The effectiveness of peroneal nerve functional electrical simulation for the reduction of bradykinesia in Parkinson's disease: A feasibility study for a randomised control trial.

OBJECTIVES: To assess the feasibility of a multi-site randomised controlled trial to evaluate the effect of functional electrical stimulation on bradykinesia in people with Parkinson's disease. DESIGN: A two-arm assessor blinded randomised controlled trial with an 18 weeks intervention period and 4 weeks post-intervention follow-up. SETTING: Two UK hospitals; a therapy outpatient department in a district general hospital and a specialist neuroscience centre. PARTICIPANTS: A total of 64 participants with idiopathic Parkinson's disease and slow gait <1.25 ms-1. INTERVENTIONS: Functional electrical stimulation delivered to the common peroneal nerve while walking in addition to standard care compared with standard care alone. MAIN MEASURES: Feasibility aims included the determination of sample size, recruitment and retention rates, acceptability of the protocol and confirmation of the primary outcome measure. The outcome measures were 10 m walking speed, Unified Parkinson's Disease Rating Scale (UPDRS), Mini Balance Evaluation Systems Test, Parkinson's Disease Questionnaire-39, EuroQol 5-dimension 5-level, New Freezing of Gait questionnaire, Falls Efficacy Score International and falls diary. Participants opinion on the study design and relevance of outcome measures were evaluated using an embedded qualitative study. RESULTS: There was a mean difference between groups of 0.14 ms-1 (CI 0.03, 0.26) at week 18 in favour of the treatment group, which was maintained at week 22, 0.10 ms-1 (CI -0.05, 0.25). There was a mean difference in UPDRS motor examination score of -3.65 (CI -4.35, 0.54) at week 18 which was lost at week 22 -0.91 (CI -2.19, 2.26). CONCLUSION: The study design and intervention were feasible and supportive for a definitive trial. While both the study protocol and intervention were acceptable, recommendations for modifications are made.

HeART of Stroke: randomised controlled, parallel-arm, feasibility study of a community-based arts and health intervention plus usual care compared with usual care to increase psychological well-being in people following a stroke.

INTRODUCTION: People often experience distress following stroke due to fundamental challenges to their identity. OBJECTIVES: To evaluate (1) the acceptability of 'HeART of Stroke' (HoS), a community-based arts and health group intervention, to increase psychological well-being; and (2) the feasibility of a definitive randomised controlled trial (RCT). DESIGN: Two-centre, 24-month, parallel-arm RCT with qualitative and economic components. Randomisation was stratified by centre and stroke severity. Participant blinding was not possible. Outcome assessment blinding was attempted. SETTING: Community. PARTICIPANTS: Community-dwelling adults ≤2 years poststroke recruited via hospital clinical teams/databases or community stroke/rehabilitation teams. INTERVENTIONS: Artist-facilitated arts and health group intervention (HoS) (ten 2-hour sessions over 14 weeks) plus usual care (UC) versus UC. OUTCOMES: The outcomes were self-reported measures of well-being, mood, capability, health-related quality of life, self-esteem and self-concept (baseline and 5 months postrandomisation). Key feasibility parameters were gathered, data collection methods were piloted, and participant interviews (n=24) explored the acceptability of the intervention and study processes. RESULTS: Despite a low recruitment rate (14%; 95% CI 11% to 18%), 88% of the recruitment target was met, with 29 participants randomised to HoS and 27 to UC (57% male; mean (SD) age=70 (12.1) years; time since stroke=9 (6.1) months). Follow-up data were available for 47 of 56 (84%; 95% CI 72% to 91%). Completion rates for a study-specific resource use questionnaire were 79% and 68% (National Health Service and societal perspectives). Five people declined HoS postrandomisation; of the remaining 24 who attended, 83% attended ≥6 sessions. Preliminary effect sizes for candidate primary outcomes were in the direction of benefit for the HoS arm. Participants found study processes acceptable. The intervention cost an estimated £456 per person and was well-received (no intervention-related serious adverse events were reported). CONCLUSIONS: Findings from this first community-based study of an arts and health intervention for people poststroke suggest a definitive RCT is feasible. Recruitment methods will be revised. TRIAL REGISTRATION NUMBER: ISRCTN99728983.

