human
***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: OBJECTIVE The aim of this study was to analyze the correlation between thromboembolic complications and antiplatelet drugs before and after neurointervention . METHODS Blood sample s and radiographic data of patients who received a neurointervention ( coil embolization , stent placement or both )  were collected prospect ively . Rapid platelet function assay-aspirin ( RPFA-ASA ) was used to calculate aspirin resistance in aspirin reaction units ( ARU ) . For clopidogrel resistance , a P2Y12 assay was used to analyze the percentage of platelet inhibition . ARU > 550 and platelet inhibition < 40 % were defined as aspirin and clopidogrel resistance , respectively . RESULTS Both aspirin and clopidogrel oral pills were administered in fifty-three patients before and after neurointerventional procedures . The mean resistance values of all patients were 484 ARU and < 39 % . Ten ( 17.0 % ) of 53 patients showed resistance to aspirin  with an average of 597 ARU , and 33 ( 62.3 % ) of 53 patients showed resistance to clopidogrel  with an average of < 26 % . Ten patients demonstrated resistance to both drugs , 5 of which suffered a thromboembolic complication after neurointervention ( mean values : 640 ARU and platelet inhibition < 23 % ) . Diabetic patients and patients with hypercholesterolemia displayed mean aspirin resistances of 513.7 and 501.8 ARU , and mean clopidogrel resistances of < 33.8 % and < 40.7 % , respectively . CONCLUSION Identifying individuals with poor platelet inhibition using st and ard regimens is of great clinical importance and may help prevent cerebral ischemic events in the future . Neurointerventional research should focus on ideal doses , timing , choices , safety , and reliable measurements of antiplatelet drug therapy , as well as confirming the clinical relevance of aggregometry in cerebrovascular patients Essential thrombocythemia ( ET ) is characterized by enhanced platelet generation and thrombotic complications . Once-daily low-dose aspirin incompletely inhibits platelet thromboxane A(2 ) ( TXA(2 ) ) in the majority of ET patients . In the present study , we investigated the determinants of aspirin-insensitive platelet TXA(2 ) bio synthesis and whether it could be further suppressed by changing the aspirin dose , formulation , or dosing interval . In 41 aspirin-treated ET patients , the immature platelet count predicted serum TXB(2 ) independently of platelet count , age , JAK-2 V617F mutation , or cytoreduction ( β = 3.53 , P = .001 ) . Twenty-one aspirin-treated patients with serum TXB(2 ) ≥ 4 ng/mL at 24 hours after dosing were r and omized to the following 7-day regimens in a crossover design : enteric-coated aspirin 100 mg twice daily , enteric-coated aspirin 200 mg once daily , or plain aspirin 100 mg once daily . A twice-daily regimen caused a further 88 % median ( IQR , 78%-92 % , P < .001 ) TXB(2 ) reduction and normalized the functional platelet response  to  aspirin , as assessed by urinary 11-dehydro-TXB(2 ) excretion and the VerifyNow Aspirin assay . Doubling the aspirin dose reduced serum TXB(2 ) only partially by 39 % median ( IQR , 29%-54 % , P < .05 ) . We conclude that the abnormal megakaryopoiesis characterizing ET accounts for a shorter-lasting antiplatelet effect of low-dose aspirin through faster renewal of platelet cyclooxygenase-1 , and impaired platelet inhibition can be rescued by modulating the aspirin dosing interval rather than the dose Prognosis studies are investigations of future events or the evaluation of associations between risk factors and health outcomes in population s of patients ( 1 ) . The results of such studies improve our underst and ing of the clinical course of a disease and assist clinicians in making informed decisions about how best to manage patients . Prognostic research also informs the design of intervention studies by helping define subgroups of patients who may benefit from a new treatment and by providing necessary information about the natural history of a disorder ( 2 ) . There has recently been a rapid increase in the use of systematic review methods to synthesize the evidence on research questions related to prognosis . It is essential that investigators conducting systematic review s thoroughly appraise the method ologic quality of included studies to be confident that a study 's design , conduct , analysis , and interpretation have adequately reduced the opportunity for bias ( 3 , 4 ) . Caution is warranted , however , because inclusion of method ologically weak studies can threaten the internal validity of a systematic review ( 4 ) . This follows abundant empirical evidence that inadequate attention to biases can cause invalid results and inferences ( 5 - 9 ) . However , there is limited consensus on how to appraise the quality of prognosis studies ( 1 ) . A useful framework to assess bias in such studies follows the basic principles of epidemiologic research ( 10 , 11 ) . We focus on 6 areas of potential bias : study participation , study