving TT were younger (median, 74 vs. 79 years), more had intermediate-high Halabi risk scores (59% vs. 35%), had higher opioid use (42% vs. 22%), median PSA (116 vs. 48 ng/mL), alkaline phosphatase (112 vs. 87 U/L), and lactate dehydrogenase (254 vs. 201 U/L), and had lower hemoglobin (11.2 vs. 12.3 g/dL) and albumin levels (3.8 vs. 4.0 g/dL); all P .001. Response rates were higher with second-line TT versus ART (clinical response, 44.2% vs. 24.7%; P = .006; PSA response, 44.5% vs. 28.7%; P = .004). OS did not differ between cohorts (hazard ratio [HR], 0.90; P = .511). Among patients with a poor prognosis (hemoglobin 11 g/d; albumin lower limit of normal), those receiving second-line TT versus ART showed improved OS (HR, 0.52; P = .004 and HR, 0.36; P = .003, respectively).Despite more severe disease profiles, patients with mCRPC receiving second-line TT versus ART achieved higher response rates after initial ART. Poor prognosis patients had improved OS with second-line TT versus ART.

The relation between elevated lipoprotein(a) [Lp(a)] with total ASCVD residual risk specially in persons with known ASCVD on statin therapy is not well-established. We examined the first and total recurrent ASCVD risk among this population using the AIM-HIGH cohort. We studied 3,359 adults (mean

Routine clinical practice data often differ from clinical trials. This study describes real-world treatment patterns and effectiveness among patients with metastatic colorectal cancer (mCRC) receiving ziv-aflibercept in non-academic, community oncology practices in the USA. De-identified electronic medical records from Vector Oncology and Altos Solutions databases were analysed. We identified 218 patients diagnosed with mCRC who had received prior oxaliplatin therapy and initiated ziv-aflibercept as part of second-line or later-line therapy. Overall survival (OS) and progression-free survival (PFS) were estimated using Kaplan–Meier analysis. Mean age was 62.8 years at ziv-aflibercept initiation. Most patients (91.7%) received bevacizumab before ziv-aflibercept, 95.4% initiated ziv-aflibercept with FOLFIRI or another irinotecan-based regimen, and 59.6% had received prior irinotecan. Overall, 24.8% of patients initiated ziv-aflibercept in second line, 31.7% in third line, 21.6% in fourth line and 22.0% in later lines of therapy. Mean duration of ziv-aflibercept treatment was 5.3 months. For patients initiating ziv-aflibercept in second-, third- and fourth-line therapy, median OS was 11.9 (95% confidence interval 5.1–16.2), 11.1 (6.9–16.7) and 8.1 (5.2–11.4) months, respectively, and median PFS was 4.4 (2.8–6.5), 4.3 (2.9–6.3) and 3.4 (2.2–5.2) months, respectively. Common adverse events (AEs) (any grade) included gastrointestinal disorders (64.7%) and asthenia/fatigue (63.3%). In routine clinical practice, ziv-aflibercept was frequently initiated in third line or later lines of therapy. Although patients receiving ziv-aflibercept were more heavily pretreated and potentially less robust compared with the VELOUR trial, median OS for patients receiving second-line ziv-aflibercept was comparable. AE rates were similar to or lower than the VELOUR trial.

It is unclear how treatment sequencing for metastatic castration-resistant prostate cancer (mCRPC) affects real-world patient outcomes. We assessed treatment sequences, patient characteristics and overall survival (OS) in post-docetaxel mCRPC patients. mCRPC patients receiving second-line cabazitaxel or androgen receptor-targeted therapy (ART; abiraterone/enzalutamide) post-docetaxel were identified using electronic medical records. OS was assessed from second-line therapy initiation using Cox regressions adjusting for: metastases; prostate-specific antigen (PSA); hemoglobin; alkaline phosphatase (ALP); albumin; second-line therapy initiation year. Following docetaxel (n = 629), 123 (19.6%) and 506 (80.4%) patients received cabazitaxel and ART, respectively. One hundred and ninety-five patients received additional treatments thereafter (54 following cabazitaxel; 141 following ART). Although patients receiving second-line cabazitaxel versus ART had similar disease characteristics at first-line therapy initiation, at second-line therapy initiation they had higher mean PSA (386.6 vs. 233.9 ng/mL) and ALP (182.0 vs. 167.3 u/L), lower mean hemoglobin (10.8 vs. 11.5 g/dL), and more frequently had intermediate/high-risk Halabi scores (61.8 vs. 48.4%); all p

