OBJECTIVE:To assess a potential efficacy signal, safety and feasibility of neuromuscular electrical stimulation (NMES) therapy as an adjunct to standard care in patients with diabetic sensorimotor polyneuropathy (DSPN).METHODS:In this single-centre, prospective, cohort, proof-of-concept study, 25 patients with DSPN consented to at least one daily 30-minute NMES therapy session (Revitive® IX) for 10 weeks, with 20 patients completing the study. The primary outcome measure was nerve conductivity assessed using a nerve conduction study of the sural, superficial peroneal, common peroneal and tibial nerves at 10 weeks compared to baseline. Secondary outcomes included superficial femoral artery (SFA) haemodynamics during NMES therapy compared to rest and quality-of-life at 10 weeks compared to baseline.RESULTS:At 10 weeks, there were significant increases in sural sensory nerve action potential amplitude and conduction velocity (p < 0.001), superficial peroneal sensory nerve action potential amplitude (p = 0.001) and conduction velocity (p = 0.002), common peroneal nerve conduction velocity (p = 0.004) and tibial nerve compound muscle action potential amplitude (p = 0.002) compared to baseline. SFA volume flow and time-averaged mean velocity significantly increased (p ≤ 0.003) during NMES compared to rest. Patient-reported Michigan Neuropathy Screening Instrument scores significantly decreased (p = 0.028) at 10 weeks compared to baseline. Three unrelated adverse events occurred, and 15 participants adhered to treatment.CONCLUSIONS:NMES therapy as an adjunct to standard care for 10 weeks significantly increased lower limb nerve conductivity in patients with DSPN and may be beneficial in the treatment of DSPN.

Introduction Hospital-acquired thrombosis (HAT) is defined as any venous thromboembolism (VTE)-related event during a hospital admission or occurring up to 90 days post discharge, and is associated with significant morbidity, mortality and healthcare-associated costs. Although surgery is an established risk factor for VTE, operations with a short hospital stay (<48 hours) and that permit early ambulation are associated with a low risk of VTE. Many patients undergoing short-stay surgical procedures and who are at low risk of VTE are treated with graduated compression stockings (GCS). However, evidence for the use of GCS in VTE prevention for this cohort is poor.Methods and analysis A multicentre, cluster randomised controlled trial which aims to determine whether GCS are superior in comparison to no GCS in the prevention of VTE for surgical patients undergoing short-stay procedures assessed to be at low risk of VTE. A total of 50 sites (21 472 participants) will be randomised to either intervention (GCS) or control (no GCS). Adult participants (18–59 years) who undergo short-stay surgical procedures and are assessed as low risk of VTE will be included in the study. Participants will provide consent to be contacted for follow-up at 7-days and 90-days postsurgical procedure. The primary outcome is the rate of symptomatic VTE, that is, deep vein thrombosis or pulmonary embolism during admission or within 90 days. Secondary outcomes include healthcare costs and changes in quality of life. The main analysis will be according to the intention-to-treat principle and will compare the rates of VTE at 90 days, measured at an individual level, using hierarchical (multilevel) logistic regression.Ethics and dissemination Ethical approval was granted by the Camden and Kings Cross Research Ethics Committee (22/LO/0390). Findings will be published in a peer-reviewed journal and presented at national and international conferences.Trial registration number ISRCTN13908683.

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.

