Cost impact of a non-invasive, portable device for patient self-administration of chronic migraine in a UK National Health Service setting

Background Chronic migraine (CM) is a neurological disorder associated with substantial disability. Botulinum toxin type A (Botox) is an approved and effective preventive treatment option for adult patients with CM. Transcranial magnetic stimulation (TMS) is an alternative treatment device delivering a brief pre-set magnetic pulse used for self-administration by the patient at home. Despite being available in a risk share scheme TMS is perceived to be more costly in the UK. The objective of this study was to analyse the incremental costs of TMS compared to Botox in refractory CM patients both for a UK individual funding request setting as well as for an average UK specialist center setting. Methods Cost impact results were derived from a decision-tree model simulating treatment pathways over 1 year. Costs were applied from the most recently available UK data sources. Sensitivity analysis was performed for all variables. Results Based on published utilisation data 45.5 % of CM patients would continuously receive Botox over 1 year, whereas 53.7 % of TMS patients would be still on treatment at the end of year one. Total costs of Botox treatment accrue to £2923 in an individual funding request NHS cost setting, whereas TMS treatment results in £1466 in the first year. Applying a time-based NHS cost setting expenditures accrue to £1747 for the Botox treatment and to £1361 for the TMS treatment. In both cost settings variation of cost assumptions did have a minor impact on the cost increment from Botox to TMS. Conclusion The current risk share based remuneration model of TMS allows the UK NHS to reimburse only the cost of those patients experiencing reduction in migraine days resulting in lower costs for treating migraine attacks. Treatment of chronic refractory migraine using TMS implies a substantial cost reduction potential for the management of chronic treatment of refractory migraine patients compared to conventional Botox treatment

Transauricular nerve stimulation in acute ischaemic stroke requiring mechanical thrombectomy: Protocol for a phase 2A, proof-of-concept, sham-controlled randomised trial.

BACKGROUND: Labile blood pressure after acute ischaemic stroke requiring mechanical thrombectomy is independently associated with poor patient outcomes. OBJECTIVES: This study protocol describes is designed to determine whether transauricular nerve stimulation, improves baroreflex sensitivity, reduces blood pressure variability in the first 24 hours after acute ischaemic stroke requiring mechanical thrombectomy. DESIGN: PHASE 2A, PROOF-OF-CONCEPT, SHAM-CONTROLLED RANDOMISED TRIAL: Methods and Analysis: 36 individuals undergoing mechanical thrombectomy for acute ischaemic stroke with established hypertension aged >18 years will be randomly allocated to receive bilateral active or sham transauricular nerve stimulation for the duration of the mechanical thrombectomy procedure (AffeX-CT/001 investigational device). The intervention will be repeated for 1h the morning following the mechanical thrombectomy. Non-invasive blood pressure will be measured ≥2h for 24h after mechanical thrombectomy. Holter electrocardiographic monitoring will be recorded during transauricular nerve stimulation. Participants, clinicians and investigators will be masked to treatment allocations. The primary outcome will be the coefficient of variation of systolic blood pressure. Secondary outcomes include additional estimates of blood pressure variability and time/frequency-domain measures of autonomic cardiac modulation An adjusted sample size of 36 patients is required to have a 90% chance of detecting, as significant at the 5% level, a difference in the coefficient of variation in systolic blood pressure of 5±4mmHg between sham and active stimulation [assuming 5% non-compliance rate in each group]. Ethics: confirmed on 16 March 2023 by HRA and Health and Care Research Wales ethics committee (reference 23/WA/0013). DISCUSSION: This study will provide proof-of-concept data that examines whether non-invasive autonomic neuromodulation can be used to favourably modify blood pressure and autonomic control after acute ischaemic stroke requiring mechanical thrombectomy. TRIAL REGISTRATION: Trial registration number: NCT05417009

Exploring Large Document Repositories with RDF Technology: The DOPE Project

This thesaurus-based search system uses automatic indexing, RDF-based querying, and concept-based visualization of results to support exploration of large online document repositories

Realism about the Wave Function

A century after the discovery of quantum mechanics, the meaning of quantum mechanics still remains elusive. This is largely due to the puzzling nature of the wave function, the central object in quantum mechanics. If we are realists about quantum mechanics, how should we understand the wave function? What does it represent? What is its physical meaning? Answering these questions would improve our understanding of what it means to be a realist about quantum mechanics. In this survey article, I review and compare several realist interpretations of the wave function. They fall into three categories: ontological interpretations, nomological interpretations, and the \emph{sui generis} interpretation. For simplicity, I will focus on non-relativistic quantum mechanics.Comment: Penultimate version for Philosophy Compas

α-Fetoprotein and human chorionic gonadotrophin-β as prognostic markers in neuroendocrine tumour patients

Serum chromogranin A is the most useful general and prognostic tumour marker available for neuroendocrine tumour (NET) patients. The role of other tumour markers is less clear. In order to determine the diagnostic and prognostic value of serum α-fetoprotein (AFP) and human chorionic gonadotrophin-β (hCGβ) in NETs, a database containing biochemical, histological, and survival data on 360 NET patients was constructed. This data was statistically assessed, using Statistical Package for the Social Sciences, to determine the utility of commonly measured tumour markers with particular emphasis on AFP and hCGβ. α-Fetoprotein and hCGβ were raised in 9.5 and 12.3% of patients respectively and jointly raised in 9.1% of patients in whom it was measured. α-Fetoprotein levels associated strongly and positively with tumour grade, serum CgA and hCGβ levels, and worse survival. Human chorionic gonadotrophin-β levels also associated strongly and positively with serum CgA and AFP levels, and worsening survival. α-Fetoprotein and hCGβ are elevated in high-grade NETs, with a rapidly progressive course and poorer survival. They also correlate with chromogranin-A, which is known to be a marker of tumour burden and to have prognostic value. Thus AFP and hCGβ are clinically important in NETs and when elevated are poor prognostic markers

