A multicentre non-blinded randomised controlled trial to assess the impact of regular early specialist symptom control treatment on quality of life in malignant mesothelioma (RESPECT-MESO): Study protocol for a randomised controlled trial

Background: Malignant pleural mesothelioma is an incurable cancer caused by exposure to asbestos. The United Kingdom has the highest death rate from mesothelioma in the world and this figure is increasing. Median survival is 8 to 12 months, and most patients have symptoms at diagnosis. The fittest patients may be offered chemotherapy with palliative intent. For patients not fit for systemic anticancer treatment, best supportive care remains the mainstay of management. A study from the United States examining advanced lung cancer showed that early specialist palliative care input improved patient health related quality of life and depression symptoms 12 weeks after diagnosis. While mesothelioma and advanced lung cancer share many symptoms and have a poor prognosis, oncology and palliative care services in the United Kingdom, and many other countries, vary considerably compared to the United States. The aim of this trial is to assess whether regular early symptom control treatment provided by palliative care specialists can improve health related quality of life in patients newly diagnosed with mesothelioma. Methods: This multicentre study is an non-blinded, randomised controlled, parallel group trial. A total of 174 patients with a new diagnosis of malignant pleural mesothelioma will be minimised with a random element in a 1:1 ratio to receive either 4weekly regular early specialist symptom control care, or standard care. The primary outcome is health related quality of life for patients at 12 weeks. Secondary outcomes include health related quality of life for patients at 24 weeks, carer health related quality of life at 12 and 24 weeks, patient and carer mood at 12 and 24 weeks, overall survival and analysis of healthcare utilisation and cost. Discussion: Current practice in the United Kingdom is to involve specialist palliative care towards the final weeks or months of a life-limiting illness. This study aims to investigate whether early, regular specialist care input can result in significant health related quality of life gains for patients with mesothelioma and if this change in treatment model is cost-effective. The results will be widely applicable to many institutions and patients both in the United Kingdom and internationally. Trial registration: Current controlled trials ISRCTN18955704.Date ISRCTN assigned: 31 January 2014

Randomised placebo-controlled cross-over study examining the role of anamorelin in mesothelioma (The ANTHEM study): Rationale and protocol

Introduction Cachexia is common in malignant mesothelioma (MM); half of patients have malnutrition and low skeletal muscle mass. Malnourished patients have worse quality of life (QoL). Weight loss is strongly associated with poor survival. Anamorelin is an oral ghrelin receptor agonist that improves appetite, body weight and QoL in advanced cancer. The aim of this study is to examine the efficacy of anamorelin in improving appendicular skeletal muscle mass (ASM) and patient-reported outcomes in patients with MM with cachexia. Methods and analysis A single-centre, phase II, randomised, placebo-controlled cross-over pilot study with 28-day treatment periods and 3-day washout. Forty patients will be randomised. Primary outcome is change in ASM relative to height measured by dual energy X-ray absorptiometry at end of period 1. Secondary outcomes include cancer-specific and cachexia-related QoL, objective physical activity, dietary intake and adverse events. Eligible patients will have confirmed MM, Eastern Cooperative Oncology Group 0-2, expected survival \u3e 3 months and cachexia (defined as \u3e 5% weight loss in 6 months or body mass index \u3c 20 kg/m 2 with weight loss \u3e2%). Ethics and dissemination Ethical approval has been granted. Results will be reported in peer-reviewed publications. Trial registration number Australian New Zealand Clinical Trials Registry (U1111-1240-6828). © © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ

Autoantibodies and cancer among asbestos-exposed cohorts in Western Australia

Asbestos exposure is associated with many adverse health conditions including malignant mesothelioma and lung cancer as well as production of autoantibodies. Autoantibodies may serve as biomarkers for asbestos exposure in patients with cancer, and autoimmune dysfunction has been linked to increased rates of various cancers. The aim of this study was to examine the hypothesis that autoantibodies are more frequent in asbestos-exposed individuals with either lung cancer or mesothelioma than those without these conditions. Asbestos-exposed individuals from Western Australia who had lung cancer (n = 24), malignant mesothelioma (n = 24), or no malignancy (n = 51) were tested for antinuclear autoantibodies (ANA) using indirect immunofluorescence and specific extractable nuclear autoantibodies (ENA) employing a multiplexed addressable laser bead immunoassay. Contrary to the hypothesis, data demonstrated that individuals without malignancy were more likely to be positive for ANA compared to those with cancer. However, autoantibodies to histone and Ro-60 were found to be associated with lung cancer. These results support a possible predictive value for specific autoantibodies in the early detection of lung cancer and/or in our understanding of the role of autoimmune processes in cancer. However, further studies are needed to identify specific target antigens for the antibodies

Development of a video-based education and process change intervention to improve advance cardiopulmonary resuscitation decision-making

