Neuromuscular Electrical Stimulation for Intermittent Claudication (NESIC): multicentre, randomized controlled trial

\ua9 The Author(s) 2023. Published by Oxford University Press on behalf of BJS Society Ltd. METHODS: This was an open, multicentre, randomized controlled trial. Patients with intermittent claudication attending vascular surgery outpatient clinics were randomized (1:1) to receive either neuromuscular electrical stimulation (NMES) or not in addition to local standard care available at study centres (best medical therapy alone or plus supervised exercise therapy (SET)). The objective of this trial was to investigate the clinical efficacy of an NMES device in addition to local standard care in improving walking distances in patients with claudication. The primary outcome was change in absolute walking distance, measured by a standardized treadmill test at 3 months. Secondary outcomes included intermittent claudication (IC) distance, adherence, quality of life, and haemodynamic changes. RESULTS: Of 200 participants randomized, 160 were included in the primary analysis (intention to treat, Tobit regression model). The square root of absolute walking distance was analysed (due to a right-skewed distribution) and, although adjunctive NMES improved it at 3 months, no statistically significant effect was observed. SET as local standard care seemed to improve distance compared to best medical therapy at 3 months (3.29 units; 95 per cent c.i., 1.77 to 4.82; P < 0.001). Adjunctive NMES improved distance in mild claudication (2.88 units; 95 per cent c.i., 0.51 to 5.25; P = 0.02) compared to local standard care at 3 months. No serious adverse events relating to the device were reported. CONCLUSION: Supervised exercise therapy is effective and NMES may provide further benefit in mild IC.This trial was supported by a grant from the Efficacy and Mechanism Evaluation Program, a Medical Research Council and National Institute for Health and Care Research partnership. Trial registration: ISRCTN18242823.Patients with intermittent claudication experience pain in their legs during walking or exercise which ends with rest. This severely impairs physical activity and quality of life. Treatment for such patients typically involves best medical therapy, which includes exercise advice. This study aimed to determine whether a neuromuscular electrical stimulation device improved the walking distance of patients with intermittent claudication compared to local standard care available (which may include supervised exercise therapy) in a trial. Supervised exercise improved walking distances but there was no difference in those that received a device in this patient group

Achievements and prospects of genomics-assisted breeding in three legume crops of the semi-arid tropics

Advances in next-generation sequencing and genotyping technologies have enabled generation of large-scale genomic resources such as molecular markers, transcript reads and BAC-end sequences (BESs) in chickpea, pigeonpea and groundnut, three major legume crops of the semi-arid tropics. Comprehensive transcriptome assemblies and genome sequences have either been developed or underway in these crops. Based on these resources, dense genetic maps, QTL maps as well as physical maps for these legume species have also been developed. As a result, these crops have graduated from ‘orphan’ or ‘less-studied’ crops to ‘genomic resources rich’ crops. This article summarizes above mentioned advances in genomics and genomics-assisted breeding applications in the form of marker-assisted selection (MAS) for hybrid purity assessment in pigeonpea; marker-assisted backcrossing (MABC) for introgressing QTL region for drought-tolerance related traits, Fusarium wilt (FW) resistance and Ascochyta blight (AB) resistance in chickpea; late leaf spot (LLS), leaf rust and nematode resistance in groundnut. We critically present the case of use of other modern breeding approaches like marker-assisted recurrent selection (MARS) and genomic selection (GS) to utilize the full potential of genomics-assisted breeding for developing superior cultivars with enhanced tolerance to various environmental stresses. In addition, this article recommends the use of advanced- backcross (AB-backcross) breeding and development of specialized populations such as multi-parents advanced generation intercross (MAGIC) for creating new variations that will help developing superior lines with broadened genetic base. In summary, we propose the use of integrated genomics and breeding approach in these legume crops to enhance crop productivity in marginal environments ensuring food security in developing countries

Effect of footplate neuromuscular electrical stimulation on functional and quality‐of‐life parameters in patients with peripheral artery disease: pilot, and subsequent randomized clinical trial