Can digital health apps provide patients with support to promote structured diabetes education and ongoing self-management? A real-world evaluation of myDiabetes usage

Objective Structured diabetes education has evidenced benefits yet reported uptake rates for those referred to traditional in-person programmes within 12 months of diagnosis were suboptimal. Digital health interventions provide a potential solution to improve diabetes education delivery at population scale, overcoming barriers identified with traditional approaches. myDiabetes is a cloud-based interactive digital health self-management app. This evaluation analysed usage data for people with type 2 diabetes focusing on digital structured diabetes education. Methods Descriptive quantitative analyses were conducted on existing anonymised user data over 12 months (November 2019–2020) to evaluate whether digital health can provide additional support to deliver diabetes education. Data was divided into two equal 6-month periods. As this overlapped the onset of COVID-19, analyses of its effect on usage were included as a secondary outcome. All data was reported via myDiabetes. Users were prescribed myDiabetes by National Health Service healthcare primary care teams. Those who registered for app use within the study period (n = 2783) were assessed for eligibility (n = 2512) and included if activated. Results Within the study period, n = 1245/2512 (49.6%) registered users activated myDiabetes. No statistically significant differences were observed between gender (p = 0.721), or age (p = 0.072) for those who activated (59.2 years, SD 12.93) and those who did not activate myDiabetes (57.6 years, SD 13.77). Activated users (n = 1119/1245 (89.8%)) viewed 11,572 education videos. No statistically significant differences were observed in education video views across age groups (p = 0.384), gender (p = 0.400), diabetes treatment type (p = 0.839) or smoking status (p = 0.655). Comparison of usage pre-COVID-19 and post-COVID-19 showed statistically significant increases in app activity (p ≤0.001). Conclusion Digital health is rapidly evolving in its role of supporting patients to self-manage. Since COVID-19 the benefits of digital technology have become increasingly recognised. There is potential for increasing diabetes education rates by offering patients a digital option in combination with traditional service delivery which should be substantiated through future research

Isolation of Primary Human Hepatocytes from Normal and Diseased Liver Tissue: A One Hundred Liver Experience

Successful and consistent isolation of primary human hepatocytes remains a challenge for both cell-based therapeutics/transplantation and laboratory research. Several centres around the world have extensive experience in the isolation of human hepatocytes from non-diseased livers obtained from donor liver surplus to surgical requirement or at hepatic resection for tumours. These livers are an important but limited source of cells for therapy or research. The capacity to isolate cells from diseased liver tissue removed at transplantation would substantially increase availability of cells for research. However no studies comparing the outcome of human hepatocytes isolation from diseased and non-diseased livers presently exist. Here we report our experience isolating human hepatocytes from organ donors, non-diseased resected liver and cirrhotic tissue. We report the cell yields and functional qualities of cells isolated from the different types of liver and demonstrate that a single rigorous protocol allows the routine harvest of good quality primary hepatocytes from the most commonly accessible human liver tissue samples

The unexplained success of stentplasty vasospasm treatment

Background Cerebral vasospasm (CVS) following subarachnoid hemorrhage occurs in up to 70% of patients. Recently, stents have been used to successfully treat CVS. This implies that the force required to expand spastic vessels and resolve vasospasm is lower than previously thought. Objective We develop a mechanistic model of the spastic arterial wall to provide insight into CVS and predict the forces required to treat it. Material and Methods The arterial wall is modelled as a cylindrical membrane using a constrained mixture theory that accounts for the mechanical roles of elastin, collagen and vascular smooth muscle cells (VSMC). We model the pressure diameter curve prior to CVS and predict how it changes following CVS. We propose a stretch-based damage criterion for VSMC and evaluate if several commercially available stents are able to resolve vasospasm. Results The model predicts that dilatation of VSMCs beyond a threshold of mechanical failure is sufficient to resolve CVS without damage to the underlying extracellular matrix. Consistent with recent clinical observations, our model predicts that existing stents have the potential to provide sufficient outward force to successfully treat CVS and that success will be dependent on an appropriate match between stent and vessel. Conclusion Mathematical models of CVS can provide insights into biological mechanisms and explore treatment approaches. Improved understanding of the underlying mechanistic processes governing CVS and its mechanical treatment may assist in the development of dedicated stents

The Influence of Mate Choice Motivation on Non-Financial Altruism

Several studies have found that individuals are more altruistic towards potential mates than others, suggesting altruistic behavior may be a mating signal. Much of the literature focuses on financial altruism using economic games, however altruism can also comprise of non-financial acts, which this experiment examined in an attempt to replicate and refine previous findings. A study was conducted with 199 participants, who viewed both high attractive and low attractive opposite-sex images and were asked how likely they would be to altruistically share their research credits with the person in the image, whilst controlling for self-rated attractiveness. The findings suggest that both men and women were more altruistic towards pictures of high attractive than low attractive potential mating partners (Cohen’s d = 0.37). This study therefore partially replicates previous research examining the role of mate choice effects when exploring non-financial altruism