Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

Oxidative stress on mammalian cell cultures during recombinant protein expression

When the cell is under stress arising from oxidation, heat, infection, toxic contamination or any other stressful condition, proteins may unfold and expose residues in their structure that under normal physiological conditions are hidden and shielded from chemical reactions. In this licentiate thesis the effects of general oxidative stress on the production of recombinant protein by mammalian cells are considered. The work consisted of a broad literary review focused on oxidative stress and cellular response, cross-protection, gene regulation in response to oxidative stress and the relevance of this to pharmaceutical industry. A series of oxidative stressors is described and examined for experimental use. Experimental cultivation and maintenance of several mammalian cell lines was performed and several candidate stressing agents were proven on these cell lines. Menadione was selected as a powerful and consistent stressing agent, and so several experiments were performed where batches of cells were exposed to varying degrees of stress. The performance of the cells in regard to production of recombinant protein was then examined by ELISA, showing a strong downregulation of production under stressful conditions. Recombinant protein taken from stressed and control cultures is then isolated, purified and examined with MALDI-TOF spectrometry. Finally mRNA from the cells is isolated and examined by means of microarray. Genes that are significantly regulated are examined, and those genes that may have significance in the area of stress regulation and reaction are listed. The results of the study show that mitomycin C exerts oxidative stress on the industrial protein expressing mammalian cell lines tested

Gathering Customer Insights from Social Media: The Impact on New Product Development and Supply Chain Design

The purpose of this study is to understand what insights could be gathered from customer posts on social media that would benefit operations and supply chains. This research analyses social media posts to uncover the themes that could be related to new product development (NPD) and the design of ‘end-to-end’ supply chains. Consumer posts will be analysed from social media platforms of two well-known multinational food and beverage companies. Social media analytics can be used to gather knowledge and intelligence for organisations aiming to have consumer-centric supply chains

Augmented Reality and User Behaviour: A Socially Practised Affordance Perspective

This paper explores Augmented Reality (AR) user behaviour, by focusing on user experiences and expectations and the role these play in the context of AR adoption rates. It focuses on the usability of AR and underlying motives that drive users to adopt or reject AR technology. To achieve this aim, multiple sources and qualitative methods, e.g., online reviews and users’ reflections, have been used as they can give context-specific and rich understanding to help inform how individuals make use of AR apps. This study sheds new light on how AR apps, users, and social practices are interconnected by integrating affordance and social practice theories. Affordance theory has been used through the process of the ‘walkthrough technique’ to investigate potential affordances arising from the application of AR technologies in the service sector. Our preliminary findings identified ten AR App affordances that potential users might actualise where there is coherence between specific Social Practice theory (SPT) elements. The next step of this research is to apply SPT elements (meanings, materials, and competency), to better understand three major characteristics of usability (interactivity, compatibility, and credibility) associated with current AR apps that might promote and/or prevent potential users from actualising their affordances