Background Supervised exercise programmes for intermittent claudication have poor access and limited compliance. Neuromuscular electrical stimulation (NMES) may be an effective alternative. A proof‐of‐concept study and RCT were conducted. Methods In study 1, eligible patients underwent baseline assessment; treadmill testing for initial (ICD) and maximum (MCD) claudication distance; EuroQoL Five Dimensions five‐level instrument (EQ‐5D‐5L™) and Intermittent Claudication Questionnaire (ICQ) assessment; and measurement of ultrasound haemodynamics of the superficial femoral artery. After familiarization with the NMES device, participants underwent a 30‐min session of stimulation with concomitant recording of haemodynamic measures at 15 min, and after device cessation. Measurements were repeated after 6 weeks of daily use of NMES. In study 2, consecutive patients underwent baseline assessment before online randomization to a supervised exercise programme only, or adjunctive NMES treatment for 6 weeks, followed by repeat measurements. Results Study 1 (20 patients) showed a significant improvement in MCD (46 per cent; P < 0·001) and ICD (71 per cent; P < 0·001). The RCT (42 patients) showed a significant adjunctive benefit of NMES in ICD (46 per cent; P = 0·014). Improvements were seen in the ICQ (9 points; P = 0·009) and EQ‐5D‐5L™ (P = 0·007) in study 1, and there was a significant adjunctive benefit of NMES on the ICQ score in patients who did supervised exercise (11·2 points; P = 0·031). Blood volume flow and time‐adjusted mean velocity increased significantly with the device on (P < 0·050). Overall, NMES compliance exceeded 95 per cent. Conclusion Footplate NMES significantly improved walking distance in patients with intermittent claudication when used independently and also as an adjunct to supervised exercise. Registration number: trial 1, NCT02436200; trial 2, NCT02429310 (http://www.clinicaltrials.gov)

Are Brain Natriuretic Peptide Levels Related to Flow through Autologous Aterio-Venous Fistulae for Chronic Haemodialysis?

Formation of arterio-venous-fistulae (AVF) may exacerbate cardiac failure in the ever increasing, elderly population on haemodialysis. Brain Natriuretic Peptide (BNP) may prove a useful marker of cardiac failure in this population. We aimed to determine effect of creation of an AVF and flow in AVF on BNP levels. Ten patients undergoing primary formation of an upper limb autologous AVF (pre-dialysis), were recruited. Serum BNP (pg/ml) and flow in AVF (cm3/s) were documented pre-operatively, and then 2, 6 and 12 weeks post-operatively. The relationship between flow and BNP levels was assessed. Ten patients (6 male), mean age of 66yrs were recruited. Five patients had a radio-cephalic and 5 had a brachio-cephalic AVF formed. There was no correlation between BNP levels and flow within the AVF (r=0.34, p=0.28) at any time point. There was a general trend towards increased flow in the AVF over time, with only the change between flow at 2-weeks and 3-months postoperatively reaching significance, p=0.043. There was a general trend for BNP to fall over time in the postoperative period, with no significant change between the postoperative sampling time points. BNP levels do not correlate with flow across an AVF

A randomised controlled trial of neuromuscular stimulation in non-operative venous disease improves clinical and symptomatic status

Background This randomised controlled trial investigates the dosing effect of neuromuscular electrical stimulation (NMES) in patients with chronic venous disease (CVD). Methods Seventy-six patients with CEAP C3-C5 were randomised to Group A (no NMES), B (30 minutes of NMES daily) or C (60 minutes of NMES daily). Primary outcome was percentage change in Femoral Vein Time Averaged Mean Velocity (TAMV) at 6 weeks. Clinical severity scores, disease-specific and generic quality of life (QoL) were assessed. Results Seventy-six patients were recruited - mean age 60.8 (SD14.4) and 47:29 male. Six patients lost to follow-up. Percentage change in TAMV (p<0.001) was significantly increased in Groups B and C. Aberdeen Varicose Veins Questionnaire Score (-6.9, p=0.029) and Venous Clinical Severity Score (-4, p-0.003) improved in Group C, and worsened in Group A (+1, p=0.025). Conclusions Daily NMES usage increases flow parameters, with twice daily usage improving QoL and clinical severity at 6 weeks in CVD patients

Neuromuscular electrical stimulation (NMES) for the prevention of venous thromboembolism (VTE)

