Budget impact of introducing subcutaneous vedolizumab as a maintenance therapy in biologic-naïve and biologic-experienced patients with ulcerative colitis in France.

BACKGROUND: Inflammatory bowel disease poses significant social and economic burdens. We assessed the budget impact of including the recently approved subcutaneous (SC) formulation of vedolizumab as maintenance therapy (MT) in patients with ulcerative colitis (UC) in France. METHODS: A decision-analytic model was developed from a French payer's perspective over 5 years to assess budget impact of including vedolizumab SC as MT for UC following induction therapy with vedolizumab intravenous (IV), by subtracting outcomes of a 'world without vedolizumab SC' from a 'world with vedolizumab SC.' Comparators included approved therapies: infliximab (branded/biosimilar), adalimumab (branded/biosimilar), golimumab, ustekinumab, and vedolizumab IV. The model predicts drug, medical, and total costs, including indirect costs in a scenario analysis. A one-way sensitivity analysis explored the impact of varying individual parameters. RESULTS: Including vedolizumab SC as MT following vedolizumab IV induction yielded total cost savings of €59,176,842 (biologic-naïve) and €22,004,135 (biologic-experienced) versus a world without vedolizumab SC. Including indirect costs yielded cost savings in biologic-naïve (€62,600,716) and biologic-experienced (€24,314,915) populations in a world with vedolizumab SC. CONCLUSIONS: Introducing vedolizumab SC as MT after IV induction is expected to have substantial cost savings to a health plan from a French payer's perspective versus a world without vedolizumab SC.

Cost-effectiveness of intravenous vedolizumab vs subcutaneous adalimumab for moderately to severely active ulcerative colitis.

BACKGROUND: The efficacy of intravenous (IV) vedolizumab vs subcutaneous (SC) adalimumab for the treatment of moderately to severely active ulcerative colitis (UC) was assessed in the VARSITY clinical trial, which demonstrated for the first time in a head-to-head clinical trial setting the superiority of IV vedolizumab with respect to clinical remission and endoscopic improvement. Both therapies offer better clinical outcomes compared with immunomodulators and corticosteroids but are often more expensive than other pharmacologic treatment options. Thus, payers and decision makers face the task of leveraging finite resources for optimal health benefits, which can be aided by the use of cost-effectiveness models. OBJECTIVE: To assess the cost-effectiveness of IV vedolizumab vs SC adalimumab from a US payer perspective using head-to-head data from the VARSITY trial. METHODS: A cohort decision tree was developed to estimate the costs and clinical outcomes associated with IV vedolizumab vs SC adalimumab to treat adults with moderately to severely active UC. Simulated cohorts began the model at treatment induction and continued to maintenance treatment with vedolizumab or adalimumab unless experiencing nonresponse or serious adverse drug reaction (ADR), in which case those patients transitioned to second-line treatment with tofacitinib, infliximab, or golimumab, where they could achieve response and/or remission or not. Those who still did not achieve response or remission or who had a serious ADR transitioned to a state of nonresponse for the remainder of the model or received surgery. The process was modeled for patients who were treatment naive and treatment experienced at baseline separately. Efficacy and safety inputs for vedolizumab and adalimumab were taken from the VARSITY trial, and corresponding inputs for other biologics were derived from a network meta-analysis. All clinical inputs were extrapolated over 2 years. Direct medical costs (expressed in 2019 US dollars) included those related to drug acquisition and administration, ADRs, routine monitoring, and additional treatment procedures. Outcomes were not discounted given the short time horizon. Univariate sensitivity and scenario analysis were applied to evaluate the robustness of the model to underlying parameter and structural uncertainty. RESULTS: Initial treatment with vedolizumab was associated with a higher remission rate at 2 years (73.5% vs 71.5%) and higher persistence (22.0% vs 14.4%) compared with adalimumab. Total direct medical costs were lower for the vedolizumab cohort ($100,022 vs $151,133), primarily driven by the lower annual drug acquisition cost of vedolizumab ($85,953 vs $137,492). When endoscopic improvement was used as the outcome measure, IV vedolizumab was also associated with higher endoscopic remission and lower overall costs. CONCLUSIONS: With better clinical outcomes and lower direct medical costs over a 2-year model horizon, vedolizumab IV was the dominant treatment strategy vs adalimumab SC in adults with moderately to severely active UC. Outcomes were driven primarily by the probability of major ADRs and induction response. DISCLOSURES: This study was supported by Takeda Pharmaceuticals U.S.A., Inc. (Lexington, MA). Schultz and Turpin are employees of Takeda Pharmaceuticals U.S.A., Inc. Turpin has stock or stock options in Takeda Pharmaceuticals. Diakite, Carter, and Snedecor are employees of OPEN Health (Bethesda, MD), which received payment from Takeda for the design and execution of this study. This study was presented at the European Crohn's and Colitis Organisation (ECCO) 2020 Congress and Digestive Disease Week (DDW), 2020 Virtual Congress.

