Surgical site infection prophylaxis strategies for cardiothoracic surgery: a decision-analytic model.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of invasive surgical site infection (SSI) in the USA. Antimicrobial prophylaxis for SSI typically includes a cephalosporin. Vancomycin is used to provide MRSA coverage, but the timing of administration is challenging. Linezolid is an attractive agent for SSI prophylaxis, particularly for the prevention of SSI due to MRSA. METHODS: We developed a decision-analytic model to evaluate linezolid use for cardiothoracic SSI prophylaxis. A theoretical cohort of 10,000 cardiothoracic surgery patients was followed through 2 stages: (1) occurrence of SSI, and (2) mortality after SSI. All patients were administered cefuroxime, vancomycin, or linezolid between 1 and 180 min prior to surgical incision. SSIs were categorized into 3 pathogen categories: (1) methicillin-susceptible Gram-positive, (2) methicillin-resistant Gram-positive, and (3) other organisms. The most effective strategy resulted in the fewest SSIs. Assumptions for antibiotic effectiveness, impact of administration time, and pathogens were based on the published literature. RESULTS: Compared with cefuroxime, there was a 1% increase in the total number of SSIs in the linezolid group (mean SSI increase = 7), while there was a 12% increase in the vancomycin group (mean SSI increase = 86). Linezolid prophylaxis resulted in fewer SSIs due to methicillin-resistant Gram-positive infections (n = 108) compared with cefuroxime (n = 200, 46% reduction in the linezolid group) and vancomycin (n = 119, 9% reduction in the linezolid group). CONCLUSIONS: This simulation indicates that linezolid may offer benefits for SSI prophylaxis over existing prophylactic agents, particularly for the prevention of SSI due to Gram-positive methicillin-resistant pathogens.

Discontinuation rates and health care costs in adult patients starting generic versus brand SSRI or SNRI antidepressants in commercial health plans.

BACKGROUND: Generic antidepressants offer significant prescription drug cost savings compared with brand-name antidepressants, but critics of managed care interventions promoting generic medication use suggest that some generic antidepressants are not as safe or effective as the brand alternatives. OBJECTIVE: To assess (a) rates of discontinuation of the initially dispensed medication and (b) disease-specific and total health care costs and pharmacy costs, comparing patients who initiated therapy with brand versus generic selective serotonin reuptake inhibitors (SSRI) or selective norepinephrine reuptake inhibitors (SNRI). METHODS: Antidepressant users aged 18 to 64 years with no pharmacy claims for an SSRI/SNRI in the 180 days prior to the start of SSRI/SNRI therapy (baseline) were identified in the MarketScan database between July 1, 2005, and June 30, 2007, and were followed for 180 days (followup). All study patients met the following criteria: (a) continuously eligible from baseline through follow-up; (b) at least 1 medical claim with a primary or secondary diagnosis of major depressive disorder (ICD-9-CM codes 296.2 or 296.3) in either the baseline or follow-up period; and (c) no pharmacy claims for antipsychotic medications in the baseline period. For brand versus generic antidepressant initiators, logistic regression was used to determine the odds of 6-month therapy discontinuation, defined as no medication refills or absence of a refill for the initially dispensed medication within 1.5 times the days supply dispensed, adjusted for important covariates. Costs were measured as total plan allowed charges including member cost share. Adjusted mean (least squares means holding covariates at mean values) all-cause medical costs, disease-specific (claims with a ICD-9-CM diagnosis code for major depressive disorder in the primary or secondary diagnosis field) medical costs, all-cause pharmacy costs, and SSRI/SNRI antidepressant costs were compared for brand versus generic initiators using generalized linear regression models, also adjusted for baseline covariates. RESULTS: Of 16,659 new SSRI/SNRI users, 47.8% (n=7,955) initiated a brand-name medication and 52.2% (n=8,704) initiated a generic product. Of the 7,955 who initiated a brand-name antidepressant, 46.8% (n=3,723) discontinued the initially dispensed drug within 180 days, compared with 44.2% (n=3,843) of the 8,704 who initiated a generic. The adjusted odds of discontinuation among generic and brand drug users did not significantly differ (odds ratio [OR]=1.09, 95% CI=0.98-1.22). Adjusted all-cause 6-month average health care costs in patients initiating therapy on a generic antidepressant were $3,660 (95% CI=$3,538-$3,787) compared with $4,587 (95% CI=$4,422-$4,757) for patients initiating on a brand-name antidepressant. Adjusted average 6-month SSRI/SNRI antidepressant costs were 43.7% lower in patients initiating on a generic drug ($174 vs. $309). CONCLUSIONS: The likelihood of discontinuation was similar for patients who initiated therapy with brand or generic antidepressants, and shortterm health care costs and pharmacy costs were lower in patients starting a generic SSRI/SNRI. The results suggest that the use of generic antidepressants as first-line agents in the treatment of major depressive disorder is associated with continuation rates similar to initiation with brand antidepressants but with lower health care costs.

