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 Evidence from diabetic animal models suggests that cilostazol , a cyclic AMP phosphodiesterase inhibitor used in the treatment of claudication , is efficacious in the treatment of peripheral neuropathy , although this is unproven in humans . The main aim of this study was to assess the effects of cilostazol on neuropathic symptomatology in diabetic patients with peripheral arterial disease ( PAD ) . Methods Diabetic patients with PAD were prospect ively recruited to a r and omized double-blinded placebo-controlled trial . Baseline clinical data were recorded prior to trial commencement following medical optimization . Neurological assessment included the Toronto Clinical Neuropathy Scoring system ( TCNS ) and vibration perception thresholds ( VPT ) with a neurothesiometer  at baseline , 6 weeks , and 24 weeks . Results Twenty-six patients were recruited from December 2004 to January 2006 , which included 20 males . Baseline patient allocation to treatment arms was matched for age , sex , and medical comorbidities . There was no significant difference in neurological assessment between the treatment groups using the TCNS and VPT at 6 and 24 weeks . Conclusions Despite extensive animal-based evidence that cilostazol attenuates neuropathic symptomatology , our results do not support this effect in human diabetic PAD patients Cilostazol is an antiplatelet agent and vasodilator marketed in Japan for treatment of ischemic symptoms of peripheral vascular disease . It is currently being evaluated in the United States for treatment of symptomatic intermittent claudication ( IC ) .  Cilostazol has been shown to improve walking distance in patients with IC . In addition to its reported vasodilator and antiplatelet effects , cilostazol has been proposed to have beneficial effects on plasma lipoproteins . We examined the effect of cilostazol versus placebo on plasma lipoproteins in 189 patients with IC . After 12 weeks of therapy with 100 mg cilostazol BID , plasma triglycerides decreased 15 % ( P<0.001 ) . Cilostazol also increased plasma high density lipoprotein cholesterol ( HDL-C ) ( 10 % ) and apolipoprotein ( apo ) A1 ( 5.7 % ) significantly ( P<0.001 and P<0.01 , respectively ) . Both HDL3 and HDL2 subfractions were increased by cilostazol ; however , the greatest percentage increase was observed in HDL2 . Individuals with baseline hypertriglyceridemia ( > 140 mg/dL ) experienced the greatest changes in both HDL-C and triglycerides with cilostazol treatment . In that subset of patients , HDL-C was increased 12.2 % and triglycerides were decreased 23 % . With cilostazol , there was a trend ( 3 % ) toward decreased apoB as well as increased apoA1 , result ing in a significant ( 9.8 % , P<0.002 ) increase in the apoA1 to apoB ratio . Low density lipoprotein cholesterol and lipoprotein(a ) concentrations were unaffected . Cilostazol treatment result ed in a 35 % increase in treadmill walking time ( P=0.0015 ) and a 9.03 % increase in ankle-brachial index ( P<0.001 ) . These results indicate that in addition to improving the symptoms of IC , cilostazol also favorably modifies plasma lipoproteins in patients with peripheral arterial disease . The mechanism of this effect is currently unknown EMATAP , a r and omized stratified , placebo-controlled double-blind multicentre trial was performed in Argentina in order to confirm the effect of ticlopidine in the prevention of thrombotic events in patients with intermittent claudication . Twenty-one clinical centres enrolled 615 patients , 304 ( 88 diabetic and 216 non diabetic ) were assigned to the ticlopidine group and 311 ( 95 diabetic and 216 non diabetic ) to the placebo group . Treatments were given for 24 weeks . The baseline characteristics were identical in both groups . The compliance was good and only 34 patients ( 17 in each group ) did not reach the last visit . Their status however was checked and known at that time and according to the protocol , there was no patient lost to follow-up . Twenty-five patients experienced a first event during the follow-up period and the results show a very dramatic reduction of events in the ticlopidine group ( 5 vs 20 ) , the difference being highly significant ( p = 0.002 ) in intention-to-treat analysis . If we consider the subgrouping of outcome events : sudden deaths , myocardial infa rct ions and strokes on the one h and , vascular surgery on the other h and , a significant reduction is found in the ticlopidine group . Taking into account the total deaths plus non-fatal events ( 9 vs 21 ) , the results were also significant ( p = 0.027 ) . These above results therefore demonstrate a consistent reduction in all outcome events . As regard side effects there were fewer gastro-intestinal disturbances and skin reactions than seen in North American trials . ( ABSTRACT TRUNCATED AT 250 WORDS Twenty four male hypertensive patients suffering also from peripheral obstructive arterial disease were r and omly subdivided in two groups and after a period of farmacological wash-out of one month Group I was treated with