***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: This study used data from a multinational phase III r and omized , double-blind , vehicle-controlled trial to evaluate the cost-effectiveness of tirilazad mesylate ( Freedox ) in the treatment of aneurysmal subarachnoid hemorrhage . In men , therapy with 6 mg/kg per day of tirilazad mesylate was associated with significantly increased survival , increased cost of care , and ratios of cost per death averted that compare favorably with the ratios of other life and death interventions . In women , it appeared to have no effects on costs or survival . Further clinical studies may provide additional information about the cost-effectiveness of this intervention PURPOSE The purpose of this study was to determine the cost-effectiveness of carotid endarterectomy for treating asymptomatic patients with > or = 60 % internal carotid stenosis , based on outcomes reported in the Asymptomatic Carotid Atherosclerosis Study ( ACAS ) . METHODS A cost-effectiveness analysis was performed using a Markov decision model in which the probabilities for base-case analysis ( average age , 67 years ; 66 % male ; perioperative stroke plus death rate , 2.3 % ; ipsilateral stroke rate during medical management , 2.3 % per year ) were based on ACAS . The model assumed that patients who had TIAs or minor strokes during medical management crossed over to surgical treatment , and used the NASCET data to model the outcome of these now-symptomatic patients . Average cost of surgery ( $ 8500 ) , major stroke ( $ 34,000 plus $ 18,000 per year ) , and other costs were based on local cost determinations plus a review of the published literature . Cost-effectiveness was calculated as the incremental cost of  surgery  per quality -adjusted life year ( QALY ) saved when compared with medical treatment , discounting at 5 % per year . Sensitivity analysis was performed to determine the impact of key variables on cost-effectiveness . RESULTS In the base-case analysis , surgical treatment  improved quality -adjusted life expectancy from 7.87 to 8.12 QALYs , at an incremental lifetime cost of $ 2041 . This yielded an incremental cost-effectiveness ratio of $ 8,000 per QALY saved by surgical compared with medical treatment . The high cost of care after major stroke during medical management largely offset the initial cost of endarterectomy in the surgical group . Furthermore , 26 % of medically managed patients eventually underwent endarterectomy because of symptom development , which also decreased the cost differential . Sensitivity analysis demonstrated that the relative cost of surgical treatment increased substantially with increasing age , increasing perioperative stroke rate , and decreasing stroke rate during medical management . CONCLUSION For the typical asymptomatic patient in ACAS with > or = 60 % carotid stenosis , our results indicate that carotid endarterectomy is cost-effective when compared with other commonly accepted health care practice s. Surgery does not appear cost-effective in very elderly patients , in setting s where the operative stroke risk is high , or in patients with very low stroke risk without surgery Cost-effectiveness analyses of stroke management are hampered by paucity of economic data . We made an up date of the direct and indirect costs of stroke in Sweden ( population , 8.5 million ) . Methods Direct costs ( ie , the costs for hospital and outpatient care and social services ) were estimated on the basis of two prospect i ve population -based studies of stroke and of two nationwide cross-sectional inventories of bed-days and diagnoses . Indirect costs ( ie , the costs for loss of productivity and early retirement ) were based on official statistics . Results The direct annual costs of care for stroke patients in 1991 equaled 7836 million Swedish krona ( SKr ) ( $ 1306 million in US dollars ) , and the indirect costs , 2430 million SKr ( $ 405 million ) . The cost of stroke care was 1208 SKr ( $ 201 ) per inhabitant in Sweden . The expected direct costs per patient from first stroke to death were 440 000 SKr ( $ 73 333 ) . When prestroke costs for other diseases and advanced age were subtracted , the sum was reduced to 180 000 SKr ( $ 30 000 ) . Conclusions Costs for hospital and outpatient care and social services accounted for 76 % of Swedish stroke costs and for 24 % of costs for loss of production and early retirement . Only 41 % of direct costs were stroke-related Stroke occurs in more than 500 000 persons annually and is the leading cause of long-term illness and the third leading cause of death in the United States [ 1 ] . The debilitating nature of a new-onset stroke is compounded by a high risk for subsequent neurologic and cardiac events [ 2 - 4 ] . The annual cost of