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: Background — Prior primary prevention trials of statin therapy that used cholesterol criteria for enrollment have not reported significant decreases in stroke risk . We evaluated whether statin therapy might reduce stroke rates among individuals with low levels of cholesterol but elevated levels of high-sensitivity C-reactive protein . Methods and Results — In Justification for the Use of statins in Prevention : an Intervention Trial Evaluating Rosuvastatin ( JUPITER ) , 17 802 apparently healthy men and women with low-density lipoprotein cholesterol levels < 130 mg/dL and high-sensitivity C-reactive protein levels ≥2.0 mg/L were r and omly allocated to rosuvastatin 20 mg daily or placebo and then followed up for the occurrence of a first stroke . After a median follow-up of 1.9 years ( maximum , 5.0 years ) , rosuvastatin result ed in a 48 % reduction in the hazard of fatal and nonfatal stroke as compared with placebo ( incidence rate , 0.18 and 0.34 per 100 person-years of observation , respectively ; hazard ratio 0.52 ; 95 % confidence interval , 0.34 to 0.79 ; P=0.002 ) , a finding that was consistent across all examined subgroups . This finding was due to a 51 % reduction in the rate of ischemic stroke ( hazard ratio , 0.49 ; 95 % confidence interval , 0.30 to 0.81 ; P=0.004 ) , with no difference in the rates of hemorrhagic stroke between the active and placebo arms ( hazard ratio , 0.67 ; 95 % confidence interval , 0.24 to 1.88 ; P=0.44 ) . Conclusion — Rosuvastatin reduces by more than half the incidence of ischemic stroke among men and women with low levels of low-density lipoprotein cholesterol levels who are at risk because of elevated levels of high-sensitivity C-reactive protein . Clinical Trial Registration — clinical trial.gov . Unique identifier : NCT00239681 Objectives : For large scale follow up studies with non-demented patients in which cognition is an endpoint , there is a need for short , inexpensive , sensitive , and reliable neuropsychological tests that are suitable for repeated measurements . The commonly used Mini-Mental-State-Examination fulfils only the first two requirements . Methods : In the PROspect i ve Study of Pravastatin in the Elderly at Risk ( PROSPER ) , 5804 elderly subjects aged 70 to 82 years were examined using a  learning test ( memory ) , a coding test ( general speed )  , and a short version of the Stroop test ( attention ) .  Data presented here were collected at dual baseline , before r and omisation for active treatment . Results : The tests proved to be reliable ( with test/retest reliabilities ranging from acceptable ( r=0.63 ) to high ( r=0.88 ) and sensitive to detect small differences in subjects from different age categories . All tests showed significant practice effects : performance increased from the first measurement to the first follow up after two weeks . Conclusion : Normative data are provided that can be used for one time neuropsychological testing as well as for assessing individual and group change . Methods for analysing cognitive change are proposed Objective The CARDS trial , a multicentre , r and omized , controlled trial , found that atorvastatin 10 mg/day for patients with type 2 diabetes mellitus and normal low-density lipoprotein (LDL)-cholesterol significantly reduced cardiovascular ( CV ) events , including stroke . We estimated the cost effectiveness of atorvastatin as primary prevention against CV disease from the short-term and lifetime US payer perspectives . Research design and methods We constructed a decision analytic ( Markov ) model to evaluate long-term costs and outcomes for atorvastatin 10 mg/day versus no HMG-CoA reductase inhibitor ( statin ) therapy for patients with type 2 diabetes and no history of a CV event .  