Eva A. Enns

Prevalence of Inappropriate Antibiotic Prescriptions Among US Ambulatory Care Visits, 2010-2011

IMPORTANCE The National Action Plan for Combating Antibiotic-Resistant Bacteria set a goal of reducing inappropriate outpatient antibiotic use by 50% by 2020, but the extent of inappropriate outpatient antibiotic use is unknown. OBJECTIVE To estimate the rates of outpatient oral antibiotic prescribing by age and diagnosis, and the estimated portions of antibiotic use that may be inappropriate in adults and children in the United States. DESIGN, SETTING, AND PARTICIPANTS Using the 2010-2011 National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey, annual numbers and population-adjusted rates with 95% confidence intervals of ambulatory visits with oral antibiotic prescriptions by age, region, and diagnosis in the United States were estimated. EXPOSURES Ambulatory care visits. MAIN OUTCOMES AND MEASURES Based on national guidelines and regional variation in prescribing, diagnosis-specific prevalence and rates of total and appropriate antibiotic prescriptions were determined. These rates were combined to calculate an estimate of the appropriate annual rate of antibiotic prescriptions per 1000 population. RESULTS Of the 184,032 sampled visits, 12.6% of visits (95% CI, 12.0%-13.3%) resulted in antibiotic prescriptions. Sinusitis was the single diagnosis associated with the most antibiotic prescriptions per 1000 population (56 antibiotic prescriptions [95% CI, 48-64]), followed by suppurative otitis media (47 antibiotic prescriptions [95% CI, 41-54]), and pharyngitis (43 antibiotic prescriptions [95% CI, 38-49]). Collectively, acute respiratory conditions per 1000 population led to 221 antibiotic prescriptions (95% CI, 198-245) annually, but only 111 antibiotic prescriptions were estimated to be appropriate for these conditions. Per 1000 population, among all conditions and ages combined in 2010-2011, an estimated 506 antibiotic prescriptions (95% CI, 458-554) were written annually, and, of these, 353 antibiotic prescriptions were estimated to be appropriate antibiotic prescriptions. CONCLUSIONS AND RELEVANCE In the United States in 2010-2011, there was an estimated annual antibiotic prescription rate per 1000 population of 506, but only an estimated 353 antibiotic prescriptions were likely appropriate, supporting the need for establishing a goal for outpatient antibiotic stewardship.

Population Strategies to Decrease Sodium Intake and the Burden of Cardiovascular Disease: A Cost-Effectiveness Analysis

BACKGROUND Sodium consumption raises blood pressure, increasing the risk for heart attack and stroke. Several countries, including the United States, are considering strategies to decrease population sodium intake. OBJECTIVE To assess the cost-effectiveness of 2 population strategies to reduce sodium intake: government collaboration with food manufacturers to voluntarily cut sodium in processed foods, modeled on the United Kingdom experience, and a sodium tax. DESIGN A Markov model was constructed with 4 health states: well, acute myocardial infarction (MI), acute stroke, and history of MI or stroke. DATA SOURCES Medical Panel Expenditure Survey (2006), Framingham Heart Study (1980 to 2003), Dietary Approaches to Stop Hypertension trial, and other published data. TARGET POPULATION U.S. adults aged 40 to 85 years. TIME HORIZON Lifetime. PERSPECTIVE Societal. OUTCOME MEASURES Incremental costs (2008 U.S. dollars), quality-adjusted life-years (QALYs), and MIs and strokes averted. RESULTS OF BASE-CASE ANALYSIS Collaboration with industry that decreases mean population sodium intake by 9.5% averts 513 885 strokes and 480 358 MIs over the lifetime of adults aged 40 to 85 years who are alive today compared with the status quo, increasing QALYs by 2.1 million and saving

Cost-Effectiveness of Treatment of Diabetic Macular Edema

32.1 billion in medical costs. A tax on sodium that decreases population sodium intake by 6% increases QALYs by 1.3 million and saves

Assessing effectiveness and cost-effectiveness of concurrency reduction for HIV prevention

22.4 billion over the same period. RESULTS OF SENSITIVITY ANALYSIS Results are sensitive to the assumption that consumers have no disutility with modest reductions in sodium intake. LIMITATION Efforts to reduce population sodium intake could result in other dietary changes that are difficult to predict. CONCLUSION Strategies to reduce sodium intake on a population level in the United States are likely to substantially reduce stroke and MI incidence, which would save billions of dollars in medical expenses. PRIMARY FUNDING SOURCE Department of Veterans Affairs, Stanford University, and National Science Foundation.

Network analysis of cattle movements in Uruguay: Quantifying heterogeneity for risk-based disease surveillance and control.

