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Biomedical subjects

A N Tosteson

Publications and source records attributed to A N Tosteson.

At least 19 recordsLinked to original sources

Perceptions of breast cancer risk and screening effectiveness in women younger than 50 years of age.

BACKGROUND: The National Cancer Institute has recently changed its approach and has substituted summary-of-evidence statements for specific recommendations for breast cancer screening in women 40-50 years of age, leaving these women with a greater share of decision-making responsibility. To make an informed decision about breast cancer screening, women need accurate information about their breast cancer risk and the benefit of screening. Although it has been suggested that women younger than 50 years of age overestimate this risk and benefit, their estimates have not been quantified. PURPOSE: The purpose of this study was to determine how women 40-50 years of age perceive their risk of breast cancer and the effectiveness of screening and how these perceptions compare with estimates derived from epidemiologic studies of breast cancer incidence and randomized clinical trials of screening. METHODS: We mailed a questionnaire to 200 women, identified through the computerized medical records of Dartmouth-Hitchock Medical Center, who were between 40 and 50 years of age and had no history of breast cancer. Each woman was asked about her risk factors for breast cancer and asked to estimate her probabilities of developing breast cancer and dying of it within 10 years, with and without screening. The women's answers were compared with individual probabilities derived from the Gail et al. model, age-specific probabilities of developing and dying of breast cancer in the United States, and the results of randomized clinical trials of screening. RESULTS: The mailed questionnaire was completed and returned by 145 (73%) of the 200 women. Respondents over-estimated their probability of dying of breast cancer within 10 years by more than 20-fold (median, 22.3; interquartile range, 11.1-74.2). Assuming a 10% relative risk reduction from screening, respondents overestimated the relative risk reduction by sixfold (median, 6.0; interquartile range, 5.0-7.5) and the absolute risk reduction more than 100-fold (median, 127.5; interquartile range, 47.1-399.6). The median perceived estimate of absolute risk reduction was 6.0 breast cancer deaths per 100 women; the median calculated estimate was only 0.04 per 100 women. CONCLUSION: These findings suggest that many women younger than 50 years of age substantially overestimate their breast cancer risk and the effectiveness of screening. IMPLICATIONS: A balanced presentation of information about breast cancer risk and screening effectiveness may improve decision making for women younger than 50 years of age and reduce their anxiety about breast cancer, regardless of whether they choose to be screened.

Adult

Changes in dyspnea, health status, and lung function in chronic airway disease.

The purpose of this study was to examine longitudinal changes in clinical parameters in patients with chronic obstructive pulmonary disease (COPD). We postulated that progressive dyspnea and decline in lung function over time would influence or impact patient's health status. Clinical ratings of dyspnea, general health status, and physiologic lung function were measured every 6 mo over a 2-yr period in an original group of 110 male patients with stable but symptomatic COPD and no significant comorbidity. At enrollment, age was 67 +/- 8 yr (mean +/- SD), forced expiratory volume in one second (FEV1) was 1.28 +/- 0.59 I (44 +/- 17% of predicted), and forced vital capacity (FVC) was 2.84 +/- 0.84 I (68 +/- 18% of predicted). A total of 34 patients "dropped out" because of death (n = 20), relocation (n = 7), and other reasons (n = 7). Dyspnea was measured using the transition dyspnea index (TDI), which represented changes from the baseline state; general health status was measured using the Medical Outcomes Study (MOS) 20-item short-form survey; physiologic lung function was assessed by spirometry (FVC and FEV1) and inspiratory muscle strength (PImax). Statistical analyses were performed using all available data for each patient, including results until the time at which patients died or were lost to follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Clinical efficacy of SPECT bone imaging for low back pain.

