Comparison of the EQ-HWB and EQ-HWB-S With Other Preference-Based Measures Among United States Informal Caregivers.

OBJECTIVES: Several measures have been used or developed to capture the health and well-being of caregivers, including the EQ Health and Well-being (EQ-HWB) and its short form, EQ-HWB-S. This study aimed to evaluate the psychometric properties and construct validity of the EQ-HWB/EQ-HWB-S in a US caregiver population. METHODS: A cross-sectional survey was conducted involving 504 caregivers. Eligible participants were 18+ years old, provided unpaid care to a relative/friend aged 18+ in the past 6 months, and spent on average of at least 1 hour per week caregiving. Survey included the following measures: EQ-HWB, Adult Social Care Outcomes Toolkit for Carers-Carer, CarerQol, and EQ-5D-5L. Psychometric properties were assessed using response distributions, floor/ceiling effects, Spearman's correlation for convergent validity, and effect sizes (ES) for known-group validity based on caregiving situations and intensity. RESULTS: The average age of caregivers was 49.2 (SD = 15.4), with 57.5% being female. More than half (54.4%) reported high caregiving intensity, and 68.3% lived with the care recipient. The EQ-HWB-S index showed a strong positive correlation with the EQ-5D-5L (rs = 0.72), Adult Social Care Outcomes Toolkit for Carers (rs = 0.54), and CarerQol (rs = 0.54) indices. Notably, the EQ-HWB-S index showed the largest ES among measures in differentiating caregiving scenarios with a large ES for caregiver's general health (d = 1.00) and small ES for caregiving intensity (d = 0.39). CONCLUSIONS: Results support construct validity of EQ-HWB and EQ-HWB-S as measures for assessing health and well-being of adult informal caregivers in comparison with other validated instruments. Differing levels of known-group validity across anchors emphasize the importance of selecting appropriate measures for caregivers, depending on research question and/or intervention aims.

Understanding caregiver burden from multiple perspectives: dyadic agreement between caregiver and care recipient.

PURPOSE: Caregiver burden (CB) is typically self-assessed by caregivers. However, an emerging concept is assessment of CB by the recipients of care, i.e., the patient. The specific objectives are (1) to assess the level of agreement between care recipients' and caregivers' view on CB, across financial, physical, emotional, and social domains; (2) to explore two care recipient perspectives: their self-perceived burden (CR-SPB), and their interpretation of the caregiver's view (Proxy-CB). METHODS: Data were collected from 504 caregiver-care recipient dyads in the U.S. using an online Qualtrics panel. The survey assessed caregiver burden using CarerQol and newly developed items. The level of agreement between responses was quantified using weighted kappa (κ) coefficients for individual items and intraclass correlation coefficients (ICC) for index/summary scores. RESULTS: The average age of caregivers was 49.2 years, and 62.7 years for care recipients. Dyads most commonly consisted of spouses/partners (34.5%); 68.3% lived together. Proxy-CB aligned more closely with caregiver's view, with moderate to substantial agreement across CB domains (from κ = 0.48 for emotional to κ = 0.66 for financial). In the same perspective, the CarerQol-7D Index showed moderate agreement (ICC = 0.58) and the summary score of CB items substantial agreement (ICC = 0.76). Care recipients generally overestimated  CB in the Proxy-CB perspective, while they underestimated it in the CR-SPB perspective. CONCLUSION: Results demonstrate there is a difference between perspectives. Strong agreement in Proxy-CB perspective suggests that care recipients can potentially substitute for caregivers depending on the domain. CR-SPB agrees less with caregivers and may provide complementary information.

P042 Early Versus Later Use of Vedolizumab In IBD: Patient Characteristics And Treatment Patterns In The Real World (RALEE).