CV event rates and survival were based on risk equations calibrated to CARDS and applied to a US type 2 diabetes population ; the atorvastatin effect on CV events was based on hazard ratios from CARDS ; direct medical care costs were based on US treatment patterns and published costs analyses of patients with diabetes . Costs were valued in $ US , year 2005 values ; costs and benefits were discounted at 3 % per annum . Results Within the time horizon of the trial ( 5 years ) , the cost effectiveness of atorvastatin was $ US137 276 per QALY . At 10 years , the incremental cost per QALY improved to $ US3640 per QALY . At 25 years , overall costs were lower and QALYs higher in the atorvastatin arm . Costs of managing CV events were lower after 5 years for patients treated with atorvastatin . Conclusions For patients with type 2 diabetes and one additional risk factor for CV disease , normal LDL-cholesterol and no history of a CV event , primary prevention with atorvastatin appears to be cost saving and improve outcomes over 25 years , although it is costly from a short-term US payer perspective . From both a medical and an economic viewpoint , primary prevention is desirable in this patient population Aims Patients with Type 2 diabetes have an elevated risk of stroke . The role of lipid levels and diabetes‐specific factors in risk prediction of stroke is unclear , and estimates of efficacy of lipid‐lowering therapy vary between trials . We examined predictors of stroke and the effect of atorvastatin on specific stroke subtypes in Type 2 diabetes in the Collaborative Atorvastatin Diabetes Study ( CARDS ) [ a trial of 2838 participants with mean low‐density lipoprotein cholesterol < 4.14 mmol/l , no history of macrovascular disease and r and omized to atorvastatin 10 mg daily or placebo ] Lipid-lowering therapy in individuals with high risk of cardiovascular disease reduces the incidence of coronary heart disease . However , few studies have assessed the benefits of cholesterol lowering for primary prevention of coronary heart disease in hypertensive patients with mild dyslipidemia or without conventional dyslipidemia . The large , r and omized Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese Study showed a 33 % reduction in coronary heart disease incidence with pravastatin as the primary prevention in Japanese patients . We conducted an exploratory analysis of the effect of diet plus pravastatin therapy on the primary prevention of cardiovascular events ( coronary heart disease , coronary heart disease plus cerebral infa rct ion , and cardiovascular disease ) in the 3277 patients with hypertension during the 5-year follow-up . There were no significant differences in mean baseline total cholesterol , blood pressure levels , or variation in blood pressure during the 5-year period between the diet ( n=1664 ) and diet plus pravastatin ( n=1613 ) groups . In the diet plus pravastatin group , the relative risk of coronary heart disease plus cerebral infa rct ion was reduced by 35 % ( hazard ratio : 0.65 ; CI : 0.46 to 0.93 ; P=0.02 ) , cerebral infa rct ion by 46 % ( hazard ratio : 0.54 ; CI : 0.29 to 0.98 ; P=0.04 ) , and cardiovascular disease by 33 % ( hazard ratio : 0.67 ; CI : 0.49 to 0.91 ; P=0.01 ) . In patients without a history of cardiovascular disease who have hypertension and mildly elevated cholesterol , pravastatin was effective in reducing the incidence of cardiovascular disease , particularly cerebral infa rct ion . Hence , in patients with hypertension with mildly elevated cholesterol levels , treatment with a statin is advisable to reduce the burden of cardiovascular disease CONTEXT Previous studies indicate that industry-sponsored trials tend to draw proindustry conclusions . OBJECTIVE To explore whether the association between funding and conclusions in r and omized drug trials reflects treatment effects or adverse events . DESIGN Observational study of 370 r and omized drug trials included in meta-analyses from Cochrane review s selected from the Cochrane Library , May 2001 . From a r and om sample of 167 Cochrane review s , 25 contained eligible meta-analyses ( assessed a binary outcome ; pooled at least 5 full-paper trials of which at least 1 reported adequate and 1 reported inadequate allocation concealment ) . The primary binary outcome from each meta- analysis was considered the primary outcome for all trials included in each meta- analysis . The association between funding and conclusions was analyzed by logistic regression with adjustment for treatment effect , adverse events , and additional confounding factors ( method ological quality , control intervention , sample size , publication year , and place of publication ) . MAIN OUTCOME MEASURE Conclusions in trials , classified into whether the experimental drug was recommended as the treatment of choice or not . RESULTS The