stroke in the United States , including the indirect costs of lost productivity , has been estimated to be $ 15 billion to $ 30 billion [ 5 ] . Cardiovascular sources of emboli may account for 15 % to 45 % of all strokes [ 6 ] . Transesophageal echocardiography has allowed placement of a higher-frequency ultrasonic transducer closer to cardiac structures , thereby producing images with better resolution than those produced by transthoracic echocardiography . Transesophageal echocardiography has substantially improved the identification of thrombi in the left atrium and left atrial appendage . When surgical inspection is used as the gold st and ard , the sensitivity and specificity of transesophageal echocardiography have been shown to exceed 99 % [ 7 ] . Transesophageal echocardiography has also improved detection of patent foramen ovale , atrial septal defects , atrial septal aneurysms , spontaneous echocardiographic contrast in the left atrium [ 8 - 14 ] , and protruding atheromata in the ascending aorta and aortic arch [ 15 , 16 ] . Recent studies [ 16 , 17 ] showed that patients with cardiovascular sources of emboli have a worse prognosis than do patients without cardiovascular sources of emboli . Identification of potential sources of emboli is an important step in reducing recurrent strokes and future expenditures . Anticoagulation has repeatedly been shown to be beneficial in subgroups of patients at risk for stroke [ 18 ] . The extent of the benefit of anticoagulation in patients who have had stroke and who have documented or possible thrombi on transesophageal echocardiography is currently unknown and must be weighed against the increased risk for intracranial hemorrhage in such patients . The indications for cardiovascular imaging in patients who have had stroke are inconsistent [ 19 ] . Performance of cardiovascular imaging varies among physicians : Some physicians routinely order echocardiography , some use echocardiography in accordance with the patient 's clinical history , and some rarely order cardiac imaging studies in patients who have had stroke . Concern about the cost of echocardiography  may influence practice patterns . To evaluate the benefits , risks , and costs of different diagnostic approaches , we performed a cost-effectiveness analysis of common cardiovascular imaging strategies used in patients who have had stroke . Methods Design A Markov decision analysis [ 20 ] was done by using a commercially available computer program ( Decision-Maker 7.0 , Pratt Medical Group , Boston , Massachusetts ) to evaluate nine diagnostic strategies in a hypothetical cohort of 65-year-old patients in normal sinus rhythm with new-onset stroke ( Figure 1 ) . ( See the Glossary for definitions of terms . ) The treat-none and treat-all strategies did not include imaging . In the all-transthoracic , all-transesophageal , and all-sequential strategies , imaging was done in all patients . In the selective-transthoracic , selective-esophageal , and selective-sequential-1 strategies , imaging was done only in patients who had a history of cardiac problems ( left ventricular dysfunction or valvular disease ) . The selective-sequential-2 strategy used a sequential approach in patients with a history of cardiac problems and used transesophageal echocardiography in patients with no such history . Figure 1 . Nine possible diagnostic strategies for patients with stroke . The cohort consisted of patients with four types of underlying pathologic condition : thrombi in the left atrium , other potential cardiac sources of emboli , aortic plaque only , and no identifiable cardiovascular source of emboli ( Figure 2 ) . Identification of the underlying condition depended on the imaging strategy used ( Figure 1 ) . For example , the all-transesophageal strategy identified all potential sources of emboli , the all-transthoracic strategy identified only some of the sources , and the treat-none strategy identified none of the sources . Anticoagulation was started on the basis of the results of the imaging studies . For the imaging strategies included in the base-case analysis , only patients with thrombus received anticoagulants ; other patients received aspirin . Figure 2 . Health states for the Markov model . The cohort was then followed through monthly cycles for events , including recurrent cerebrovascular accident , intracranial hemorrhage , gastrointestinal bleeding , and death ( Figure 2 ) . Event and mortality rates were calculated on the basis of the underlying condition and treatment . Costs and outcomes for each health state were summed over the cycles . Patients in the cohort were followed over a lifetime horizon to provide the most relevant analysis from a societal perspective . Major Clinical Assumptions Several assumptions