BACKGROUND: Pivotal trials in inflammatory bowel disease (IBD) demonstrate that earlier use of biologics is associated with greater likelihood of response/remission, but multiple studies have identified that in the real world, biologic treatment is often delayed, thereby limiting optimal effectiveness and increasing likelihood of adverse outcomes. Further assessment of patient, provider, and payor factors that contribute to therapy choice is needed. We assessed utilization of vedolizumab (VDZ) and performed a real-world assessment using administrative datasets. Here, we describe the different treatment patterns and demographics of patients who received VDZ. METHODS: We identified VDZ-treated patients (aged ≥18 years) with Crohn's disease (CD) or ulcerative colitis (UC) in the MarketScan commercial and Medicare claims databases from 2017 to 2019 and included those who had continuous enrollment in the same health plan for ≥12 months prior to their initial IBD diagnostic claim, ≥1 VDZ claim after the initial IBD diagnosis, and continuous enrollment for ≥12 months prior to and after their initial UC or CD diagnosis. Patients exposed to VDZ, anti-TNF, or other biologic therapy in the 12-month pre-index period were excluded. We pre-defined 5 treatment pathways: (1) EARLY VDZ - VDZ within 30 days of first IBD diagnostic claim; (2) DELAYED VDZ 1 - immunomodulators and then switch to VDZ; (3) DELAYED VDZ 2 - corticosteroids with immunomodulators prior to VDZ; (4) DELAYED VDZ 3 - 5-ASA with corticosteroids prior to VDZ; or (5) DELAYED VDZ 4 - 5-ASA with corticosteroids and immunomodulators prior to VDZ. Differences in patient baseline characteristics among these treatment pathways were analyzed descriptively. RESULTS: We identified 136,315 patients with UC and 103,591 with CD, from which 1,342 patients with UC (median age 43 years; 51.0% male; 96.4% commercially insured; 86.4% diagnosed in 2017) and 964 with CD (median age 45 years; 43.6% male; 94.6% commercially insured; 88.6% diagnosed in 2017) received VDZ and met criteria. The proportions of patients by treatment pathway were (UC|CD): EARLY VDZ (6.6%|9.6%); DELAYED VDZ 1 (7.5%|19.0%); DELAYED VDZ 2 (14.8%|36.8%); DELAYED VDZ 3 (37.6%|19.0%); DELAYED VDZ 4 (33.4%|15.6%). Among patients with UC, EARLY VDZ vs DELAYED VDZ cohorts had median age of 40 vs 44 years and proportion of men of 46.1% vs 51.4%. Among patients with CD, EARLY VDZ vs DELAYED VDZ had median age of 43 vs 45 years and proportion of men of 39.8%% vs 43.9%. For both indications, no meaningful differences among treatment groups by geographic region, payor type (i.e., commercial vs Medicare), and year of diagnosis were observed. CONCLUSION: In this administrative real-world dataset, fewer than 10% of patients with IBD were treated with VDZ within 30 days of diagnosis, and these patients were more likely to be younger and women. These findings are distinct from guidelines suggesting VDZ may be used earlier, or due to its safety profile, preferentially in older patients at higher risk for infection. Further analyses of safety and effectiveness outcomes are underway.

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.

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.

A classification of diabetic foot infections using ICD-9-CM codes: application to a large computerized medical database.

BACKGROUND: Diabetic foot infections are common, serious, and varied. Diagnostic and treatment strategies are correspondingly diverse. It is unclear how patients are managed in actual practice and how outcomes might be improved. Clarification will require study of large numbers of patients, such as are available in medical databases. We have developed and evaluated a system for identifying and classifying diabetic foot infections that can be used for this purpose. METHODS: We used the (VA) Diabetes Epidemiology Cohorts (DEpiC) database to conduct a retrospective observational study of patients with diabetic foot infections. DEpiC contains computerized VA and Medicare patient-level data for patients with diabetes since 1998. We determined which ICD-9-CM codes served to identify patients with different types of diabetic foot infections and ranked them in declining order of severity: Gangrene, Osteomyelitis, Ulcer, Foot cellulitis/abscess, Toe cellulitis/abscess, Paronychia. We evaluated our classification by examining its relationship to patient characteristics, diagnostic procedures, treatments given, and medical outcomes. RESULTS: There were 61,007 patients with foot infections, of which 42,063 were classifiable into one of our predefined groups. The different types of infection were related to expected patient characteristics, diagnostic procedures, treatments, and outcomes. Our severity ranking showed a monotonic relationship to hospital length of stay, amputation rate, transition to long-term care, and mortality. CONCLUSIONS: We have developed a classification system for patients with diabetic foot infections that is expressly designed for use with large, computerized, ICD-9-CM coded administrative medical databases. It provides a framework that can be used to conduct observational studies of large numbers of patients in order to examine treatment variation and patient outcomes, including the effect of new management strategies, implementation of practice guidelines, and quality improvement initiatives.