attrition , prognostic factor measurement , confounding measurement and account , outcome measurement , and analysis . The main objectives of our review of review s are to describe methods used to assess the quality of prognosis studies and to describe how well current practice s assess potential biases . Our secondary objective is to develop recommendations to guide future quality appraisal , both within single studies of prognostic factors and within systematic review s of the evidence . We hope this work facilitates future discussion and research on biases in prognosis studies and systematic review s. Methods Literature Search and Study Selection We identified systematic review s of prognosis studies by search ing MEDLINE ( 1966 to October 2005 ) using the search strategy recommended by McKibbon and colleagues ( 12 ) . This strategy combines broad search terms for systematic review s ( systematic review .mp ; meta- analysis .mp ) and a sensitive search strategy for prognosis studies ( cohort , incidence , mortality , follow-up studies , prognos * , predict * , or course ) . We also search ed the reference lists of included review s and method ologic papers to identify other relevant publications . We restricted our search to English- language publications . One review er conducted the search and selected the studies . Systematic review s , defined as review s of published studies with a comprehensive search and systematic selection , were included if they assessed the method ologic quality of the included studies by using 1 or more explicit criteria . We excluded studies if they were meta-analyses of independent patient data only , if their primary goal was to investigate the effectiveness of an intervention or specific diagnostic or screening tests , or if they included studies that were not done on humans . Data Extraction and Synthesis Individual items included in the quality assessment of the systematic review s were recorded as they were reported in the publication ( that is , the information that would be available to readers and future review ers ) . We review ed journal Web sites and contacted the authors of the systematic review s for additional information when authors made such an offer in their original papers . When review s assessed different study design s by using different sets of quality items , we extracted only those items used to assess cohort studies . We constructed a comprehensive list of distinct items that the review s used to assess the quality of their included studies . The full text of each review was screened . All items used by the review authors to assess the quality of studies were extracted into a computerized spreadsheet by 1 review er . Two experienced review ers , a clinical epidemiologist and an epidemiologist , independently synthesized the quality items extracted from the prognosis review s to determine how well the systematic review s assessed potential biases . We did this in 3 steps : 1 ) identified distinct concepts or domains addressed by the quality items ; 2 ) grouped each extracted quality item into the appropriate domain or domains ; and 3 ) identified the domains necessary to assess potential biases in prognosis studies . We then used this information to assess how well the review s ' quality assessment included items from the domains necessary to assess potential biases . After completing each of the first 3 steps , the review ers met to attempt to reach a consensus . The consensus process involved each review er presenting his or her observations and results , followed by discussion and debate . A third review er was available in cases of persistent disagreement or uncertainty . In the first step , all domains addressed by the quality items were identified . The first review er iteratively and progressively defined the domains as items were extracted from the included review s. The second review er defined domains from a r and om list of all extracted quality items . Limited guidance was provided to the review ers so that their assessment s and definitions of domains would be independent . The review ers agreed on a final set of domains that adequately and completely defined all of the extracted items . In the second step , review ers independently grouped each extracted item into the appropriate domains . Review ers considered each extracted item by asking , What is each particular quality item addressing ? or What are the review 's authors getting at with the particular quality assessment item ? . Items were grouped into the domain or domains that best represented the concepts being addressed . For example , the extracted items at least 80 % of the group originally identified was located for follow-up and follow-up was sufficiently complete or does n't jeopardize validity were each independently classified by both review ers as assessing the domain completeness of follow-up adequate , whereas the extracted item quantification and description of all subjects lost to follow-up was classified as assessing the domain completeness of