experimental drug was recommended as treatment of choice in 16 % of trials funded by nonprofit organizations , 30 % of trials not reporting funding , 35 % of trials funded by both nonprofit and for-profit organizations , and 51 % of trials funded by for-profit organizations ( P<.001 ; chi2 test ) . Logistic regression analyses indicated that funding , treatment effect , and double blinding were the only significant predictors of conclusions . Adjusted analyses showed that trials funded by for-profit organizations were significantly more likely to recommend the experimental drug as treatment of choice ( odds ratio , 5.3 ; 95 % confidence interval , 2.0 - 14.4 ) compared with trials funded by nonprofit organizations . This association did not appear to reflect treatment effect or adverse events . CONCLUSIONS Conclusions in trials funded by for-profit organizations may be more positive due to biased interpretation of trial results . Readers should carefully evaluate whether conclusions in r and omized trials are supported by data Background Simvastatin reduces cardiovascular mortality and morbidity but , as with other HMG-CoA reductase inhibitors , can cause significant muscle toxicity and has been associated with elevations of liver transaminases . Methods Muscle and liver adverse effects of simvastatin 40 mg daily were evaluated in a r and omized placebo-controlled trial involving 20,536 UK patients with vascular disease or diabetes ( in which a substantial reduction of cardiovascular mortality and morbidity has previously been demonstrated ) . Results The excess incidence of myopathy in the simvastatin group was < 0.1 % over the 5 years of the trial , and there were no significant differences between the treatment groups in the incidence of serious hepatobiliary disease . Conclusion Among the many different types of high-risk patient studied ( including women , older individuals and those with low cholesterol levels ) , there was a very low incidence ( < 0.1 % ) of myopathy during 5 years treatment with simvastatin 40 mg daily . The risk of hepatitis , if any , was undetectable even in this very large long-term trial . Routine monitoring of liver function tests during treatment with simvastatin 40 mg is not useful . Trial Registration IS RCT BACKGROUND Increased levels of the inflammatory biomarker high-sensitivity C-reactive protein predict cardiovascular events . Since statins lower levels of high-sensitivity C-reactive protein as well as cholesterol , we hypothesized that people with elevated high-sensitivity C-reactive protein levels but without hyperlipidemia might benefit from statin treatment . METHODS We r and omly assigned 17,802 apparently healthy men and women with low-density lipoprotein ( LDL ) cholesterol levels of less than 130 mg per deciliter ( 3.4 mmol per liter ) and high-sensitivity C-reactive protein levels of 2.0 mg per liter or higher to rosuvastatin , 20 mg daily , or placebo and followed them for the occurrence of the combined primary end point of myocardial infa rct ion , stroke , arterial revascularization , hospitalization for unstable angina , or death from cardiovascular causes . RESULTS The trial was stopped after a median follow-up of 1.9 years ( maximum , 5.0 ) . Rosuvastatin reduced LDL cholesterol levels by 50 % and high-sensitivity C-reactive protein levels by 37 % . The rates of the primary end point were 0.77 and 1.36 per 100 person-years of follow-up in the rosuvastatin and placebo groups , respectively ( hazard ratio for rosuvastatin , 0.56 ; 95 % confidence interval [ CI ] , 0.46 to 0.69 ; P<0.00001 ) , with corresponding rates of 0.17 and 0.37 for myocardial infa rct ion ( hazard ratio , 0.46 ; 95 % CI , 0.30 to 0.70 ; P=0.0002 ) , 0.18 and 0.34 for stroke ( hazard ratio , 0.52 ; 95 % CI , 0.34 to 0.79 ; P=0.002 ) , 0.41 and 0.77 for revascularization or unstable angina ( hazard ratio , 0.53 ; 95 % CI , 0.40 to 0.70 ; P<0.00001 ) , 0.45 and 0.85 for the combined end point of myocardial infa 
    Output:
    
agent
Total cholesterol and LDL cholesterol were reduced in all trials but there was evidence of heterogeneity of effects .
There was no evidence of any serious harm caused by statin prescription .
Evidence available to date showed that primary prevention with statins is likely to be cost-effective and may improve patient quality of life .
