Karen M. Kuntz

Decision Analysis — Effects of Prophylactic Mastectomy and Oophorectomy on Life Expectancy among Women with BRCA1 or BRCA2 Mutations

BACKGROUND Women with BRCA1 or BRCA2 mutations have an increased risk of breast cancer and ovarian cancer. Prophylactic mastectomy and oophorectomy are often considered as ways of reducing these risks, but the effect of the procedures on life expectancy has not been established. METHODS In a decision analysis, we compared prophylactic mastectomy and prophylactic oophorectomy with no prophylactic surgery among women who carry mutations in the BRCA1 or BRCA2 gene. We used available data about the incidence of cancer, the prognosis for women with cancer, and the efficacy of prophylactic mastectomy and oophorectomy in preventing breast and ovarian cancer to estimate the effects of these interventions on life expectancy among women with different levels of risk of cancer. RESULTS We calculated that, on average, 30-year-old women who carry BRCA1 or BRCA2 mutations gain from 2.9 to 5.3 years of life expectancy from prophylactic mastectomy and from 0.3 to 1.7 years of life expectancy from prophylactic oophorectomy, depending on their cumulative risk of cancer. Gains in life expectancy decline with age at the time of prophylactic surgery and are minimal for 60-year-old women. Among 30-year-old women, oophorectomy may be delayed 10 years with little loss of life expectancy. CONCLUSIONS On the basis of a range of estimates of the incidence of cancer, prognosis, and efficacy of prophylactic surgery, our model suggests that prophylactic mastectomy provides substantial gains in life expectancy and prophylactic oophorectomy more limited gains for young women with BRCA1 or BRCA2 mutations.

Cost Effectiveness of Aspirin, Clopidogrel, or Both for Secondary Prevention of Coronary Heart Disease

BACKGROUND Both aspirin and clopidogrel reduce the rate of cardiovascular events in patients with coronary heart disease. We estimated the cost effectiveness of the increased use of aspirin, clopidogrel, or both for secondary prevention in patients with coronary heart disease. METHODS We used the Coronary Heart Disease Policy Model, a computer simulation of the U.S. population, to estimate the incremental cost effectiveness (in dollars per quality-adjusted years of life gained) of four strategies in patients over 35 years of age with coronary disease from 2003 to 2027: aspirin for all eligible patients (i.e., those who were not allergic to or intolerant of aspirin), aspirin for all eligible patients plus clopidogrel for patients who were ineligible for aspirin, clopidogrel for all patients, and the combination of aspirin for all eligible patients plus clopidogrel for all patients. RESULTS The extension of aspirin therapy from the current levels of use to all eligible patients for 25 years would have an estimated cost-effectiveness ratio of about

Estimating the Energy Gap Among US Children: A Counterfactual Approach

11,000 per quality-adjusted year of life gained. The addition of clopidogrel for the 5 percent of patients who are ineligible for aspirin would cost about

HER-2 Testing and Trastuzumab Therapy for Metastatic Breast Cancer: A Cost-Effectiveness Analysis

31,000 per quality-adjusted year of life gained. Clopidogrel alone in all patients or in routine combination with aspirin had an incremental cost of more than

Cost-effectiveness of donepezil in the treatment of mild or moderate Alzheimer’s disease

130,000 per quality-adjusted year of life gained and remained financially unattractive across a wide range of assumptions. However, clopidogrel alone or in combination with aspirin would cost less than

Model for incorporating social context in health behavior interventions: applications for cancer prevention for working-class, multiethnic populations

50,000 per quality-adjusted year of life gained if its price were reduced by 70 to 82 percent, to

Benefits of Colonoscopic surveillance and prophylactic colectomy in patients with hereditary nonpolyposis colorectal cancer mutations

1.00 and

Phenotypic variability associated with progranulin haploinsufficiency in patients with the common 1477C→T (Arg493X) mutation: an international initiative

0.60 per day, respectively. CONCLUSIONS Increased prescription of aspirin for secondary prevention of coronary heart disease is attractive from a cost-effectiveness perspective. Because clopidogrel is more costly, its incremental cost effectiveness is currently unattractive, unless its use is restricted to patients who are ineligible for aspirin.