follow-up described . In the third step , we identified the domains necessary to assess potential biases . Each review er considered the ability of the identified domains to adequately address , at least in part , 1 of the following 6 potential biases : 1 ) study participation , 2 ) study attrition , 3 ) prognostic factor measurement , 4 ) confounding measurement and account , 5 ) outcome measurement , and 6 ) analysis . Domains were considered to adequately address part of the framework if information garnered from that domain would inform the assessment of potential bias . For example , both review ers judged that the identified domain study population represents source population or population of interest assessed potential bias in a prognosis study , whereas the domain research question definition did not , although the latter is an important consideration in assessing the inclusion of studies in a systematic review . Finally , on the basis of our previous ratings , we looked at whether each review included items from the domains necessary to assess the 6 potential biases . We calculated the frequency of systematic review s by assessing each potential bias and the number of review s that adequately assessed bias overall . From this systematic synthesis , we developed recommendations for improving quality appraisal in future systematic review s of prognosis studies . We used Microsoft Access and Excel 2002 ( Microsoft Corp. , Redmond , Washington ) for data management and SAS for Windows , version 9.1 ( SAS Institute , Inc. , Cary , North Carolina ) for descriptive statistics . Role of the Funding Sources The funding sources , the Canadian Institutes of Health Research , the Canadian Chiropractic Research Foundation , the Ontario Chiropractic Association , and the Ontario Ministry of Health and Long Term Care , did not have a role in the collection , analysis , or interpretation of the data or in the decision to su bmi t the manuscript for publication . Results We identified 1384 potentially relevant articles . Figure 1 shows a flow chart of studies that were included and excluded . Figure 2 shows the number of review s identified by year of publication . We excluded 131 systematic review s of prognosis studies that did not seem to include any quality assessment of the included studies ; this represented 44 % of prognosis review s. We included 163 review s of prognosis studies in our analysis ( 13 - 175 ) . The most common topics were cancer ( 15 % ) , musculoskeletal disorders and rheumatology ( 13 % ) , cardiovascular ( 10 % ) , neurology ( 10 % ) , and obstetrics ( 10 % ) . Other review s included a wide range of health and health care topics . Sixty-three percent of the review s investigated the association between a specific prognostic factor and a particular outcome ; the remainder investigated multiple prognostic factors or models . The number of primary studies included in each systematic review ranged from 3 to 167 ( median , 18 [ interquartile range , 12 to 31 ] ) . A complete description of the included review s is available from the authors on request . Figure 1 . Flow diagram of inclusion and exclusion criteria of systematic review s. Figure 2 . Number of systematic review s of prognosis studies identified over time . Quality Items One hundred fifty-three review s provided adequate detail to allow extraction of quality items . Eight hundred eighty-two distinct quality items were extracted from the review s. Most review s developed their own set of quality items , with only a few applying criteria from previous review s. Most quality items Abstract Background : Aspirin resistance may increase up to more then threefold the risk of major cardiovascular events ( MACE ) in patients with stable coronary artery disease . Aim : The aim of our study was to determine ; the prevalence of aspirin resistance in patients with acute coronary syndromes , the role of aspirin resistance on outcome in the follow-up and the effect of clopidogrel therapy in the prevention of MACE in aspirin resistant subjects . Material and methods : We detected the prevelance of aspirin resistance in 105 patients with acute coronary syndrome .  Platelet functions were analyzed in Platelet Function Analyzer (PFA)-100 ( Dade Behring , Germany ) with collagen and /or epinephrine ( Col/Epi ) and collagen and /or ADP ( Col/ADP ) cartridges . Primary end points of the study were myocardial infa rct ion , unstable angina , cardiac death . Results : 19 % ( n = 20 ) of patients were aspirin resistant by PFA-100 . In the follow-up , MACE occured in 9 patients ( 45 % ) with aspirin resistance and in 10 patients ( 11.7 % ) with aspirin sensitive platelet aggreg 
    Output:
    
agent
Results indicated that some PFTs may have some prognostic utility , i.e. a trend for more clinical events to be associated with groups classified as ' aspirin resistant ' .
Study -level effect sizes were generally small and absolute outcome risk was not substantially different between ' aspirin resistant ' and ' aspirin sensitive ' design ations .