Captopril ( C 50 mg bid ) or Ticlopidine ( T 250 mg bid ) for three months and then with the association C plus T for three months again . After placebo administration for one month , patients were further treated with C plus T at low doses ( 25 mg bid and respectively 250 mg daily ) . In the first part of the study , patients of Group II received an inverse sequence of the drugs ( before Ticlopidine 250 mg bid and then Captopril 50 bid ) . In both groups of patients C induced a significant decrease of blood pressure and an increase of PFWD , TWD , and WI . T did not modify blood pressure but slightly increased PFWD , TWD , and WI . The improvement was more evident during administration of C plus T , whereas placebo administration induced a trend toward baseline values . Finally , the chronic administration of C plus T for twelve months induced a further improvement of all considered parameters . In conclusion , chronic administration of C plus T may be useful in the treatment of hypertensive patients suffering from intermittent claudication  , improving significantly PFWD and TWD BACKGROUND Peripheral arterial occlusion disease ( PAOD ) is caused mainly by chronic inflammation and endothelium dysfunction , and is often treated with cilostazol . However , because this drug 's influence on atherogenic cytokines is still not well known , this study examined the effect of cilostazol on the serum levels of soluble CD40 lig and ( sCD40L ) , adiponectin and high-sensitivity C-reactive protein ( hs-CRP ) in patients with type 2 diabetes and PAOD . METHODS AND RESULTS The 92 type 2 diabetics with PAOD and 100 non-PAOD diabetics were enrolled and r and omly assigned to a group receiving either cilostazol or placebo for 6 months . The atherogenic cytokines were measured at the beginning and completion of the study . In the PAOD groups , those in the cilostazol group had significant changes in the levels of hs-CRP , sCD40L and adiponectin ( P=0.001 , P=0.05 , P=0.004 , respectively ) . Changes in the levels of adiponectin and sCD40L were more significant in the PAOD group treated with cilostazol than in the non-PAOD group also treated with the drug ( P=0.01 and P=0.008 , respectively ) . CONCLUSIONS Cilostazol can decrease hs-CPR and sCD40L levels and increase that of adiponectin , and then delay the progression of atherogenesis and chronic inflammation in type 2 diabetics , especially those with PAOD In a recent double‐blind trial lasting over 6 months , 40 patients suffering from intermittent claudication were r and omly allocated to receive 300 mg of suloctidil per day or exactly matching placebo capsules . In addition to treadmill walking distance , other objective criteria including ankle blood pressure response and muscle blood flow measured by 133Xe clearance were used to assess the effectiveness of therapy CONTEXT Few data document current cardiovascular ( CV ) event rates in stable patients with atherothrombosis in a community setting . Differential event rates for patients with documented coronary artery disease ( CAD ) , cerebrovascular disease ( CVD ) , or peripheral arterial disease ( PAD ) or those at risk of these diseases have not been previously evaluated in a single international cohort . OBJECTIVE To establish contemporary , international , 1-year CV event rates in out patients with established arterial disease or with multiple risk factors for atherothrombosis . DESIGN , SETTING , AND PARTICIPANTS The Reduction of Atherothrombosis for Continued Health ( REACH ) Registry is an international , prospect i ve cohort of 68 236 patients with either established atherosclerotic arterial disease ( CAD , PAD , CVD ; n = 55 814 ) or at least 3 risk factors for atherothrombosis ( n = 12 422 ) , who were enrolled from 5587 physician practice s in 44 countries in 2003 - 2004 . MAIN OUTCOME MEASURES Rates of CV death , myocardial infa rct ion ( MI ) , and stroke . RESULTS As of July 2006 , 1-year outcomes were available for 95.22 % ( n = 64 977 ) of participants . Cardiovascular death , MI , or stroke rates were 4.24 % overall : 4.69 % for those with established atherosclerotic arterial disease vs 2.15 % for patients with multiple risk factors only . Among patients with established disease , CV death , MI , or stroke rates were 4.52 % for patients with CAD , 6.47 % for patients with CVD , and 5.35 % for patients with PAD . The incidences of the end point of CV death , MI , or stroke or of hospitalization for atherothrombotic event(s ) were 15.20 % for CAD , 14.53 % for CVD , and 21.14 % for PAD patients with established disease . These event rates increased with the number of symptomatic arterial disease locations , ranging from 5.31 % for patients with risk factors only to 12.58 % for patients with 1 , 21.14 % for patients with 2 , and 26.27 % for patients with 3 symptomatic arterial disease locations ( P<.001 for trend ) . CONCLUSIONS In this large , contemporary , international study , out patients with established atherosclerotic arterial disease , or at risk of atherothrombosis , experienced relatively high annual CV event rates . Multiple disease