Recent findings from the Cholesterol Treatment Trialists study using individual patient data meta- analysis indicate that these benefits are similar in people at lower ( < 1 % per year ) risk of a major cardiovascular event .
AUTHORS ' CONCLUSIONS Reductions in all-cause mortality , major vascular events and revascularisations were found with no excess of adverse events among people without evidence of CVD treated with statins
***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: Background — Prior primary prevention trials of statin therapy that used cholesterol criteria for enrollment have not reported significant decreases in stroke risk . We evaluated whether statin therapy might reduce stroke rates among individuals with low levels of cholesterol but elevated levels of high-sensitivity C-reactive protein . Methods and Results — In Justification for the Use of statins in Prevention : an Intervention Trial Evaluating Rosuvastatin ( JUPITER ) , 17 802 apparently healthy men and women with low-density lipoprotein cholesterol levels < 130 mg/dL and high-sensitivity C-reactive protein levels ≥2.0 mg/L were r and omly allocated to rosuvastatin 20 mg daily or placebo and then followed up for the occurrence of a first stroke . After a median follow-up of 1.9 years ( maximum , 5.0 years ) , rosuvastatin result ed in a 48 % reduction in the hazard of fatal and nonfatal stroke as compared with placebo ( incidence rate , 0.18 and 0.34 per 100 person-years of observation , respectively ; hazard ratio 0.52 ; 95 % confidence interval , 0.34 to 0.79 ; P=0.002 ) , a finding that was consistent across all examined subgroups . This finding was due to a 51 % reduction in the rate of ischemic stroke ( hazard ratio , 0.49 ; 95 % confidence interval , 0.30 to 0.81 ; P=0.004 ) , with no difference in the rates of hemorrhagic stroke between the active and placebo arms ( hazard ratio , 0.67 ; 95 % confidence interval , 0.24 to 1.88 ; P=0.44 ) . Conclusion — Rosuvastatin reduces by more than half the incidence of ischemic stroke among men and women with low levels of low-density lipoprotein cholesterol levels who are at risk because of elevated levels of high-sensitivity C-reactive protein . Clinical Trial Registration — clinical trial.gov . Unique identifier : NCT00239681 Objectives : For large scale follow up studies with non-demented patients in which cognition is an endpoint , there is a need for short , inexpensive , sensitive , and reliable neuropsychological tests that are suitable for repeated measurements . The commonly used Mini-Mental-State-Examination fulfils only the first two requirements . Methods : In the PROspect i ve Study of Pravastatin in the Elderly at Risk ( PROSPER ) , 5804 elderly subjects aged 70 to 82 years were examined using a  learning test ( memory ) , a coding test ( general speed )  , and a short version of the Stroop test ( attention ) .  Data presented here were collected at dual baseline , before r and omisation for active treatment . Results : The tests proved to be reliable ( with test/retest reliabilities ranging from acceptable ( r=0.63 ) to high ( r=0.88 ) and sensitive to detect small differences in subjects from different age categories . All tests showed significant practice effects : performance increased from the first measurement to the first follow up after two weeks . Conclusion : Normative data are provided that can be used for one time neuropsychological testing as well as for assessing individual and group change . Methods for analysing cognitive change are proposed Objective The CARDS trial , a multicentre , r and omized , controlled trial , found that atorvastatin 10 mg/day for patients with type 2 diabetes mellitus and normal low-density lipoprotein (LDL)-cholesterol significantly reduced cardiovascular ( CV ) events , including stroke . We estimated the cost effectiveness of atorvastatin as primary prevention against CV disease from the short-term and lifetime US payer perspectives . Research design and methods We constructed a decision analytic ( Markov ) model to evaluate long-term costs and outcomes for atorvastatin 10 mg/day versus no HMG-CoA reductase inhibitor ( statin ) therapy for patients with type 2 diabetes and no history of a CV event .  