Based on assumptions of PFTs being able to accurately identify patients at high risk of clinical events and such patients benefiting from treatment modification , the economic model found that a test-treat strategy was likely to be cost-effective .
However , neither assumption is currently evidence based .
***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: OBJECTIVE The aim of this study was to analyze the correlation between thromboembolic complications and antiplatelet drugs before and after neurointervention . METHODS Blood sample s and radiographic data of patients who received a neurointervention ( coil embolization , stent placement or both )  were collected prospect ively . Rapid platelet function assay-aspirin ( RPFA-ASA ) was used to calculate aspirin resistance in aspirin reaction units ( ARU ) . For clopidogrel resistance , a P2Y12 assay was used to analyze the percentage of platelet inhibition . ARU > 550 and platelet inhibition < 40 % were defined as aspirin and clopidogrel resistance , respectively . RESULTS Both aspirin and clopidogrel oral pills were administered in fifty-three patients before and after neurointerventional procedures . The mean resistance values of all patients were 484 ARU and < 39 % . Ten ( 17.0 % ) of 53 patients showed resistance to aspirin  with an average of 597 ARU , and 33 ( 62.3 % ) of 53 patients showed resistance to clopidogrel  with an average of < 26 % . Ten patients demonstrated resistance to both drugs , 5 of which suffered a thromboembolic complication after neurointervention ( mean values : 640 ARU and platelet inhibition < 23 % ) . Diabetic patients and patients with hypercholesterolemia displayed mean aspirin resistances of 513.7 and 501.8 ARU , and mean clopidogrel resistances of < 33.8 % and < 40.7 % , respectively . CONCLUSION Identifying individuals with poor platelet inhibition using st and ard regimens is of great clinical importance and may help prevent cerebral ischemic events in the future . Neurointerventional research should focus on ideal doses , timing , choices , safety , and reliable measurements of antiplatelet drug therapy , as well as confirming the clinical relevance of aggregometry in cerebrovascular patients Essential thrombocythemia ( ET ) is characterized by enhanced platelet generation and thrombotic complications . Once-daily low-dose aspirin incompletely inhibits platelet thromboxane A(2 ) ( TXA(2 ) ) in the majority of ET patients . In the present study , we investigated the determinants of aspirin-insensitive platelet TXA(2 ) bio synthesis and whether it could be further suppressed by changing the aspirin dose , formulation , or dosing interval . In 41 aspirin-treated ET patients , the immature platelet count predicted serum TXB(2 ) independently of platelet count , age , JAK-2 V617F mutation , or cytoreduction ( β = 3.53 , P = .001 ) . Twenty-one aspirin-treated patients with serum TXB(2 ) ≥ 4 ng/mL at 24 hours after dosing were r and omized to the following 7-day regimens in a crossover design : enteric-coated aspirin 100 mg twice daily , enteric-coated aspirin 200 mg once daily , or plain aspirin 100 mg once daily . A twice-daily regimen caused a further 88 % median ( IQR , 78%-92 % , P < .001 ) TXB(2 ) reduction and normalized the functional platelet response  to  aspirin , as assessed by urinary 11-dehydro-TXB(2 ) excretion and the VerifyNow Aspirin assay . Doubling the aspirin dose reduced serum TXB(2 ) only partially by 39 % median ( IQR , 29%-54 % , P < .05 ) . We conclude that the abnormal megakaryopoiesis characterizing ET accounts for a shorter-lasting antiplatelet effect of low-dose aspirin through faster renewal of platelet cyclooxygenase-1 , and impaired platelet inhibition can be rescued by modulating the aspirin dosing interval rather than the dose Prognosis studies are investigations of future events or the evaluation of associations between risk factors and health outcomes in population s of patients ( 1 ) . The results of such studies improve our underst and ing of the clinical course of a disease and assist clinicians in making informed decisions about how best to manage patients . Prognostic research also informs the design of intervention studies by helping define subgroups of patients who may benefit from a new treatment and by providing necessary information about the natural history of a disorder ( 2 ) . There has recently been a rapid increase in the use of systematic review methods to synthesize the evidence on research questions related to prognosis . It is essential that investigators conducting systematic review s thoroughly appraise the method ologic quality of included studies to be confident that a study 's design , conduct , analysis , and interpretation have adequately reduced the opportunity for bias ( 3 , 4 ) . Caution is warranted , however , because inclusion of method ologically weak studies can threaten the internal validity of a systematic review ( 4 ) . This follows abundant empirical evidence that inadequate attention to biases can cause invalid