Background Peripheral arterial disease is common and associated with increased cardiovascular morbidity and mortality. While patients with peripheral arterial disease are known to benefit from supervised exercise therapy, it is not always available. Neuromuscular electrical stimulation devices may offer a similar benefit. A randomised controlled trial was required to ascertain whether such devices can benefit patients who receive supervised exercise therapy and those who do not. Objective(s) The primary objective was to assess the mean difference in absolute walking distance at 3 months in intermittent claudication patients receiving either a neuromuscular electrical stimulation device and local standard care (intervention), or local standard care alone (control). Design A pragmatic, multicentre, randomised controlled trial stratified by centre. Setting Secondary-care National Health Service hospitals in the United Kingdom. Participants Patients aged ≥18 years, with a diagnosis of intermittent claudication according to the Edinburgh Claudication Questionnaire and ankle–brachial pressure index (or stress test), without contraindications to neuromuscular electrical stimulation were deemed eligible to partake. Interventions Participants were randomised 1 : 1 to either local standard care or local standard care and neuromuscular electrical stimulation. Due to the nature of the intervention, it was unfeasible to blind the research nurse or participant to the study allocation. Main outcome measures The primary outcome measure was absolute walking distance measured by treadmill testing at 3 months. Secondary outcomes included change in initial claudication distance, quality of life, compliance with interventions and haemodynamic assessments. Results Two hundred patients underwent randomisation, with 160 patients having analysable primary outcome data for the intention-to-treat analysis intervention (n = 80); control (n = 80). As the data were right-censored, a Tobit regression model was used to analyse the primary outcome, utilising the square root of the absolute walking distance to accommodate the skewed data. However, as this made the data difficult to interpret, a Tobit regression model using raw absolute walking distance data was used as well. Neuromuscular electrical stimulation improved the difference in absolute walking distance at 3 months but this was not statistically significant (square root of absolute walking distance: 0.835 units, 95% confidence interval −0.67 to 2.34 units; p = 0.28/absolute walking distance raw data: 27.18 m, 95% confidence interval −26.92 to 81.28 m; p = 0.323). Supervised exercise therapy participants showed a markedly improved absolute walking distance compared with patients receiving best medical therapy only at 3 months (square root of absolute walking distance: 3.295 units 95% confidence interval 1.77 to 4.82; p < 0.001/absolute walking distance raw data: 121.71 m, 95% confidence interval 67.32 to 176.10; p ≤ 0.001). Neuromuscular electrical stimulation significantly improved absolute walking distance at 3 months for mild claudicants (square root of absolute walking distance: 2.877 units, 95% confidence interval 0.51 to 5.25; p = 0.019/absolute walking distance raw data: 120.55 m, 95% confidence interval 16.03 to 225.06; p = 0.03) compared to the control arm. This was an unplanned (post hoc) analysis. There were no clear differences in mechanistic measurements between the two treatment groups over the follow-up period. Serious adverse events were evenly reported between the two groups; all being classified as either not related or unlikely to be related to the study device. Limitations Absolute walking distance was used as the primary outcome measure; there was a large range of baseline distances in both groups with right-skewed distribution. We did not stratify by baseline absolute walking distance for the primary outcome analysis. Additionally, only 160 patients had analysable primary outcome data due to missing treadmill data. Conclusions Supervised exercise therapy is an effective treatment for intermittent claudication. Neuromuscular electrical stimulation appears to be beneficial as an adjunct to supervised exercise therapy and on its own in mild claudicants. Future work Further studies are needed to confirm the effectiveness of neuromuscular electrical stimulation in combination with supervised exercise therapy, and in mild to moderate claudicants in a larger sample size. Study registration This trial is registered as ISRCTN18242823. Funding This project was funded by the Efficacy and Mechanism Evaluation (EME) Programme, a Medical Research Council (MRC) and National Institute for Health and Care Research (NIHR) partnership (project number 15/180/68). This will be published in full in Efficacy and Mechanism Evaluation; Vol. 10, No. 2. See the NIHR Journals Library website for further project information. Infrastructure support for this research was provided by the NIHR Imperial Biomedical Research Centre (BRC) (with others, e.g. NIHR Imperial CRF, Imperial College ECMC, NIHR Imperial PSTRC, NIHR London MIC, etc.).

Chronic obstruction of the iliac veins or inferior vena cava can occur as a result of deep vein thrombosis, or owing to extrinsic compression in nonthrombotic iliac vein lesions (NIVLs). This obstruction can manifest as post-thrombotic syndrome (PTS) after deep vein thrombosis or as chronic venous disease (CVD) in NIVL. Little evidence exists to support the use of deep venous stents in established PTS or NIVLs, and the evidence for its use in the prevention of PTS is inconclusive. A provisional health economic analysis over 5 years found that the incremental cost-effectiveness ratio of stenting versus no stenting over a 5-year period was between £7,500 and £52,000 per quality-adjusted life-year for treatment of established PTS.

Introduction Peripheral arterial disease (PAD) is a key risk factor for cardiovascular disease, foot ulceration and lower limb amputation in people with diabetes. Early diagnosis of PAD can enable optimisation of therapies to manage these risks. Its diagnosis is fundamental, though challenging in the context of diabetes. Although a variety of diagnostic bedside tests are available, there is no agreement as to which is the most accurate in routine clinical practice. The aim of this study is to determine the diagnostic performance of a variety of tests (audible waveform assessment, visual waveform assessment, ankle brachial pressure index (ABPI), exercise ABPI and toe brachial pressure index (TBPI)) for the diagnosis of PAD in people with diabetes as determined by a reference test (CT angiography (CTA) or magnetic resonance angiography (MRA)). In selected centres, we also aim to evaluate the performance of a new point-of-care duplex ultrasound scan (PAD-scan). Methods and analysis A prospective multicentre diagnostic accuracy study (ClinicalTrials.gov Identifier NCT05009602). We aim to recruit 730 people with diabetes from 18 centres across the UK, covering primary and secondary healthcare. Consenting participants will undergo the tests under investigation. Reference tests (CTA or MRA) will be performed within 6 weeks of the index tests. Imaging will be reported by blinded consultant radiologists at a core imaging lab, using a validated scoring system, which will also be used to categorise PAD severity. The presence of one or more arterial lesions of ≥50% stenosis, or tandem lesions with a combined value of ≥50%, will be used as the threshold for the diagnosis of PAD. The primary outcome measure of diagnostic performance will be test sensitivity. Ethics and dissemination The study has received approval from the National Research Ethics Service (NRES) (REC reference 21/PR/1221). Results will be disseminated through research presentations and papers. Trial registration number NCT05009602.

