Context:

Women with inherited BRCA1/2 mutations are at high risk for breast cancer, which mammography often misses. Screening with contrast-enhanced breast magnetic resonance imaging (MRI) detects cancer earlier but increases costs and results in more false-positive scans.

Objective:

To evaluate the cost-effectiveness of screening BRCA1/2 mutation carriers with mammography plus breast MRI compared with mammography alone.

Design, Setting, and Patients:

A computer model that simulates the life histories of individual BRCA1/2 mutation carriers, incorporating the effects of mammographic and MRI screening was used. The accuracy of mammography and breast MRI was estimated from published data in high-risk women. Breast cancer survival in the absence of screening was based on the Surveillance, Epidemiology and End Results database of breast cancer patients diagnosed in the prescreening period (1975-1981), adjusted for the current use of adjuvant therapy. Utilization rates and costs of diagnostic and treatment interventions were based on a combination of published literature and Medicare payments for 2005.

Main Outcome Measures:

The survival benefit, incremental costs, and cost-effectiveness of MRI screening strategies, which varied by ages of starting and stopping MRI screening, were computed separately for BRCA1 and BRCA2 mutation carriers.

Results:

Screening strategies that incorporate annual MRI as well as annual mammography have a cost per quality-adjusted life-year (QALY) gained ranging from less than $45 000 to more than $700 000, depending on the ages selected for MRI screening and the specific BRCA mutation. Relative to screening with mammography alone, the cost per QALY gained by adding MRI from ages 35 to 54 years is $55 420 for BRCA1 mutation carriers, $130 695 for BRCA2 mutation carriers, and $98 454 for BRCA2 mutation carriers who have mammographically dense breasts.

Conclusions:

Breast MRI screening is more cost-effective for BRCA1 than BRCA2 mutation carriers. The cost-effectiveness of adding MRI to mammography varies greatly by age.

Objective: Unnecessary prescribing of antibiotics is a major problem in the U.S. and worldwide, contributing to the problem of antimicrobial resistance (AMR). This review examines the effects of quality improvement strategies on reducing inappropriate prescribing of antibiotics, targeting both prescribing of antibiotics for non-bacterial illnesses ("the antibiotic treatment decision") and prescribing of broad-spectrum antibiotics when narrow-spectrum agents are indicated ("the antibiotic selection decision").

Search Strategy and Inclusion Criteria: We evaluated studies examining the effectiveness of quality improvement (QI) strategies targeting outpatient antibiotic prescribing for acute illnesses. Studies were identified by searching the Cochrane Collaboration's Effective Practice and Organisation of Care registry and MEDLINE®. We included randomized and quasi-randomized controlled trials, controlled before-after studies, and interrupted time series that reported measures of antimicrobial use. QI strategies were classified as clinician education, patient education, provision of delayed prescriptions, audit and feedback, clinician reminders, and financial or regulatory incentives. Our primary outcomes were the percentage of patients prescribed an antibiotic (for antibiotic treatment studies); or the percentage of patients prescribed a recommended antibiotic or guideline-concordant antibiotic therapy (for antibiotic selection studies). Secondary outcomes included effects on antimicrobial resistance, intervention safety (disease outcomes and adverse events), prescribing costs, and patient satisfaction.

Data Collection and Analysis: Two reviewers abstracted data on the components of the QI intervention, study population, targets, and outcomes. We compared the effects of QI strategies in terms of the median effect achieved for the primary outcomes, using nonparametric tests; studies not eligible for median effects analysis were summarized qualitatively.

Main Results: Fifty-four studies reporting a total of 74 trials met the inclusion criteria; 34 studies (reporting 41 trials) addressed the treatment decision, and 26 studies (reporting 33 trials) addressed the selection decision. Six studies evaluated both decisions. Study methodologic quality was generally fair. Nearly all studies took place in outpatient primary care clinics.