Objective To evaluate the long-term urinary tract infection (UTI) rates after endoscopic correction of vesicoureteral reflux and the possible risk factors for urinary infection. Materials and Methods A retrospective study of patients who underwent endoscopic management of vesicoureteral reflux at a single institution from 2001 to 2011 was performed. Patients were followed up for a minimum of 1 year. Voiding cystourethrograms were completed 3 months postoperatively. UTI questionnaire pertaining to the patient's UTI history before and after the surgery was mailed to each patient. Data were first evaluated looking only at culture-confirmed UTIs, and a second analysis included all patient-reported and culture-confirmed urinary infections. Factors considered in the analysis included sex, age, preoperative dimercaptosuccinic acid (DMSA) scan, reflux on postoperative voiding cystourethrogram, voiding dysfunction, and preoperative reflux grade. Results Data on 175 patients for a minimum of 1 year were collected. There were 34 of 175 confirmed UTIs after endoscopic management, and 11 confirmed febrile UTIs. There were no significant predictors of febrile or afebrile UTIs in this group. Fifty-three of 175 patients (30%) experienced any UTI, 19 of which were febrile (10%). In this group, recurrent reflux was the only significant predictor of UTI ( P = .03) and febrile UTIs ( P = .04). Patients with more UTIs preoperatively were more likely to have a postoperative febrile UTI. Conclusion Rates of UTI and febrile UTI in endoscopic management are similar and no better than those for open ureteral reimplantation. Longer follow-up suggests an association of recurrent reflux and preoperative UTI rates as predictors of postoperative febrile UTIs. These patients benefit from closer postoperative observation.

Endoscopic dextranomer/hyaluronic acid (Dx/HA) injection by subureteric transurethral injection (STING) or hydrodistention implantation technique (HIT) for treatment of vesicoureteral reflux (VUR) has variable results with HIT reporting better outcomes. We determined outcomes with each technique comparing reflux resolution rates and evaluating predictors of treatment success and failure.Univariate and multivariate analysis compared 163 patients (246 ureters) who underwent a single endoscopic Dx/HA injection from December 2001 to April 2010. Data on pre, peri, and post-operative variables were prospectively collected. Resolution was defined as no reflux on voiding cystourethrogram (VCUG) at 3 month follow up. Calculated ellipsoid volume (CEV) of Dx/HA mounds was defined as (4/3π(height/2) × (length/2) × (width/2)) based on post-operative ultrasound dimensions.Ureter resolution was 79.75% and 80.84% for STING and HIT, respectively (p = 0.86). Patient resolution was 70.0% and 74.3% for STING and HIT, respectively (p = 0.57). Multivariate ureter analysis revealed lower pre-operative grade (p = 0.004) and injected Dx/HA volume 0.80-1.00 mL (p = 0.039) as predictors of success. CEV0.20 mL (p = 0.002) and CEV/injected-volume25% (p = 0.006) were predictors of failure. Volcano morphology (p = 0.004) and lower pre-op grade (p = 0.015) were predictors of success for STING and HIT, respectively.We found no differences in ureter or patient resolution between endoscopic Dx/HA injection techniques STING or HIT. Lower pre-operative grade and moderated Dx/HA volume were predictors of success regardless of technique.

ALA induction in transplantation has been shown to reduce the need for maintenance immunosuppression. We report the outcome of 25 pediatric renal transplants between 2007 and 2010 using ALA induction followed by tacrolimus maintenance monotherapy. Patient ages were 1-19 yr (mean 14 ± 4.1 yr). Time of follow-up was 7-51 months (mean 26 ± 13 months). Tacrolimus monotherapy was maintained in 48% of patients, and glucocorticoids were avoided in 80% of recipients. Mean plasma creatinine and GFR at one yr post-transplant were 0.88 ± 0.3 mg/dL and 104.4 ± 25 mL/min/1.73m(2) , respectively. One, two, and three-yr actuarial patient and graft survival rates were 100%. The incidence of early AR (

Objective: This study aims to compare the effectiveness of insulin glargine 300 U/mL (Gla-300) with its accompanying patient support program with that of other basal insulin and available patient support programs in patients with type 2 diabetes (T2D) in a real-world setting in terms of achieving HEDIS (Healthcare Effectiveness Data and Information Set) individualized glycemic targets without documented symptomatic hypoglycemia. Methods: Achieve Control is a US-based, multicenter, randomized, open-label, active-controlled, parallel group pragmatic Phase IV trial in insulin-naïve patients with T2D uncontrolled on ≥2 oral antidiabetes drugs (OAD) and/or glucagon-like peptide-1 receptor antagonists (GLP-1 RA). Inclusion criteria include a diagnosis of T2D, age ≥18 years, and glycated hemoglobin (HbA1c) between 8.0% and 11.0%. Patients will be assigned to either the Gla-300 or other basal insulin group. The primary end point is the proportion of patients achieving HEDIS HbA1c targets (Conclusion: Pragmatic clinical trials offer the potential to assess comparative effectiveness in broadly based patient populations receiving care (with or without a corresponding educational support program) in real-world clinical settings. The results of Achieve Control should elucidate the benefits of management of T2D with Gla-300 versus other basal insulins in terms of patient outcomes, experiences, and perceptions, and its impact on healthcare resource utilization and cost. Clinical trial registration: www.clinicaltrials.gov identifier is NCT02451137.