Cost Comparison of Urate-Lowering Therapies in Patients with Gout and Moderate-to-Severe Chronic Kidney Disease.

BACKGROUND: Patients with chronic kidney disease (CKD) are at increased risk for developing gout and having refractory disease. Gout flare prevention relies heavily on urate-lowering therapies such as allopurinol and febuxostat, but clinical decision making in patients with moderate-to-severe CKD is complicated by significant comorbidity and the scarcity of real-world cost-effectiveness studies. OBJECTIVE: To compare total and disease-specific health care expenditures by line of therapy in allopurinol and febuxostat initiators after diagnosis with gout and moderate-to-severe CKD. METHODS: A retrospective observational cohort study was conducted to compare mean monthly health care cost (in 2012 U.S. dollars) among gout patients with CKD (stage 3 or 4) who initiated allopurinol or febuxostat. The primary outcome was total mean monthly health care expenditures, and the secondary outcome was disease-specific (gout, diabetes, renal, and cardiovascular disease [CVD]) expenditures. Gout patients (ICD-9-CM 274.xx) aged ≥ 18 years with concurrent CKD (stage 3 or 4) were selected from the MarketScan databases (January 2009-June 2012) upon allopurinol or febuxostat initiation. Patients were followed until disenrollment, discontinuation of the qualifying study agent, or use of the alternate study agent. Patients initiating allopurinol were subsequently propensity score-matched (1:1) to patients initiating febuxostat. Five generalized linear models (GLMs) were developed, each controlling for propensity score, to identify the incremental costs (vs. allopurinol) associated with febuxostat initiation in first-line (without prior allopurinol exposure) and second-line (with prior allopurinol exposure) settings. RESULTS: Propensity score matching yielded 2 cohorts, each with 1,486 patients (64.6% male, mean [SD] age 67.4 [12.8] years). Post-match, 74.6% of patients had stage 3 CKD; 82.9% had CVD; and 42.1% had diabetes. The post-match sample was well balanced on numerous comorbidities and medication exposures with the following exception: 50.0% of febuxostat initiators were treated in the second-line setting; that is, they had baseline exposure to allopurinol, whereas only 4.2% of allopurinol initiators had baseline exposure to febuxostat. Unadjusted mean monthly cost was $1,490 allopurinol and $1,525 febuxostat (P = 0.809). GLM results suggest that first-line febuxostat users incurred significantly (P = 0.009) lower cost than allopurinol users ($1,299 vs. $1,487), whereas second-line febuxostat initiators incurred significantly (P = 0.001) higher cost ($1,751 vs. $1,487). Febuxostat initiators in both settings had significantly (P < 0.001) higher gout-specific cost, due to higher febuxostat acquisition cost. Increased gout-specific cost in the first-line febuxostat cohort was offset by significantly (P < 0.001) lower CVD ($288 vs. $459) and renal-related cost ($86 vs. $216). There were no significant differences in either renal or CVD costs (adjusted) between allopurinol initiators treated almost exclusively in the first-line setting and second-line febuxostat patients. CONCLUSIONS: Gout patients with concurrent CKD, initiating treatment with febuxostat in a first-line setting, incurred significantly less total cost than patients initiating allopurinol during the first exposure to each agent. Conversely, patients treated with second-line febuxostat following allopurinol incurred significantly higher total cost than patients initiating allopurinol. There was no significant difference in total cost between the agents across line of therapy. Although study findings suggest the potential for CVD and renal-related savings to offset febuxostat's higher acquisition cost in gout patients with moderate-to-severe CKD, this is the first such retrospective evaluation. Future research is warranted to both demonstrate the durability of study findings and to better elucidate the mechanism by which associated cost offsets occur. DISCLOSURES: No outside funding supported this study. Turpin is an employee of Takeda Pharmaceuticals U.S.A. Mitri and Wittbrodt were employees of Takeda Pharmaceuticals U.S.A. at the time of this study. Tidwell and Schulman are employees of Outcomes Research Solutions, consultants to Takeda Pharmaceuticals U.S.A. All authors contributed to the design of the study and to the writing and review of the manuscript. All authors read and approved the final manuscript. Tidwell and Schulman collected the data, and all authors participated in data interpretation.

The Challenges and Opportunities Associated with Reimbursement for Obesity Pharmacotherapy in the USA.