Variation in antibiotic treatment for diabetic patients with serious foot infections: a retrospective observational study.

BACKGROUND: Diabetic foot infections are common, serious, and diverse. There is uncertainty about optimal antibiotic treatment, and probably substantial variation in practice. Our aim was to document whether this is the case: A finding that would raise questions about the comparative cost-effectiveness of different regimens and also open the possibility of examining costs and outcomes to determine which should be preferred. METHODS: We used the Veterans Health Administration (VA) Diabetes Epidemiology Cohorts (DEpiC) database to conduct a retrospective observational study of hospitalized patients with diabetic foot infections. DEpiC contains computerized VA and Medicare patient-level data for VA patients with diabetes since 1998, including demographics, ICD-9-CM diagnostic codes, antibiotics prescribed, and VA facility. We identified all patients with ICD-9-CM codes for cellulitis/abscess of the foot and then sub-grouped them according to whether they had cellulitis/abscess plus codes for gangrene, osteomyelitis, skin ulcer, or none of these. For each facility, we determined: 1) The proportion of patients treated with an antibiotic and the initial route of administration; 2) The first antibiotic regimen prescribed for each patient, defined as treatment with the same antibiotic, or combination of antibiotics, for at least 5 continuous days; and 3) The antibacterial spectrum of the first regimen. RESULTS: We identified 3,792 patients with cellulitis/abscess of the foot either alone (16.4%), or with ulcer (32.6%), osteomyelitis (19.0%) or gangrene (32.0%). Antibiotics were prescribed for 98.9%. At least 5 continuous days of treatment with an unchanged regimen of one or more antibiotics was prescribed for 59.3%. The means and (ranges) across facilities of the three most common regimens were: 16.4%, (22.8%); 15.7%, (36.1%); and 10.8%, (50.5%). The range of variation across facilities proved substantially greater than that across the different categories of foot infection. We found similar variation in the spectrum of the antibiotic regimen. CONCLUSIONS: The large variations in regimen appear to reflect differences in facility practice styles rather than case mix. It is unlikely that all regimens are equally cost-effective. Our methods make possible evaluation of many regimens across many facilities, and can be applied in further studies to determine which antibiotic regimens should be preferred.

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 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.

Defining success in diabetes disease management: digging deeper in the data.

We evaluated the effectiveness of a diabetes life coach program designed to address the concerns of limited coordination and collaboration of care for chronically ill patients in the physician office. The program emphasized lipid, blood pressure, and glycemic control, using personal coaching, group classes, reminders, and customized feedback. The target population was all health plan members over age 18 with type 1 or 2 diabetes mellitus in 6 primary care practice sites in the Hampton Roads area of Virginia. Primary outcomes were 1 Health Plan Employer Data and Information Set measure (A1c poor control of >9% or no test), 3 American Diabetes Association (ADA) measures (A1c <7%, blood pressure of <130/80 mmHg, low-density lipoprotein cholesterol [LDL-C] of <100 mg/dL), 1 pharmacy measure (percentage of patients filling at least 1 insulin prescription), and 2 self-reported behavioral measures (percentage adherent to a meal plan and percentage adherent to an activity plan). We assessed overall program outcomes and differences between individual physician practices and evaluated outcomes separately for engaged compared with non-engaged program participants. Outcomes for 1117 participants were evaluated. Statistically significant improvement at P < 0.05 was noted in all 7 targeted measures compared with baseline. Participants who were engaged in the life coach program were 40% less likely to experience poor control of their A1c, 50% more likely to meet the ADA A1c goal of < 7%, 11% more likely to meet their blood pressure goal of <130/80 mmHg, and 7% more likely to meet their LDL-C goal of <100 mg/dL compared with those not engaged. Patients who became engaged in the program performed significantly better in the key diabetes indicators that ultimately lead to reductions in the complications of the disease over time. Our study contributes to the evidence that clinical multidisciplinary, collaborative models of care can influence and improve the management of diabetes.

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.

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.

Major Cardiovascular Events in Patients with Gout and Associated Cardiovascular Disease or Heart Failure and Chronic Kidney Disease Initiating a Xanthine Oxidase Inhibitor.