Widespread use of statins has improved hypercholesterolemia management, yet a significant proportion of patients remain at risk for cardiovascular (CV) events. Analyses of treatment patterns reveal inadequate intensity and duration of statin therapy among patients with hypercholesterolemia, and little is known about real-world statin use, specifically in subgroups of patients at high risk for CV events.To examine patterns of statin use and outcomes among patients with high-risk features who newly initiated statin monotherapy.Adult patients (aged18 years) at high CV risk who received1 prescription for statin monotherapy and who had not received lipid-modifying therapy during the previous 12 months were identified from the Truven MarketScan Commercial and Medicare Supplemental databases (from January 2007 to June 2013). Patients with atherosclerotic cardiovascular disease (ASCVD) or diabetes were hierarchically classified into 5 mutually exclusive CV risk categories (listed here in order from highest to lowest risk): (1) recent CV event (subcategorized by hospitalization for acute coronary syndrome [ACS] or other non-ACS CV event within 90 days of index); (2) coronary heart disease (CHD); (3) history of ischemic stroke; (4) peripheral artery disease (PAD); and (5) diabetes. Outcomes of interest included changes in therapy, proportion of days covered (PDC), time to discontinuation, and proportion of patients with ASCVD-related inpatient visit during the follow-up period. Statin therapy was subdivided into high-intensity treatment (atorvastatin 40 mg or 80 mg, rosuvastatin 20 mg or 40 mg, or simvastatin 80 mg) or moderate- to low-intensity treatment (all other statins and statin dosing regimens). Follow-up data were obtained from the index date (statin initiation) until the end of continuous enrollment.A total of 541,221 patients were included in the analysis. The majority of patients were stratified in the diabetes cohort (61.1%), followed in frequency by recent ACS event (15.8%), recent non-ACS CV event (9.9%), PAD (4.7%), CHD (4.4%), and history of ischemic stroke (4.1%). Only 15.0% of the population initiated therapy with a high-intensity statin, and 22.5% of these high-intensity statin initiators switched to a moderate- to low-intensity regimen during the follow-up period. Median time to statin discontinuation was approximately 15 months. Duration of treatment was longer among those who were treated with a high-intensity versus a moderate- to low-intensity statin regimen (21 and 15 months, respectively). The PDC was highest in the recent ACS hospitalization cohort (66.4%) and lowest in the diabetes cohort (55.5%). The PDC was significantly greater among patients who initiated treatment with a high-intensity statin regimen than with a moderate- to low-intensity statin regimen (62.1% vs. 57.5%, respectively; P0.001). At 1 year, Kaplan-Meier estimates of the cumulative rates for ASCVD-related hospitalizations ranged from 3.5% (diabetes) to 21.8% (recent ACS hospitalization).Patients at high risk for CV events are suboptimally dosed with statins, have high rates of discontinuation, and have low rates of adherence. Despite the use of statin therapy, ASCVD-related inpatient visit rates were high, particularly among those patients at highest risk because of a recent ACS hospitalization. Future interventions are required to ensure that high-risk patients are effectively managed to reduce subsequent morbidity and mortality.Support for this research was provided by Regeneron Pharmaceuticals, Tarrytown, New York, and Sanofi US, Bridgewater, New Jersey. Menzin and Lin are employees of Boston Health Economics, which received consulting fees from Sanofi. Friedman is a consultant to Boston Health Economics. Lin, Friedman, and Menzin have received research support from Sanofi US. Sung, Mallya, Panaccio, and Koren are employees of Sanofi US and also have ownership interest in Sanofi US. Sanchez is an employee of and has ownership interest in Regeneron Pharmaceuticals. Neumann has served on advisory boards for MerckCo, Takeda Pharmaceutical Company, Genentech, Novartis, Bayer AG, UCB, Sanofi US, Robert Wood Johnson Foundation, and Cubist and serves as consultant for Boston Health Economics, Forrest, P urdue, and Smith and Nephew. This research has been presented in part at the International Society for Pharmacoeconomics and Outcomes Research, 20th Annual International Meeting, May 16-20, 2015, Philadelphia, Pennsylvania. All authors contributed to the study design, protocol development, and results interpretation. Lin and Menzin were responsible for conducting the study analyses. All authors were involved in manuscript development and approved the submitted version.

