***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 : High-frequency neuromuscular electrical stimulation increases exercise tolerance in patients with advanced chronic obstructive pulmonary disease ( COPD patients ) . However , it is conceivable that its benefits are more prominent in patients with better-preserved peripheral muscle function and structure . OBJECTIVE : To investigate the effects of high-frequency neuromuscular electrical stimulation in COPD patients with better-preserved peripheral muscle function . Design : Prospect i ve and cross-over study . METHODS : Thirty COPD patients were r and omly assigned to either home-based , high-frequency neuromuscular electrical stimulation or sham stimulation for six weeks . The training intensity was adjusted according to each subject 's tolerance . Fat-free mass , isometric strength , six-minute walking distance and time to exercise intolerance ( Tlim ) were assessed . RESULTS : Thirteen ( 46.4 % ) patients responded to high-frequency neuromuscular electrical stimulation ; that is , they had a post/pre ΔTlim > 10 % after stimulation ( unimproved after sham stimulation ) . Responders had a higher baseline fat-free mass and six-minute walking distance than their seventeen ( 53.6 % ) non-responding counterparts . Responders trained at higher stimulation intensities ; their mean amplitude of stimulation during training was significantly related to their fat-free mass ( r = 0.65 ; p<0.01 ) . Logistic regression revealed that fat-free mass was the single independent predictor of Tlim improvement ( odds ratio [ 95 % CI ] = 1.15 [ 1.04 - 1.26 ] ; p<0.05 ) . CONCLUSIONS : We conclude that high-frequency neuromuscular electrical stimulation improved the exercise capacity of COPD patients with better-preserved fat-free mass because they tolerated higher training stimulus levels . These data suggest that early training with high-frequency neuromuscular electrical stimulation before tissue wasting begins might enhance exercise tolerance in patients with less advanced COPD INTRODUCTION In severely disabled patients who are not capable of following formal pulmonary rehabilitation ( PR ) and /or tolerating higher training intensities , neuromuscular electrical stimulation ( NMES ) has been successfully utilized as a localized training method . MATERIAL S AND METHODS In this non-r and omized controlled observational study 50 patients with severe chronic obstructive pulmonary disease ( COPD ) , who were allocated into two groups . Endurance training group ( ET ) ( n= 27 ) and NMES group ( n= 23 ) . To compare the effects of NMES and ET on health-related quality of life ( HRQOL ) , exercise capacity , muscle strength , dyspnea , psychological status , and body composition in patients with severe COPD . Before and after PR program , the study parameters were assessed using the Medical Research Council ( MRC ) scale , incremental and endurance shuttle walking tests ( ISWT , ESWT ) , manual muscle testing ( MMT ) , the St. George 's Respiratory Question naire ( SGRQ ) , bioelectrical impedance analysis , and the Hospital Anxiety and Depression Scale ( HADS ) . RESULTS After the PR program , walking distance and endurance time significantly increased in both groups ( p < 0.001 for each ) , whereas the MRC scores of both groups significantly decreased ( p < 0.001 for each ) . In the ET group , significant decreases were noted in all domains of SGRQ and HADS . In the NMES group , significant improvements were observed in the HADS scores and in all SGRQ domain except symptom domain . No significant differences were observed between the NMES and ET groups regarding the changes from baseline to after PR program in walking distance ( p= 0.140 ) , endurance time ( p= 0.376 ) , the MRC ( p= 0.540 ) , HRQOL ( p > 0.05 ) and HADS ( p > 0.05 ) scores , body-mass index ( BMI ) ( p= 0.49 ) , fat-free mass ( FFM ) ( p= 0.50 ) and fat-free mass index ( FFMI ) ( p= 0.94 ) . CONCLUSION NMES can be used as an effective treatment strategy in PR programs for peripheral muscle training in patients with severe COPD Cross-education enhances the performance of muscles not directly involved in the chronic conditioning of the muscles in a remote limb . Substantial cross-education occurs after training with eccentric contractions or with contractions evoked by electromyostimulation ( EMS ) . Since during EMS and eccentric contractions , skin and muscle afferents are activated that have excitatory effects on contralateral