Development of non-esterified fatty acid (NEFA) electrochemical biosensor for energy metabolism studies

PhD ThesisThere are many energy metabolism studies ongoing, including those for cardiovascular diseases and type-2-diabetes. With an increase in people being diagnosed with type-2-diabetes, there should be more ways to monitor not only the blood glucose levels but also the other biomarkers associated with type-2-diabetes. The metabolism biomarkers are essential in understanding the cause of diabetes early on. These biomarkers include: glucose, non-esterified fatty acid, lactate, urea, creatinine, glycosylated haemoglobin and cholesterol. Whilst glucose measurement has a clear role in type-2-diabetes management, the potential value of non-esterified fatty acid has not been explored or highlighted yet. The aim of this project is to develop an electrochemical biosensor for the non-esterified fatty acid in human blood, as non-esterified fatty acid can cause -cell loss in type-2-diabetes. Exploration of this biomarker would be a step forward in increasing research and patient understanding of the dynamic processes involved in establishing good metabolism control. The project uses the enzymes in commercial optical methods for non-esterified fatty acid detection. Oleic acid was used as the standard non-esterified fatty acid in this work. The electrochemical techniques employed are cyclic voltammetry, linear sweep voltammetry, chronoamperometry and electrochemical impedance spectroscopy. Enzyme electrodes were fabricated using the layer-by-layer immobilization of alternating polymer and enzyme combinations on carbon, cobalt phthalocyanine and single wall carbon nanotube screen printed electrodes. A chronoamperometric non-esterified fatty acid sensor was developed with the linear detection range of 0.10 mM to 0.90 mM oleic acid and with a sensitivity of 0.6562 A/mM oleic acid. This sensor was then further fabricated to detect non-esterified fatty acid concentrations in human plasma and serum samples. Commercial UV optical methods were used as method of validation of the blood sample concentrations. This work produced a platform for further non-esterified fatty acid detection studies.EPSRC

Best practice in radiofrequency denervation of the lumbar facet joints : a consensus technique

Background Radiofrequency denervation is used to treat selected people with low back pain. Recent trials have been criticised for using a sub-optimal intervention technique. Objectives To achieve consensus on a best practice technique for administering radiofrequency denervation of the lumbar facet joints to selected people with low back pain. Study design A consensus of expert professionals in the area of radiofrequency denervation of the lumbar facet joints. Methods We invited a clinical member from the 30 most active UK departments in radiofrequency pain procedures and two overseas clinicians with specific expertise to a 1 day consensus meeting. Drawing on the known anatomy of the medial branch, the theoretical basis of radiofrequency procedures, a survey of current practice and collective expertise, delegates were facilitated to reach consensus on the best practice technique. Results The day was attended by 24 UK and international clinical experts. Attendees agreed a best practice technique for the conduct of radiofrequency denervation of the lumbar facet joints. Limitations This consensus was based on a 1 day meeting of 24 clinical experts who attended and took part in the discussions. The agreed technique has not been subject to input from a wider community of experts. Conclusions Current best practice for radiofrequency denervation has been agreed for use in a UK trial. Group members intend immediate implementation in their respective trusts. We propose using this in a planned Randomised Controlled Trial (RCT) of radiofrequency denervation for selected people with low back pain

Does a Screening Trial for Spinal Cord Stimulation in Patients with Chronic Pain of Neuropathic Origin have Clinical Utility and Cost-Effectiveness? (TRIAL-STIM Study): study protocol for a randomised controlled trial

Abstract Background The TRIAL-STIM Study aims to assess the diagnostic performance, clinical outcomes and cost-effectiveness of a screening trial prior to full implantation of a spinal cord stimulation (SCS) device. Methods/design The TRIAL-STIM Study is a superiority, parallel-group, three-centre, randomised controlled trial in patients with chronic neuropathic pain with a nested qualitative study and economic evaluation. The study will take place in three UK centres: South Tees Hospitals NHS Foundation Trust (The James Cook University Hospital); Basildon and Thurrock University Hospitals NHS Foundation Trust; and Leeds Teaching Hospitals NHS Trust. A total of 100 adults undergoing SCS implantation for the treatment of neuropathy will be included. Subjects will be recruited from the outpatient clinics of the three participating sites and randomised to undergo a screening trial prior to SCS implant or an implantation-only strategy in a 1:1 ratio. Allocation will be stratified by centre and minimised on patient age (≥ 65 or < 65 years), gender, presence of failed back surgery syndrome (or not) and use of high frequency (HF10™) (or not). The primary outcome measure is the numerical rating scale (NRS) at 6 months compared between the screening trial and implantation strategy and the implantation-only strategy. Secondary outcome measures will include diagnostic accuracy, the proportion of patients achieving at least 50% and 30% pain relief at 6 months as measured on the NRS, health-related quality-of-life (EQ-5D), function (Oswestry Disability Index), patient satisfaction (Patients’ Global Impression of Change) and complication rates. A nested qualitative study will be carried out in parallel for a total of 30 of the patients recruited in each centre (10 at each centre) to explore their views of the screening trial, implantation and overall use of the SCS device. The economic evaluation will take the form of a cost–utility analysis. Discussion The TRIAL-STIM Study is a randomised controlled trial with a nested qualitative study and economic evaluation aiming to determine the clinical utility of screening trials of SCS as well as their cost-effectiveness. The nested qualitative study will seek to explore the patient’s view of the screening trials, implantation and overall use of SCS. Trial registration ISRCTN, ISRCTN60778781. Registered on 15 August 2017

Additional file 1: of Does a Screening Trial for Spinal Cord Stimulation in Patients with Chronic Pain of Neuropathic Origin have Clinical Utility and Cost-Effectiveness? (TRIAL-STIM Study): study protocol for a randomised controlled trial

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