Vesicoureteral reflux (VUR) is the most common uropathy affecting children. Compared to children without VUR, those with VUR have a higher rate of pyelonephritis and renal scarring following urinary tract infection (UTI). Options for treatment include observation with or without antibiotic prophylaxis and surgical repair. Surgical intervention may be necessary in patients with persistent reflux, renal scarring, and recurrent or breakthrough febrile UTI. Both open and endoscopic approaches to reflux correction are successful and reduce the occurrence of febrile UTI. Estimated success rates of open and endoscopic reflux correction are 98.1% (95% CI 95.1, 99.1) and 83.0% (95% CI 69.1, 91.4), respectively. Factors that affect the success of endoscopic injection include pre-operative reflux grade and presence of functional or anatomic bladder abnormalities including voiding dysfunction and duplicated collecting systems. Few studies have evaluated the long-term outcomes of endoscopic injection, and with variable results. In patients treated endoscopically, recurrent febrile UTI occurred in 0–21%, new renal damage in 9–12%, and recurrent reflux in 17–47.6% of treated ureters with at least 1 year follow-up. These studies highlight the need for standardized outcome reporting and longer follow-up after endoscopic treatment.

The Aliskiren in the Evaluation of Proteinuria in Diabetes (AVOID) trial demonstrated that adding aliskiren, an oral direct renin inhibitor, at a dosage of 300 mg/d to the highest approved dosage of losartan and optimal antihypertensive therapy reduces albuminuria over 6 mo among patients with type 2 diabetes, hypertension, and albuminuria. The cost-effectiveness of this therapy, however, is unknown. Here, we used a Markov model to project progression to ESRD, life years, quality-adjusted life years, and lifetime costs for aliskiren plus losartan versus losartan. We used data from the AVOID study and the Irbesartan in Diabetic Nephropathy Trial (IDNT) to estimate probabilities of progression of renal disease. We estimated probabilities of mortality for ESRD and other comorbidities using data from the US Renal Data System, US Vital Statistics, and published studies. We based pharmacy costs on wholesale acquisition costs and based costs of ESRD and transplantation on data from the US Renal Data System. We found that adding aliskiren to losartan increased time free of ESRD, life expectancy, and quality-adjusted life expectancy by 0.1772, 0.1021, and 0.0967 yr, respectively. Total expected lifetime health care costs increased by $2952, reflecting the higher pharmacy costs of aliskiren and losartan ($7769), which were partially offset by savings in costs of ESRD ($4860). We estimated the cost-effectiveness of aliskiren to be $30,500 per quality-adjusted life year gained. In conclusion, adding aliskiren to losartan and optimal therapy in patients with type 2 diabetes, hypertension, and albuminuria may be cost-effective from a US health care system perspective.

Background: Resistant hypertension, or failure to attain blood pressure (BP) goals while treated with ≥3 antihypertensives (including a diuretic), occurred in 15% to 18% of patients in prospective cohort trials. Objectives: The aims of this work were to identify the prevalence of resistant hypertension in an ambulatory care setting and to describe the characteristics of patients with resistant hypertension. Methods: Adults with hypertension were retrospectively identified in a US electronic medical record from November 1, 2002, through November 30, 2005. Antihypertensive treatment and BP values were assessed to identify those with BP ≥140/90 mm Hg (>130/80 mm Hg for those with diabetes mellitus or kidney disease). Patients treated with ≥3 agents (including a thiazide) who had ≥1 BP level above target were classified as having resistant hypertension. Baseline characteristics were compared between those with and those without resistant hypertension. Results: Of 29,474 study patients aged ≥18 years, 21,460 (72.8%) had ≥1 prescription order for an antihypertensive and 19,202 (65.1%) had a follow-up BP level above target. The analysis found that 2670 patients (9.1% overall or 12.4% of those who were treated) were classified as having resistant hypertension. Relative to those without resistant hypertension, a greater proportion of those with resistant hypertension were female (65.6% vs 60.5%), were older (66.2 vs 63.0 years), had a higher body mass index (31.6 vs 30.4 kg/m 2 ), had higher baseline BP levels (148/81 vs 138/80 mm Hg), and had higher rates of diabetes mel-litus (35.2% vs 20.1%) or kidney disease (4.9% vs 2.7%) than those without resistant hypertension (all comparisons, P Conclusions: This retrospective, observational pilot study of usual community practice supports the findings from prospective trials that resistant hypertension is an important clinical problem. More effective management is needed to enable patients with, or at risk for, resistant hypertension to achieve BP goals.