Trial of intraoperative cell salvage versus transfusion in ovarian cancer (TIC TOC): protocol for a randomised controlled feasibility study.

INTRODUCTION: Ovarian cancer is the leading cause of death from gynaecological cancer, with more than 7000 new cases registered in the UK in 2014. In patients suitable for surgery, the National Institute of Health and Care Excellence guidance for treatment recommends surgical resection of all macroscopic tumour, followed by chemotherapy. The surgical procedure can be extensive and associated with substantial blood loss which is conventionally replaced with a donor blood transfusion. While often necessary and lifesaving, the use of donor blood is associated with increased risks of complications and adverse surgical outcomes. Intraoperative cell salvage (ICS) is a blood conservation strategy in which red cells collected from blood lost during surgery are returned to the patient thus minimising the use of donor blood. This is the protocol for a feasibility randomised controlled trial with an embedded qualitative study and feasibility economic evaluation. If feasible, a later definitive trial will test the effectiveness and cost-effectiveness of ICS reinfusion versus donor blood transfusion in ovarian cancer surgery. METHODS AND ANALYSIS: Sixty adult women scheduled for primary or interval ovarian cancer surgery at participating UK National Health Service Trusts will be recruited and individually randomised in a 1:1 ratio to receive ICS reinfusion or donor blood (as required) during surgery. Participants will be followed up by telephone at 30 days postoperatively for adverse events monitoring and by postal questionnaire at 6 weeks and 3 monthly thereafter, to capture quality of life and resource use data. Qualitative interviews will capture participants' and clinicians' experiences of the study. ETHICS AND DISSEMINATION: This study has been granted ethical approval by the South West-Exeter Research Ethics Committee (ref: 16/SW/0256). Results will be disseminated via peer-reviewed publications and will inform the design of a larger trial. TRIAL REGISTRATION NUMBER: ISRCTN19517317.

Interventions for preventing or treating malnutrition in homeless problem-drinkers: a systematic review.

BACKGROUND: Excessive drinking leads to poor absorption of nutrients and homeless problem-drinkers often have nutritionally inadequate diets. Depletion of nutrients such as vitamin B1 can lead to cognitive impairment, which can hinder efforts to reduce drinking or engage with services. This review aimed to assess effectiveness of interventions designed to prevent or treat malnutrition in homeless problem-drinkers. METHODS: We systematically searched nine electronic databases and 13 grey literature sources for studies evaluating interventions to improve nutrition in homeless populations, without regional or language restrictions. Screening for inclusion was done in duplicate. One reviewer extracted data and assessed risk of bias, and another checked the extractions. Primary outcomes were nutrition status/deficiency, liver damage, and cognitive function. Secondary outcomes included abstinence, comorbidities, resource use, acceptability and engagement with intervention. Results were synthesised narratively. RESULTS: We included 25 studies (2 Randomised Controlled Trials; 15 uncontrolled before and after; 7 surveys; 1 case-control). Nine studies evaluated educational and support interventions, five food provision, and three supplement provision. Eight studies evaluated a combination of these interventions. No two interventions were the same, and all studies were at high risk of bias. Nutritional status (intake/ deficiency) were reported in 11 studies and liver function in one. Fruit and vegetable intake improved with some education and support interventions (n = 4 studies) but not others (n = 2). Vitamin supplements appeared to improve vitamin deficiency levels in the blood (n = 2). Free or subsidised meals (n = 4) and food packs (n = 1) did not always fulfil dietary needs, but were usually considered acceptable by users. Some multicomponent interventions improved nutrition (n = 3) but acceptability varied (n = 3). No study reported cost effectiveness. CONCLUSIONS: The evidence for any one intervention for improving malnutrition in homeless problem-drinkers was based on single studies at high risk of bias. Various food and supplement provision interventions appear effective in changing nutritional status in single studies. Educational and multicomponent interventions show improved nutritional behaviour in some studies but not others. Further better quality evidence is required before these interventions can be recommended for implementation. Any future studies should seek the end user input in their design and conduct. TRIAL REGISTRATION: Registered with PROSPERO: CRD42015024247 .