• Studies addressing the antibiotic treatment decision: Most studies addressed prescribing for acute respiratory infections (ARIs). Interventions were effective at reducing prescribing, with a median absolute effect of -8.9% [interquartile range (IQR) -12.4% to -6.7%]. No individual QI strategy (or combination of strategies) was more effective at reducing prescribing. Within clinician education, active educational strategies appeared more effective than passive strategies. When extrapolated to a population level, strategies targeting general antibiotic prescribing appeared to reduce antibiotic prescribing more than strategies targeting prescribing for a single condition. Few studies addressed secondary endpoints; patient satisfaction was not worsened by QI interventions, but effects on AMR or costs could not be assessed.
• Studies addressing the antibiotic selection decision: Interventions targeted prescribing for ARIs or urinary tract infections (UTIs). Interventions were effective, with a median absolute improvement in prescribing of recommended antibiotics of 10.6% (IQR 3.4% to 18.2%). Clinician education alone appeared more effective than education in combination with audit and feedback, but this finding likely represents confounding. Very few studies addressed secondary outcomes.

Background: Anticoagulation (AC) with warfarin reduces the risk of thromboembolism (TE) in a variety of applications, yet despite compelling evidence of the value and importance of high quality AC, warfarin remains underused, and dosing is often suboptimal. Approaches to improve AC quality include (1) an AC service (ACS), which allows the physician to delegate day-to-day details of AC management to another provider dedicated to AC care, and (2) incorporating into the treatment plan patient self-testing (PST) under which, after completing a training program, patients perform their own blood testing (typically, using a finger-stick blood analyzer), have dosage adjustments guided by a standard protocol, and forward test results, dosing and other information to the provider. Studies have suggested that PST can improve the quality of AC and perhaps lower TE and bleed rates.The purpose of Department of Veterans Affairs (VA) Cooperative Studies Program (CSP) #481, "The Home INR Study" (THINRS) is to compare AC management with frequent PST using a home monitoring device to high quality AC management (HQACM) implemented by an ACS with conventional monitoring of prothrombin time by international normalized ratio (INR) on major health outcomes. PST in THINRS involves use of an INR monitoring device that is FDA approved for home use.

Study Design: Sites are VA Medical Centers where the ACS has an active roster of more than 400 patients. THINRS includes patients with atrial fibrillation (AF) and/or mechanical heart valve (MHV) expected to be anticoagulated indefinitely. THINRS has two parts. In Part 1, candidates for PST are evaluated for 2 to 4 weeks for their ability to use home monitoring devices. In Part 2, individuals capable of performing PST are randomized to (1) HQACM with testing every 4 weeks and as indicated for out of range values, medication/clinical changes, or (2) PST with testing every week and as indicated for out of range values, medication/clinical changes.The primary outcome measure is event rates, defined as the percent of patients who have a stroke, major bleed, or die. Secondary outcomes include total time in range (TTR), other events (myocardial infarction (MI), non-stroke TE, minor bleeds), competence and compliance with PST, satisfaction with AC, AC associated quality of life (QOL), and cost-effectiveness.To assess the effect of PST frequency on TTR and other outcomes, at selected sites patients randomized to perform PST are assigned one of three test frequencies (weekly, twice weekly, or once every four weeks).

BACKGROUND: Cervical-cancer screening strategies that involve the use of conventional cytology and require multiple visits have been impractical in developing countries. METHODS: We used computer-based models to assess the cost-effectiveness of a variety of cervical-cancer screening strategies in India, Kenya, Peru, South Africa, and Thailand. Primary data were combined with data from the literature to estimate age-specific incidence and mortality rates for cancer and the effectiveness of screening for and treatment of precancerous lesions. We assessed the direct medical, time, and program-related costs of strategies that differed according to screening test, targeted age and frequency, and number of clinic visits required. Single-visit strategies involved the assumption that screening and treatment could be provided in the same day. Outcomes included the lifetime risk of cancer, years of life saved, lifetime costs, and cost-effectiveness ratios (cost per year of life saved). RESULTS: The most cost-effective strategies were those that required the fewest visits, resulting in improved follow-up testing and treatment. Screening women once in their lifetime, at the age of 35 years, with a one-visit or two-visit screening strategy involving visual inspection of the cervix with acetic acid or DNA testing for human papillomavirus (HPV) in cervical cell samples, reduced the lifetime risk of cancer by approximately 25 to 36 percent, and cost less than 500 dollars per year of life saved. Relative cancer risk declined by an additional 40 percent with two screenings (at 35 and 40 years of age), resulting in a cost per year of life saved that was less than each country's per capita gross domestic product--a very cost-effective result, according to the Commission on Macroeconomics and Health. CONCLUSIONS: Cervical-cancer screening strategies incorporating visual inspection of the cervix with acetic acid or DNA testing for HPV in one or two clinical visits are cost-effective alternatives to conventional three-visit cytology-based screening programs in resource-poor settings.