results and inferences ( 5 - 9 ) . However , there is limited consensus on how to appraise the quality of prognosis studies ( 1 ) . A useful framework to assess bias in such studies follows the basic principles of epidemiologic research ( 10 , 11 ) . We focus on 6 areas of potential bias : study participation , study attrition , prognostic factor measurement , confounding measurement and account , outcome measurement , and analysis . The main objectives of our review of review s are to describe methods used to assess the quality of prognosis studies and to describe how well current practice s assess potential biases . Our secondary objective is to develop recommendations to guide future quality appraisal , both within single studies of prognostic factors and within systematic review s of the evidence . We hope this work facilitates future discussion and research on biases in prognosis studies and systematic review s. Methods Literature Search and Study Selection We identified systematic review s of prognosis studies by search ing MEDLINE ( 1966 to October 2005 ) using the search strategy recommended by McKibbon and colleagues ( 12 ) . This strategy combines broad search terms for systematic review s ( systematic review .mp ; meta- analysis .mp ) and a sensitive search strategy for prognosis studies ( cohort , incidence , mortality , follow-up studies , prognos * , predict * , or course ) . We also search ed the reference lists of included review s and method ologic papers to identify other relevant publications . We restricted our search to English- language publications . One review er conducted the search and selected the studies . Systematic review s , defined as review s of published studies with a comprehensive search and systematic selection , were included if they assessed the method ologic quality of the included studies by using 1 or more explicit criteria . We excluded studies if they were meta-analyses of independent patient data only , if their primary goal was to investigate the effectiveness of an intervention or specific diagnostic or screening tests , or if they included studies that were not done on humans . Data Extraction and Synthesis Individual items included in the quality assessment of the systematic review s were recorded as they were reported in the publication ( that is , the information that would be available to readers and future review ers ) . We review ed journal Web sites and contacted the authors of the systematic review s for additional information when authors made such an offer in their original papers . When review s assessed different study design s by using different sets of quality items , we extracted only those items used to assess cohort studies . We constructed a comprehensive list of distinct items that the review s used to assess the quality of their included studies . The full text of each review was screened . All items used by the review authors to assess the quality of studies were extracted into a computerized spreadsheet by 1 review er . Two experienced review ers , a clinical epidemiologist and an epidemiologist , independently synthesized the quality items extracted from the prognosis review s to determine how well the systematic review s assessed potential biases . We did this in 3 steps : 1 ) identified distinct concepts or domains addressed by the quality items ; 2 ) grouped each extracted quality item into the appropriate domain or domains ; and 3 ) identified the domains necessary to assess potential biases in prognosis studies . We then used this information to assess how well the review s ' quality assessment included items from the domains necessary to assess potential biases . After completing each of the first 3 steps , the review ers met to attempt to reach a consensus . The consensus process involved each review er presenting his or her observations and results , followed by discussion and debate . A third review er was available in cases of persistent disagreement or uncertainty . In the first step , all domains addressed by the quality items were identified . The first review er iteratively and progressively defined the domains as items were extracted from the included review s. The second review er defined domains from a r and om list of all extracted quality items . Limited guidance was provided to the review ers so that their assessment s and definitions of domains would be independent . The review ers agreed on a final set of domains that adequately and completely defined all of the extracted items . In the second step , review ers independently grouped each extracted item into the appropriate domains . Review ers considered each extracted item by asking , What is each particular quality item addressing ? or What are the review 's authors getting at with the particular quality assessment item ? . Items were grouped into the domain or domains that best represented the concepts being addressed . For example , the extracted items at least 80 % of the group originally identified was located for follow-up