Cost-effectiveness of screening for anal squamous intraepithelial lesions and anal cancer in human immunodeficiency virus-negative homosexual and bisexual men.

OBJECTIVE. Our goal was to quantify the magnitude of energy imbalance responsible for the increase in body weight among US children during the periods 1988–1994 and 1999–2002. METHODS. We adopted a counterfactual approach to estimate weight gains in excess of normal growth and the implicit “energy gap”—the daily imbalance between energy intake and expenditure. On the basis of Centers for Disease Control and Prevention growth charts, we constructed weight, height, and BMI percentile distributions for cohorts 2 to 4 and 5 to 7 years of age in the 1988–1994 National Health and Nutrition Examination Survey (N = 5000). Under the counterfactual “normal-growth-only” scenario, we assumed that these percentile distributions remained the same as the cohort aged 10 years. Under this assumption, we projected the weight and height distributions for this cohort at 12 to 14 and 15 to 17 years of age on the basis of their baseline weight-for-age and stature-for-age percentiles. We compared these distributions with those for corresponding age groups in the 1999–2002 National Health and Nutrition Examination Survey (N = 3091) ∼10 years after the 1988–1994 National Health and Nutrition Examination Survey. We calculated differences between the counterfactual and observed weight distributions and translated this difference into the estimated average energy gap, adjusting for increased total energy expenditure attributable to weight gain. In addition, we estimated the average excess weight accumulated among overweight adolescents in the 1999–2002 National Health and Nutrition Examination Survey, validating our counterfactual assumptions by analyzing longitudinal data from the National Longitudinal Survey of Youth and Bogalusa Heart Study. RESULTS. Compared with the counterfactual scenario, boys and girls who were aged 2 to 7 in the 1988–1994 National Health and Nutrition Examination Survey gained, on average, an excess of 0.43 kg/year over the 10-year period. Assuming that 3500 kcal leads to an average of 1-lb weight gain as fat, our results suggest that a reduction in the energy gap of 110–165 kcal/day could have prevented this increase. Among overweight adolescents aged 12 to 17 in 1999–2002, results indicate an average energy imbalance ranging from 678 to 1017 kcal/day because of an excess of 26.5 kg accumulated over 10 years. CONCLUSIONS. Quantifying the energy imbalance responsible for recent changes in weight distribution among children can provide salient targets for population intervention. Consistent behavioral changes averaging 110 to 165 kcal/day may be sufficient to counterbalance the energy gap. Changes in excess dietary intake (eg, eliminating one sugar-sweetened beverage at 150 kcal per can) may be easier to attain than increases in physical activity levels (eg, a 30-kg boy replacing sitting for 1.9 hours with 1.9 hours walking for an extra 150 kcal). Youth at higher levels of weight gain will likely need changes in multiple behaviors and environments to close the energy gap.

Cost-effectiveness of fusion with and without instrumentation for patients with degenerative spondylolisthesis and spinal stenosis

PURPOSE Trastuzumab therapy has been shown to benefit metastatic breast cancer patients whose tumors exhibit HER-2 protein overexpression or gene amplification. Several tests of varying accuracy and cost are available to identify candidates for trastuzumab. We estimated the cost-effectiveness of alternative HER-2 testing and trastuzumab treatment strategies. PATIENTS AND METHODS We performed a decision analysis using a state-transition model to simulate clinical practice in a hypothetical cohort of 65-year-old metastatic breast cancer patients. Outcomes were quality-adjusted life-years (QALYs), lifetime cost, and incremental cost-effectiveness ratio (ICER). Interventions included testing with the HercepTest (DAKO, Carpinteria, CA) immunohistochemical assay alone, fluorescence in situ hybridization (FISH) alone, and both tests, followed by trastuzumab and chemotherapy for patients with positive test results and chemotherapy alone for patients with negative test results. RESULTS In the base case, initial HercepTest with FISH confirmation of all positive results had an ICER of