BACKGROUND: Several observational studies and meta-analyses have suggested that treating hyperuricemia in patients with gout and moderate or severe chronic kidney disease (CKD) may improve renal and cardiovascular (CV) outcomes. OBJECTIVE: To evaluate the impact of initiating allopurinol or febuxostat treatment on major CV events in patients with gout, preexisting CV disease (CVD) or heart failure (HF), and stage 3 or 4 CKD in a real-world setting. METHODS: Patients with gout (aged >18 years) who initiated allopurinol or febuxostat treatment between 2009 and 2013 after a diagnosis of stage 3 or 4 CKD and CVD-including coronary artery disease (CAD), cerebrovascular disease, and peripheral vascular disease (PVD)-or HF were selected from the MarketScan databases. The major CV events included CAD-specific, cerebrovascular disease-specific, and PVD-specific events. Cox proportional hazards modeling identified the predictors of major CV events in aggregate, and of CAD, cerebrovascular disease, and PVD events, individually. RESULTS: During follow-up, 2426 patients (370 receiving febuxostat and 2056 receiving allopurinol; 63% male; mean age, 73 years) had 162 major CV events (3.8% in those receiving febuxostat vs 7.2% in those receiving allopurinol; P = .015). The rates of major CV events per 1000 person-years were 51.8 (95% confidence interval [CI], 28-87) in patients initiating febuxostat and 99.3 (95% CI, 84-117) among those initiating allopurinol. Overall, 49.4% of patients had a CAD event, 32.5% had a PVD event, and 23.5% had a cerebrovascular disease-specific event. Febuxostat initiation was associated with a significantly lower risk for a major CV event versus patients who initiated allopurinol (hazard ratio, 0.52; P = .02), driven in large part by lower PVD-specific events (P = .026). CONCLUSION: Patients with moderate-to-severe CKD and CVD or HF who initiated febuxostat treatment had a significantly lower rate of major CV events than patients who initiated allopurinol.

Time to initiation of fluconazole therapy impacts mortality in patients with candidemia: a multi-institutional study.

BACKGROUND: Inadequate antimicrobial treatment is an independent determinant of hospital mortality, and fungal bloodstream infections are among the types of infection with the highest rates of inappropriate initial treatment. Because of significant potential for reducing high mortality rates, we sought to assess the impact of delayed treatment across multiple study sites. The goals our analyses were to establish the frequency and duration of delayed antifungal treatment and to evaluate the relationship between treatment delay and mortality. METHODS: We conducted a retrospective cohort study of patients with candidemia from 4 medical centers who were prescribed fluconazole. Time to initiation of fluconazole therapy was calculated by subtracting the date on which fluconazole therapy was initiated from the culture date of the first blood sample positive for yeast. RESULTS: A total of 230 patients (51% male; mean age +/- standard deviation, 56 +/- 17 years) were identified; 192 of these had not been given prior treatment with fluconazole. Patients most commonly had nonsurgical hospital admission (162 patients [70%]) with a central line catheter (193 [84%]), diabetes (68 [30%]), or cancer (54 [24%]). Candida species causing infection included Candida albicans (129 patients [56%]), Candida glabrata (38 [16%]), Candida parapsilosis (25 [11%]), or Candida tropicalis (15 [7%]). The number of days to the initiation of antifungal treatment was 0 (92 patients [40%]), 1 (38 [17%]), 2 (33 [14%]) or > or = 3 (29 [12%]). Mortality rates were lowest for patients who began therapy on day 0 (14 patients [15%]) followed by patients who began on day 1 (9 [24%]), day 2 (12 [37%]), or day > or = 3 (12 [41%]) (P = .0009 for trend). Multivariate logistic regression was used to calculate independent predictors of mortality, which include increased time until fluconazole initiation (odds ratio, 1.42; P < .05) and Acute Physiology and Chronic Health Evaluation II score (1-point increments; odds ratio, 1.13; P < .05). CONCLUSION: A delay in the initiation of fluconazole therapy in hospitalized patients with candidemia significantly impacted mortality. New methods to avoid delays in appropriate antifungal therapy, such as rapid diagnostic tests or identification of unique risk factors, 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.

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 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.