Karen M. Kuntz

Objectives. We sought to quantify the impact of the 1998 US Food and Drug Administration (FDA) folic acid fortification policy by estimating folate intake at the population level. Methods. We analyzed total folate intake levels (from food and supplements) according to gender, age, and race/ethnicity, using data from 2 National Health and Nutrition Examination Surveys. We measured pre- and postfortification folate intake distributions, adjusted for measurement error, and examined proportions of the population who reached certain thresholds of daily total folate intake. Results. Mean daily food and total folate intake increased by approximately 100 μg/day after fortification. The proportion of women aged 15–44 years who consume more than 400 μg/day of folate has increased since fortification, but has not yet reached the FDA’s 50% target and varies by race/ethnicity from 23% to 33%. Among persons aged 65 years and older who may be at risk for masking a vita-μg/day (the min B₁₂ deficiency, the percentage who consume more than 1000 “tolerable upper intake level”) has at least doubled among Whites and Black men, but has remained less than 5% for all groups. Conclusions. Since fortification, folic acid intake among the US population has increased, and there are substantial variations by age, gender, and race/ethnicity.

BACKGROUND: The distribution of prostate‐specific antigen (PSA) values for men with or without prostate carcinoma are confounded because of verification bias. Correcting for verification bias, the means and variances of PSA values were estimated in specific clinical scenarios.METHODS: Existing receiver operating characteristic (ROC) curves, adjusted for the presence of verification bias in a screening population, were used to estimate the mean and variance of PSA values for men with or without prostate carcinoma, stratified by age and the presence or absence of benign prostatic hyperplasia. Men with a suspicious digital rectal exam (nodular) were excluded from analysis.RESULTS: Among men with cancer and the absence of benign prostatic hyperplasia, mean PSA values were 2.05 ng/mL and 2.66 ng/mL for younger (<60 yr) and older (≥60 yrs) men, respectively. These estimates were 2.56 ng/mL and 3.90 ng/mL in the presence of benign prostatic hyperplasia for younger and older men, respectively. For men without prostate carcinoma, these values were 0.78 ng/mL and 1.23 ng/mL for younger and older men, respectively, among those without benign prostatic hyperplasia, and 0.97 ng/mL and 1.75 ng/mL for younger and older men, respectively, among those with benign prostatic hyperplasia.CONCLUSIONS: Accurate estimates of the mean and variance of PSA values for men with or without cancer may provide PSA thresholds for biopsy that are specific for age and prostate size as assessed by digital rectal exam. Therefore, the current threshold of 4.0 ng/mL should not be applied indiscriminately. Cancer 2006. © 2006 American Cancer Society.

The sensitivity and specificity of a screening test are biased when disease status is not verified in all subjects and when the likelihood of confirmation depends on the test result itself. We assessed the screening characteristics of the prostate-specific antigen (PSA) measurement after correction for verification bias.

An important assumption made when constructing a Markov model is that all persons residing in a health state are identical. Failure to adjust for population heterogeneity caused by unobserved variables can therefore cause bias in model results. The authors used a simple model to evaluate the potential impact of heterogeneity bias, defined as the percentage change in the life expectancy gain with an intervention predicted by a model that does not adjust for heterogeneity (unadjusted model) compared to one that does (adjusted model). The life expectancy gains were consistently greater in the unadjusted model compared to the adjusted model (positive bias). For an annual probability of developing disease of 1%, the heterogeneity bias exceeded 50% when the relative risk of disease with the heterogeneity factor versus without the factor was greater than 15 and the prevalence of the heterogeneity factor was between 5% and 25%. When constructing decision-analytic models, analysts need to be cognizant of unobserved factors that introduce heterogeneity into the cohort. This analysis provides a general framework to determine when issues of heterogeneity may be important.

Because of the variability of HIV, the first AIDS vaccine is likely to be only partially effective. There is some concern among scientists that a low-efficacy vaccine could worsen the HIV epidemic if vaccinated individuals increase their risk behavior under the false assumption of immunity. To address this concern, we constructed a dynamic compartmental model that simulated the course of the HIV/AIDS epidemic in a population of injection drug users in Bangkok, Thailand. The model calculated long-term HIV prevalence, number of AIDS cases, and total population size for two scenarios: vaccination program versus no vaccination program. We used sensitivity analyses to evaluate the impact of postvaccination risk behavior change on HIV prevalence. A 75% effective vaccine led to a 40-year HIV prevalence of 37% with vaccination and 50% without vaccination. Postvaccination behavior change had only a limited effect on the results with a 75% effective vaccine but a significant effect with a 30% effective vaccine. If 90% of low-risk individuals responded to a 30% effective vaccine with increased high-risk behavior, the benefit of vaccination disappeared. These results agree with analyses of the epidemic among gay men. If injection drug behavior is indeed modifiable, our findings have significant policy and planning implications. Address correspondence and reprint requests to Karen M. Kuntz, Center for Risk Analysis, Harvard School of Public Health, 718 Huntington Avenue, Boston, MA 02115, U.S.A.; e-mail: [email protected] Manuscript received July 26, 2001; accepted October 24, 2001. © 2002 Lippincott Williams & Wilkins, Inc.