Objective Venous thromboembolism (VTE), encompassing deep vein thrombosis (DVT) and pulmonary embolism (PE), is a significant cause of morbidity and mortality, affecting 1 in 1000 adults per year. Neuromuscular electrical stimulation (NMES) is the transcutaneous application of electrical impulses to elicit muscle contraction, preventing venous stasis. This review aims to investigate the evidence underlying the use of NMES in thromboprophylaxis. Methods The Medline and Embase databases were systematically searched, adhering to PRISMA guidelines, for articles relating to electrical stimulation and thromboprophylaxis. Articles were screened according to a priori inclusion and exclusion criteria. Results The search strategy identified 10 randomised controlled trials, which were used in three separate meta-analyses; 5 trials compared NMES to control, favouring NMES (odds ratio (OR) of DVT 0.29, 95%CI 0.13-0.65; P=.003); 3 trials compared NMES to heparin, favouring heparin (OR of DVT 2.00, 95%CI 1.13-3.52; P=.02); 3 trials compared NMES as an adjunct to heparin versus heparin only, demonstrating no significant difference (OR of DVT 0.33, 95%CI 0.10-1.14; P=.08). Conclusion NMES significantly reduces the risk of deep vein thrombosis compared to no prophylaxis. It is inferior to heparin in preventing DVT and there is no evidence for its use as an adjunct to heparin

Neuromuscular electrical stimulation for intermittent claudication (NESIC): multicentre, randomised controlled trial

METHODS: This was an open, multicentre, randomized controlled trial. Patients with intermittent claudication attending vascular surgery outpatient clinics were randomized (1:1) to receive either neuromuscular electrical stimulation (NMES) or not in addition to local standard care available at study centres (best medical therapy alone or plus supervised exercise therapy (SET)). The objective of this trial was to investigate the clinical efficacy of an NMES device in addition to local standard care in improving walking distances in patients with claudication. The primary outcome was change in absolute walking distance, measured by a standardized treadmill test at 3 months. Secondary outcomes included intermittent claudication (IC) distance, adherence, quality of life, and haemodynamic changes. RESULTS: Of 200 participants randomized, 160 were included in the primary analysis (intention to treat, Tobit regression model). The square root of absolute walking distance was analysed (due to a right-skewed distribution) and, although adjunctive NMES improved it at 3 months, no statistically significant effect was observed. SET as local standard care seemed to improve distance compared to best medical therapy at 3 months (3.29 units; 95 per cent c.i., 1.77 to 4.82; P < 0.001). Adjunctive NMES improved distance in mild claudication (2.88 units; 95 per cent c.i., 0.51 to 5.25; P = 0.02) compared to local standard care at 3 months. No serious adverse events relating to the device were reported. CONCLUSION: Supervised exercise therapy is effective and NMES may provide further benefit in mild IC.This trial was supported by a grant from the Efficacy and Mechanism Evaluation Program, a Medical Research Council and National Institute for Health and Care Research partnership. Trial registration: ISRCTN18242823

A multicenter randomized controlled study to evaluate whether neuromuscular electrical stimulation improves the absolute walking distance in patients with intermittent claudication compared with best available treatment

Objective: To assess the clinical efficacy of an NMES device to improve the absolute walking distance (AWD) in patients with IC, as an adjunct to the local standard care available at the study sites compared to local standard care alone. Methods: An open, multicentre, randomised controlled trial including eight participating centres in England. Sites are equally distributed between those that provide SET programmes and those that do not. Patients with IC meeting the inclusion and exclusion criteria, and providing consent will be randomised, depending on the centre type, to either NMES and locally available standard care or standard care alone. The primary endpoint, AWD, will be measured at 3 months (the end of the intervention period) by treadmill testing. Secondary outcomes include quality of life assessment, compliance with the interventions, economic evaluation of the NMES device, and lower limb haemodynamic measures to further the understanding of underlying mechanisms. Recruitment is due to commence in February 2018 and will continue for a total of 15 months. The NESIC trial is funded by the UK Efficacy and Mechanism Evaluation (EME) Programme, Medical Research Council (MRC) and National Institute for Health Research (NIHR) partnership. ISRCTN 18242823