The clinical- and cost-effectiveness of functional electrical stimulation and ankle-foot orthoses for foot drop in Multiple Sclerosis: a multicentre randomized trial

Objective: To compare the clinical- and cost-effectiveness of ankle-foot orthoses (AFOs) and functional electrical stimulation (FES) over 12 months in people with Multiple Sclerosis with foot drop. Design: Multicentre, powered, non-blinded, randomized trial. Setting: Seven Multiple Sclerosis outpatient centres across Scotland. Subjects: Eighty-five treatment-naïve people with Multiple Sclerosis with persistent (>three months) foot drop. Interventions: Participants randomized to receive a custom-made, AFO (n = 43) or FES device (n = 42). Outcome measures: Assessed at 0, 3, 6 and 12 months; 5-minute self-selected walk test (primary), Timed 25 Foot Walk, oxygen cost of walking, Multiple Sclerosis Impact Scale-29, Multiple Sclerosis Walking Scale-12, Modified Fatigue Impact Scale, Euroqol five-dimension five-level questionnaire, Activities-specific Balance and Confidence Scale, Psychological Impact of Assistive Devices Score, and equipment and National Health Service staff time costs of interventions. Results: Groups were similar for age (AFO, 51.4 (11.2); FES, 50.4(10.4) years) and baseline walking speed (AFO, 0.62 (0.21); FES 0.73 (0.27) m/s). In all, 38% dropped out by 12 months (AFO, n = 21; FES, n = 11). Both groups walked faster at 12 months with device (P < 0.001; AFO, 0.73 (0.24); FES, 0.79 (0.24) m/s) but no difference between groups. Significantly higher Psychological Impact of Assistive Devices Scores were found for FES for Competence (P = 0.016; AFO, 0.85(1.05); FES, 1.53(1.05)), Adaptability (P = 0.001; AFO, 0.38(0.97); FES 1.53 (0.98)) and Self-Esteem (P = 0.006; AFO, 0.45 (0.67); FES 1 (0.68)). Effects were comparable for other measures. FES may offer value for money alternative to usual care. Conclusion: AFOs and FES have comparable effects on walking performance and patient-reported outcomes; however, high drop-outs introduces uncertainty

An exploration of the experiences and utility of functional electrical stimulation for foot drop in people with multiple sclerosis

Purpose: Functional electrical stimulation (FES) is effective in improving walking in people with multiple sclerosis (MS) with foot drop. There is limited research exploring people’s experiences of using this device. This study aims to explore the utility, efficacy, acceptability, and impact on daily life of the device in people with MS. Methods: An interpretative phenomenological approach was employed. Ten participants who had used FES for 12 months were interviewed. Transcripts were analysed, and emergent themes identified. Results: Nine participants continued to use the device. Three relevant super-ordinate themes were identified; impact of functional electrical stimulation, sticking with functional electrical stimulation, and autonomy and control. Participants reported challenges using the device; however, all reported positive physical and psychological benefits. Intrinsic and external influences such as; access to professional help, the influence of others, an individual’s ability to adapt, and experiences using the device, influenced their decisions to continue with the device. A thematic model of these factors was developed. Conclusions: This study has contributed to our understanding of people with MS experiences of using the device and will help inform prescribing decisions and support the continued, appropriate use of FES over the longer term

A comparison of the initial orthotic effects of functional electrical stimulation and ankle-foot orthoses on the speed and oxygen cost of gait in multiple sclerosis

Foot drop affects walking in people with multiple sclerosis (pwMS). This study compares the initial orthotic effects of two treatments for foot drop: ankle-foot orthoses (AFO) and functional electrical stimulation (FES), on the speed and oxygen cost of walking in MS. Method and materials: Seventy-eight pwMS were randomised to receive AFO or FES (ODFS PACE (OML, Salisbury, UK)). Participants completed the 25-ft walk test (25ftWT) and 5-min self-selected walk test (5minSSWT), from which oxygen cost was determined, with and without their device. Between-, within- and sub-group analyses (based on baseline walking speed of <0.8 m/s (slow) or ≥0.8 m/s (fast)) were undertaken. Results: No significant differences between baseline measures were observed. The AFO group walked significantly slower than the FES group (5minSSWT, p = 0.037, 0.11 m/s). The AFO group walked significantly slower with than without AFO (25ftWT, p = 0.037), particularly in the fast-walking group ( p = 0.011). The slow-walking FES group walked significantly faster with FES than without (25ftWT; p = 0.029, 5minSSWT; p = 0.037). There were no differences in the fast-walking FES group or in the oxygen cost for either device. Conclusion: AFO reduced walking speed, particularly in fast walkers. FES increased walking speed in slow, but not fast walkers

EOSCpilot Ethics: Supporting Document to D3.3 Draft Policy Recommendations

This paper discusses how an ethical dimension can best be included within the policies, structures and services of the developing European Open Science Cloud (EOSC). Although the inclusion of ethical principles and policies are seen as of fundamental importance to the EOSC, it is difficult to anticipate all the ethical issues that may emerge as the scientific, technical, social and political landscape evolves. It is therefore seen as crucially important to have governance mechanisms in place that can ensure ethical issues are appropriately dealt with in the future, however and whenever they are presented, as well as identifying and proposing responses to current issues. An analysis of ethical issues relating to organisational conduct and policies, research conduct, research decision making, the use of data, especially sensitive personal data, and the interaction between science and society, serves to underline the complexity and diversity of potential issues

Functional electrical stimulation for foot drop in multiple sclerosis: a systematic review and meta-analysis of the effect on gait speed

Objective: To review the efficacy of functional electrical stimulation (FES) used for foot drop in people with multiple sclerosis (pwMS) on gait speed in short and long walking performance tests. Data sources: Five databases (Cochrane Library, CINAHL, Embase, MEDLINE, Pubmed) and reference lists were searched. Study selection: Studies of both observational and experimental design where gait speed data in pwMS could be extracted were included. Data extraction: Data were independently extracted and recorded. Methodological quality was assessed using the Effective Public Health Practice Project (EPHPP) tool. Data synthesis: Nineteen studies (described in 20 articles) recruiting 490 pwMS were identified and rated moderate or weak, with none gaining a strong rating. All studies rated weak for blinding. Initial and ongoing orthotic and therapeutic effects were assessed with regards to the impact of FES on gait speed in short and long walking tests. Meta-analyses of the short walk tests revealed a significant initial orthotic effect (t = 2.14, p = 0.016) with a mean increase in gait speed of 0.05 meters per second (m/s) and ongoing orthotic effect (t = 2.81, p = 0.003) with a mean increase of 0.08m/s. There were no initial or ongoing effect on gait speed in long walk tests and no therapeutic effect on gait speed in either short or long walk tests. Conclusions: FES used for foot drop has a positive initial and ongoing effect on gait speed in short walking tests. Further fully-powered randomized controlled trials comparing FES with alternative treatments are required

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society