***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 : To assess the acute metabolic and cardiovascular responses to walking exercise at an intensity corresponding to the heart rate of claudication pain onset and to investigate the effects of a 12-week walking training program at this intensity on walking capacity . METHODS : Twenty-nine patients with intermittent claudication were r and omly allocated to the  walking training  ( n = 17 ) or control ( CO , n = 12 ) group . The walking training group performed an acute exercise session comprising 15 × 2-min bouts of walking at the heart rate of claudication pain onset , with 2-min interpolated rest intervals . The claudication symptoms and cardiovascular and metabolic responses were evaluated . Walking training was then performed at the same intensity twice each week for 12 weeks , while the control group engaged in twice weekly stretching classes  . The claudication onset distance and total walking distance were evaluated before and after the interventions . Brazilian Registry Clinical Trials : RBR-7M3D8W . RESULTS : During the acute exercise session , the heart rate was maintained within tight limits . The exercise intensity was above the anaerobic threshold and > 80 % of the heart rate peak and VO2peak . After the exercise training period , the walking exercise group ( n = 13 ) showed increased claudication onset distance ( 309±153 vs. 413±201 m ) and total walking distance ( 784±182 vs. 1,100±236 m ) compared to the control group ( n = 12 ) ( p<0.05 ) . CONCLUSION : Walking exercise prescribed at the heart rate of claudication pain onset enables patients with intermittent claudication to exercise with tolerable levels of pain and improves walking performance BACKGROUND This prospect i ve , r and omized controlled clinical trial determined whether an optimal exercise program length exists to efficaciously change claudication onset time ( COT ) and peak walking time ( PWT ) in patients with peripheral artery disease and claudication . METHODS The study r and omized 142 patients to supervised exercise ( n = 106 ) or a usual care control group ( n = 36 ) , with 80 completing the exercise program and 27 completing the control intervention .  The exercise program consisted of intermittent walking to nearly maximal claudication pain 3 days per week . COT and PWT were the primary outcomes obtained from a treadmill exercise test at baseline and bimonthly during the study . RESULTS After exercise , changes in COT ( P < .001 ) and PWT ( P < .001 ) were consistently greater than changes after the control intervention . In the exercise program , COT and PWT increased from baseline to month 2 ( P < .05 ) and from months 2 to 4 ( P < .05 ) but did not significantly change from months 4 to 6 ( P > .05 ) . When changes were expressed per mile walked during the first 2 months , middle 2 months , and final 2 months of exercise , COT and PWT only increased during the first 2 months ( P < .05 ) . CONCLUSIONS Exercise-mediated gains in COT and PWT occur rapidly within the first 2 months of exercise rehabilitation and are maintained with further training . The clinical significance is that a relatively short 2-month exercise program may be preferred to a longer program to treat claudication because adherence is higher , costs associated with personnel and use of facilities are lower per patient , and more patients can be trained for a given amount of personnel time and re source utilization BACKGROUND In patients with intermittent claudication , a supervised walking exercise program increases peak exercise performance and community-based functional status .  Patients with peripheral arterial disease also have muscle weakness in the affected extremity that may contribute to the walking impairment . However , the potential benefits of training modalities other than walking exercise , such as strength training , have not been critically evaluated in this patient population . The present study tested the hypothesis that a strength training program would be as effective as treadmill walking exercise and that combinations of strengthening and walking exercise would be more effective than either alone in improving exercise performance . METHODS AND RESULTS Twenty-nine patients with disabling claudication were r and omized to 12 weeks of supervised walking exercise on a treadmill ( 3 h/wk at a work intensity sufficient to produce claudication ) , strength training ( 3 h/wk of resistive training of five muscle groups of each leg ) , or a nonexercising control group . Grade d treadmill testing was performed to maximally tolerated claudication pain to define changes in peak exercise performance . After 12 weeks , patients in the treadmill training program had a 74 + /- 58 % increase in peak walking time as well as improvements in peak oxygen consumption ( VO2 ) and the onset of claudication pain . Patients in the strength-trained group had a 36 + /- 48 % increase in peak walking time but no change in peak VO2 or claudication onset time . Control subjects had no changes in any of these measures over the 12-week period . After the first 12 weeks , patients in the initial walking exercise group continued for 12 more weeks of supervised treadmill training . This result ed in an additional 49 + /- 53 % increase in peak walking time ( total of 128 + /- 99 % increase over the 24 weeks ) . After the initial 12 weeks , patients in the strength-trained group began 12 weeks of supervised treadmill training , and patients in the control group participated in a 12-week combined program of strengthening and treadmill walking exercise . The combined strength and treadmill training program and treadmill training after 12 weeks of strength training result ed in increases in peak exercise performance similar to those observed with 12 weeks of treadmill training alone . CONCLUSIONS A supervised treadmill walking exercise program is an effective means to improve exercise performance in patients with intermittent claudication , with continued improvement over 24 weeks of training . In contrast , 12 weeks of strength training was less effective than 12 weeks of supervised treadmill walking exercise . Finally , strength training , whether sequential or concomitant , did not augment the response to a walking exercise program PURPOSE A pilot study was conducted to test the feasibility of supervised treadmill exercise training to improve functioning in study participants with peripheral arterial disease who did not have classical symptoms of intermittent claudication . METHODS For this study , 32 men and women with peripheral arterial disease but no symptoms of claudication were r and omized to exercise training or usual care .  The intervention was a 12-week supervised treadmill walking program . Outcomes included 6-minute walk distance , maximum treadmill walking distance , and 4-meter walking velocity . Participant-reported community walking ability was measured with the Walking Impairment Question naire ( WIQ ) . Inflammatory blood factor levels also were measured . RESULTS Altogether , 25 participants who completed follow-up testing were included in intention-to-treat analyses . Of 24 participants ( 58 % ) r and omized to exercise , 14 completed the entire exercise training program . The participants r and omized to the intervention showed greater improvement in their WIQ walking speed score than the control subjects ( P = .05 ) . The participants r and omized to the intervention showed improvements in their 6-minute walk distance ( 1134 + /- 347 vs 1266 + /- 295 feet ; P = .03 ) , maximal treadmill walking distance ( 389 + /- 248 vs 585 + /- 293 feet ; P < .001 ) , WIQ distance score ( 52.3 + /- 29.1 vs 63.1 + /- 25.1 ; P = .002 ) , and WIQ speed score ( 48.7 + /- 26.8 vs 59.7 + /- 22.7 ; P = .008 ) . The participants r and omized to the control condition showed improvements in maximal treadmill walking distance ( 362 + /- 180 vs 513 + /- 237 feet ; P = .014 ) . There were no significant changes in the inflammatory blood factors after exercise . CONCLUSIONS This pilot study demonstrated that a supervised treadmill walking program may be feasible and may improve functioning for individuals with peripheral arterial disease who do not have classical symptoms of intermittent claudication . Further study is needed with a larger sample to identify optimal exercise methods that improve lower extremity functioning in men and women with peripheral arterial disease who do not have intermittent claudication Patients with atherosclerotic peripheral arterial disease ( PAD ) of the lower extremities have impaired walking ability due to exercise-induced muscle ischemia and the result ant pain of intermittent claudication . To evaluate the benefit of exercise training as a treatment for patients with PAD , as well as possible mechanisms associated with improvement , we r and omly assigned 19 men with disabling claudication to treated and control groups . Treatment consisted of supervised treadmill walking ( 1 hr/day , 3 days/wk , for 12 weeks ) with progressive increases in speed and grade as tolerated . Grade d treadmill testing was performed to maximal toleration of claudication pain on entry and after 12 weeks of training to define changes in peak exercise performance . After 12 weeks , treated subjects had increased their peak walking time 123 % , peak oxygen consumption 30 % , and pain-free walking time 165 % ( all p less than 0.05 ) . Control subjects had no change in peak oxygen consumption , but after 12 weeks , peak walking time increased 20 % ( p less than 0.05 ) . In treated subjects , maximal calf blood flow ( measured by a plethysmograph ) increased 38 + /- 45 % ( p less than 0.05 ) , but the change in flow was not correlated to the increase in peak walking time . Elevated plasma concentrations of acylcarnitines have been associated with the functional impairment of PAD and may reflect the metabolic state of ischemic skeletal muscle . In treated subjects , a 26 % decrease in resting plasma short-chain acylcarnitine concentration was correlated with improvement in peak walking time ( r = -0.78 , p less than 0.05 ) . ( ABSTRACT TRUNCATED AT 250 WORDS Background — This prospect i ve , r and omized , controlled clinical trial compared changes in exercise performance and daily ambulatory activity in peripheral artery disease patients with intermittent claudication after a home-based exercise program , a supervised exercise program , and usual-care control . Methods and Results — Of the 119 patients r and omized , 29 completed home-based exercise  , 33 completed  supervised exercise , and 30 completed usual-care control . Both exercise programs consisted of intermittent walking to nearly maximal claudication pain for 12 weeks . Patients wore a step activity monitor during each exercise session . Primary outcome measures included claudication onset time and peak walking time obtained from a treadmill exercise test ; secondary outcome measures included daily ambulatory cadences measured during a 7-day monitoring period . Adherence to home-based and supervised exercise was similar ( P=0.712 ) and exceeded 80 % . Both exercise programs increased claudication onset time ( P<0.001 ) and peak walking time ( P<0.01 ) , whereas only home-based exercise increased daily average cadence ( P<0.01 ) . No changes were seen in the control group ( P>0.05 ) . The changes in claudication onset time and peak walking time were similar between the 2 exercise groups ( P>0.05 ) , whereas the change in daily average cadence was greater with home-based exercise ( P<0.05 ) . Conclusions — A home-based exercise program , quantified with a step activity monitor , has high adherence and is efficacious in improving claudication measures similar to a st and ard supervised exercise program . Furthermore , home-based exercise appears more efficacious in increasing daily ambulatory activity in the community setting than supervised exercise . Clinical Trial Registration — URL : http://www . Clinical Trials . Gov . Unique identifier : NCT00618670 Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more BACKGROUND The molecular mechanisms by which physical training improves peripheral and coronary artery disease are poorly understood . Bone marrow-derived endothelial progenitor cells ( EPCs ) are thought to exert beneficial effects on atherosclerosis , angiogenesis , and vascular repair . METHODS AND RESULTS To study the effect of physical activity on the bone marrow , EPCs were quantified by fluorescence-activated cell sorter analysis in mice r and omized to running wheels ( 5.1+/-0.8 km/d , n=12 to 16 per group ) or no running wheel .  Numbers of EPCs circulating in the peripheral blood of trained mice were enhanced to 267+/-19 % , 289+/-22 % , and 280+/-25 % of control levels after 7 , 14 , and 28 days , respectively , accompanied by a similar increase of EPCs in the bone marrow and EPCs exp and ed from spleen-derived mononuclear cells . eNOS-/- mice and wild-type mice treated with N(G)-nitro-l-arginine methyl ester showed lower EPC numbers at baseline and a significantly attenuated increase of EPC in response to physical activity . Exercise NO dependently increased serum levels of vascular endothelial growth factor and reduced the rate of apoptosis in spleen-derived EPCs . Running inhibited neointima formation after carotid artery injury by 22+/-2 % . 
    Output:
    
Subgroup analyses indicated that a lesser improvement in MWD was observed in the subgroup with more diabetes patients , and that the subgroup with better baseline walking ability exhibited greater improvement in walking performance .
In addition , similar improvements in walking performance were observed for exercise programs of different duration s and modalities .
Regardless of exercise length and modality , regularly intensive walking exercise improves walking ability in PAD patients more than usual care .
The presence of diabetes may attenuate the improvements in walking performance in patients with PAD following exercise