METHODS: We conducted a comprehensive structured review of the literature, analyzing 940 citations from 1966 through September 1993 and completed a narrative review. We also attempted quantitative synthesis of the accuracy of SPECT evaluation of low back pain. RESULTS: We found thirteen reports on accuracy. Only three provided a reasonable gold standard reference test and allowed the calculation of sensitivity and specificity. There is weak evidence that SPECT is useful in: (a) detecting pseudarthroses after failed spinal fusion, (b) evaluating young patients with back pain and (c) distinguishing benign from malignant lesions in cancer patients. SPECT has not been sufficiently studied in any other setting. We found no reports on the clinical outcome of SPECT or its cost-effectiveness. CONCLUSION: The decision to use SPECT in most patients with low back pain cannot be supported by clinical trials. Its effect on clinical management and cost-effectiveness are unknown. The medical community should mount a large-scale, prospective evaluation of SPECT in low back pain.

Cost-Benefit Analysis

Guidelines for meta-analyses evaluating diagnostic tests.

OBJECTIVES: To introduce guidelines for the conduct, reporting, and critical appraisal of meta-analyses evaluating diagnostic tests and to apply these guidelines to recently published meta-analyses of diagnostic tests. DATA SOURCES: Based on current concepts of how to assess diagnostic tests and conduct meta-analyses. They are applied to all meta-analyses evaluating diagnostic tests published in English-language journals from January 1990 through December 1991, identified through MEDLINE searching and by experts in the field. STUDY SELECTION: Meta-analyses were included if at least two of three independent readers regarded their main purpose as the evaluation of diagnostic tests against a concurrent reference standard. DATA EXTRACTION: By three independent readers on the extent to which meta-analyses fulfilled each guideline, with consensus defined as agreement by at least two readers. DATA SYNTHESIS: The guidelines are concerned with determining the objective of the meta-analysis, identifying the relevant literature and extracting the data, estimating diagnostic accuracy, and identifying the extent to which variability is explained by study design characteristics and characteristics of the patients and diagnostic test. In general, the guidelines were only partially fulfilled. CONCLUSION: Meta-analysis is potentially important in the assessment of diagnostic tests. Those reading meta-analyses evaluating diagnostic tests should critically appraise them; those doing meta-analyses should apply recently developed methods. The conduct and reporting of primary studies on which meta-analyses are based require improvement.

Bias

ROC curve regression analysis: the use of ordinal regression models for diagnostic test assessment.

Diagnostic tests commonly are characterized by their true positive (sensitivity) and true negative (specificity) classification rates, which rely on a single decision threshold to classify a test result as positive. A more complete description of test accuracy is given by the receiver operating characteristic (ROC) curve, a graph of the false positive and true positive rates obtained as the decision threshold is varied. A generalized regression methodology, which uses a class of ordinal regression models to estimate smoothed ROC curves has been described. Data from a multi-institutional study comparing the accuracy of magnetic resonance (MR) imaging with computed tomography (CT) in detecting liver metastases, which are ideally suited for ROC regression analysis, are described. The general regression model is introduced and an estimate for the area under the ROC curve and its standard error using parameters of the ordinal regression model is given. An analysis of the liver data that highlights the utility of the methodology in parsimoniously adjusting comparisons for covariates is presented.

Algorithms

Cost effectiveness of thrombolytic therapy with streptokinase in elderly patients with suspected acute myocardial infarction.