Background There are few comprehensive estimates of the cost of psoriasis in the United States. Objective We sought to quantify the incremental direct medical and indirect work loss costs associated with psoriasis. Methods A de-identified claims database from 31 self-insured employers during the period 1998 to 2005 was used. Patients with at least two psoriasis diagnosis claims (N = 12,280) were compared with 3 control subjects (matched on year of birth and sex) without psoriasis. Multivariate two-part regression analysis was used to isolate the incremental cost of psoriasis by controlling for comorbidities and other confounding factors. Results After multivariate adjustment, the incremental direct and indirect costs of psoriasis were approximately $900 and $600 ( P Limitations The database used in this study does not contain information on patient out-of-pocket costs or loss of productivity costs at work. Conclusion The incremental cost of psoriasis is approximately $1500 per patient per year, with work loss costs accounting for 40% of the cost burden.

Introduction: The clinical and economic impact of statin intolerance (SI) in high CV risk patients is unknown due, in part, to a lack of consensus in its definition. We sought to define and validate an SI algorithm for use in an administrative database (AD) among high-CV risk patients Methods: Adults with ≥1 qualifying change (See Table 1) in statin therapy and ≥1 prior diagnosis of hyperlipidemia, hypercholesterolemia, or mixed dyslipidemia were identified from the AD of the Health Alliance Plan at Henry Ford Health System (HFHS). A sample of 1000 patients was drawn from the pool of eligible adults and stratified by high CV risk based on presence of comorbid conditions including diabetes, coronary heart disease, and peripheral artery disease. Statin utilization and adverse events data were abstracted both from the AD and the HFHS electronic medical record (EMR). SI was defined using both a primary definition inclusive of all possible statin related adverse events and a secondary definition that included only musculoskeletal events. SI was categorized as absolute (AI) or titration (TI) intolerance. The performance of the AD algorithm was assessed using measures of concordance (Cohen’s kappa [κ]) and accuracy (sensitivity, specificity, positive predictive value [PPV]) with the EMR as reference. Results: A total of 353 patients (48% female, 44% Caucasian, mean (SD) age 63 (12) years) were identified as high CV risk with 33% having a history of CHD, 77% diabetes and 2% PAD. Forty-two percent of patients were on simvastatin, 35% atorvastatin, 11% lovastatin, 7% rosuvastatin and 6% pravastatin/fluvastatin. Table 1 characterizes the validation sample. SI was identified in 19.3% and 20.7%, AI in 3.1% and 2.8%, and TI in 16.7% and 18.7% of patients in the EMR and AD, respectively. The algorithm identifying any SI had robust concordance (κ=0.73), good sensitivity (80.9%) and PPV (75.3%). The TI algorithm performed better (κ=0.78, sensitivity=86.4%, PPV=77.3%) than the AI algorithm (κ=0.56, sensitivity=54.5%, PPV=60.0%). Specificity was high (>94%) across all 3 algorithms. Conclusion: This study successfully defined SI among high-CV risk patients using an evidence-based validated algorithm. To our knowledge, this is the first such algorithm for use in AD to be made available to decision-makers.

Introduction Previous studies have estimated the costs of skeletal-related events (SREs) for patients with bone metastases of solid tumors by tallying costs for services specifically attributable to these events. This approach may underestimate costs if SREs indirectly increase use of other services. Methods This is a retrospective observational study using a large health insurance claims database. Patients with bone metastases of lung cancer who experienced ≥1 SRE were matched to similar patients without SREs based on propensity scores. Kaplan-Meier estimated total medical care costs were compared for propensity-matched samples of patients with SREs and without SREs. Results We identified 534 patients with lung cancer and bone metastases, including 295 (55%) with ≥1 SRE. After matching, there were 162 patients each in the SRE and no-SRE groups with mean follow-up of 5.3 and 3.9 months, respectively. In the SRE group, costs of treatment of SREs were $9,480 (95% CI $7,625 to $11,374) per patient. Total medical care costs were $27,982 (95% CI $15,921 to $40,625) greater for SRE versus no-SRE patients ( p Conclusions The costs of SREs in patients with lung cancer and bone metastases are substantial and potentially greater than previously estimated.

Background: The third Adult Treatment Panel (ATP III) of the National Cholesterol Education Program defines clinical criteria for diagnosis of the metabolic syndrome, which increases cardiovascular risk and is a target for therapy. Aim: We analysed the third National Health and Nutrition Examination Survey (NHANES III; 1988–94) to determine how many US adults meet these criteria and are recommended for lipid-modifying drug therapy by ATP III. Methods: NHANES III data were used to estimate the number of individuals with the metabolic syndrome and the number recommended for treatment by ATP III, based on 1990 census data. Results: An estimated 36.3 million (23%) US adults have the metabolic syndrome. Of these, 84% met the criterion for obesity, 76% for blood pressure, 75% for HDL-C, 74% for triglycerides and 41% for glucose. Most (54%) are in the higher risk categories of ATP III, yet only 39% overall are recommended for drug therapy by ATP III cutpoints; of these, most will achieve LDL-C targets with reductions of 35–40%. Of the 15.3 million individuals with the metabolic syndrome and triglycerides ≥2.26 mmol/l (200 mg/dl), non-HDL-C is above ATP III recommendations in 11.6 million. Conclusions: Of the large number of Americans with the metabolic syndrome, ATP III recommends drug therapy for only a minority, because LDL-C typically is not substantially elevated. Instead, high triglycerides and low HDL-C are more common; clinical trial data are needed to determine whether optimal therapy should focus on reductions in LDL-C or on comprehensive improvements to the lipid profile.