Obesity has become a serious public health problem that has stimulated primordial and primary prevention efforts, and a triad of management options (lifestyle, pharmacotherapy, and surgical interventions). A growing body of evidence supports the need for a multi-pronged, clinic-based approach that leverages the synergy between pharmaceutical and lifestyle modification. Recent US policy changes-namely, the passage of the Patient Protection and Affordable Care Act coupled with recognition of obesity as a disease by the American Medical Association-suggest that financial incentives and attitudes towards obesity management are changing. This paradigm shift has implications for current and future obesity pharmacotherapy. However, barriers to pharmacotherapy utilization include patient and physician perceptions of modest efficacy, historical safety issues, regulatory obstacles, and lack of reimbursement. The shifting attitudes and challenges associated not only with a multi-payer system, but also the lack of clearly defined cross-payer reimbursement strategies, prompted a survey to determine coverage for obesity treatment. Participants indicated that federal/state mandates and growth of quality-driven healthcare initiatives will eventually drive wider pharmacotherapy reimbursement within 1-5 years. There are signs that federal/state programs are already moving towards reimbursement by improving quality measures to track obesity outcomes and reduce costs. Future research on clinical and economic outcomes of combination weight-management programs coupled with innovative approaches (e.g., eHealth) in the real-world setting that demonstrate value to patients, healthcare providers, payers, and employers will help reshape obesity management by reducing barriers and broadening reimbursement coverage for anti-obesity pharmacotherapy.

A retrospective, observational study of patient outcomes for critically ill patients receiving parenteral nutrition.

OBJECTIVE: To evaluate health care-related utilization for critically ill patients receiving parenteral nutrition (PN) administered via a premixed multichamber bag (MCB) or compounded solutions (COM). DESIGN: A retrospective database analysis of critically ill patients (intensive care unit stay ≥ 3 days) receiving PN and discharged between January 1, 2010, and June 30, 2011, using the Premier Hospital Database. Patients were identified as receiving MCB or COM on the basis of product description codes. Primary outcomes were length of stay (LOS) and total costs. Comorbidities and clinical outcomes were identified using International Classificaion of Diseases, Ninth Revision diagnosis codes. All costs reported were for inpatient services only. Patients receiving MCB and COM were matched on key patient and hospital characteristics using a propensity score methodology. Multivariate regression models for cost and LOS used generalized linear models with a log link and gamma distribution. RESULTS: A total of 42,631 patients met the inclusion criteria (MCB = 5,679; COM = 36,952), and the final matched population included 3,559 patients from each cohort. Baseline patient and hospital characteristics were well matched between groups. Adjusted multivariate models demonstrated a small difference between groups for LOS (MCB = 9.40 days vs. COM = 9.65 days; P = 0.014). In addition, patients receiving MCB incurred approximately 9.1% less in total costs (MCB = $37,790 vs. COM = $41,569; P < 0.001). CONCLUSIONS: Overall, patients receiving MCB and COM experienced similar LOS, though patients receiving MCB had significantly lower overall costs. Interpretation of the study findings is subject to several limitations, and additional studies that include explicit identification of the method for compounding are needed.

Cost-effectiveness of recombinant human hyaluronidase-facilitated subcutaneous versus intravenous rehydration in children with mild to moderate dehydration.

OBJECTIVE: To evaluate the cost-effectiveness of recombinant human hyaluronidase-facilitated subcutaneous (rHFSC) fluid administration compared to intravenous (IV) fluid administration in children with mild to moderate dehydration in the emergency department (ED). METHODS: A decision analytic model was created based on the results of a controlled clinical trial that compared the administration of isotonic fluids via rHFSC or IV for rehydration. The costs were determined from the hospital's perspective. The effectiveness unit was successful rehydration in the ED without the need for hospitalization for continued hydration. Mean estimates were determined for both the cost and effectiveness of each treatment. The incremental differences in costs and effectiveness were determined between treatments. Sensitivity analysis testing was also conducted. RESULTS: The treatment success rate was 93% with rHFSC fluids and 76% for IV fluids. Across all ages, the mean cost of rHFSC fluids was $722, compared to $889 for IV fluids. The difference in effectiveness was due to the larger number of patients for whom IV access could not be established, necessitating a rescue route of administration to deliver parenteral fluids. The difference in the overall cost was primarily due to the shorter time in the ED for patients receiving rHFSC fluids versus those treated with IV fluids. The cost-effectiveness of rHFSC compared to IV was most apparent in younger patients (<3 years of age), where IV access was more difficult to obtain. CONCLUSION: Analysis of this clinical trial data revealed that rHFSC fluid administration demonstrated greater treatment effectiveness and cost-effectiveness than traditional IV fluid administration in the ED. The primary reasons for this were the ease of obtaining parenteral access via rHFSC in young patients (especially those under 3) where IV access is difficult, and a shorter ED stay with rHFSC fluid administration.

Characteristics and current practice of parenteral nutrition in hospitalized patients.