Diabetic neuropathy (DN) is a common complication of diabetes that is becoming an increasing concern as the prevalence of diabetes rapidly rises. There are several types of DN, but the most prevalent and studied type is distal symmetrical polyneuropathy, which is the focus of this review and is simply referred to as DN. It can lead to a wide range of sensorimotor and psychosocial symptoms and is a major risk factor for diabetic foot ulceration and Charcot neuropathic osteoarthropathy, which are associated with high rates of lower limb amputation and mortality. The prevention and management of DN are thus critical, and clinical guidelines recommend several strategies for these based on the best available evidence. This article aims to provide a narrative review of DN prevention and management strategies by discussing these guidelines and the evidence that supports them. First, the epidemiology and diverse clinical manifestations of DN are summarized. Then, prevention strategies such as glycemic control, lifestyle modifications and footcare are discussed, as well as the importance of early diagnosis. Finally, neuropathic pain management strategies and promising novel therapies under investigation such as neuromodulation devices and nutraceuticals are reviewed.

Distal symmetrical polyneuropathy (DSPN) is a serious complication of diabetes associated with significant disability and mortality. Although more than 50% of people with diabetes develop DSPN, its pathogenesis is still relatively unknown. This lack of understanding has limited the development of novel disease-modifying therapies and left the reasons for failed therapies uncertain, which is critical given that current management strategies often fail to achieve long-term efficacy. In this article, the pathogenesis of DSPN is reviewed, covering pathogenic changes in the peripheral nervous system, microvasculature and central nervous system (CNS). Furthermore, the successes and limitations of current therapies are discussed, and potential therapeutic targets are proposed. Recent findings on its pathogenesis have called the definition of DSPN into question and transformed the disease model, paving the way for new research prospects.

Objective No agreement has been reached regarding which bedside test is the most useful for the diagnosis of peripheral arterial disease (PAD) in patients with diabetes. The aim of the present systematic review and meta-analysis was to evaluate the performance of bedside tests for the detection of PAD in individuals with diabetes. Methods MEDLINE and EMBASE databases were systematically searched for studies providing data on the diagnostic performance of bedside tests used for the detection of PAD in those with diabetes. A meta-analysis was performed to obtain pooled estimates of sensitivity and specificity for the diagnosis of PAD. Results A total of 18 studies, reporting on a total of 3016 limbs of diabetic patients, were included in our qualitative review. Of these, 11 studies (1543 limbs) were included in the meta-analysis of diagnostic accuracy: ankle-brachial pressure index (9 studies and 1368 limbs; sensitivity, 63.5% [95% confidence interval (CI), 51.7%-73.9%]; specificity, 89.3% [95% CI, 81.1%-94.2%]); toe-brachial pressure index (3 studies and 221 limbs; sensitivity, 83.0% [95% CI, 59.1-94.3%]; specificity, 66.3% [95% CI, 41.3%-84.6%]); and tibial waveform assessment (4 studies and 397 limbs; sensitivity, 82.8% [95% CI, 73.3%-89.4%], specificity, 86.8% [95% CI, 75.5%-93.3%]). Overall, we found a high risk of bias across the studies, most frequently relating to patient selection and the lack of blinding. Conclusions The toe-brachial pressure index, pulse oximetry, and tibial arterial waveform assessment demonstrated some promise, warranting further investigation.

Objectives The aim of this systematic review is to assess the performance of graduated compression stockings (GCS) in comparison to no venous thromboembolism (VTE) prophylaxis in the prevention of hospital-acquired thrombosis in low-risk surgical patients undergoing short-stay procedures. Methods Aligning with PRISMA guidelines, online databases MEDLINE and EMBASE, Cochrane Library® and trial registries were searched. Eligible articles reported the VTE rate in low-risk surgical patients either receiving GCS or no VTE prophylaxis. Results Narrative synthesis was performed on a single eligible article. The included study arm consisted of participants undergoing knee arthroscopy with the use of GCS alone reporting a total of 29 VTE events (4.4%), 16 of which were asymptomatic DVTs (2.4%). Conclusion There is a complete lack of evidence to support the use of GCS in the prevention of HAT for low-risk surgical patients. An adequately powered trial is required to provide level-IA evidence to support this practice.

Belantamab Mafodotin (B, GSK2857916) is an antibody drug conjugate targeting BCMA. In the first-in-human clinical trial, a response rate of 60% and median progression free survival of 12 months was demonstrated for patients with relapsed/ refractory myeloma (MM). Blurring of vision and thrombocytopenia were the most significant toxicities requiring dose reduction.