Context Current therapies for diabetic macular edema include laser treatment, intraocular injections of triamcinolone or drugs that inhibit vascular endothelial growth factor (VEGF), and combinations of laser treatment plus injections of triamcinolone or a VEGF inhibitor. Contribution The investigators compared the lifetime costs and effectiveness of alternative treatments by using mathematical models that incorporated what was already known about each treatment. Caution Long-term outcome data are limited. Implication The most effective treatment of diabetic macular edema is VEGF inhibitor injection with or without laser treatment. This therapy is as cost-effective as acceptable treatments for many other conditions. The Editors Diabetes affects approximately 26 million patients in the United States, accounts for

Optimal link removal for epidemic mitigation: A two-way partitioning approach

1 in

From network analysis to risk analysis-An approach to risk-based surveillance for bovine tuberculosis in Minnesota, US

10 spent on health care, and is the leading cause of new-onset blindness among adults (1). Dilated eye examinations identify diabetic retinopathy, which ranges from mild (retinal hemorrhages) to severe (ischemia-induced neovascularization and fibrovascular proliferation, with potential hemorrhage, retinal detachment, or glaucoma). These examinations also identify diabetic macular edema (DME), which is central retinal edema resulting from increased vascular permeability of the retina. Diabetic macular edema affects central vision and is the most common cause of vision loss in patients with diabetes (2). Its prevalence is 9% among these patients (3), with approximately 75 000 new cases annually (4). Untreated DME can cause progressive vision decline (5) and medical costs that are 29% higher than those for unaffected patients with diabetes (6). The goal of DME treatment is to stop decline and, ideally, to recover vision. Successful treatment can enable a patient to resume driving, depending on the degree of vision impairment. Standard therapy has been macular laser treatment, which targets leaking microaneurysms and mildly stimulates subretinal cells to decrease edema. More recently, treatment of this condition has included intravitreal (intraocular) injections of triamcinolone acetonide or vascular endothelial growth factor (VEGF) inhibitors, which reduce vascular permeability and allow fluid reabsorption. Unlike laser treatment, which has potentially long-lasting effects, injections require periodic retreatment. Vascular endothelial growth factor inhibitors include bevacizumab, ranibizumab, and the newer VEGF Trap-Eye (aflibercept). In contrast to monotherapy, combination therapies of laser treatment and intravitreal injections aim to provide the long-term benefits of laser treatment and short-term benefits of fluid reabsorption. Treatment costs per injection differ substantially, from approximately

Potential cost-effectiveness of supervised injection facilities in Toronto and Ottawa, Canada

50 (off-label bevacizumab) to

Identifying Best-Fitting Inputs in Health-Economic Model Calibration A Pareto Frontier Approach