BACKGROUND: There is a lack of consensus among cardiologists about the potential benefit of thrombolytic therapy for suspected acute myocardial infarction in older patients. To investigate this issue, we constructed a decision-analytic model for patients 75 years of age or older who present with ST-segment elevation within six hours of the onset of symptoms suggesting acute myocardial infarction. METHODS: The variables incorporated in this model were the probability that the patient has an acute myocardial infarction, the probability of in-hospital death among patients with acute myocardial infarction who do not receive thrombolytic therapy, the probability of a fatal or incapacitating complication resulting from thrombolytic therapy, and the expected relative reduction in the risk of death associated with thrombolytic therapy in patients with acute myocardial infarction. Our analyses were based primarily on the use of streptokinase as the thrombolytic agent. RESULTS: Given our base-line assumptions, the probability of dying in the hospital was 21.4 percent if thrombolytic therapy was given and 24.4 percent if it was not given. In one-way sensitivity analyses, thrombolytic therapy decreased the risk of dying if the probability that the patient had an acute myocardial infarction was assumed to be greater than 9 percent, if the probability of dying in the hospital after an acute myocardial infarction without thrombolytic therapy was assumed to be greater than 3 percent, if the rate of fatal or incapacitating complications due to thrombolytic therapy was assumed to be 4 percent or less, or if the relative reduction in the risk of death associated with thrombolytic therapy was assumed to be greater than 1 percent. On the basis of our base-line assumptions, our estimate of the cost effectiveness of streptokinase therapy (the cost per year of life saved) for an 80-year-old patient with suspected acute myocardial infarction was $21,200. For a wide range of assumptions about risks, benefits, and costs, the cost per year of life saved remained less than $55,000. CONCLUSIONS: Within the limitations imposed by the assumptions used in our analysis, thrombolytic therapy with streptokinase was found to be a beneficial and cost-effective treatment for suspected acute myocardial infarction in elderly patients in a wide variety of clinical circumstances.

Age Factors

Immediate results and long-term follow-up after repeat balloon aortic valvuloplasty.

Balloon aortic valvuloplasty (BAV) was performed in 219 elderly patients with aortic stenosis between December 1985 and April 1990. Forty-three patients underwent repeat BAV for symptomatic restenosis of the aortic valve 13 +/- 8 mo following initial BAV. To evaluate the outcome following initial and repeat BAV, hemodynamic results were analyzed according to the following subgroups: BAV 1--initial BAV for all patients (n = 219); BAV 1/1--initial BAV in those who had only one BAV (n = 176); BAV 1/2--the initial BAV in those who had repeat BAV (n = 43); and BAV 2--repeat BAV (n = 43). The mean age of patients undergoing BAV 2 was 82 +/- 6 yr compared to 78 +/- 10 yr for all patients undergoing BAV 1 (p = .01). At the time of BAV 1 there was no difference in baseline or post-valvuloplasty aortic valve area (AVA) or peak aortic valve gradient (AVG) for patients having BAV 1/1 compared to those having BAV 1/2. However, for patients having repeat BAV, although the magnitude of the hemodynamic improvement of BAV 1/2 (AVA increased from 0.6 to 0.9 cm2, AVG decreased from 68 to 34 mm Hg, p less than .001) was similar to the magnitude of the hemodynamic improvement of BAV 2 (AVA increased from 0.5 to 0.8 cm2, AVG decreased from 65 to 34 mm Hg, p less than .001), the baseline AVA (0.5 cm2 at BAV 2 vs. 0.6 at BAV 1/2) and the post-valvuloplasty AVA (0.8 cm2 at BAV 2 vs. 0.9 at BAV 1/2) were significantly smaller (p less than .004).(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis

Predictors of event-free survival after balloon aortic valvuloplasty.

BACKGROUND: Balloon aortic valvuloplasty was developed as an alternative to aortic-valve replacement in selected elderly patients with aortic stenosis. The use of this procedure is limited, however, by a high incidence of restenosis. METHODS: Between December 1985 and April 1989, valvuloplasty was performed in 205 patients. We evaluated 40 demographic and hemodynamic variables as univariate predictors of event-free survival by Cox regression analysis and identified independent predictors of event-free survival by stepwise multivariate analysis. RESULTS: Early hemodynamic results indicated a decrease in the peak transaortic-valve pressure gradient from 67 +/- 28 to 33 +/- 15 mm Hg after valvuloplasty and an increase in aortic-valve area from 0.6 +/- 0.2 to 0.9 +/- 0.3 cm2 (P less than 0.001 for both comparisons). The rate of event-free survival (defined as survival without recurrent symptoms, repeated valvuloplasty, or aortic-valve replacement) was 18 percent over the mean (+/- SD) follow-up period of 24 +/- 12 months (range, 1 to 47). Significant predictors of event-free survival included the left ventricular ejection fraction and the left ventricular and aortic systolic pressure before valvuloplasty, and the percent reduction in the aortic-valve pressure gradient; the pulmonary-capillary wedge pressure was inversely associated with event-free survival. Although the predicted event-free survival rate for the entire patient group was 50 percent at one year (95 percent confidence interval, 43 to 57 percent) and 25 percent at two years (95 percent confidence interval, 19 to 31 percent), the probability of event-free survival at one year varied between 23 and 65 percent when patients were stratified according to three independent predictors: the aortic systolic pressure, the pulmonary-capillary wedge pressure, and the percent reduction in the peak aortic-valve gradient. CONCLUSIONS: The most important predictors of event-free survival after balloon aortic valvuloplasty were related to base-line left ventricular performance. The best long-term results after valvuloplasty were observed among patients who would also have been expected to have excellent long-term results after aortic-valve replacement.

