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Biomedical subjects

A M Garber

Publications and source records attributed to A M Garber.

At least 55 records · Page 3Linked to original sources

Should we be measuring blood cholesterol levels in young adults?

Should we measure blood cholesterol levels in all adults, or only in those at high risk of coronary heart disease (CHD)? Most men under the age of 35 years and women under the age of 45 years--roughly half the adult population--are at very low short-term risk of CHD. One consequence is that drug treatment to lower high blood cholesterol levels in the average young adult is an extremely expensive means of prolonging life; the estimated $1 million to $10 million per year of life is 100 to 1000 times the cost of other approaches. Individualized dietary treatment is somewhat cheaper but relatively ineffective. Another consequence of the low CHD risk in young adults is the greater likelihood that intervention may have harmful effects that outweight the benefits. Meta-analysis of primary prevention trials in middle-aged men reveal an increase in non-CHD deaths among those randomized to cholesterol interventions, an unexpected finding that is more substantial than the decrease in CHD deaths. This raises the possibility that one or more of the cholesterol interventions could have very serious adverse effects among young adults, whose risk of non-CHD death is normally 100 times their risk of CHD death. We conclude that the policy of screening and treating high blood cholesterol levels in young adults is neither cost-effective, nor does it satisfy ethical standards requiring strong evidence that preventive interventions do more good than harm. Fortunately, cholesterol screening in young adults is also not necessary: most CHD events associated with high blood cholesterol levels in this population will not occur for decades and can be prevented by treatment that is begun in middle age. Cholesterol screening and treatment in young adults should be limited to individuals with known coronary disease or other unusual factors that place them at high short-term risk of CHD death.

Adult↗

Is high-flux dialysis cost-effective?

High-flux dialysis is a new method for providing routine-maintenance hemodialysis to patients with end-stage renal disease. It promises to shorten the duration of the dialysis session, but poses potential clinical risks to patients and financial risks to dialysis centers because of the high unit cost of purchasing new dialysis equipment. We retrospectively evaluated the cost-effectiveness of high-flux dialysis compared to conventional dialysis in a hospital-based center. The center provided only conventional dialysis until March 1989, when it initiated high-flux dialysis. The estimated annual costs of treatment were US $31,249 (high-flux) and $32,562 (conventional). The rate of hospital admissions was almost identical in both groups (conventional, 1.29 admissions per year; high-flux, 1.24 admissions per year; p = 0.23). Predicted prolongation of life expectancy with high-flux dialysis was significantly higher after statistical adjustment for observable patient characteristics (1.8 to 4.5 years; p < 0.01). The cost-effectiveness ratio was $28,188 per life-year saved for high-flux compared to conventional dialysis. These findings suggest that the added capital expense of purchasing high-flux equipment can be justified from the perspective of its societal cost-effectiveness.

California↗

No price too high?

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Drug Administration Schedule↗

Creating the costliest orphan. The Orphan Drug Act in the development of Ceredase.

The FDA recently approved Ceredase, a new treatment for Gaucher's disease, under the provisions of the Orphan Drug Act. Ceredase is unusually expensive, but there are no satisfactory alternative therapies. It appears likely that Ceredase would not have become available without the protection of the Orphan Drug Act, but its expense and the lack of information about its long-term effects on health raise questions about whether the ODA provides appropriate incentives to develop cost-effective technologies.

Adolescent↗

A multivariate analysis of mortality and hospital admissions with high-flux dialysis.

The use of high-flux dialysis in clinical practice increased rapidly despite an absence of reports on the clinical effectiveness of the technique. Mortality and hospital admission rates of patients treated with high-flux dialysis were evaluated and compared with those of patients treated with conventional dialysis in a hospital-based renal dialysis unit in northern California. By use of a retrospective, cross-over design, 253 patients enrolled in the dialysis unit from January 1987 to January 1991 were studied. During this period, 107 patients were treated with high-flux dialysis for at least 1 month, and all but 17 of them had received conventional dialysis before switching to high-flux dialysis. The remaining 146 patients were treated with only conventional dialysis. Of the 80 patients who died during the study period, 69 were receiving conventional dialysis and 11 were receiving high-flux dialysis. The multivariate analyses, adjusted for age, gender, ethnic background, type of renal failure, comorbid conditions, and duration of ESRD, showed that annual mortality was substantially less for patients treated with high-flux dialysis compared with that for patients treated with conventional dialysis (7 versus 20%; P < 0.001). The difference in the rate of hospital admissions was not statistically significant. In this nonexperimental study, methods were applied to control for selectivity bias and other factors that might confound the apparent treatment effect. The findings suggest that the potential benefits of high-flux dialysis are sufficient to justify further confirmation in a randomized, controlled trial.