BACKGROUND: For 40 years, parenteral nutrition (PN) has provided therapeutic benefits to patients unable to receive oral/enteral nutrition. Very limited published evidence exists to describe modern PN practices or characteristics of patients receiving PN. The aim of this article was to describe the characteristics of hospitalized patients receiving PN in 196 U.S. hospitals to define patient groups at risk for PN-related complications. This will provide researchers a baseline understanding about who is receiving hospital-based PN to maximize generalizability and validity of future research. METHODS: Claims data from the Premier Perspective database, the largest inpatient clinical database in the United States, were used to evaluate hospital-based PN practices. Data gathered between January 2005 and December 2007 included a total of 106,374 patients receiving PN. A total of 68,984 adults (age ≥ 18 years), 34,307 infants (age <1 year), and 3083 pediatric patients (age 1-17 years) were evaluated. Key variables such as admitting diagnosis, infection rates, in-hospital mortality, and costs were extracted. RESULTS: Hospitalized patients requiring PN in the United States are older and more often white than the overall hospitalized population. Hospitalized PN patients are more likely to be admitted emergently and have a higher severity of illness. Bloodstream infection rates in adult PN patients (25.5%) were considerably higher than in pediatric (14.7%) or neonatal patients (1.7%) receiving PN. CONCLUSIONS: These findings are the first large-scale description of "real-world" hospital-based PN practices in the United States, helping set a baseline for future PN research.

Methods to identify and compare parenteral nutrition administered from hospital-compounded and premixed multichamber bags in a retrospective hospital claims database.

PURPOSE: Use of parenteral nutrition (PN) is indicated for patients who are unable to meet their needs enterally. PN may be administered via custom-compounded mix or commercially available ready-to-use multichamber bags (MCB), but little is known about potential differences in clinical outcomes between these delivery systems. This study was undertaken to assess the feasibility of comparing custom-compounded and MCB PN in a large hospital claims database. METHODS: Hospital claims data from the Premier Perspective Comparative Hospital Database (PCD) reported from 2005 through 2007 were analyzed. The authors searched the data for patients who received any PN products, including compounded PN and MCB PN. Coding algorithms for identifying patient characteristics, risk factors, and outcomes of interest were explored. RESULTS: Using hospital billing claims, the authors identified patients in the database treated with premixed PN from multichamber bags ("MCB only," n = 4699) and patients treated with custom-compounded PN solution ("compounded PN," n = 64,315). Methods of identifying PN administration groups, patient characteristics and risk factors, outcomes of interest, and data limitations are described. CONCLUSIONS: Exploratory analysis suggests that comparisons of PN administered via compounding and MCB are possible using the Premier data. The ability to control for many identifiable risk factors allows data to be presented for the use of PN and related outcomes in both a clinically sensible and relevant manner, albeit with some limitations.

Nutrition therapy cost analysis in the US: pre-mixed multi-chamber bag vs compounded parenteral nutrition.

BACKGROUND: Bloodstream infections (BSI) occur in up to 350 000 inpatient admissions each year in the US, with BSI rates among patients receiving parenteral nutrition (PN) varying from 1.3% to 39%. BSI-attributable costs were estimated to approximate $US12 000 per episode in 2000. While previous studies have compared the cost of different PN preparation methods, this analysis evaluates both the direct costs of PN and the treatment costs for BSI associated with different PN delivery methods to determine whether compounded or manufactured pre-mixed PN has lower overall costs. OBJECTIVE: The purpose of this study was to compare costs in the US associated with compounded PN versus pre-mixed multi-chamber bag (MCB) PN based on underlying infection risk. METHODS: Using claims information from the Premier Perspective™ database, multivariate logistic regression was used to estimate the risk of infection. A total of 44 358 hospitalized patients aged ≥18 years who received PN between 1 January 2005 and 31 December 2007 were included in the analyses. A total of 3256 patients received MCB PN and 41 102 received compounded PN. The PN-associated costs and length of stay were analysed using multivariate ordinary least squares regression models constructed to measure the impact of infectious events on total hospital costs after controlling for baseline and clinical patient characteristics. RESULTS: There were 7.3 additional hospital days attributable to BSI. After adjustment for baseline variables, the probability of developing a BSI was 30% higher in patients receiving compounded PN than in those receiving MCB PN (16.1% vs 11.3%; odds ratio = 1.56; 95% CI 1.37, 1.79; p < 0.0001), demonstrating 2172 potentially avoidable infections. The observed daily mean PN acquisition cost for patients receiving MCB PN was $US164 (including all additives and fees) compared with $US239 for patients receiving compounded PN (all differences p < 0.001). With a mean cost attributable to BSI of $US16 141, the total per-patient savings (including avoided BSI and PN costs) was $US1545. CONCLUSION: In this analysis of real-world PN use, MCB PN is associated with lower costs than compounded PN with regards to both PN acquisition and potential avoidance of BSI. Our base case indicates that $US1545 per PN patient may be saved; even if as few as 50% of PN patients are candidates for standardized pre-mix formulations, a potential savings of $US773 per patient may be realized.

Impact of surgical site infections on length of stay and costs in selected colorectal procedures.