Aortic Valve Stenosis

Impact of physician experience on triage of emergency room patients with acute chest pain at three teaching hospitals.

PURPOSE: To determine whether the experience of the physician (as measured by postgraduate training level or time during the academic year) who performs the initial evaluation affects the triage of patients with acute chest pain. PATIENTS AND METHODS: Prospective data on the presenting clinical features, initial triage, final diagnosis, and complications were collected for 7,857 patients who presented to the emergency rooms of three teaching hospitals, including 1,118 (14%) with acute myocardial infarction (AMI), 2,477 (32%) with acute ischemic heart disease (AIHD) (i.e., AMI or unstable angina), and 335 (4%) with major complications. The experience of the evaluating physicians, who were in their first three postgraduate years in 93% of cases, was measured in three ways: (1) postgraduate training level, (2) month during the academic year, and (3) number of patients with acute chest pain previously evaluated. Multivariate logistic regression analyses that adjusted for hospital site and 20 clinical variables estimated the odds ratios for admission to the coronary care unit (CCU) and hospital associated with each incremental increase in physician experience. RESULTS: With more experience (as measured by postgraduate training level or time during the academic year), the sensitivity of physicians for admitting patients with AMI, AIHD, or major complications to the hospital increased. For example, each incremental increase in postgraduate training level carried a 1.4 increase in the adjusted odds ratio for admission of a patient with AIHD to the hospital (p less than 0.05), corresponding to an increase in the probability of admission from 93% to 97%. However, increasing physician experience was also associated with an elevated false-positive rate in admitting patients without these diagnoses to the CCU and hospital. Thus, each incremental increase in postgraduate training level carried a 1.2 increase in the adjusted odds ratio for admission of a patient without AIHD to the CCU and hospital (p less than 0.005), corresponding to an increase in the probability of admission from 34% to 47%. By receiver operating characteristic curve (ROC) regression analyses, these changes in triage patterns were consistent with movement along a single ROC curve, rather than a shift to a new or better ROC curve. CONCLUSIONS: As the experience of the physician who performed the initial evaluation increased, there was a lower threshold for admitting all patients with and without AMI, AIHD, or major complications to the CCU and hospital without a detectable improvement in diagnostic accuracy.

Adult

Cost-effectiveness of hormone replacement therapy after the menopause.

The net resource costs and net health benefits of treating perimenopausal women with hormone replacement therapy were evaluated within the framework of cost-effectiveness analysis. Data from the epidemiological literature were used to estimate changes in discounted life expectancy from hip fracture, ischaemic heart disease and breast cancer that are associated with hormone replacement therapy under a variety of assumptions. Economic data were used to estimate changes in total discounted costs that result from the use of hormone replacement therapy. For women with a previous hysterectomy, 10- and 15-year courses of unopposed oestrogen were evaluated. The baseline assumptions for unopposed oestrogen were that breast cancer incidence would be increased for current users by 36% and that deaths from ischaemic heart disease would be reduced by 50% relative to non-users. Under these assumptions, oestrogen replacement therapy was found to be cost-effective, with ratios ranging from $9130 to $12,620 per additional year of life saved. For women who have not had a hysterectomy, 10- and 15-year courses of oestrogen combined with progestin were evaluated. The baseline assumptions for combined therapy were that breast cancer incidence and ischaemic heart disease deaths were unaffected. Under these assumptions, combined therapy was more costly, with ratios ranging from $86,100 to $88,500. Unless combined therapy is found to confer protection against ischaemic heart disease, the most cost-effective strategies for women with no prior hysterectomy may involve screening perimenopausal women to detect women at highest risk of hip fracture followed by selective treatment.