Objective The objective of this study was to describe an approach to modeling the efficiency of an intervention by focusing on an established intermediate end point directly. A case study addresses the economic efficiency of obtaining dual glycemic control over time, according to initial choice of treatment. Methods From the perspective of a payer in the United States, instead of the usual approach of basing the model on projecting long-term diabetic complications from glycemic control, this model focuses directly on glycemic control. Treatment changes and associated health-care utilization needed to address postprandial glucose. After assigning each of 10,000 drug-naive patients, HbA 1c , age, race, and sex based on distributions from a randomized clinical trial, the model applies the efficacy of nateglinide compared to metformin. Sensitivity analyses were carried out for all parameters. Costs are reported in year 2000 US dollars and discounted at 3%. Results In the base case, starting on nateglinide and increasing the time in dual glycemic control over 3 years by 2.4 months led to savings of US $295 compared to starting on metformin. Savings increased with stricter treatment criteria but decreased if glycemic control was better initially. Conclusions This study illustrates the use of an efficiency model that focuses directly on the relevant short-term end point: glycemic control. Starting patients with nateglinide is shown to be an efficient way of obtaining dual glycemic control during the first 3 years of treatment.

OBJECTIVE—Clinical trials provide information regarding the safety and efficacy of medications used to manage type 2 diabetes but do not elucidate drug effectiveness in a typical managed care environment. The aim of this study was to characterize “real-world” drug utilization patterns from both a prescriber and a patient perspective. RESEARCH DESIGN AND METHODS—We conducted a retrospective analysis of a large administrative pharmacy claims database, using data on continuously pharmacy benefit–eligible members prescribed oral hypoglycemic agents (OHAs). RESULTS—The 12-month persistence rate for the OHA cohort was low, ranging from 31% for α-glucosidase inhibitors to 60% for metformin; compliance rates varied between 70 and 80%. During the first 12 months of therapy, 36% of the patients remaining on therapy at 12 months had one or more therapy modifications. The mean number of therapy changes increased with the length of patient follow-up, with more than half of all patients experiencing at least one therapy change over the duration of follow-up. CONCLUSIONS—These findings document the wide variation in utilization patterns associated with pharmacological management of type 2 diabetes, suggesting that opportunity exists to optimize its pharmacological management.

The Patient Satisfaction with Asthma Medication (PSAM) questionnaire was developed because no treatment satisfaction questionnaire could be identified that was comprehensive yet brief enough for use in clinical trials. Adult moderate asthmatics residing in Canada using an inhaled medication (either salmeterol, formoterol, or albuterol) self-administered the questionnaire, which also included the Asthma Quality of Life Questionnaire (AQLQ). A total of 53 asthmatics (70% female, 45% married, mean age: 47 years) completed the questionnaire. Using variable clustering, four PSAM scales were identified: Inhaler Properties, Comparison with Other Medications, Overall Perception of Medication, and Relief. Internal-consistency reliability provided evidence of reliability and lack of redundancy (Cronbach's Alpha: 0.82–0.88). Test-retest reliability was acceptable (ICC values at or near 0.70). As expected, interscale PSAM correlations were moderate to high; correlations between the PSAM and the AQLQ were low to moderate. To assess known groups validity, respondents were categorized by self-reported degree of asthma control: ‘very well controlled’ ‘somewhat controlled’, and ‘not well controlled’. Significant between-groups differences were found on all PSAM scales except Inhaler Properties. Patients categorized as ‘very well controlled’ tended to report highest PSAM scale scores. The PSAM questionnaire demonstrated reliability and validity in moderate asthmatics. Responsiveness should be assessed in future, prospective studies.