BACKGROUND: Length of stay (LOS) and inpatient costs for open-abdomen colorectal procedures have not been examined recently. The aim of this study was to determine LOS and costs for several colorectal procedures in the context of factors potentially associated with surgical site infection (SSI). METHODS: We used a large U.S. hospital database to identify the variables associated with longer LOS and higher costs for colorectal procedures from January 1, 2005, through June 30, 2006. The study population consisted of all patients >18 years, identified via International Classification of Disease, Ninth Revision, procedural codes for elective colorectal surgery. Patient demographics, surgical procedure, and a modified Study of the Efficacy of Nosocomial Infection Control (SENIC) infection risk score were examined using logistic regression as predictors of LOS >or=1 week and cost >or=$15,000. Patients given cefotetan as surgical prophylaxis were compared with patients given cefazolin/metronidazole. Superficial and deep SSIs were considered; intra-abdominal infection was not. RESULTS: The 25,825 patients were of average age 63 years, with 53% being female and 75% being Caucasian. The overall infection rate was 3.7%. The mean LOS was 7.25 days, and the mean +/- standard deviation total cost per patient $13,746 +/- $13,330. Rates of infection, LOS, and mean hospital costs were all greater for patients with a high SENIC score and increasing disease acuity. Values for these outcome variables were highest for procedures involving stoma formation, followed by operations on the small bowel and large bowel. Variables independently predictive of longer LOS were SSI (odds ratio [OR] 11.74; 95% confidence interval [CI] 9.67, 14.26), age >or=65 years (OR 1.90; 95% CI 1.81, 2.01), and high SENIC score (OR 1.79; 95% CI 1.67, 1.92), whereas Caucasian race (OR 0.86; 95% CI 0.81, 0.91) was predictive of a shorter LOS. Cefazolin/metronidazole was not predictive of a shorter LOS compared with cefotetan (OR 1.06; 95% CI 0.96, 1.17) but was associated with significantly more hospitalizations with costs >or=$15,000 (OR 1.39; 95% CI 1.23, 1.56). CONCLUSIONS: Length of stay and cost rise proportionally with SENIC score, disease acuity, and patient characteristics such as age. Surgical site infections are significantly and independently associated with LOS and cost and contribute to inpatient morbidity and expense. Cefotetan has limited availability, and substitutions are utilized increasingly. Although equally efficacious in elective colon procedures, cefotetan used as surgical prophylaxis was associated with lower hospitalization costs than cefazolin plus metronidazole.

Burden of illness associated with lower urinary tract symptoms including overactive bladder/urinary incontinence.

OBJECTIVES: To determine the effect of lower urinary tract symptoms, including overactive bladder/urinary incontinence, on health outcomes. METHODS: Data were obtained from the 2006 U.S. National Health and Wellness Survey. Cases (those who reported experiencing a sudden overwhelming urge to urinate, a frequent urge to urinate, or urinating >8 times/d) were matched 1:1 with controls (those not experiencing any symptoms) by age, race, sex, educational attainment, and comorbidity status. The outcome measures assessed included health resource use, work productivity loss/activity impairment, and health-related quality of life. RESULTS: Of the 62,833 respondents to the 2006 U.S. National Health and Wellness Survey, 13,957 case-control pairs were matched. The presence of lower urinary tract symptoms, including OAB/UI symptoms, was significantly associated with increased resource use (emergency room visits, odds ratio -1.57, 95% confidence interval -1.47-1.68; hospitalizations, odds ratio -1.56, 95% confidence interval 1.43-1.69; medical provider visits, odds ratio -1.52, 95% confidence interval 1.41-1.63), 8.03% greater overall work productivity loss (P < .001), 12.88% greater activity impairment (P < .001), and decreased health- related quality of life (mental scores, 4.07 points lower [P < .001]; physical scores, 4.14 points lower [P < .001]). CONCLUSIONS: The burden of illness associated with lower urinary tract conditions, including OAB/UI, extend beyond the diagnosed population. The appropriate diagnosis and treatment of symptoms could lead to better clinical, economic, and humanistic outcomes.

Comparative costs of ertapenem and cefotetan as prophylaxis for elective colorectal surgery.