Background: Advance cardiopulmonary resuscitation (CPR) decision-making and escalation of care discussions are variable in routine clinical practice. We aimed to explore physician barriers to advance CPR decision-making in an inpatient hospital setting and develop a pragmatic intervention to support clinicians to undertake and document routine advance care planning discussions. Methods: Two focus groups, which involved eight consultants and ten junior doctors, were conducted following a review of the current literature. A subsequent iterative consensus process developed two intervention elements: (i) an updated ‘Goals of Patient Care’ (GOPC) form and process; (ii) an education video and resources for teaching advance CPR decision-making and communication. A multidisciplinary group of health professionals and policymakers with experience in systems development, education and research provided critical feedback. Results: Three key themes emerged from the focus groups and the literature, which identified a structure for the intervention: (i) knowing what to say; (ii) knowing how to say it; (iii) wanting to say it. The themes informed the development of a video to provide education about advance CPR decision-making framework, improving communication and contextualising relevant clinical issues. Critical feedback assisted in refining the video and further guided development and evolution of a medical GOPC approach to discussing and recording medical treatment and advance care plans. Conclusion: Through an iterative process of consultation and review, video-based education and an expanded GOPC form and approach were developed to address physician and systemic barriers to advance CPR decisionmaking and documentation. Implementation and evaluation across hospital settings is required to examine utility and determine effect on quality of care

Interactions between Glucocorticoid Treatment and Cis-Regulatory Polymorphisms Contribute to Cellular Response Phenotypes

Glucocorticoids (GCs) mediate physiological responses to environmental stress and are commonly used as pharmaceuticals. GCs act primarily through the GC receptor (GR, a transcription factor). Despite their clear biomedical importance, little is known about the genetic architecture of variation in GC response. Here we provide an initial assessment of variability in the cellular response to GC treatment by profiling gene expression and protein secretion in 114 EBV-transformed B lymphocytes of African and European ancestry. We found that genetic variation affects the response of nearby genes and exhibits distinctive patterns of genotype-treatment interactions, with genotypic effects evident in either only GC-treated or only control-treated conditions. Using a novel statistical framework, we identified interactions that influence the expression of 26 genes known to play central roles in GC-related pathways (e.g. NQO1, AIRE, and SGK1) and that influence the secretion of IL6

Older People’s Needs and Opportunities for Assistive Technologies

Older adults experience a disconnect between their needs and adoption of technologies that have potential to assist and to support more independent living. This paper reviewed research that links people’s needs with opportunities for assistive technologies. It searched 13 databases identifying 923 papers with 34 papers finally included for detailed analysis. The research papers identified needs in the fields of health, leisure, living, safety, communication, family relationship and social involvement. Amongst these, support for activities of daily living category was of most interest. In specific sub-categories, the next most reported need was assistive technology to support walking and mobility followed by smart cooking/kitchen technology and assistive technology for social contacts with family member/other people. The research aimed to inform a program of research into improving the adoption of technologies where they can ameliorate identified needs of older people

The continual search for ideal biomarkers for mesothelioma: The hurdles

Malignant pleural mesothelioma (MPM) is an aggressive tumour predominately caused by exposure to asbestos. Asbestos consumption continues to increase worldwide, particularly among developing nations in Asia. Although actual data on mesothelioma incident rates are unavailable from several of the world’s largest asbestos consuming nations including Russia, China and India (1), rates are predicted to surge in Asia reflecting the increased use of asbestos (2). Presently one person dies every four hours from mesothelioma in the United Kingdom

Up-regulation of the extrinsic coagulation pathway in acute asthma-A case Study

Introduction. In the normal airway, the hemostatic balance is antithrombotic and favors fibrinolysis. Acute asthma is associated with inflammatory cell infiltrate and plasma exudation in the airways. Postmortem specimens following status asthmaticus suggest a role for the activation of the extrinsic coagulation cascade and intraluminal fibrin formation. The authors report a chance observation of fibrin formation in the airways of a patient with moderate asthma 5 days before a severe exacerbation requiring hospital admission. Methods. Alpha-2 macroglobulin, an index of plasma leakage, coagulation factors, and D-dimers were measured by enzyme-linked immunosorbent assay (ELISA) in hypertonic saline-induced sputum, as part of a study into airway repair in stable asthma. All subjects were required to have stable symptoms and measures of asthma prior to sampling. Results. The subject's baseline forced expiratory volume in one second (FEV1) was 94 predicted and fraction of exhaled nitric oxide (FeNO) level was 30 ppb prior to sputum induction. Differential sputum cell count revealed an airways neutrophilia (neutrophils 81.1, eosinophils 0.19). D-dimers were 70-fold and 22-fold higher than the median value for patients with stable moderate and severe asthma, respectively. Plasma exudation was 42-fold higher than in stable moderate asthma, but on a par with levels found in severe stable asthma, and locally produced coagulation factors may therefore be involved. Levels of fibrinogen, plasminogen, plasminogen activator inhibitor (PAI)-1 and thrombin-activatable fibrinolysis inhibitor (TAFI) were all at least an order of magnitude higher than those seen in stable moderate or severe asthma. Conclusions. Acute exacerbation of moderate asthma appears to be associated with a shift to a profibrinogenic, possibly antifibrinolytic, environment in the airways. © 2010 Informa Healthcare USA, Inc