The goal of this study was to quantify the incremental direct medical and indirect work-loss costs associated with patients diagnosed with atopic dermatitis (AD). A de-identified administrative claims database was used comprising 5.1 million covered beneficiaries from 31 Fortune 500 self-insured employers between 1998 and 2005. Patients with at least two AD diagnosis claims (N = 13,749) were compared with three matched controls (based on yr of birth and gender) with no AD diagnosis (N = 41,247). In addition, a multivariate two-part regression analysis was used to isolate the cost increase attributable to AD by controlling for confounding factors such as age, gender, health plan type, comorbidities, organ transplantation, industry of employer, region, and year. Direct medical and indirect work-loss costs for the AD group were higher on average by $88 and $64 per patient per month, respectively (both P.001). After multivariate adjustment, the total incremental cost per patient per month for the AD group was $83 (direct: $52, P.001; indirect: $31, P.001). Employer-payers experience a significant annual cost burden of $991 per patient attributable to AD. Employee disability and increased sick days account for 38% of the cost burden.

The objective of this study was to assess the consequences of atopic dermatitis/ eczema on two areas: (1) the quality of life of parents/caregivers and (2) resource utilization from two large group practices. Data from 414 patients with atopic dermatitis, aged two to 12 years, were collected between January 2001 and December 2003. Parents/caregivers completed the Parent's Index of Quality of Life-Atopic Dermatitis (PIQoL-AD). One-way analysis of variance and analysis of covariance models determined statistical significance. Pairwise significance testing was performed to determine statistical differences (P.05). Mean patient age was 6.7 years and 55% of patients were males; mild and moderate atopic dermatitis was present in 82% and 13% of patients, respectively. Mean PIQoL-AD scores worsened (5.9 +/- 5.4 vs. 3.0 +/- 3.6, P.001) for caregivers whose child had disease flares versus those without disease flares. Patients with atopic dermatitis incurred an additional 1.8 unscheduled visits annually at a cost of $93.54 per patient. It was determined that atopic dermatitis may have considerable quality-of-life and financial consequences to both family and community.

e14554 Background: Real-world treatment patterns and effectiveness often differ from those in clinical trials. This study describes the real-world treatment patterns and effectiveness among mCRC pa...

e16029 Background: Treatment of mCRPC has evolved in the last decade with approval of new chemotherapies and androgen receptor (AR)-targeted therapies. Despite trial data showing clinical efficacy ...

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%) withor = 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.

MA17 was a randomised placebo-controlled trial of letrozole 2.5 mg/day in 5187 estrogen receptor-positive, 50% node-negative, postmenopausal women (median age 62 years at enrollment) with early breast cancer, post-5 years' adjuvant tamoxifen therapy. The objective of this evaluation was to extrapolate the findings from the MA17 trial to estimate the lifetime cost effectiveness of letrozole in this setting.A Markov model was used to estimate the incremental cost per QALY gained with extended adjuvant letrozole versus no therapy. Probabilities of disease progression and death were estimated using data from the MA17 study and other secondary sources. Costs of breast cancer care (letrozole therapy, surveillance, recurrences, terminal care) and treatment of osteoporosis and utilities were derived from literature. A full probabilistic sensitivity analysis was undertaken. The analysis was conducted from the perspective of the UK National Health Service (NHS) and cost estimates reflect 2004 values. All costs and outcomes were discounted at 3.5%.Extended adjuvant letrozole resulted in a gain of 0.36 QALYs per patient (13.66 vs 13.30 with no therapy). These benefits were obtained at an additional expected lifetime cost of 3732 pounds per patient (10,833 pounds letrozole vs 7101 pounds with no therapy). Cost effectiveness was estimated at 10,338 pounds per QALY gained (95% CI 5276, 43,828). The results were robust to sensitivity analyses.Five years of letrozole therapy appears to be cost effective from the NHS perspective and should be considered in women with early breast cancer, following tamoxifen adjuvant therapy.

Background The impact of chronic hand dermatitis (ChHD) on patient-reported outcomes and economic costs has not been assessed in a US population. Objective We sought to evaluate the quality of life, work productivity, activity impairment, and health care costs of patients with ChHD versus those without ChHD. Methods A 13-item self-assessment questionnaire to identify ChHD was developed and validated. Skindex-29 and Work Productivity and Activity Impairment questionnaires were used to assess quality of life and work productivity for ChHD. The survey was mailed to a random sample of 1380 members of a Massachusetts managed care organization (N = 507, response rate=36.74%). Univariate and multivariate analyses were conducted to determine the incremental effect of ChHD on quality of life, work productivity, and activity impairment. Health insurance claims were used to assess medical costs. Results Quality of life, along with work productivity and activity impairment, were significantly worse for patients with CHD than for those without ChHD; however, there was no significant difference in work time missed. After adjusting for significant covariates, a 25% cost increase in total medical costs was found attributable to ChHD, which translates to an incremental cost of $70 per patient per month. Limitations Survey response rate is not high; the survey respondents may not be completely representative of the nonrespondents. The cost burden of ChHD is underestimated because of the omission of over-the-counter drug and indirect costs. The multivariate models had a low goodness of fit indicated by the low R 2 statistics. Conclusions ChHD has a significant detrimental effect on quality of life, work productivity, activity impairment, and heath care costs. More awareness and treatment of this condition are needed to improve patient outcomes and decrease health care cost.