Acute epilepsy exacerbations in patients switched between A-rated anti-epileptic drugs.

BACKGROUND: Concerns have been raised over the use of different manufacturers' versions of A-rated antiepileptic drug (AED) formulations in epilepsy patients. OBJECTIVE: To estimate the association between acute epilepsy exacerbations and switching between different A-rated AEDs. METHODS: A nested case-control study was conducted using pharmacy and medical claims data from January 1, 2005 through December 31, 2007. 18-65-year-olds who had an epilepsy diagnosis and received AED therapy during 2005 were eligible for study. Cases were defined as individuals with a documented exacerbation of epilepsy in the form of a 2006 or 2007 inpatient or emergency room claim for epilepsy. Controls were from the same population and matched on baseline epilepsy diagnosis and follow-up time since January 1, 2006. The exposure was a switch between A-rated AEDs in the 90 days prior to the matching date. Conditional logistic regression was used to estimate the odds of an epilepsy exacerbation after a switch controlling for important covariates. RESULTS: A total of 34 216 individuals were eligible for study, of whom 2949 cases were matched to 8847 controls. The unadjusted odds ratio (OR) between a switch and an epilepsy exacerbation was 1.51 (95% CI: 1.29-1.76). After adjusting for potential confounders, the odds ratio was 1.08 (95% CI: 0.91-1.29). Treatment with three or more AEDs or a change in outpatient diagnosis from baseline resulted in ORs of 2.96 (95% CI: 2.48-3.49) and 2.53 (95% CI: 2.28-2.82), respectively. CONCLUSIONS: After addressing potential confounders, no evidence that A-rated switching was associated with increased acute exacerbations of epilepsy was found. Study limitations include potentially incomplete identification of seizures, no information on indication for medication use, and limited information on duration and severity of disease. This study provides additional insight into the relationship between A-rated AED switching and acute exacerbations of epilepsy.

Economic model of first-line drug strategies to achieve recommended glycaemic control in newly diagnosed type 2 diabetes mellitus.

OBJECTIVE: To assess the short-term direct medical costs and effectiveness associated with achieving recommended glycaemic goals using commonly prescribed first-line oral antihyperglycaemic medications in type 2 diabetes mellitus. MATERIALS AND METHODS: A literature-based, decision-tree model was developed to project the number of patients achieving glycosylated haemoglobin values of <7% on oral therapies and the associated costs over a 3-year timeframe. For each first-line strategy, patients could progress to combination therapy using two or more agents prior to the introduction of insulin. The overall cost of treatment included costs (2001/2002 values; US dollars) of comprehensive medical care, laboratory tests, patient education, drug therapy, home glucose monitoring and adverse events. RESULTS: At 3 years, the overall cost of treatment for the various first-line strategies was 6,106 US dollars for glipizide gastrointestinal therapeutic system, 6,727 US dollars for metformin immediate release, 6,826 US dollars for metformin extended release, 7,141 US dollars for glibenclamide (glyburide)/metformin, 7,759 US dollars for rosiglitazone and 9,298 US dollars for repaglinide. Costs of comprehensive routine medical care ranged from approximately 1,538-2,128 US dollars in year 1 and from approximately 952-1,543 US dollars in subsequent years, for controlled and uncontrolled patients, respectively. Adverse events represented <1%, and drug therapies represented approximately 50%, of the overall cost, respectively. Substantial cost differences between the strategies were seen within the first year. Regardless of first-line therapy, patients progressed quickly to combination therapies, with effectiveness among the agents being similar. CONCLUSIONS: Short-term costs required to provide comprehensive diabetes care and achieve glycemic goals can be substantial. The model suggests a sulphonylurea strategy may provide similar effectiveness with cost savings over other agents and should be considered when selecting an initial drug therapy in newly diagnosed patients with type 2 diabetes mellitus.