were necessary to implement the Markov model . First , patients had no obvious clinical cause of stroke ( that is , no evidence of periprocedural stroke , recent myocardial infa rct ion , prosthetic valve , known endocarditis , and so on ) . Second , patients were not receiving anticoagulants or antiplatelet agents at the time of stroke . Third , the subtype of ischemic stroke ( such as lacunar or cortical ) was independent of the underlying condition . Fourth , transesophageal echocardiography did not cause enough discomfort to decrease quality of life . Fifth , given the same underlying condition , the risk for recurrent stroke was independent of the history of cardiac disease ( angina , valvular disease , and so on ) . Sixth , only the first major complication after stroke was considered in the analysis ( for example , patients could not have both recurrent stroke and intracranial hemorrhage ) . Finally , new-onset and recurrent strokes were assumed to have similar relative effects on quality of life and on risk for death . Results of Diagnostic Imaging and Occurrence of Subsequent Events We performed a systematic review of the literature to gather the best available evidence about the prevalence of various cardiovascular sources of emboli in patients who have had stroke . A MEDLINE search from 1990 to 1995 was done by using cerebrovascular accident and transesophageal echocardiography as keywords ( before 1990 , transesophageal echocardiography was not a keyword ) . References from papers identified in the MEDLINE search were used to find relevant studies published before 1990 . Studies were chosen if they reported the prevalence of potential cardiovascular sources of emboli identified by transesophageal echocardiography in a defined cohort of patients who had had stroke [ 8 - 1417 , 21 , 22 ] ( Table 1 and Table 4 ) . Studies were distinguished with respect to four characteristics : patient selection ( all patients who had had stroke rather than only patients referred for echocardiography ) , performance of intracardiac contrast studies , blinding of image readers to clinical history , and use of multiple readers . Only single-plane and biplane probes were used in the studies . Thrombi in the left atrium or left atrial appendage were more often identified in studies with selected patients , but other cardiac sources of emboli were identified at similar rates in selected and nonselected patients . Major findings on transesophageal echocardiography did not significantly differ among the studies with regard to use of echocardiographic contrast , blinded readers , or multiple readers . In the papers in which it was mentioned , positive cardiac history was generally defined as atrial fibrillation ( patients with atrial fibrillation were excluded from our cohort ) ,  decreased left ventricular function , or valvular disease known at the time of transthoracic or transesophageal echocardiography .  Rates of identification of aortic plaques varied widely , in part because of poor st and ardization of diagnostic criteria . Because no group of studies was clearly superior in design and conduct , base-case imaging results were obtained from the mean of the results weighted by the number of participants in each study . Table 1 . Systematic Review of the Literature on Transesophageal Echocardiography after Stroke , 1989 - 1995 Table 4 . Table 1 . Continued Secondary event rates and mortality rates ( including the rate of death from nonvascular causes ) were determined by using the best available estimates in the literature ( Table 2 ) [ 1 - 418 , 23 - 30 ] . The estimated relative risk reduction for recurrent stroke ( that is , efficacy ) with anticoagulation ranged from 0 % [ 23 ] to 84 % [ 24 ] . Meta-analyses of studies of patients with atrial fibrillation estimated the efficacy of anticoagulation to be 60 % to 67 % and the efficacy of aspirin to be 33 % compared with that of no therapy [ 18 , 25 ] . Ezekowitz and colleagues [ 26 ] estimated a relative risk reduction of 40 % for anticoagulation in patients with a history of atrial fibrillation and stroke , a patient population that may be similar to our patients who had stroke and documented thrombus in the left atrium or left atrial appendage . We chose a relative risk reduction of 33 % for anticoagulation compared with aspirin and used a wide range ( 17 % to 67 % ) for sensitivity analysis . Table 2 . Input Variables Prospect i ve information on the incidence of intracranial hemorrhage with anticoagulation after a stroke is also scarce . In a previous decision analysis , Eck 
    Output:
    
Different studies addressing the cost-effectiveness of screening asymptomatic carotid stenosis result ed in strikingly divergent conclusions , from being cost-effective to being detrimental .