Risks and benefits of screening for intracranial aneurysms in first-degree relatives of patients with sporadic subarachnoid hemorrhage.
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BACKGROUND: The first-degree relatives of patients who have subarachnoid hemorrhage from ruptured intracranial aneurysms are themselves at risk for subarachnoid hemorrhage. We studied the benefits and risks of screening for aneurysms in the first-degree relatives of patients with sporadic subarachnoid hemorrhage. METHODS: We screened 626 first-degree relatives (parents, siblings, or children) of 160 patients with sporadic subarachnoid hemorrhage, from a prospective series of 193 consecutive index patients. Magnetic resonance angiography was the screening tool, and conventional angiography was used as the reference test in subjects thought to have aneurysms. Six months after elective operation, outcome was assessed by means of the modified Rankin scale of neurologic function. This observational study design was combined with a decision-analysis model to estimate the effectiveness of screening. The efficiency of screening was defined by the number of relatives who needed to be screened in order to prevent one subarachnoid hemorrhage. RESULTS: Aneurysms were found in 25 of 626 first-degree relatives (4.0 percent; 95 percent confidence interval, 2.6 to 5.8 percent). Eighteen underwent surgery, which resulted in a decrease in function in 11 (disabling in 1). Five had aneurysms that were 5 to 11 mm in diameter, 11 had aneurysms that were less than 5 mm, and 2 had both small and medium-sized aneurysms. On average, surgery increased estimated life expectancy by 2.5 years for these 18 subjects (or by 0.9 month per person screened), at the expense of 19 years of decreased function per person. The number of relatives who would need to be screened in order to prevent 1 subarachnoid hemorrhage on a lifetime basis was 149, and 298 would have to be screened in order to prevent 1 fatal subarachnoid hemorrhage. CONCLUSIONS: Implementation of a screening program for the first-degree relatives of patients with sporadic subarachnoid hemorrhage does not seem warranted at this time, since the resulting slight increase in life expectancy does not offset the risk of postoperative sequelae. (+info)
Should this patient be screened for cancer?
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CONTEXT: Advances in imaging technology have provided numerous opportunities for cancer screening but have also raised numerous questions. GENERAL QUESTION: Who should be screened and how exactly should screening be performed? SPECIFIC RESEARCH CHALLENGE: If spiral computed tomography (spiral CT) were being considered for lung cancer screening, for example, important questions would need to be answered: Should nonsmokers be screened? How often should screening take place? What should the diagnostic work-up be after abnormal findings were seen on spiral CT? STANDARD APPROACH: Randomized, controlled trials (RCTs) are the most valid method for determining which medical interventions are most effective. These trials are particularly useful in the evaluation of screening because they eliminate the early detection biases that may result in groosly misleading survival statistics. POTENTIAL DIFFICULTIES: Randomized, controlled trials of screening are subject to other biases, and their results may be difficult to generalize. In addition, because they require an enormous number of participants and many years of follow-up, RCTs can be applied only to a small proportion of the questions about cancer screening. ALTERNATE APPROACH: Quantitative decision analysis can be applied to the remaining questions and help inform decision making about cancer screening. (+info)
Decision analysis on alternative treatment strategies for favorable-prognosis, early-stage Hodgkin's disease.
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PURPOSE: To compare the therapeutic outcomes of various treatment strategies in early-stage, favorable-prognosis Hodgkin's disease (HD) using methods of decision analysis. METHODS: We constructed a decision-analytic model to determine the life expectancy and quality-adjusted life expectancy for a hypothetical cohort of clinically or pathologically staged 25-year-old patients with early-stage, favorable-prognosis HD treated with varying degrees of initial therapy. Markov models were used to simulate the lifetime clinical course of patients, and baseline probability estimates were derived from published study results. RESULTS: Among patients with pathologic stage (PS) I to II, mantle and para-aortic (MPA) radiotherapy was favored over combined-modality therapy (CMT), mantle radiotherapy, and chemotherapy by 1.18, 1.33, and 1.55 years, respectively. For patients with clinical stage (CS) I to II, the treatment options of MPA-splenic radiotherapy, CMT, and chemotherapy yielded similar survival outcomes. Sensitivity analysis showed that the decision between CMT and MPA-splenic radiotherapy was highly influenced by the precise values of the estimates of treatment efficacy and long-term morbidity, the quality-of-life value assigned to the postsplenic irradiation state, and the time discount value used in the model. Probabilistic sensitivity analysis demonstrated that even if future studies doubled the precision of the estimates of the treatment-related variables, it would be impossible to demonstrate the superiority of one treatment over the other. CONCLUSION: Our model predicted that on average, MPA radiotherapy was clearly the preferred treatment for PS I to II patients. For CS I to II patients the treatment decision is a toss-up between MPA-splenic radiotherapy and CMT, emphasizing the importance of patient preference exploration and shared decision making between patient and physician when choosing between treatments. (+info)
Improved microbial gene identification with GLIMMER.
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The GLIMMER system for microbial gene identification finds approximately 97-98% of all genes in a genome when compared with published annotation. This paper reports on two new results: (i) significant technical improvements to GLIMMER that improve its accuracy still further, and (ii) a comprehensive evaluation that demonstrates that the accuracy of the system is likely to be higher than previously recognized. A significant proportion of the genes missed by the system appear to be hypothetical proteins whose existence is only supported by the predictions of other programs. When the analysis is restricted to genes that have significant homology to genes in other organisms, GLIMMER misses <1% of known genes. (+info)
A short-term cost-of-treatment model for type 2 diabetes: comparison of glipizide gastrointestinal therapeutic system, metformin, and acarbose.