This prospective study was designed to determine whether incorporating formoterol into a standardized respiratory therapist-directed protocol for administering bronchodilators to hospitalized patients with obstructive airway disease would reduce health care resource use and provide a safety advantage. All patients admitted to Washington Hospital Center with asthma and chronic obstructive pulmonary disease (CODP) are administered bronchodilators under a standardized respiratory therapist-directed protocol. Formoterol was the primary bronchodilator for the intervention period from January through March 2002, with levalbuterol, albuterol, and ipratropium available as needed. Results for the intervention period were compared against two historical control periods. From January through March 2000, the bronchodilators in the protocol were albuterol and ipratropium, and from January through March 2001 levalbuterol, albuterol, and ipratropium were available. Health care resource use was determined by the number of bronchodilator treatments administered per admission. Costs (adjusted to 2002 dollars) for supplies, therapist time, and drugs were calculated for the three time periods. Adverse events related to bronchodilator administration were recorded in a standardized manner for all three time periods. Bronchodilator treatments per admission, respiratory therapist visits per admission, and time spent per admission, and cost per bronchodilator treatment significantly decreased in 2002. Significantly fewer adverse events related to bronchodilator treatments were reported in 2002 than 2000. The addition of formoterol to a respiratory therapist-directed protocol for administering bronchodilators reduced health care resource use and adverse events for patients with asthma and COPD.

Background We hypothesized that child cognitive disability would be a significant risk factor for non-adherence with home deferoxamine (DFO) administration and that a factor that would contribute to improved adherence would be sharing of responsibilities for chelation between parents and patients. We explored the influences on adherence of behavioral and psychological adjustment; family stress; perceived convenience of and satisfaction with the DFO regimen; and parent and patient knowledge about DFO. Procedure Fifteen pediatric patients with sickle cell disease (SCD) who had evidence of excessive iron stores, and their parents, were interviewed about adherence and responsibility for chelation therapy. A neuropsychological assessment battery was administered to the patients. Family stress, the child's emotional and behavioral status, knowledge about chelation and iron overload were explored. Adherence was rated objectively using pharmacy refill patterns and observable signs of chelation. Results Sharing of responsibilities for chelation between parents and children was related to better adherence while neuropsychological status bore a complex relation to adherence. Of the exploratory variables, low family stress were related to better adherence while satisfaction with the home care regimen and convenience ratings were not useful in predicting adherence. No one element of adherence, even objective measures, was capable of classifying adherence, while a multifactorial scheme categorizing adherent, partially adherent and non-adherent groups demonstrated good face validity. Conclusions Supporting developmentally appropriate sharing of responsibilities for self-care is critical, taking patient neurocognitive status into consideration. Clinicians should evaluate adherence using a multifactorial model that highlights the most salient targets for intervention. © 2004 Wiley-Liss, Inc.

Purpose: Patients with bone metastases from lung cancer often experience skeletal-related events (SREs) including pathological fracture, spinal cord compression, hypercalcemia or pain requiring surgery, radiotherapy or opioid analgesics. These complications result in impaired mobility and reduced quality of life and have a significant negative impact on survival. The economic consequences of SREs in patients with lung cancer have not been examined. Methods: We conducted a retrospective analysis using a large US health insurance claims database to estimate the incidence and costs of treatment of SREs in patients with bone metastases of lung cancer treated in a naturalistic setting. Study subjects had ≧2 encounters with a diagnosis of primary lung cancer and ≧2 encounters with a diagnosis of metastases to bone. SREs were identified based on the occurrence on or after the date of first diagnosis of bone metastases, of (1) ≧1 encounter with a diagnosis of pathological fracture, spinal cord compression or hypercalcemia, (2) ≧1 bone surgery or radiotherapy procedure, or (3) the initiation of opioid analgesic therapy. Survival and costs of SRE-related care in patients with SREs were estimated using Kaplan-Meier methods. Results: We identified 534 patients with lung cancer and bone metastases, including 295 (55%) with ≧1 SRE. Radiotherapy (68%) and fracture (35%) were the most common SREs. Median survival after the first identified SRE was 4.1 months (95% confidence interval: 3.6–5.5 months). The estimated lifetime SRE-related cost per patient was USD 11,979 (95% confidence interval: USD 10,193–13,766). Radiotherapy accounted for the greatest proportion of cost (61%) by SRE type. Conclusion: The economic burden of SREs in patients with bone metastases of lung cancer is substantial. Intravenous bisphosphonates, such as zoledronic acid, which have been shown to prevent these events, may reduce these costs.