BACKGROUND AND PURPOSE: The costs of treating surgical site infections can be considerable. There is a cost associated with the prophylactic use of antibiotics; however, the use of prophylactic agents may reduce infection rates and lengths of stay, thus offsetting the overall treatment cost and potentially generating cost savings to hospitals. This project was intended to determine the potential cost impact of using ertapenem 1 g vs. cefotetan 2 g as prophylaxis for elective colorectal surgery. METHODS: Cost analysis using efficacy data from the PREVENT clinical trial and drug acquisition and total hospital costs in 2005 dollars from Premier's Perspective Comparative Database in patients > or = 18 year of age, evaluable at four weeks after elective surgery of the colon or rectum and prophylactic treatment with ertapenem (n = 338) or cefotetan (n = 334). The primary outcome measures were the rate of prophylactic drug failure and the difference between the ertapenem and cefotetan groups in costs related to and total hospital stay. Prophylactic failure was defined as a surgical site infection, unexplained antibiotic use, or anastomotic leak. RESULTS: Prophylactic failure occurred in 28.1% of the patients receiving ertapenem and 42.8% of those receiving cefotetan (p < 0.05). The most common prophylactic failure was surgical site infection: 18.3% for ertapenem, 31.1% for cefotetan, difference (95% confidence interval) -13.0% (-19.5, -6.5%) (p < 0.05). The mean +/- standard deviation length of stay for all patients, including prophylactic successes and failures, was 7.6 +/- 6.6 days for ertapenem and 8.7 +/- 9.5 days for cefotetan. The mean per-patient cost of prophylactic drugs and hospital room and board was $15,245 with ertapenem and $17,428 cefotetan, a net difference of -$2,181. CONCLUSIONS: Ertapenem used in prophylaxis for elective colorectal operations results in a lower rate of surgical site infection and a shorter average length of stay than cefotetan. The calculated net difference in prophylactic antibiotic drug and hospital costs represents a saving of $2,181 per patient with ertapenem relative to cefotetan.

Cost analysis of five antimicrobial regimens for the treatment of intra-abdominal infection.

BACKGROUND: Cost of treatment is an important consideration in antimicrobial agent selection for intra-abdominal infection. We analyzed the relation between the total cost of inpatient stay and the initial selection of antimicrobial agent. METHODS: Actual costs of inpatient care were calculated for 1,234 patients treated at 22 hospitals with one of five antimicrobial regimens: Ampicillin/sulbactam (n = 428), ertapenem (n = 143), ceftriaxone (n = 101), levofloxacin (n = 245), or piperacillin/tazobactam (n = 317) for intra-abdominal infections. Length of stay (LOS), demographic data, diagnosis, disease severity index, intensive care unit (ICU) stay, and total and specific costs were obtained from a large hospital-based, service level, comparative database for five types of infection (appendicitis, cholecystitis, diverticulitis, pancreatitis, and postoperative infection). RESULTS: The LOS was shorter for appendicitis (3.8 days) and cholecystitis (4.6 days) than for diverticulitis (11.4 days), pancreatitis (8.1 days), or postoperative infection (8.4 days). Length of stay and total cost were most closely related to severity index (p < 0.01) and ICU days (p < 0.01). When patient and hospital characteristics and correlations within hospitals were accounted for in the model, piperacillin/tazobactam was associated with significantly higher cost than ertapenem, ampicillin/sulbactam, and levofloxacin. CONCLUSIONS: In assessing pharmacoeconomic outcomes in the treatment of intra-abdominal infection, cost of treatment, although lower with certain antimicrobial agents, is dependent on severity-of-illness indicators.

Comparative costs of ertapenem and piperacillin-tazobactam in the treatment of diabetic foot infections.

PURPOSE: To evaluate potential cost savings, trial data were used to determine the clinical outcomes for i.v. ertapenem given once daily and i.v. piperacillin-tazobactam given every six hours daily in treating diabetic foot infections. METHODS: A cost-minimization analysis (CMA) was conducted on the drug-dosing data of the subset of patients enrolled in a recent double-blind randomized trial who were treated solely as inpatients and were clinically evaluable at fi nal assessment (n = 99). Cost per dose was calculated from (a) average hospital acquisition price per dose for ertapenem ($40.52) or piperacillin-tazobactam ($13.58), (b) average U.S. wages and benefits for labor, based on nine published time-and-motion studies of i.v. antibiotic preparation and administration ($3.10), and (c) consumable supplies, using a 40% discount off the manufacturer list price ($2.90). For each patient, the actual number of antibiotic doses given was multiplied by total cost per dose. RESULTS: There were no significant differences between antibiotic groups with respect to patient demographics, percentage with a severe wound, and mean days of i.v. therapy. Compared with piperacillin-tazobactam, patients treated with ertapenem received significantly fewer mean doses (25.5 versus 7.5; p < 0.0001) and lower antibiotic-related costs ($502.76 versus $355.55, respectively; p < 0.001). The $147.21 difference between groups accounts for approximately 3% of total hospital Medicare reimbursements for these infections. CONCLUSION: A CMA of treatment of diabetic foot infections showed that, compared with piperacillin-tazobactam given four times daily i.v., ertapenem given once daily i.v. was associated with lower drug acquisition and supply costs and less time and labor devoted to preparation and administration of i.v. therapy.

High- versus low-dose fluconazole therapy for empiric treatment of suspected invasive candidiasis among high-risk patients in the intensive care unit: a cost-effectiveness analysis.