1200 (U.S. Food and Drug Administrationapproved ranibizumab) (711). Each strategy is well-studied, but no trial compares all therapies and few compare costs. Evidence on cost-effectiveness is conflicting. The U.K.s National Institute for Health and Clinical Excellence evaluated an industry-conducted modeling analysis of ranibizumab, and it found the cost-effectiveness of VEGF inhibitors to be unconvincing relative to that of laser treatment (12). Two published studies reached the opposite conclusion; however, they did not consider lifetime costs and benefits nor compare all major treatments (13, 14). Our study compares 6 strategies for lifetime management of DME. By comparing therapy with no treatment, we evaluate the societal effect of undiagnosed DME, which is particularly important given the increasing prevalence of diabetes. Diagnosis and proper management of DME depends on appropriate referral from primary care clinicians, who also play an important role in shared decision making with patients. Building on a relationship of long-standing trust with their primary care providers, patients often seek advice and second opinions about treatments offered by specialists. Understanding the options, vision benefits, and tradeoffs in therapy for DME will support and inform such conversations as part of comprehensive diabetes care. Methods Overview We developed a decision-analytic Markov cohort model of the natural history and treatment of DME, integrating mortality, visual acuity, treatment costs, complications, and societal costs. The model compared the effect on health, longevity, and costs of the following management strategies: no treatment; monotherapy with a VEGF inhibitor (ranibizumab, 0.3 mg); monotherapy with triamcinolone, 4 mg; laser monotherapy; combination therapy with laser treatment plus a VEGF inhibitor; and combination therapy with laser treatment plus triamcinolone. We translated vision and complications into utility-based quality-of-life measures and analyzed these from a societal perspective, broadly considering all lifetime costs and benefits, regardless of who benefited (1520). Patient Cohort The main cohort included patients with type 1 or 2 diabetes and clinically significant DME. In the model, 50% were men, age was 63 years, and visual acuity of the better eye was 20/63. Patients had no previous cataract surgery and did not receive treatment of DME within 4 months. These characteristics were similar to those of the baseline populations of major clinical trials of DME (2133). Disease Progression Health states of DME reflected vision (visual acuity categories 1 through 6 [Table 1]), treatment status, and complications (Figure 1). Because longitudinal data on the natural history of progression of DME are limited, we used expert opinion and calibration to the DRCR.net (Diabetic Retinopathy Clinical Research Network) study cohort to estimate long-term changes without treatment (transition probabilities were calculated using a Markov model with constant progression rates [Supplement]) (34). Table 2 shows input values (see Table 4 of the Supplement for visual acuity outcomes with and without treatment and Table 23 of the Supplement for uncertainty ranges). Supplement. Cost-Effectiveness of Treatment of DME Table 1. Definition of Visual Acuity Categories Used in the Model Figure 1. Markov model schematic. The 6 alternatives to the right of the decision node (square box) represent the 6 strategies for comparison, each progressing within the Markov model. The shaded boxes represent the Markov model transitions for progression of diabetic macular edema. Visual acuity categories 1 through 6 represent states of visual acuity (Table 1). Solid arrows represent possible worsening (progression) within a given month, and dashed arrows represent the potential for improvement or progression within a given month while receiving treatment. On-treatment states are subject to risk for complications (arterial thromboembolic events, glaucoma, cataracts, and other major or minor complications). In the base case, treatment was stopped after 1 y for all strategies or sooner if an arterial thromboembolic event or severe glaucoma occurred. VEGF = vascular endothelial growth factor.* Off or after treatment. Table 2. Base-Case Model Inputs* Treatment Effectiveness and Complications Primary data sources were the multicenter, randomized, double-masked clinical trials RESTORE (Ranibizumab Monotherapy or Combined With Laser Versus Laser Monotherapy for Diabetic Macular Edema) (21), DRCR.net (2226), READ-2 (Two-Year Outcomes of the Ranibizumab for Edema of the Macula in Diabetes) (27, 28), RISE (A Study of Ranibizumab Injection in Subjects With Clinically Significant Macular Edema With Center Involvement Secondary to Diabetes Mellitus) (29, 30), RIDE (A Study of Ranibizumab Injection in Subjects With Clinically Significant Macular Edema With Center Involvement Secondary to Diabetes Mellitus) (29, 30), RESOLVE (Safety and Efficacy of Ranibizumab in Diabetic Macular Edema) (31), and ETDRS (Early Treatment Diabetic Retinopathy Study) (32, 33), totaling 5009 patients. Patient characteristics reasonably reflected those in general clinical practice; however, patients in clinical trials had more homogeneous vision impairment and better-controlled diabetes. Dosage, treatment frequency, and follow-up also vary in practice. We used smaller studies in sensitivity analyses to explore these differences (4457). We modeled key complications individually: arterial thromboembolic events, glaucoma (controlled and severe or uncontrolled), and cataracts. We divided complications into major (for example, endophthalmitis) and minor (for example, eye irritation) categories (Supplement). We captured 1-time costs and quality-of-life decrements for acute complications and monthly costs and quality-of-life decrements for chronic complications (Table 2). In the main analysis, we assumed treatment of the better eye for a direct and predictable effect on vision-related quality of life. Treatment was received for 1 year except when stopped earlier because of complications (arterial thromboembolic events or uncontrolled glaucoma). We calibrated the model to match the average and the distribution of number of treatments for each strategy in clinical trials (Supplement). We selected a 1-year treatment period for consistency with primary trial end points and because greater crossover among treatment groups occurred in extended 2- and 3-year follow-up. For progression of DME after treatment, we modeled visual decline at a slower rate in strategies involving laser treatment (because clinical benefit from this therapy can be long-standing, in contrast to the short-term effect of injections) (58). We evaluated each assumption in sensitivity analyses. Additional simplifying assumptions included no crossover among treatments and no treatment resumption once a treatment had been discontinued (because of an arterial thromboembolic event or uncontrolled glaucoma orin the main analysisafter 1 year of therapy). We made these assumptions to keep the modeling tractable and because of limited data (Supplement). We validated clinical

Inferring model parameters in network-based disease simulation

We estimated the effectiveness and cost-effectiveness of changes in concurrent sexual partnerships in reducing the spread of HIV in sub-Saharan Africa. Using data from Swaziland, Tanzania, Uganda and Zambia, we estimated country-specific concurrency behaviour from sexual behaviour survey data on the number of partners in the past 12 months, and we developed a network model to compare the impact of three behaviour changes on the HIV epidemic: (1) changes in concurrent partnership patterns to strict monogamy; (2) partnership reduction among those with the greatest number of partners; and (3) partnership reduction among all individuals. We estimated the number of new HIV infections over 10 years and the cost per infection averted. Given our assumptions and model structure, we find that reducing concurrency among high-risk individuals averts the most infections and increasing monogamy the least (11.7% versus 8.7% reduction in new infections, on average, for a 10% reduction in concurrent partnerships). A campaign that costs US