A cost-effectiveness study was performed from the societal perspective. To evaluate the costs and benefits of laminectomy alone and laminectomy with concomitant lumbar fusion for patients with degenerative lumbar spondylolisthesis and spinal stenosis. Costs, probabilities, and utilities were estimated from the literature. Short-term risks considered were perioperative complications, the probability of the fusion healing, and the probability that surgery will relieve symptoms. Long-term risks considered were recurrence of symptoms and reoperation. The 10-year costs, quality-adjusted life years, and incremental cost-effectiveness ratios (reported as dollars per quality-adjusted year of life gained) were calculated using a Markov model. Sensitivity analysis was performed on all variables using clinically plausible ranges. Laminectomy with noninstrumented fusion costs $56,500 per quality-adjusted year of life versus laminectomy without fusion. The cost-effectiveness of laminectomy with noninstrumented fusion was most sensitive to the increase in quality-of-life associated with relief of severe stenosis symptoms. The cost-effectiveness ratio of instrumented fusion compared with noninstrumented fusion was $3,112,800 per quality-adjusted year of life. However, if the proportion of patients experiencing symptom relief after instrumented fusion was 90% as compared with 80% for patients with noninstrumented fusion, then the cost-effectiveness ratio of instrumented fusion compared with noninstrumented fusion would be $82,400 per quality-adjusted year of life. The cost-effectiveness of laminectomy with noninstrumented fusion compares favorably with other surgical interventions, although it depends greatly on the true effectiveness of these surgeries to alleviatesymptoms and on how patients value the quality-of-life effect of relieving severe stenosis symptoms. Instrumented fusion was very expensive compared with the incremental gain in health outcome. Better data on the effectiveness of these alternative procedures are needed.

Practice guidelines are systematically developed statements to assist practitioners and patients regarding decisions about appropriate health care under specific clinical circumstances.¹ The recent development and proliferation of clinical practice guidelines have been driven largely by the need to improve the quality of health care, reduce practice variation, and decrease costs and health-care use.^2,3 Clinical guidelines help clinicians choose appropriate care and serve a role in assessing accountability in health care delivery.^4-6

Many noninvasive tests exist to determine whether patients should undergo coronary angiography. The routine use of coronary angiography without previous noninvasive testing is typically not advocated. To determine the cost-effectiveness of diagnostic strategies for patients with chest pain. Cost-effectiveness analysis. Published data. Patients who present with chest pain, have no history of myocardial infarction, and are able to perform an exercise stress test. Lifetime. Societal. No testing, exercise electrocardiography, exercise echocardiography, exercise single-photon emission computed tomography (SPECT), and coronary angiography alone. Quality-adjusted life expectancy, lifetime cost, and incremental cost-effectiveness. The incremental cost-effectiveness ratio of routine coronary angiography compared with exercise echocardiography was $36 400 per quality-adjusted life-year (QALY) saved for 55-year-old men with typical angina. For 55-year-old men with atypical angina, exercise echocardiography compared with exercise electrocardiography cost $41 900 per QALY saved. If adequate exercise echocardiography was not available, exercise SPECT cost $54 800 per QALY saved compared with exercise electrocardiography for these patients. For 55-year-old men with nonspecific chest pain, the incremental cost-effectiveness ratio of exercise electrocardiography compared with no testing was $57 700 per QALY saved. On the basis of a probabilistic sensitivity analysis, there is a 75% chance that exercise echocardiography costs less than $50 900 per QALY saved for 55-year-old men with atypical angina. Exercise electrocardiography or exercise echocardiography resulted in reasonable cost-effectiveness ratios for patients at mild to moderate risk for coronary artery disease in terms of age, sex, and type of chest pain. Coronary angiography without previous noninvasive testing resulted in reasonable cost-effectiveness ratios for patients with a high pretest probability of coronary artery disease.