homologous muscles , it was hypothesized that exercise training with stimulated vs. voluntary eccentric contractions would lead to greater cross-education . Thirty-two women were r and omly assigned to a  voluntary ( Vol ) , an EMS , or remote EMS ( rEMS ) exercise group  and performed 840 voluntary or stimulated eccentric contractions over 6 weeks . All subjects , including nonexercising controls ( Con ) , were tested pre- and posttraining for maximal voluntary and stimulated isometric and eccentric quadriceps strength . Ipsilateral voluntary and stimulated forces increased in all groups . Changes in EMG activity paralleled those in voluntary force in each limb . No changes occurred in grip strength . The great contra- and ipsilateral strength gains after EMS training were most likely related to an additive effect of EMS and muscle lengthening Introduction Chronic obstructive pulmonary disease ( COPD ) has systemic repercussions that can lead to peripheral muscle dysfunction . Muscle atrophy reduces aerobic capacity , greatly limiting activities of daily living and quality of life . Pulmonary rehabilitation is the gold st and ard treatment for these patients , however , patients may not be able to reach sufficient training intensities for benefits to occur . Technologies such as functional electrical stimulation ( FES ) are currently being adapted and tested to enhance exercise training . We hypothesise that FES coupled with cycling ( FES-cycling ) will improve maximal uptake of oxygen ( VO2 ) and aerobic capacity more than endurance training with placebo stimulation . Methods A r and omised , single-blind , placebo-controlled crossover trial will be carried out to evaluate the effects of FES-cycling on VO2 during endurance exercise on a cycle ergometer in patients with COPD . 25 patients with COPD will carry out two 30 min sessions at a constant load ; one session with active and one with placebo FES . The primary outcome is oxygen uptake recorded with a metabolic measurement system . Secondary outcomes include ventilation equivalent for oxygen , ventilation equivalent for carbon dioxide , cardiac output , lactate values , perceived dyspnoea and perceived muscle fatigue . Results and conclusions Approval has been granted by our Institutional Review Board ( Comité de Protection des Personnes Nord-Ouest 3 ) . The results of the trial will be presented at national and international meetings and published in peer- review ed journals . Trial registration number NCT02594722 Muscle dysfunction is a major problem in chronic obstructive pulmonary disease ( COPD ) , particularly after exacerbations . We thus asked whether neuromuscular electrostimulation ( NMES ) might be directly useful following an acute exacerbation and if such a therapy decreases muscular oxidative stress and /or alters muscle fibre distribution . A pilot r and omised controlled study of NMES lasting 6 weeks was carried out in 15 in- patients ( n=9 NMES ; n=6 sham ) following a COPD exacerbation . Stimulation was delivered to the quadriceps and hamstring muscles ( 35 Hz ) . Primary outcomes were quadriceps force and muscle oxidative stress . At the end of the study , quadriceps force improvement was statistically different between groups ( p=0.02 ) , with a significant increase only in the NMES group ( median ( interquartile range ) 10 ( 4.7–11.5 ) kg ; p=0.01 ) . Changes in the 6-min walking distance were statistically different between groups ( p=0.008 ) , with a significant increase in the NMES group ( 165 ( 125–203 ) m ; p=0.003 ) . NMES did not lead to higher muscle oxidative stress , as indicated by the decrease in total protein carbonylation ( p=0.02 ) and myosin heavy chain carbonylation ( p=0.01 ) levels . Finally , we observed a significant increase in type I fibre proportion in the NMES group . Our study shows that following COPD exacerbation , NMES is effective in counteracting muscle dysfunction and decreases muscle oxidative stress BACKGROUND Skeletal muscle dysfunction and exercise intolerance are common in severe chronic obstructive pulmonary disease ( COPD ) . We assessed the effectiveness of neuromuscular electrical stimulation ( NMES ) as a home-based exercise therapy . METHODS In this double-blind , placebo-controlled trial , undertaken across three UK National Health Service sites , we r and omly assigned ( 1:1 ) adults with COPD , a forced expiratory volume in 1 s ( FEV1 ) less than 50 % predicted , and incapacitating breathlessness ( Medical Research Council dyspnoea scale ≥4 ) to receive active or placebo NMES  , daily over a 6-week period . R and omisation was by an independent system using minimisation to balance age , GOLD stage , and quadriceps strength . Participants and outcome assessors were masked to group allocation . The primary endpoint was change in 6-min walk test ( 6MWT ) distance at 6 weeks . Analysis was by intention to treat . The trial was registered as IS RCT N15985261 and is now closed . FINDINGS Between June 29 , 2012 , and July 4 , 2014 , we enrolled 73 participants , of whom 52 participants were r and omly assigned ; 25 to  receive active NMES and 27 to placebo NMES  . Change in 6MWT distance was greater in the active NMES group ( mean 29·9 [ 95 % CI 8·9 to 51·0 ] ) compared with in the placebo group ( -5·7 [ -19·9 to 8·4 ] ; mean difference at 6 weeks 35·7 m [ 95 % CI 10·5 to 60·9 ] ; p=0·005 ) . Sensitivity analyses for complete-cases and adjustment for baseline values showed similar results . 6 weeks after stopping the intervention the effect waned ( 7·3 m [ 95 % CI -32·5 to 47·0 ] ; p=0·50 ) . The proportion of participants who had adverse events was similar between groups ( five [ 20 % ] in the active NMES group and nine [ 33 % ] in the placebo group ) . Two participants , one from each group , reported persistent erythema , which was considered to be possibly related to NMES and the use of adhesive electrodes . INTERPRETATION NMES  improves functional exercise capacity in patients with severe COPD by enhancing quadriceps muscle mass and function . These data support the use of NMES in the management of patients unable to engage with conventional pulmonary rehabilitation . More work is needed to study how to maintain the effect . FUNDING National Institute for Health Research AIMS Patients with chronic heart failure ( CHF ) exhibit detrimental changes in skeletal muscle that contribute to their impaired physical performance . This study investigates the possibility of counteracting these changes by chronic low-frequency electrical stimulation ( CLFS ) of left and right thigh muscles . METHODS AND RESULTS ( mean+/-SD ) 32 CHF patients ( 53+/-10 years ) with an LVEF of 22+/-5 % , NYHA II-IV , undergoing optimized drug therapy , were r and omized in a CLFS group ( CLFSG ) or a control group ( controls ) . The groups differed in terms of the intensity of stimulation , which elicited strong muscle contractions only in the CLFSG , whereas the controls received current input up to the sensory threshold without muscle contractions . Functional capacity was assessed by peak VO(2 ) , work capacity , and a 6-min-walk ( 6-MW ) . Muscle biopsies were analyzed for myosin heavy chain ( MHC ) isoforms , citrate synthase ( CS ) and glyceraldehydephosphate dehydrogenase ( GAPDH ) activities . Peak VO(2)(mlmin(-1)kg -1 ) increased from 9.6+/-3.5 to 11.6+/-2.8 ( P<0.001 ) in the CLFSG , and decreased from 10.6+/-2.8 to 9.4+/-3.2 ( P<0.05 ) in the controls . The increase in the CLFSG was paralleled by increases in maximal workload ( P<0.05 ) and oxygen uptake at the anaerobic threshold ( P<0.01 ) . The corresponding values of the controls were unchanged , as also the 6-MW values , the MHC isoform distribution , and both CS and GAPDH activities . In the CLFSG , the 6-MW values increased ( P<0.001 ) , CS activity was elevated ( P<0.05 ) , GAPDH activity decreased ( P<0.01 ) , and the MHC isoforms were shifted in the slow direction with increases in MHCI at the expense of MHCIId/x ( P<0.01 ) . CONCLUSIONS Our results suggest that CLFS is a suitable treatment to counteract detrimental changes in skeletal muscle and to increase exercise capacity in patients with severe CHF Exercise intolerance in chronic obstructive pulmonary disease ( COPD ) results from a complex interaction between central 
    Output:
    
NMES , when applied in isolation , increased quadriceps force and endurance , 6MWD and time to symptom limitation exercising at a submaximal intensity , and reduced the severity of leg fatigue on completion of exercise testing .
It may increase VO2peak , but the true effect on this outcome measure could be trivial .
Although there were no additional gains in quadriceps force with NMES plus conventional exercise training , there was evidence of an increase in 6MWD .
Further , in people who were the most debilitated , the addition of NMES may have accelerated the achievement of a functional milestone , that is , the first time someone sits out of bed