and follow-up was sufficiently complete or does n't jeopardize validity were each independently classified by both review ers as assessing the domain completeness of follow-up adequate , whereas the extracted item quantification and description of all subjects lost to follow-up was classified as assessing the domain completeness of follow-up described . In the third step , we identified the domains necessary to assess potential biases . Each review er considered the ability of the identified domains to adequately address , at least in part , 1 of the following 6 potential biases : 1 ) study participation , 2 ) study attrition , 3 ) prognostic factor measurement , 4 ) confounding measurement and account , 5 ) outcome measurement , and 6 ) analysis . Domains were considered to adequately address part of the framework if information garnered from that domain would inform the assessment of potential bias . For example , both review ers judged that the identified domain study population represents source population or population of interest assessed potential bias in a prognosis study , whereas the domain research question definition did not , although the latter is an important consideration in assessing the inclusion of studies in a systematic review . Finally , on the basis of our previous ratings , we looked at whether each review included items from the domains necessary to assess the 6 potential biases . We calculated the frequency of systematic review s by assessing each potential bias and the number of review s that adequately assessed bias overall . From this systematic synthesis , we developed recommendations for improving quality appraisal in future systematic review s of prognosis studies . We used Microsoft Access and Excel 2002 ( Microsoft Corp. , Redmond , Washington ) for data management and SAS for Windows , version 9.1 ( SAS Institute , Inc. , Cary , North Carolina ) for descriptive statistics . Role of the Funding Sources The funding sources , the Canadian Institutes of Health Research , the Canadian Chiropractic Research Foundation , the Ontario Chiropractic Association , and the Ontario Ministry of Health and Long Term Care , did not have a role in the collection , analysis , or interpretation of the data or in the decision to su bmi t the manuscript for publication . Results We identified 1384 potentially relevant articles . Figure 1 shows a flow chart of studies that were included and excluded . Figure 2 shows the number of review s identified by year of publication . We excluded 131 systematic review s of prognosis studies that did not seem to include any quality assessment of the included studies ; this represented 44 % of prognosis review s. We included 163 review s of prognosis studies in our analysis ( 13 - 175 ) . The most common topics were cancer ( 15 % ) , musculoskeletal disorders and rheumatology ( 13 % ) , cardiovascular ( 10 % ) , neurology ( 10 % ) , and obstetrics ( 10 % ) . Other review s included a wide range of health and health care topics . Sixty-three percent of the review s investigated the association between a specific prognostic factor and a particular outcome ; the remainder investigated multiple prognostic factors or models . The number of primary studies included in each systematic review ranged from 3 to 167 ( median , 18 [ interquartile range , 12 to 31 ] ) . A complete description of the included review s is available from the authors on request . Figure 1 . Flow diagram of inclusion and exclusion criteria of systematic review s. Figure 2 . Number of systematic review s of prognosis studies identified over time . Quality Items One hundred fifty-three review s provided adequate detail to allow extraction of quality items . Eight hundred eighty-two distinct quality items were extracted from the review s. Most review s developed their own set of quality items , with only a few applying criteria from previous review s. Most quality items Abstract Background : Aspirin resistance may increase up to more then threefold the risk of major cardiovascular events ( MACE ) in patients with stable coronary artery disease . Aim : The aim of our study was to determine ; the prevalence of aspirin resistance in patients with acute coronary syndromes , the role of aspirin resistance on outcome in the follow-up and the effect of clopidogrel therapy in the prevention of MACE in aspirin resistant subjects . Material and methods : We detected the prevelance of aspirin resistance in 105 patients with acute coronary syndrome .  Platelet functions were analyzed in Platelet Function Analyzer (PFA)-100 ( Dade Behring , Germany ) with collagen and /or epinephrine ( Col/Epi ) and collagen and /or ADP ( Col/ADP ) cartridges . Primary end points of the study were myocardial infa rct ion , unstable angina , cardiac death . Results : 19 % ( n = 20 ) of patients were aspirin resistant by PFA-100 . In the follow-up , MACE occured in 9 patients ( 45 % ) with aspirin resistance and in 10 patients ( 11.7 % ) with aspirin sensitive platelet aggreg 
    Output:
    