'HeART of Stroke (HoS)', a community-based Arts for Health group intervention to support self-confidence and psychological well-being following a stroke: protocol for a randomised controlled feasibility study.

INTRODUCTION: Over 152,000 people in the UK have strokes annually and a third experience residual disability. Low mood also affects a third of stroke survivors; yet psychological support is poor. While Arts for Health interventions have been shown to improve well-being in people with mild-to-moderate depression post-stroke, their role in helping people regain sense of self, well-being and confidence has yet to be evaluated. The main aim of this study is to explore the feasibility of conducting a pragmatic multicentre randomised controlled trial to assess the effectiveness and cost-effectiveness of an Arts for Health group intervention ('HeART of Stroke' (HoS)) for stroke survivors. HoS is a 10-session artist-facilitated group intervention held in the community over 14 weeks. It offers a non-judgemental, supportive environment for people to explore sense of self, potentially enhancing well-being and confidence. METHODS AND ANALYSIS: Sixty-four people, up to 2 years post-stroke, recruited via secondary care research staff or community stroke/rehabilitation teams in two UK centres will be randomised to either HoS plus usual care or usual care only. Self-reported outcomes, measured at baseline and approximately 5 months postrandomisation, will include stroke-related, well-being, mood, self-esteem, quality of life and process measures. Analyses will focus on estimating key feasibility parameters (eg, rates of recruitment, retention, intervention attendance). We will develop outcome and resource use data collection methods to inform an effectiveness and cost-effectiveness analysis in the future trial. Interviews, with a sample of participants, will explore the acceptability of the intervention and study processes, as well as experiences of the HoS group. ETHICS AND DISSEMINATION: National Health Service (NHS), Research and Development and University ethical approvals have been obtained. Two peer-reviewed journal publications are planned plus one service user led publication. Findings will be disseminated at key national conferences, local stakeholder events and via institutional websites. TRIAL REGISTRATION NUMBER: ISRCTN99728983.

Local anaesthetic wound infiltration in addition to standard anaesthetic regimen in total hip and knee replacement: long-term cost-effectiveness analyses alongside the APEX randomised controlled trials.

BACKGROUND: The Arthroplasty Pain Experience (APEX) studies are two randomised controlled trials in primary total hip (THR) and total knee replacement (TKR) at a large UK orthopaedics centre. APEX investigated the effect of local anaesthetic wound infiltration (LAI), administered before wound closure, in addition to standard analgesia, on pain severity at 12 months. This article reports results of the within-trial economic evaluations. METHODS: Cost-effectiveness was assessed from the health and social care payer perspective in relation to quality adjusted life years (QALYs) and the primary clinical outcome, the WOMAC Pain score at 12-months follow-up. Resource use was collected from hospital records and patient-completed postal questionnaires, and valued using unit cost estimates from local NHS Trust finance department and national tariffs. Missing data were addressed using multiple imputation chained equations. Costs and outcomes were compared per trial arm and plotted in cost-effectiveness planes. If no arm was dominant (i.e., more effective and less expensive than the other), incremental cost-effectiveness ratios were estimated. The economic results were bootstrapped incremental net monetary benefit statistics (INMB) and cost-effectiveness acceptability curves. One-way deterministic sensitivity analyses explored any methodological uncertainty. RESULTS: In both the THR and TKR trials, LAI was the dominant treatment: cost-saving and more effective than standard care, in relation to QALYs and WOMAC Pain. Using the £20,000 per QALY threshold, in THR, the INMB was £1,125 (95 % BCI, £183 to £2,067) and the probability of being cost-effective was over 98 %. In TKR, the INMB was £264 (95 % BCI, -£710 to £1,238), but there was only 62 % probability of being cost-effective. When considering an NHS perspective only, LAI was no longer dominant in THR, but still highly cost-effective, with an INMB of £961 (95 % BCI, £50 to £1,873). CONCLUSIONS: Administering LAI is a cost-effective treatment option in THR and TKR surgeries. The evidence, because of larger QALY gain, is stronger for THR. In TKR, there is more uncertainty around the economic result, and smaller QALY gains. Results, however, point to LAI being cheaper than standard analgesia, which includes a femoral nerve block. TRIAL REGISTRATION: ISRCTN96095682 , 29/04/2010.

