Takayasu arteritis in childhood: retrospective experience from a tertiary referral centre in the United Kingdom.

Takayasu arteritis (TA) is an idiopathic large-vessel vasculitis affecting the aorta and its major branches. Although the disease rarely affects children, it does occur, even in infants. The objective of this study was to evaluate the clinical features, disease activity, treatment and outcome of childhood TA in a tertiary UK centre

Health within the Leeds Roma Community: Final Report

This report illustrates the findings from a piece of health-related research carried out within the Roma community in Leeds in 2012. The research aimed to explore Roma community member’s health status and associated health needs. Based upon data gathered from questionnaires and focus groups with Roma community members and interview data from health professionals working with them, this report presents evidence from the data gathered. The findings reported here relate to the migrant population of Roma resident within the UK, not the indigenous Gypsy and Traveller population of the UK. UK and Irish Travellers, despite sharing common experiences to the Roma in terms of discrimination and exclusion, are a distinct community and are not of Roma origin and thus are not the focus of this report

Health within the Leeds Migrant Roma Community; An Exploration of Health Status and Needs within One UK Area

Existing evidence shows that many Roma communities have received little attention in relation to their health requirements. Evidence illustrates how Roma communities suffer from poorer health and unhealthier living conditions when compared to majority populations, with their poor health closely linked to wider social determinants. This study explored the health status and associated health needs of the Leeds Roma migrant community, a hard to reach and under-explored group across Europe. Questionnaires (n = 70) and focus groups (n = 43) with Roma community members as well as interviews with health professionals (n = 5) working with them were used. The study found language was a key barrier to accessing health care and understanding health messages. Furthermore, participant’s understandings of the health system were hindered by their different experiences within their countries of origin. Self-reports illustrated low mental well-being, high levels of stress and unhealthy lifestyles as common issues. The research also highlighted several wider determinants of health as key concerns within the Roma community including housing, employment opportunities and money. The findings of this study contribute to increasing understandings of this community’s health needs, their support requirements and the barriers faced by them. These need to be considered to inform strategies and ways of working as mechanisms to tackle health inequalities and promote health within this community

Elicitation of expert prior opinion:application to the MYPAN trial in childhood polyarteritis nodosa

Objectives Definitive sample sizes for clinical trials in rare diseases are usually infeasible. Bayesian methodology can be used to maximise what is learnt from clinical trials in these circumstances. We elicited expert prior opinion for a future Bayesian randomised controlled trial for a rare inflammatory paediatric disease, polyarteritis nodosa (MYPAN, Mycophenolate mofetil for polyarteritis nodosa). Methods A Bayesian prior elicitation meeting was convened. Opinion was sought on the probability that a patient in the MYPAN trial treated with cyclophosphamide would achieve disease remission within 6-months, and on the relative efficacies of mycophenolate mofetil and cyclophosphamide. Expert opinion was combined with previously unseen data from a recently completed randomised controlled trial in ANCA associated vasculitis. Results A pan-European group of fifteen experts participated in the elicitation meeting. Consensus expert prior opinion was that the most likely rates of disease remission within 6 months on cyclophosphamide or mycophenolate mofetil were 74% and 71%, respectively. This prior opinion will now be taken forward and will be modified to formulate a Bayesian posterior opinion once the MYPAN trial data from 40 patients randomised 1:1 to either CYC or MMF become available. Conclusions We suggest that the methodological template we propose could be applied to trial design for other rare diseases

Elicitation of expert prior opinion: application to the MYPAN trial in childhood polyarteritis nodosa.

OBJECTIVES: Definitive sample sizes for clinical trials in rare diseases are usually infeasible. Bayesian methodology can be used to maximise what is learnt from clinical trials in these circumstances. We elicited expert prior opinion for a future Bayesian randomised controlled trial for a rare inflammatory paediatric disease, polyarteritis nodosa (MYPAN, Mycophenolate mofetil for polyarteritis nodosa). METHODS: A Bayesian prior elicitation meeting was convened. Opinion was sought on the probability that a patient in the MYPAN trial treated with cyclophosphamide would achieve disease remission within 6-months, and on the relative efficacies of mycophenolate mofetil and cyclophosphamide. Expert opinion was combined with previously unseen data from a recently completed randomised controlled trial in ANCA associated vasculitis. RESULTS: A pan-European group of fifteen experts participated in the elicitation meeting. Consensus expert prior opinion was that the most likely rates of disease remission within 6 months on cyclophosphamide or mycophenolate mofetil were 74% and 71%, respectively. This prior opinion will now be taken forward and will be modified to formulate a Bayesian posterior opinion once the MYPAN trial data from 40 patients randomised 1:1 to either CYC or MMF become available. CONCLUSIONS: We suggest that the methodological template we propose could be applied to trial design for other rare diseases

Health related quality of life measure in systemic pediatric rheumatic diseases and its translation to different languages: An international collaboration

Background: Rheumatic diseases in children are associated with significant morbidity and poor health-related quality of life (HRQOL). There is no health-related quality of life (HRQOL) scale available specifically for children with less common rheumatic diseases. These diseases share several features with systemic lupus erythematosus (SLE) such as their chronic episodic nature, multi-systemic involvement, and the need for immunosuppressive medications. HRQOL scale developed for pediatric SLE will likely be applicable to children with systemic inflammatory diseases. Findings: We adapted Simple Measure of Impact of Lupus Erythematosus in Youngsters (SMILEY) to Simple Measure of Impact of Illness in Youngsters (SMILY-Illness) and had it reviewed by pediatric rheumatologists for its appropriateness and cultural suitability. We tested SMILY-Illness in patients with inflammatory rheumatic diseases and then translated it into 28 languages. Conclusion: SMILY-Illness is a brief, easy to administer and score HRQOL scale for children with systemic rheumatic diseases. It is suitable for use across different age groups and literacy levels. SMILY-Illness with its available translations may be used as useful adjuncts to clinical practice and research

In Vitro and In Vivo Antagonism of a G Protein-Coupled Receptor (S1P3) with a Novel Blocking Monoclonal Antibody

Background: S1P 3 is a lipid-activated G protein-couple receptor (GPCR) that has been implicated in the pathological processes of a number of diseases, including sepsis and cancer. Currently, there are no available high-affinity, subtypeselective drug compounds that can block activation of S1P3. We have developed a monoclonal antibody (7H9) that specifically recognizes S1P3 and acts as a functional antagonist. Methodology/Principal Findings: Specific binding of 7H9 was demonstrated by immunocytochemistry using cells that over-express individual members of the S1P receptor family. We show, in vitro, that 7H9 can inhibit the activation of S1P3mediated cellular processes, including arrestin translocation, receptor internalization, adenylate cyclase inhibiton, and calcium mobilization. We also demonstrate that 7H9 blocks activation of S1P3 in vivo, 1) by preventing lethality due to systemic inflammation, and 2) by altering the progression of breast tumor xenografts. Conclusions/Significance: We have developed the first-reported monoclonal antibody that selectively recognizes a lipidactivated GPCR and blocks functional activity. In addition to serving as a lead drug compound for the treatment of sepsi