Adult

Expected gains in life expectancy from various coronary heart disease risk factor modifications.

BACKGROUND: Despite much evidence that modifying risk factors for coronary heart disease can decrease morbidity and mortality, little is known about the impact of risk-factor modification on life expectancy. METHODS AND RESULTS: We used the Coronary Heart Disease Policy Model, a state-transition computer simulation of the US population, to forecast potential gains in life expectancy from risk-factor modification for the cohort of Americans turning age 35 in 1990. Among 35-year-old men, we projected that the population-wide increase in life expectancy would be about 1.1 years from strict blood pressure control, 0.8 years from smoking cessation, 0.7 years from reduction of serum cholesterol to 200 mg/dl, and about 0.6 years from weight loss to ideal body weight. For women, reducing cholesterol to 200 mg/dl would have the greatest estimated impact-a gain of 0.8 years-whereas smoking cessation, blood pressure control, or weight loss would yield population-wide gains of 0.7, 0.4, and 0.4 years, respectively. Gains for 35-year-old individuals having a given risk factor are greater. We estimate that, on average, male smokers would gain 2.3 years from quitting smoking; males with hypertension would gain 1.1-5.3 years from reducing their diastolic blood pressure to 88 mm Hg; men with serum cholesterol levels exceeding 200 mg/dl would gain 0.5-4.2 years from lowering their serum cholesterol level to 200 mg/dl; and overweight men would gain an average of 0.7-1.7 years from achieving ideal body weight. Corresponding projected gains for at-risk women are 2.8 years from quitting smoking, 0.9-5.7 years from lowering blood pressure, 0.4-6.3 years from decreasing serum cholesterol, and 0.5-1.1 years from losing weight. Eliminating coronary heart disease mortality is estimated to extend the average life expectancy of a 35-year-old man by 3.1 years and a 35-year-old woman by 3.3 years. CONCLUSIONS: Population-wide gains in life expectancy from single risk-factor modifications are modest, but gains to individuals at risk can be more substantial.

Adult

Primary prophylaxis for Pneumocystis carinii pneumonia in HIV-infected people with CD4 counts below 200/mm3: a cost-effectiveness analysis.

We developed a decision-analytic model to assess the effectiveness and costs of dapsone, trimethoprim-sulfamethoxazole, or aerosolized pentamidine as initial prophylaxis for Pneumocystis carinii pneumonia in human immunodeficiency virus-infected people without prior symptoms AIDS and with CD4 counts less than 200/mm3. Each strategy increased life expectancy by about 18% compared with no prophylaxis; annual per-person costs were $440, $700, and $1,680 for dapsone, trimethoprim-sulfamethoxazole, and aerosolized pentamidine, respectively. These cost differences make a strategy beginning with dapsone most cost effective, with an incremental cost-effectiveness ratio of $13,400 per life year saved compared with no prophylaxis. Aerosolized pentamidine was substantially less cost effective, but the incremental cost effectiveness ratios were highly dependent on estimates for quality of life, efficacy, toxicity, and compliance. We conclude that, based on currently available data, initial prophylaxis with either dapsone or trimethoprim-sulfamethoxazole is most cost effective. For every 100,000 people treated, starting prophylaxis with trimethoprim-sulfamethoxazole or dapsone--with crossover to aerosolized pentamidine if oral therapy is not tolerated--may save between $98 million and $124 million per year.

Acquired Immunodeficiency Syndrome

Cost effectiveness of screening perimenopausal white women for osteoporosis: bone densitometry and hormone replacement therapy.