BACKGROUND: High-dose fluconazole is an alternative for patients with candidemia caused by Candida glabrata or other Candida species with decreased fluconazole susceptibility. However, empiric high-dose fluconazole is not currently recommended and may result in higher drug costs and toxicity. OBJECTIVE: To determine the cost-effectiveness of using empiric high-dose fluconazole in intensive care unit (ICU) with suspected invasive candidiasis. DESIGN: Decision analytic model. TARGET POPULATION: ICU patients with suspected invasive candidiasis. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTIONS: Low-dose fluconazole (loading dose of 800 mg followed by 400 mg daily) vs. high-dose fluconazole (loading dose of 1600 mg followed by 800 mg daily). Generic fluconazole costs were used for the analysis. OUTCOME MEASURES: Incremental life expectancy and incremental cost per discounted life year (DLY) saved. RESULT OF BASE-CASE ANALYSIS: Based on current national levels of fluconazole resistance and ability to correctly identify patients with candidemia, high-dose fluconazole was the more effective but more expensive treatment strategy. Empiric high-dose fluconazole therapy decreased the mortality rate by 0.15% compared to low-dose strategy with a cost-effectiveness rate of $55,526 per DLY saved. RESULTS OF SENSITIVITY ANALYSIS: Empirical high-dose fluconazole was an acceptable treatment strategy (using $100,000 per DLY saved as threshold) unless the physical age of an ICU survivor was 66 years or older. Empirical high-dose fluconazole was an acceptable treatment strategy using $50,000 per DLY saved with minor changes in parameters estimates. LIMITATIONS: The estimates of our model may not be applicable to all ICU patients. Other hospitals with differences in fluconazole resistance, prevalence of invasive candidiasis, or duration of fluconazole therapy may produce different results. CONCLUSION: These results suggest that empiric high-dose fluconazole therapy should reduce the mortality associated with invasive candidiasis at an acceptable cost.

Economic analysis of inadequate fluconazole therapy in non-neutropenic patients with candidaemia: a multi-institutional study.

Mortality significantly increases in patients with candidaemia who receive inappropriate fluconazole therapy. The goals of this study were to compare hospital length of stay and costs for non-neutropenic patients with candidaemia treated with fluconazole based on the empirical dose and time until initiation of therapy. A retrospective cohort study was conducted of patients with candidaemia who were prescribed fluconazole at the onset of candidaemia or later. Hospital-related costs were compared based on time to initiation of fluconazole therapy and empirical fluconazole dose. A total of 192 non-neutropenic patients (55% male; mean age+/-standard deviation, 56+/-17 years) were identified. Isolated Candida species included C. albicans (59%), C. glabrata (15%), C. parapsilosis (11%), C. tropicalis (6%), C. krusei (3%) or other Candida spp. (6%). Time to initiation of fluconazole was Day 0 (35.4%), Day 1 (14.1%), Day 2 (26.6%) or Day >or=3 (23.9%). Thirty-two patients (17%) received a dose of fluconazole >or=6 mg/kg on Day 0. Total costs were lowest for patients started on fluconazole on the culture day with adequate doses ($35,459+/-25,988) compared with all other patients ($52,158+/-53,492) (P=0.0088). After controlling for covariates, each 1-day delay in fluconazole therapy was associated with increased total hospital costs of $6392+/-3000 (P=0.0344), and an adequate fluconazole dose was associated with decreased total hospital costs of $18,744+/-7173 (P=0.0097). A delay or an inadequate dose or fluconazole in patients with candidaemia was associated with increased hospital costs. Improved methods to diagnose patients with candidaemia quickly are needed.

Adherence to infectious diseases society of America guidelines for empiric therapy for patients with community-acquired pneumonia in a commercially insured cohort.

BACKGROUND: There is little published research addressing how the 2003 Infectious Diseases Society of America (IDSA) guidelines for empiric therapy of community-acquired pneumonia (CAP) are implemented in clinical practice. OBJECTIVE: This study was designed to describe antibiotic treatment patterns among patients with CAP treated in ambulatory settings in light of the IDSA guidelines. METHODS: Health insurance claims data from a large managed care organization with -30 million enrollees located in geographically diverse regions of the United States were analyzed. Patients > or =18 years of age with CAP who received a prescription for any antibiotic in an ambulatory setting during 2004 were identified via International Classification of Diseases, Ninth Revision, Clinical Modification codes for diagnosis (481-486). Recent antibiotic use was defined as receipt of any antibiotics <90 days before the date of diagnosis. Antibiotics were identified through National Drug Codes and from outpatient medical claims data with the use of J codes. Individuals were classified, per IDSA guidelines, as previously healthy without recent antibiotic use (group 1); previously healthy with recent antibiotic use (group 2); with comorbidities and without recent antibiotic use (group 3); and with comorbidities and recent antibiotic use (group 4). The guideline adherence was calculated using the number of patients receiving recommended treatment divided by the total number of patients in each group. RESULTS: Of 34,342 patients identified, 76.5% had no reported comorbidities. Among group-1 patients, 52.0% received the recommended empiric therapy (macrolide or doxycycline). In group-2 patients, 42.5% received the recommended therapy (respiratory quinolone alone or advanced-generation macrolide plus amoxicillin or amoxicillin-clavulanate). A high rate of compliance with recommended empiric therapy (advanced-generation macrolides or respiratory quinolones) was observed in group-3 patients (81.5%). In group-4 patients, 43.4% received the recommended therapy (respiratory quinolone or advanced-generation macrolide plus ss-lactam). Patients whose therapy was adherent with the guidelines had fewer respiratory-infection-related hospital admissions within 30 days after initiation of antibiotic treatment (overall, relative risk = 0.81 [95% CI, 0.71-0.94]). CONCLUSION: Although these data reflect a period shortly after the 2003 IDSA guidelines were published, they suggest that there is room for improvement with regard to choice of empiric antibiotic therapy among these patients with CAP treated in ambulatory settings.