locations increased the 1-year risk of CV events BACKGROUND Clopidogrel is a more potent antiplatelet agent than aspirin , result ing in greater clinical efficacy in patients with atherothrombotic disease . Furthermore , the combination of clopidogrel plus aspirin has been demonstrated to be superior to aspirin alone in the treatment of patients with acute coronary syndromes and after coronary stenting . Whether dual antiplatelet therapy is superior to aspirin monotherapy for high-risk primary prevention and secondary prevention is unknown . METHODS AND RESULTS The Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization , Management , and Avoidance ( CHARISMA ) study was design ed to evaluate the efficacy and safety of clopidogrel plus aspirin versus placebo plus aspirin in patients with established coronary , cerebral , or peripheral arterial disease or in patients with multiple risk factors for atherothrombosis who have not yet sustained an ischemic event . This r and omized , international , multicenter , double-blinded , placebo-controlled study has finished enrolling patients worldwide . A total of 15,603 patients will be followed long term . The primary end point will be the composite of vascular death , myocardial infa rct ion , or stroke . Rates of severe bleeding will also be compared between the two arms of the study . CONCLUSIONS This large-scale trial of patients at high risk for atherothrombotic events will allow determination of the value of a strategy of adding clopidogrel to the current st and ard of care , including low-dose aspirin , for a wide spectrum of patients with atherothrombosis Objective : To assess the effect of bezafibrate on the risk of coronary heart disease and stroke in men with lower extremity arterial disease . Design : Double blind placebo controlled r and omised trial . Setting : 85 general practice s and nine hospital vascular clinics . Participants : 1568 men , mean age 68.2 years ( range 35 to 92 ) at recruitment . Interventions : Bezafibrate 400 mg daily ( 783 men ) or placebo ( 785 men ) . Main outcome measures : Combination of coronary heart disease and of stroke . All coronary events , fatal and non-fatal coronary events separately , and strokes alone ( secondary end points ) . Results : Bezafibrate did not reduce the incidence of coronary heart disease and stroke . There were 150 and 160 events in the active and placebo groups respectively ( relative risk 0.96 , 95 % confidence interval 0 
    Output:
    
agent
Antiplatelet agents have a beneficial effect in reducing all cause mortality and fatal cardiovascular events in patients with IC .
***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 Evidence from diabetic animal models suggests that cilostazol , a cyclic AMP phosphodiesterase inhibitor used in the treatment of claudication , is efficacious in the treatment of peripheral neuropathy , although this is unproven in humans . The main aim of this study was to assess the effects of cilostazol on neuropathic symptomatology in diabetic patients with peripheral arterial disease ( PAD ) . Methods Diabetic patients with PAD were prospect ively recruited to a r and omized double-blinded placebo-controlled trial . Baseline clinical data were recorded prior to trial commencement following medical optimization . Neurological assessment included the Toronto Clinical Neuropathy Scoring system ( TCNS ) and vibration perception thresholds ( VPT ) with a neurothesiometer  at baseline , 6 weeks , and 24 weeks . Results Twenty-six patients were recruited from December 2004 to January 2006 , which included 20 males . Baseline patient allocation to treatment arms was matched for age , sex , and medical comorbidities . There was no significant difference in neurological assessment between the treatment groups using the TCNS and VPT at 6 and 24 weeks . Conclusions Despite extensive animal-based evidence that cilostazol attenuates neuropathic symptomatology , our results do not support this effect in human diabetic PAD patients Cilostazol is an antiplatelet agent and vasodilator marketed in Japan for treatment of ischemic symptoms of peripheral vascular disease . It is currently being evaluated in the United States for treatment of symptomatic intermittent claudication ( IC ) .  Cilostazol has been shown to improve walking distance in patients with IC . In addition to its reported vasodilator and antiplatelet effects , cilostazol has been proposed to have beneficial effects on plasma lipoproteins . We examined the effect of cilostazol versus placebo on plasma lipoproteins in 189 patients with IC . After 12 weeks of therapy with 100 mg cilostazol BID , plasma triglycerides decreased 15 % ( P<0.001 ) . Cilostazol also increased plasma high density lipoprotein cholesterol ( HDL-C ) ( 10 % ) and apolipoprotein ( apo ) A1 ( 5.7 % ) significantly ( P<0.001 and P<0.01 , respectively ) . Both HDL3 and HDL2 subfractions were increased by cilostazol ; however , the greatest percentage increase was observed in HDL2 . Individuals with baseline hypertriglyceridemia ( > 140 mg/dL ) experienced the greatest changes in both