CV event rates and survival were based on risk equations calibrated to CARDS and applied to a US type 2 diabetes population ; the atorvastatin effect on CV events was based on hazard ratios from CARDS ; direct medical care costs were based on US treatment patterns and published costs analyses of patients with diabetes . Costs were valued in $ US , year 2005 values ; costs and benefits were discounted at 3 % per annum . Results Within the time horizon of the trial ( 5 years ) , the cost effectiveness of atorvastatin was $ US137 276 per QALY . At 10 years , the incremental cost per QALY improved to $ US3640 per QALY . At 25 years , overall costs were lower and QALYs higher in the atorvastatin arm . Costs of managing CV events were lower after 5 years for patients treated with atorvastatin . Conclusions For patients with type 2 diabetes and one additional risk factor for CV disease , normal LDL-cholesterol and no history of a CV event , primary prevention with atorvastatin appears to be cost saving and improve outcomes over 25 years , although it is costly from a short-term US payer perspective . From both a medical and an economic viewpoint , primary prevention is desirable in this patient population Aims Patients with Type 2 diabetes have an elevated risk of stroke . The role of lipid levels and diabetes‐specific factors in risk prediction of stroke is unclear , and estimates of efficacy of lipid‐lowering therapy vary between trials . We examined predictors of stroke and the effect of atorvastatin on specific stroke subtypes in Type 2 diabetes in the Collaborative Atorvastatin Diabetes Study ( CARDS ) [ a trial of 2838 participants with mean low‐density lipoprotein cholesterol < 4.14 mmol/l , no history of macrovascular disease and r and omized to atorvastatin 10 mg daily or placebo ] Lipid-lowering therapy in individuals with high risk of cardiovascular disease reduces the incidence of coronary heart disease . However , few studies have assessed the benefits of cholesterol lowering for primary prevention of coronary heart disease in hypertensive patients with mild dyslipidemia or without conventional dyslipidemia . The large , r and omized Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese Study showed a 33 % reduction in coronary heart disease incidence with pravastatin as the primary prevention in Japanese patients . We conducted an exploratory analysis of the effect of diet plus pravastatin therapy on the primary prevention of cardiovascular events ( coronary heart disease , coronary heart disease plus cerebral infa rct ion , and cardiovascular disease ) in the 3277 patients with hypertension during the 5-year follow-up . There were no significant differences in mean baseline total cholesterol , blood pressure levels , or variation in blood pressure during the 5-year period between the diet ( n=1664 ) and diet plus pravastatin ( n=1613 ) groups . In the diet plus pravastatin group , the relative risk of coronary heart disease plus cerebral infa rct ion was reduced by 35 % ( hazard ratio : 0.65 ; CI : 0.46 to 0.93 ; P=0.02 ) , cerebral infa rct ion by 46 % ( hazard ratio : 0.54 ; CI : 0.29 to 0.98 ; P=0.04 ) , and cardiovascular disease by 33 % ( hazard ratio : 0.67 ; CI : 0.49 to 0.91 ; P=0.01 ) . In patients without a history of cardiovascular disease who have hypertension and mildly elevated cholesterol , pravastatin was effective in reducing the incidence of cardiovascular disease , particularly cerebral infa rct ion . Hence , in patients with hypertension with mildly elevated cholesterol levels , treatment with a statin is advisable to reduce the burden of cardiovascular disease CONTEXT Previous studies indicate that industry-sponsored trials tend to draw proindustry conclusions . OBJECTIVE To explore whether the association between funding and conclusions in r and omized drug trials reflects treatment effects or adverse events . DESIGN Observational study of 370 r and omized drug trials included in meta-analyses from Cochrane review s selected from the Cochrane Library , May 2001 . From a r and om sample of 167 Cochrane review s , 25 contained eligible meta-analyses ( assessed a binary outcome ; pooled at least 5 full-paper trials of which at least 1 reported adequate and 1 reported inadequate allocation concealment ) . The primary binary outcome from each meta- analysis was considered the primary outcome for all trials included in each meta- analysis . The association between funding and conclusions was analyzed by logistic