Diabetes disease management in Medicaid managed care: a program evaluation.

The objective of this study was to evaluate the outcomes of a diabetes disease management initiative among TennCare's Medicaid Population. A quasi-experimental group design was conducted using a control group and a diabetes disease management intervention group. Primary outcomes measures were rates for three key recommended tests (ie, microalbuminuria, lipids, and hemoglobin A1c). Secondary performance measures --patient satisfaction and program evaluation issues -- also were assessed. The study was performed among TennCare beneficiaries with diabetes mellitus. It utilized a quasi-experimental nonequivalent control group design, with 993 intervention participants in Knoxville and 1167 control group members in Chattanooga. Variables analyzed included testing rates for hemoglobin A1c, lipids, microalbuminuria, and demographics. A logistic regression model using baseline covariates was constructed to analyze the differences between the intervention and the control groups. Intracluster correlations were accounted for by generalized estimating equations. Statistical process control detected process changes in testing rates over time. There were meaningful changes in the rate of ordering recommended tests. The odds of an individual in the intervention group having at least one microalbuminuria test were 196% more (confidence interval [CI] = 1.50, 5.82; p = 0.002); the odds of having at least one lipid profile were 43% more (CI = 1.01, 2.02; p = 0.042); and the odds of having two or more hemoglobin A1c tests were 39% more (CI = 0.87, 2.23; p = 0.165) than the odds of an individual in the control group. The analysis also showed a high rate of satisfaction among patients in the intervention group. The program was successful in meeting its stated goals of providing effective disease management for TennCare patients with diabetes.

The assessment of chronic health conditions on work performance, absence, and total economic impact for employers.

OBJECTIVE: The objective of this study was to determine the prevalence and estimate total costs for chronic health conditions in the U.S. workforce for the Dow Chemical Company (Dow). METHODS: Using the Stanford Presenteeism Scale, information was collected from workers at five locations on work impairment and absenteeism based on self-reported "primary" chronic health conditions. Survey data were merged with employee demographics, medical and pharmaceutical claims, smoking status, biometric health risk factors, payroll records, and job type. RESULTS: Almost 65% of respondents reported having one or more of the surveyed chronic conditions. The most common were allergies, arthritis/joint pain or stiffness, and back or neck disorders. The associated absenteeism by chronic condition ranged from 0.9 to 5.9 hours in a 4-week period, and on-the-job work impairment ranged from a 17.8% to 36.4% decrement in ability to function at work. The presence of a chronic condition was the most important determinant of the reported levels of work impairment and absence after adjusting for other factors (P < 0.000). The total cost of chronic conditions was estimated to be 10.7% of the total labor costs for Dow in the United States; 6.8% was attributable to work impairment alone. CONCLUSION: For all chronic conditions studied, the cost associated with performance based work loss or "presenteeism" greatly exceeded the combined costs of absenteeism and medical treatment combined.

Reliability and validity of the Stanford Presenteeism Scale.

OBJECTIVE: This study reports the reliability and validity of the 13-item Stanford Presenteeism Scale (SPS). The SPS differs from similar scales by focusing on knowledge-based and production-based workers. METHODS: Data were obtained from administrative and medical claims databases and from a survey that incorporated the SPS, SF-36, and the Work Limitations Questionnaire. RESULTS: Sixty-three percent (7797) of employees responded. Cronbach's alpha (0.83) indicates adequate reliability. Factor analysis identified two underlying factors, "completing work" and "avoiding distraction." Knowledge-based workers load on "completing work" (alpha = 0.97), whereas production-based workers load on "avoiding distraction" (alpha = 0.98). There were significant and positive relationships between the SPS, SF-36, and Work Limitations Questionnaire. CONCLUSIONS: The SPS demonstrates a high degree of reliability and validity and may be ideal for employers who seek a single scale to measure health-related productivity in a diverse employee population.