Effect of local anaesthetic infiltration on chronic postsurgical pain after total hip and knee replacement: the APEX randomised controlled trials.

Total hip replacement (THR) and total knee replacement (TKR) are usually effective at relieving pain; however, 7% to 23% of patients experience chronic postsurgical pain. These trials aimed to investigate the effect of local anaesthetic wound infiltration on pain severity at 12 months after primary THR or TKR for osteoarthritis. Between November 2009 and February 2012, 322 patients listed for THR and 316 listed for TKR were recruited into a single-centre double-blind randomised controlled trial. Participants were randomly assigned (1:1) to receive local anaesthetic infiltration and standard care or standard care alone. Participants and outcomes assessors were masked to group allocation. The primary outcome was pain severity on the WOMAC Pain Scale at 12 months after surgery. Analyses were conducted using intention-to-treat and per-protocol approaches. In the hip trial, patients in the intervention group had significantly less pain at 12 months postoperative than patients in the standard care group (differences in means: 4.74; 95% confidence interval [CI]: 0.95-8.54; P = 0.015), although the difference was not clinically significant. Post hoc analysis found that patients in the intervention group were more likely to have none to moderate pain than severe pain at 12 months than those in the standard care group (odds ratio: 10.19; 95% CI: 2.10-49.55; P = 0.004). In the knee trial, there was no strong evidence that the intervention influenced pain severity at 12 months postoperative (difference in means: 3.83; 95% CI: -0.83 to 8.49; P = 0.107). In conclusion, routine use of infiltration could be beneficial in improving long-term pain relief for some patients after THR.

Acute increase of the glutamate-glutamine cycling in discrete brain areas after administration of a single dose of amphetamine.

The glutamate-glutamine cycle between neurons and glia is tightly related to excitatory glutamatergic and inhibitory GABAergic regulation in brain. The role of this neuron-astrocyte cross-talk on the neurotoxicity induced by amphetamines is not understood. Also, the impact of neurotoxic doses of amphetamines on the balance between glutamatergic and GABAergic circuits is largely unknown. The aim of this work was to assess the acute effect of a neurotoxic regimen of amphetamine (AMPH) on glutamine (GLN, an astrocytic marker) levels and on glutamine/glutamate (an index for glutamate-glutamine cycle) and GABA/glutamate ratios in rat brain. Sprague-Dawley rats were sacrificed 4 and 24 h after a single-dose regimen of AMPH (30 mg/kg, i.p.), and the caudate-putamen (CPu), frontal cortex (FC), and hippocampus (Hp) were dissected for analysis of glutamate (GLU), gamma-aminobutyric acid (GABA), and GLN. The total content of these amino acids was measured using a microbore HPLC electrochemical detector. Although AMPH did not change GLU levels, it increased both GLN content and GLN/GLU ratio (160-469%) at 4 h, but not at 24 h, in all regions after injection. Striatal GABA levels and GABA/GLU ratio were increased (46 and 100%, respectively) at 24 h. In hippocampus the GABA/GLU increase (60%) occurred as early as 4 h after treatment. To the contrary, AMPH exerted no effect in GABA/GLU balance in frontal cortex. These data strongly suggest that this neurotoxic AMPH regimen provoked an early increase in the glutamate-glutamine cycle between neurons and glia. This increase may ultimately lead to an upregulation of the inhibitory system as a compensatory response.