Bone mass measurement at menopause to identify and selectively prescribe hormone replacement therapy for women at high risk for fractures has seen limited clinical use. We used epidemiologic, clinical, and economic data in a decision-analytic model to compare the following clinical strategies for perimenopausal, asymptomatic, white women with intact uteri: no intervention; bone mineral density measurement followed by selective, long-term (15-year) estrogen-progestin therapy in women with low bone mass; and unselective, universal hormone replacement therapy. Life expectancy and direct medical cost per patient were estimated for each strategy. Strategies for screening and treating women with perimenopausal bone mineral density less than 0.9 g/cm2 or less than 1.0 g/cm2 would cost $11,700 or $22,100, respectively, per year of additional life gained. If the cost of screening is less than $84, then resource savings from hip fractures prevented would be more than the cost of screening and treatment. Universal treatment without screening would prevent additional fatal fractures but would expose many more women to the adverse effects of hormone replacement therapy and would cost an additional $349,000 per year of life gained compared with the screening strategies. When quality of life was considered, screening was found to be cost effective over a wide range of assumptions. The choice between universal treatment and screening depends on the risks (breast cancer), perceived side effects (menstrual bleeding), and benefits (prevention of ischemic heart disease) of estrogen-progestin therapy. We conclude that screening asymptomatic, perimenopausal white women to detect low bone mass and to target hormone replacement therapy at women who are at the greatest risk for fracture is a reasonably cost-effective use of health care resources. However, cost-effective screening guidelines cannot be explicitly established until further data addressing the association between bone mass measurements in the hip and hip fracture risk are available.

Aged

Cost-effectiveness of misoprostol for prophylaxis against nonsteroidal anti-inflammatory drug-induced gastrointestinal tract bleeding.

Patients who take nonsteroidal anti-inflammatory drugs (NSAIDs) are at increased risk of upper gastrointestinal tract bleeding, which may be prevented with prophylactic prescription of misoprostol. Using data from the literature, we estimated rates of gastrointestinal tract bleeding in NSAID users, direct medical costs, years of life lost, and cost-effectiveness of a 1-year course of misoprostol in three clinical populations of NSAID users: all users, users aged 60 years or older, and users with rheumatoid arthritis. The incremental cost-effectiveness ratios for misoprostol as primary prevention were $667,400 per year of life saved for all NSAID users; $186,700 per year of life saved for users aged 60 years or older; and $95,600 per year of life saved for users with rheumatoid arthritis. Misoprostol as secondary prevention for those who continued to take NSAIDs despite having had an episode of gastrointestinal tract bleeding in the previous year was associated with incremental cost-effectiveness ratios less than $40,000 per year of life saved in all patient groups. We conclude that misoprostol is costly as primary prevention for NSAID-induced gastrointestinal tract bleeding in the groups examined but may be cost-effective as secondary prevention in patients with a proved history of gastrointestinal tract bleeding.

Aged

Long-term cost-effectiveness of various initial monotherapies for mild to moderate hypertension.

To evaluate the comparative efficacy and cost-effectiveness of various antihypertensive medications in persons aged 35 through 64 years with diastolic blood pressure of 95 mm Hg or greater and no known coronary heart disease, we used the Coronary Heart Disease Policy Model, which is a computer simulation of overall mortality as well as the mortality, morbidity, and cost of coronary heart disease in the US population. From the pooled literature, we estimated the antihypertensive and total cholesterol effects of various antihypertensive regimens. For 20 years of simulated therapy from 1990 through 2010, the cost per year of life saved was projected to be $10,900 for propranolol hydrochloride; $16,400 for hydrochlorothiazide; $31,600 for nifedipine; $61,900 for prazosin hydrochloride; and $72,100 for captopril. Doubling the cholesterol effects of the agents under study did not significantly change their effectiveness because, in general, lowering diastolic blood pressure by 1 mm Hg was equivalent to lowering the cholesterol level by 6%. Although any projection requires multiple estimates, each of which may be open to debate, propranolol appears to be the preferred initial option under most of a variety of alternative assumptions.

Adult