Adult↗

Costs and benefits of prenatal screening for cystic fibrosis.

New tests promise to facilitate the prenatal detection of cystic fibrosis (CF), a fatal genetic disorder. This study examines the costs and benefits of prenatal screening and selective abortion using two types of tests: those based on restriction fragment-length polymorphisms (RFLPs), which can only be applied when genetic material is available from a CF-affected family member; and those based on probes for the newly discovered CF gene, which can be applied in the general population. When either type is applied in families of CF-affected children, even an expensive test produces substantial net benefits. Existing direct gene probe tests are not sensitive, although eventually they may become less expensive and more accurate than tests based on RFLPs. Even if these tests become highly accurate, the financial benefits of population-wide screening for CF are likely to be small or negative, particularly if testing does not lead to increases in the number of normal children as it decreases the number of births of CF-affected children. Because few children born in families without a history of CF have the disease, tests that are not perfectly specific will produce a large number of false-positive results, leading to the abortion of many normal fetuses.

Costs and Cost Analysis↗

Costs and health consequences of cholesterol screening for asymptomatic older Americans.

To predict the consequences of cholesterol screening among elderly Americans who do not have symptoms of heart disease, we explore the cost implications of a cholesterol screening program, evaluate evidence linking hypercholesterolemia to coronary heart disease and mortality in the elderly, and describe the likely effects of therapy of hypercholesterolemia. According to our calculations, if all Americans 65 years of age and older adhered to a cholesterol screening program similar to the one proposed by the National Cholesterol Education Program, minimum annual expenditures for screening and treatment would be between $1.6 billion and $16.8 billion, depending on the effectiveness of diet and the cost of the medications used to treat hypercholesterolemia. There is no direct evidence that this program would lessen overall morbidity or extend the lives of elderly Americans.

Aged↗

Screening for hypertension.

PURPOSE: To review the evidence on four questions about screening asymptomatic adults for arterial hypertension: Is hypertension a significant health problem? Is it detectable at an early, presymptomatic stage? Is treatment available and effective? Do the benefits of screening outweigh the costs and risks? DATA IDENTIFICATION AND SELECTION: We did a computerized search of the MEDLARS data base to identify community-based trials of drug therapy for mild hypertension; other relevant citations are included when appropriate. DATA SYNTHESIS: We approached the preliminary questions in our analysis by narrative review and argument. The estimates of therapeutic efficacy are based on previously published meta-analyses. The cost-effectiveness of screening was addressed by formal mathematical modeling of the effect of screening on various U.S. populations. RESULTS OF ANALYSIS: Hypertension is clearly a significant health problem. It can be detected early, and effective treatment is available. Screening asymptomatic adults for hypertension has benefits that compare favorably to the risks and costs involved. According to our estimates, screening is most cost-effective for older adults compared with younger adults and for men compared with women and is highly sensitive to the cost of therapy for mild hypertension. CONCLUSIONS: We recommend hypertension screening for all adults. We also discuss the frequency and setting of screening activities. When a low-cost therapy is used, the cost-effectiveness of screening for hypertension compares favorably with other cardiovascular interventions.

Adult↗

The resting electrocardiogram as a screening test. A clinical analysis.

PURPOSE: To review the evidence that a resting electrocardiogram (ECG) predicts cardiac disease in healthy persons and to discuss the role of this test in screening for coronary artery disease. DATA IDENTIFICATION: A manual search of the English-language literature using Index Medicus (1970-1988) and a bibliographic review of identified articles. STUDY SELECTION: We found 40 articles that described long-term survival of healthy individuals who either had had an abnormal finding on a resting ECG or had not had an abnormal finding. DATA EXTRACTION: We pooled the pertinent studies and calculated the relative risk for coronary artery disease if an ECG finding was present and the 95% confidence limits (CI) on the relative risk. RESULTS OF ANALYSIS: One reason for doing a screening SCG is to detect disease whose effects can be prevented by early treatment. In population studies of healthy middle-aged men, frequent ventricular premature beats, left axis deviation, left ventricular hypertrophy (ECG-LVH), and changes indicative of myocardial ischemia are all associated with a small but statistically significant increase in the risk of dying from coronary artery disease. There is no evidence that early detection of these findings leads to a clinical intervention that improves health outcomes. A screening ECG can also serve as a "baseline" tracing. Two studies have shown that the baseline tracing has little effect on decision making in the emergency room. CONCLUSION: The evidence does not support doing a screening ECG in men without evidence of cardiac disease or cardiovascular risk factors.