BACKGROUND: This study was designed to quantify the resources used in reestablishing contact with women who missed their scheduled cervical cancer screening visits and to assess the success of this effort in reducing loss to follow-up in a developing country setting. METHODS: Women were enrolled in this Cape Town, South Africa-based screening study between 2000 and 2003, and all had scheduled follow-up visits in 2003. Community health worker (CHW) time, vehicle use, maintenance, and depreciation were estimated from weekly logs and cost accounting systems. The percentage of women who attended their scheduled visit, those who attended after CHW contact(s), and those who never returned despite attempted contact(s) were determined. The number of CHW visits per woman was also estimated. RESULTS: 3,711 visits were scheduled in 2003. Of these, 2,321 (62.5%) occurred without CHW contact, 918 (24.8%) occurred after contact(s), and 472 (12.7%) did not occur despite contact(s). Loss to follow-up was reduced from 21% to 6%, 39% to 10%, and 50% to 24% for 6, 12, and 24-month visits. CHWs attempted 3,200 contacts in 530 trips. On average, 3 CHWs attempted to contact 6 participants over each 111 minute trip. The per-person cost (2003 Rand) for these activities was 12.75, 24.92, and 40.50 for 6, 12, and 24-month visits. CONCLUSION: CHW contact with women who missed scheduled visits increased their return rate. Cost-effectiveness analyses aimed at policy decisions about cervical cancer screening in developing countries should incorporate these findings.

Background:

Eight randomized trials have evaluated whether the prophylactic use of an implantable cardioverter-defibrillator (ICD) improves survival among patients who are at risk for sudden death due to left ventricular systolic dysfunction but who have not had a life-threatening ventricular arrhythmia. We assessed the cost-effectiveness of the ICD in the populations represented in these primary-prevention trials.

Methods:

We developed a Markov model of the cost, quality of life, survival, and incremental cost-effectiveness of the prophylactic implantation of an ICD, as compared with control therapy, among patients with survival and mortality rates similar to those in each of the clinical trials. We modeled the efficacy of the ICD as a reduction in the relative risk of death on the basis of the hazard ratios reported in the individual clinical trials.

Results:

Use of the ICD increased lifetime costs in every trial. Two trials - the Coronary Artery Bypass Graft (CABG) Patch Trial and the Defibrillator in Acute Myocardial Infarction Trial (DINAMIT) - found that the prophylactic implantation of an ICD did not reduce the risk of death and thus was both more expensive and less effective than control therapy. For the other six trials - the Multicenter Automatic Defibrillator Implantation Trial (MADIT) I, MADIT II, the Multicenter Unsustained Tachycardia Trial (MUSTT), the Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) trial, the Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) trial, and the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT)- the use of an ICD was projected to add between 1.01 and 2.99 quality-adjusted life-years (QALY) and between $68,300 and $101,500 in cost. Using base-case assumptions, we found that the cost-effectiveness of the ICD as compared with control therapy in these six populations ranged from $34,000 to $70,200 per QALY gained. Sensitivity analyses showed that this cost-effectiveness ratio would remain below $100,000 per QALY as long as the ICD reduced mortality for seven or more years.

Conclusions:

Prophylactic implantation of an ICD has a cost-effectiveness ratio below $100,000 per QALY gained in populations in which a significant device-related reduction in mortality has been demonstrated.