HDL-C and triglycerides with cilostazol treatment . In that subset of patients , HDL-C was increased 12.2 % and triglycerides were decreased 23 % . With cilostazol , there was a trend ( 3 % ) toward decreased apoB as well as increased apoA1 , result ing in a significant ( 9.8 % , P<0.002 ) increase in the apoA1 to apoB ratio . Low density lipoprotein cholesterol and lipoprotein(a ) concentrations were unaffected . Cilostazol treatment result ed in a 35 % increase in treadmill walking time ( P=0.0015 ) and a 9.03 % increase in ankle-brachial index ( P<0.001 ) . These results indicate that in addition to improving the symptoms of IC , cilostazol also favorably modifies plasma lipoproteins in patients with peripheral arterial disease . The mechanism of this effect is currently unknown EMATAP , a r and omized stratified , placebo-controlled double-blind multicentre trial was performed in Argentina in order to confirm the effect of ticlopidine in the prevention of thrombotic events in patients with intermittent claudication . Twenty-one clinical centres enrolled 615 patients , 304 ( 88 diabetic and 216 non diabetic ) were assigned to the ticlopidine group and 311 ( 95 diabetic and 216 non diabetic ) to the placebo group . Treatments were given for 24 weeks . The baseline characteristics were identical in both groups . The compliance was good and only 34 patients ( 17 in each group ) did not reach the last visit . Their status however was checked and known at that time and according to the protocol , there was no patient lost to follow-up . Twenty-five patients experienced a first event during the follow-up period and the results show a very dramatic reduction of events in the ticlopidine group ( 5 vs 20 ) , the difference being highly significant ( p = 0.002 ) in intention-to-treat analysis . If we consider the subgrouping of outcome events : sudden deaths , myocardial infa rct ions and strokes on the one h and , vascular surgery on the other h and , a significant reduction is found in the ticlopidine group . Taking into account the total deaths plus non-fatal events ( 9 vs 21 ) , the results were also significant ( p = 0.027 ) . These above results therefore demonstrate a consistent reduction in all outcome events . As regard side effects there were fewer gastro-intestinal disturbances and skin reactions than seen in North American trials . ( ABSTRACT TRUNCATED AT 250 WORDS Twenty four male hypertensive patients suffering also from peripheral obstructive arterial disease were r and omly subdivided in two groups and after a period of farmacological wash-out of one month Group I was treated with Captopril ( C 50 mg bid ) or Ticlopidine ( T 250 mg bid ) for three months and then with the association C plus T for three months again . After placebo administration for one month , patients were further treated with C plus T at low doses ( 25 mg bid and respectively 250 mg daily ) . In the first part of the study , patients of Group II received an inverse sequence of the drugs ( before Ticlopidine 250 mg bid and then Captopril 50 bid ) . In both groups of patients C induced a significant decrease of blood pressure and an increase of PFWD , TWD , and WI . T did not modify blood pressure but slightly increased PFWD , TWD , and WI . The improvement was more evident during administration of C plus T , whereas placebo administration induced a trend toward baseline values . Finally , the chronic administration of C plus T for twelve months induced a further improvement of all considered parameters . In conclusion , chronic administration of C plus T may be useful in the treatment of hypertensive patients suffering from intermittent claudication  , improving significantly PFWD and TWD BACKGROUND Peripheral arterial occlusion disease ( PAOD ) is caused mainly by chronic inflammation and endothelium dysfunction , and is often treated with cilostazol . However , because this drug 's influence on atherogenic cytokines is still not well known , this study examined the effect of cilostazol on the serum levels of soluble CD40 lig and ( sCD40L ) , adiponectin and high-sensitivity C-reactive protein ( hs-CRP ) in patients with type 2 diabetes and PAOD . METHODS AND RESULTS The 92 type 2 diabetics with PAOD and 100 non-PAOD diabetics were enrolled and r and omly assigned to a group receiving either cilostazol or placebo for 6 months . The atherogenic cytokines were measured at the beginning and completion of the study . In the PAOD groups , those in the cilostazol group had significant changes in the levels of hs-CRP , sCD40L and adiponectin ( P=0.001 , P=0.05 , P=0.004 , respectively ) . Changes in the levels of adiponectin and sCD40L were more significant in the PAOD group treated with cilostazol than in the non-PAOD group also treated with the drug ( P=0.01 and P=0.008 , respectively ) . CONCLUSIONS Cilostazol can decrease hs-CPR and sCD40L levels and increase that of adiponectin , and then delay the progression of atherogenesis and chronic inflammation in type 2 diabetics , especially those with PAOD In a recent double‐blind trial lasting over 6 months , 40 patients