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OBJECTIVE: To compare, from a managed care perspective, the 3-year costs of 3 first-line monotherapy strategies in type 2 diabetes patients: glipizide gastrointestinal therapeutic system (GITS), metformin, and acarbose. STUDY DESIGN: A Markov model, with a Monte Carlo simulation, was developed to compare the costs to achieve full glycemic control (hemoglobin A1c of < or = 7%) with each first-line strategy. PATIENTS AND METHODS: The patient population for the model was assumed to be all newly diagnosed type 2 diabetes patients eligible for monotherapy with an oral agent. Each monotherapy could be succeeded by add-on treatments. The model included the costs of routine medical care and supplies, medication, adverse events, and treatment failures. RESULTS: Using a Monte Carlo simulation, the mean 3-year cumulative costs per patient were $4971, $5273, and $5311 for glipizide GITS, metformin, and acarbose first-line strategies, respectively. The main cost drivers were drug prices. Mean 3-year cost savings for first-line glipizide GITS were $301 over metformin and $340 over acarbose. Between 83% and 85% of all simulations showed cost savings with glipizide GITS compared with the other agents. CONCLUSIONS: The model suggests first-line monotherapy with glipizide GITS should result in desirable short-term economic benefits for managed care. Because the model incorporates recommended glycemic goals and performed well in sensitivity analyses, it should be applicable to a variety of clinical practices and useful for economic assessments of new therapies. Results of this model should be verified prospectively in typical care settings. (+info)
A study in causal discovery from population-based infant birth and death records.
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In the domain of medicine, identification of the causal factors of diseases and outcomes, helps us formulate better management, prevention and control strategies for the improvement of health care. With the goal of exploring, evaluating and refining techniques to learn causal relationships from observational data, such as data routinely collected in healthcare settings, we focused on investigating factors that may contribute causally to infant mortality in the United States. We used the U.S. Linked Birth/Infant Death dataset for 1991 with more than four million records and about 200 variables for each record. Our sample consisted of 41,155 records randomly selected from the whole dataset. Each record had maternal, paternal and child factors and the outcome at the end of the first year--whether the infant survived or not. For causal discovery we used a modified Local Causal Discovery (LCD2) algorithm, which uses the framework of causal Bayesian Networks to represent causal relationships among model variables. LCD2 takes as input a dataset and outputs causes of the form variable X causes variable Y. Using the infant birth and death dataset as input, LCD2 output nine purported causal relationships. Eight out of the nine relationships seem plausible. Even though we have not yet discovered a clinically novel causal link, we plan to look for novel causal pathways using the full sample after refining the algorithm and developing a more efficient implementation. (+info)
Detecting population expansion and decline using microsatellites.
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This article considers a demographic model where a population varies in size either linearly or exponentially. The genealogical history of microsatellite data sampled from this population can be described using coalescent theory. A method is presented whereby the posterior probability distribution of the genealogical and demographic parameters can be estimated using Markov chain Monte Carlo simulations. The likelihood surface for the demographic parameters is complicated and its general features are described. The method is then applied to published microsatellite data from two populations. Data from the northern hairy-nosed wombat show strong evidence of decline. Data from European humans show weak evidence of expansion. (+info)
Is carotid endarterectomy cost-effective in symptomatic patients with moderate (50% to 69%) stenosis?
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OBJECTIVE: Recently published data from the North American Carotid Endarterectomy Trial revealed a benefit for carotid endarterectomy (CEA) in symptomatic patients with moderate (50% to 69%) carotid stenosis. This benefit was significant but small (absolute stroke risk reduction at 5 years, 6.5%; 22.2% vs 15.7%), and thus, the authors of this study were tentative in the recommendation of operation for these patients. To better elucidate whether CEA in symptomatic patients with moderate carotid stenosis is a proper allocation of societal resources, we examined the cost-effectiveness of this intervention. METHODS: A decision-analytic Markov process model was constructed to determine the cost-effectiveness of CEA versus medical treatment for a hypothetical cohort of 66-year-old patients with moderate carotid stenosis. This model allowed the comparison of not only the immediate hospitalization but also the lifetime costs and benefits of these two strategies. Our measure of outcome was the cost-effectiveness ratio (CER), defined as the incremental lifetime cost per quality-adjusted life year saved. We assumed an operative stroke and death rate of 6.6% and a declining risk of ipsilateral stroke after the ischemic event with medical treatment (first year, 9.3%; second year, 4%; subsequent years, 3%). The hospitalization cost of CEA ($6,420) and the annual costs of major stroke ($26,880), minor stroke ($798), and aspirin therapy ($63) were estimated from a hospital cost accounting system and the literature. RESULTS: CEA for moderate carotid stenosis increased the survival rate by 0.13 quality-adjusted life years as compared with medical treatment at an additional lifetime cost of $580. Thus, CEA was cost-effective with a CER of $4,462. Society is usually willing to pay for interventions with CERs of less than $60,000 (eg, CERs for coronary artery bypass grafting at $9,100 and for dialysis at $53,000). CEA was not cost-effective if the perioperative risk was greater than 11.3%, if the ipsilateral stroke rate associated with medical treatment at 1 year was reduced to 4.3%, if the age of the patient exceeded 83 years, or if the cost of CEA exceeded $13,200. CONCLUSION: CEA in patients with symptomatic moderate carotid stenosis of 50% to 69% is cost-effective. Perioperative risk of stroke or death, medical and surgical stroke risk, cost of CEA, and age are important determinants of the cost-effectiveness of this intervention. (+info)