Arrhythmias, Cardiac↗

Screening asymptomatic adults for cardiac risk factors: the serum cholesterol level.

From our review of the epidemiologic and clinical literature, we have developed recommendations for using the serum cholesterol test as a component of strategies to prevent coronary heart disease in asymptomatic adults. Total cholesterol, high-density lipoprotein, and low-density lipoprotein levels are risk factors for coronary disease and early mortality in middle-aged men. Weaker evidence suggests that hypercholesterolemia increases the risk for coronary disease in women or elderly men, or that hypertriglyceridemia increases the risk in men or women. A reduction in cholesterol levels lowers the incidence of and the mortality from coronary disease in asymptomatic, hypercholesterolemic, middle-aged men, but has not been shown to reduce overall mortality. The efficacy of treatment in women and elderly persons has not been studied. Screening and treatment plans should be individualized; a 5-year period between tests is adequate for asymptomatic, low-risk men, whereas more frequent testing is appropriate for high-risk men. Screening is optional for women and elderly persons.

Adult↗

The role of exercise testing in screening for coronary artery disease.

PURPOSE: To predict the effects of using exercise testing to screen healthy persons for coronary artery disease. DATA IDENTIFICATION: The publications of the Coronary Artery Surgery Study were the principal sources of data for the cost-effectiveness analysis; we also used data from the Veterans Administration Cooperative Study of stable angina and the publications of the European Coronary Surgery Study Group. STUDY SELECTION: We used studies that provided the data that our decision model required--life expectancy and probabilities of outcomes in persons who have or do not have coronary artery disease. DATA EXTRACTION: We did not use a structured method for abstracting data. We tested the susceptibility of our conclusions to poor quality of data by substituting a wide range of values for a variable in the decision model, and by calculating life expectancy and costs if screening was used routinely or not used. RESULTS OF DATA SYNTHESIS: We assumed that persons with an abnormal exercise test would have arteriography and that persons with severe coronary artery disease would have bypass surgery. When there were no suitable published data for the model, we made assumptions that favored screening. The model predicts that screening would increase the life expectancy of 60-year-old men at average risk by at most 12 days. Sixty-year-old men with no risk factors for coronary artery disease would derive less benefit, as would women and younger men. CONCLUSIONS: The effect of exercise testing is too small to justify doing this procedure routinely in healthy persons. If coronary bypass surgery is found to prolong life in asymptomatic persons as much as it does in angina pectoris, screening older men with risk factors for coronary artery disease may prove to be worthwhile.

Coronary Disease↗

A discrete-time model of the acquisition of antibiotic-resistant infections in hospitalized patients.

Antibiotic use is thought to promote bacterial antibiotic resistance by selectively inhibiting the growth of sensitive strains. This study investigates the relation between antibiotic use and the propagation of antibiotic-resistant hospital-acquired infections due to gram-negative bacteria in a population of hospitalized patients. It treats infection spread and hospital mortality as a Markov process, in which the transition probabilities are logistic functions of a set of personal and hospital characteristics. Data from a university hospital are used to derive the parameters of the model.

Anti-Bacterial Agents↗

Antibiotic exposure and resistance in mixed bacterial populations.

Antibiotic use is often blamed for increases in the prevalence of infections due to antibiotic-resistance bacteria. This paper clarifies the effects of antibiotic exposure on bacterial antibiotic resistance by developing models that describe the growth of competing bacterial strains whose antibiotic sensitivities differ. The analysis generalizes logistic growth models to include first-order growth parameters that are arbitrary functions of antibiotic levels. It derives closed-form solutions for population size, composition, and average antibiotic sensitivities as functions of antibiotic exposure. Strategies to minimize the bacterial population size are analyzed in the context of the model. These heuristic models explore in formal terms the population dynamics thought to underlie resistance development.

Anti-Bacterial Agents↗