suffering from intermittent claudication were r and omly allocated to receive 300 mg of suloctidil per day or exactly matching placebo capsules . In addition to treadmill walking distance , other objective criteria including ankle blood pressure response and muscle blood flow measured by 133Xe clearance were used to assess the effectiveness of therapy CONTEXT Few data document current cardiovascular ( CV ) event rates in stable patients with atherothrombosis in a community setting . Differential event rates for patients with documented coronary artery disease ( CAD ) , cerebrovascular disease ( CVD ) , or peripheral arterial disease ( PAD ) or those at risk of these diseases have not been previously evaluated in a single international cohort . OBJECTIVE To establish contemporary , international , 1-year CV event rates in out patients with established arterial disease or with multiple risk factors for atherothrombosis . DESIGN , SETTING , AND PARTICIPANTS The Reduction of Atherothrombosis for Continued Health ( REACH ) Registry is an international , prospect i ve cohort of 68 236 patients with either established atherosclerotic arterial disease ( CAD , PAD , CVD ; n = 55 814 ) or at least 3 risk factors for atherothrombosis ( n = 12 422 ) , who were enrolled from 5587 physician practice s in 44 countries in 2003 - 2004 . MAIN OUTCOME MEASURES Rates of CV death , myocardial infa rct ion ( MI ) , and stroke . RESULTS As of July 2006 , 1-year outcomes were available for 95.22 % ( n = 64 977 ) of participants . Cardiovascular death , MI , or stroke rates were 4.24 % overall : 4.69 % for those with established atherosclerotic arterial disease vs 2.15 % for patients with multiple risk factors only . Among patients with established disease , CV death , MI , or stroke rates were 4.52 % for patients with CAD , 6.47 % for patients with CVD , and 5.35 % for patients with PAD . The incidences of the end point of CV death , MI , or stroke or of hospitalization for atherothrombotic event(s ) were 15.20 % for CAD , 14.53 % for CVD , and 21.14 % for PAD patients with established disease . These event rates increased with the number of symptomatic arterial disease locations , ranging from 5.31 % for patients with risk factors only to 12.58 % for patients with 1 , 21.14 % for patients with 2 , and 26.27 % for patients with 3 symptomatic arterial disease locations ( P<.001 for trend ) . CONCLUSIONS In this large , contemporary , international study , out patients with established atherosclerotic arterial disease , or at risk of atherothrombosis , experienced relatively high annual CV event rates . Multiple disease locations increased the 1-year risk of CV events BACKGROUND Clopidogrel is a more potent antiplatelet agent than aspirin , result ing in greater clinical efficacy in patients with atherothrombotic disease . Furthermore , the combination of clopidogrel plus aspirin has been demonstrated to be superior to aspirin alone in the treatment of patients with acute coronary syndromes and after coronary stenting . Whether dual antiplatelet therapy is superior to aspirin monotherapy for high-risk primary prevention and secondary prevention is unknown . METHODS AND RESULTS The Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization , Management , and Avoidance ( CHARISMA ) study was design ed to evaluate the efficacy and safety of clopidogrel plus aspirin versus placebo plus aspirin in patients with established coronary , cerebral , or peripheral arterial disease or in patients with multiple risk factors for atherothrombosis who have not yet sustained an ischemic event . This r and omized , international , multicenter , double-blinded , placebo-controlled study has finished enrolling patients worldwide . A total of 15,603 patients will be followed long term . The primary end point will be the composite of vascular death , myocardial infa rct ion , or stroke . Rates of severe bleeding will also be compared between the two arms of the study . CONCLUSIONS This large-scale trial of patients at high risk for atherothrombotic events will allow determination of the value of a strategy of adding clopidogrel to the current st and ard of care , including low-dose aspirin , for a wide spectrum of patients with atherothrombosis Objective : To assess the effect of bezafibrate on the risk of coronary heart disease and stroke in men with lower extremity arterial disease . Design : Double blind placebo controlled r and omised trial . Setting : 85 general practice s and nine hospital vascular clinics . Participants : 1568 men , mean age 68.2 years ( range 35 to 92 ) at recruitment . Interventions : Bezafibrate 400 mg daily ( 783 men ) or placebo ( 785 men ) . Main outcome measures : Combination of coronary heart disease and of stroke . All coronary events , fatal and non-fatal coronary events separately , and strokes alone ( secondary end points ) . Results : Bezafibrate did not reduce the incidence of coronary heart disease and stroke . There were 150 and 160 events in the active and placebo groups respectively ( relative risk 0.96 , 95 % confidence interval 0 
    Output:
    