regression with adjustment for treatment effect , adverse events , and additional confounding factors ( method ological quality , control intervention , sample size , publication year , and place of publication ) . MAIN OUTCOME MEASURE Conclusions in trials , classified into whether the experimental drug was recommended as the treatment of choice or not . RESULTS The experimental drug was recommended as treatment of choice in 16 % of trials funded by nonprofit organizations , 30 % of trials not reporting funding , 35 % of trials funded by both nonprofit and for-profit organizations , and 51 % of trials funded by for-profit organizations ( P<.001 ; chi2 test ) . Logistic regression analyses indicated that funding , treatment effect , and double blinding were the only significant predictors of conclusions . Adjusted analyses showed that trials funded by for-profit organizations were significantly more likely to recommend the experimental drug as treatment of choice ( odds ratio , 5.3 ; 95 % confidence interval , 2.0 - 14.4 ) compared with trials funded by nonprofit organizations . This association did not appear to reflect treatment effect or adverse events . CONCLUSIONS Conclusions in trials funded by for-profit organizations may be more positive due to biased interpretation of trial results . Readers should carefully evaluate whether conclusions in r and omized trials are supported by data Background Simvastatin reduces cardiovascular mortality and morbidity but , as with other HMG-CoA reductase inhibitors , can cause significant muscle toxicity and has been associated with elevations of liver transaminases . Methods Muscle and liver adverse effects of simvastatin 40 mg daily were evaluated in a r and omized placebo-controlled trial involving 20,536 UK patients with vascular disease or diabetes ( in which a substantial reduction of cardiovascular mortality and morbidity has previously been demonstrated ) . Results The excess incidence of myopathy in the simvastatin group was < 0.1 % over the 5 years of the trial , and there were no significant differences between the treatment groups in the incidence of serious hepatobiliary disease . Conclusion Among the many different types of high-risk patient studied ( including women , older individuals and those with low cholesterol levels ) , there was a very low incidence ( < 0.1 % ) of myopathy during 5 years treatment with simvastatin 40 mg daily . The risk of hepatitis , if any , was undetectable even in this very large long-term trial . Routine monitoring of liver function tests during treatment with simvastatin 40 mg is not useful . Trial Registration IS RCT BACKGROUND Increased levels of the inflammatory biomarker high-sensitivity C-reactive protein predict cardiovascular events . Since statins lower levels of high-sensitivity C-reactive protein as well as cholesterol , we hypothesized that people with elevated high-sensitivity C-reactive protein levels but without hyperlipidemia might benefit from statin treatment . METHODS We r and omly assigned 17,802 apparently healthy men and women with low-density lipoprotein ( LDL ) cholesterol levels of less than 130 mg per deciliter ( 3.4 mmol per liter ) and high-sensitivity C-reactive protein levels of 2.0 mg per liter or higher to rosuvastatin , 20 mg daily , or placebo and followed them for the occurrence of the combined primary end point of myocardial infa rct ion , stroke , arterial revascularization , hospitalization for unstable angina , or death from cardiovascular causes . RESULTS The trial was stopped after a median follow-up of 1.9 years ( maximum , 5.0 ) . Rosuvastatin reduced LDL cholesterol levels by 50 % and high-sensitivity C-reactive protein levels by 37 % . The rates of the primary end point were 0.77 and 1.36 per 100 person-years of follow-up in the rosuvastatin and placebo groups , respectively ( hazard ratio for rosuvastatin , 0.56 ; 95 % confidence interval [ CI ] , 0.46 to 0.69 ; P<0.00001 ) , with corresponding rates of 0.17 and 0.37 for myocardial infa rct ion ( hazard ratio , 0.46 ; 95 % CI , 0.30 to 0.70 ; P=0.0002 ) , 0.18 and 0.34 for stroke ( hazard ratio , 0.52 ; 95 % CI , 0.34 to 0.79 ; P=0.002 ) , 0.41 and 0.77 for revascularization or unstable angina ( hazard ratio , 0.53 ; 95 % CI , 0.40 to 0.70 ; P<0.00001 ) , 0.45 and 0.85 for the combined end point of myocardial infa 
    Output:
    