Ankylosing spondylitis: genomic and functional characterization of candidate genes and their repercussion in clinical practice

RESUMO: Introdução: A espondilite anquilosante (EA) é uma doença inflamatória crónica caracterizada pela inflamação das articulações sacroilíacas e da coluna. A anquilose progressiva motiva uma deterioração gradual da função física e da qualidade de vida. O diagnóstico e o tratamento precoces podem contribuir para um melhor prognóstico. Neste contexto, a identificação de biomarcadores, assume-se como sendo muito útil para a prática clínica e representa hoje um grande desafio para a comunidade científica. Objetivos: Este estudo teve como objetivos: 1 - caracterizar a EA em Portugal; 2 - investigar possíveis associações entre genes, MHC e não-MHC, com a suscetibilidade e as características fenotípicas da EA; 3 - identificar genes candidatos associados a EA através da tecnologia de microarray. Material e Métodos: Foram recrutados doentes com EA, de acordo com os critérios modificados de Nova Iorque, nas consultas de Reumatologia dos diferentes hospitais participantes. Colecionaram-se dados demográficos, clínicos e radiológicos e colhidas amostras de sangue periférico. Selecionaram-se de forma aleatória, doentes HLA-B27 positivos, os quais foram tipados em termos de HLA classe I e II por PCR-rSSOP. Os haplótipos HLA estendidos foram estimados pelo algoritmo Expectation Maximization com recurso ao software Arlequin v3.11. As variantes alélicas dos genes IL23R, ERAP1 e ANKH foram estudadas através de ensaios de discriminação alélica TaqMan. A análise de associação foi realizada utilizando testes da Cochrane-Armitage e de regressão linear, tal como implementado pelo PLINK, para variáveis qualitativas e quantitativas, respetivamente. O estudo de expressão génica foi realizado por Illumina HT-12 Whole-Genome Expression BeadChips. Os genes candidatos foram validados usando qPCR-based TaqMan Low Density Arrays (TLDAs). Resultados: Foram incluídos 369 doentes (62,3% do sexo masculino, com idade média de 45,4 ± 13,2 anos, duração média da doença de 11,4 ± 10,5 anos). No momento da avaliação, 49,9% tinham doença axial, 2,4% periférica, 40,9% mista e 7,1% entesopática. A uveíte anterior aguda (33,6%) foi a manifestação extra-articular mais comum. Foram positivos para o HLA-B27, 80,3% dos doentes. Os haplótipo A*02/B*27/Cw*02/DRB1*01/DQB1*05 parece conferir suscetibilidade para a EA, e o A*02/B*27/Cw*01/DRB1*08/DQB1*04 parece conferir proteção em termos de atividade, repercussão funcional e radiológica da doença. Três variantes (2 para IL23R e 1 para ERAP1) mostraram significativa associação com a doença, confirmando a associação destes genes com a EA na população Portuguesa. O mesmo não se verificou com as variantes estudadas do ANKH. Não se verificou associação entre as variantes génicas não-MHC e as manifestações clínicas da EA. Foi identificado um perfil de expressão génica para a EA, tendo sido validados catorze genes - alguns têm um papel bem documentado em termos de inflamação, outros no metabolismo da cartilagem e do osso. Conclusões: Foi estabelecido um perfil demográfico e clínico dos doentes com EA em Portugal. A identificação de variantes génicas e de um perfil de expressão contribuem para uma melhor compreensão da sua fisiopatologia e podem ser úteis para estabelecer modelos com relevância em termos de diagnóstico, prognóstico e orientação terapêutica dos doentes. -----------ABSTRACT: Background: Ankylosing Spondylitis (AS) is a chronic inflammatory disorder characterized by inflammation in the spine and sacroiliac joints leading to progressive joint ankylosis and in progressive deterioration of physical function and quality of life. An early diagnosis and early therapy may contribute to a better prognosis. The identification of biomarkers would be helpful and represents a great challenge for the scientific community. Objectives: The present study had the following aims: 1- to characterize the pattern of AS in Portuguese patients; 2- to investigate MHC and non-MHC gene associations with susceptibility and phenotypic features of AS and; 3- to identify candidate genes associated with AS by means of whole-genome microarray. Material and Methods: AS was defined in accordance to the modified New York criteria and AS cases were recruited from hospital outcares patient clinics. Demographic and clinical data were recorded and blood samples collected. A random group of HLA-B27 positive patients and controls were selected and typed for HLA class I and II by PCR-rSSOP. The extended HLA haplotypes were estimated by Expectation Maximization Algorithm using Arlequin v3.11 software. Genotyping of IL23R, ERAP1 and ANKH allelic variants was carried out with TaqMan allelic discrimination assays. Association analysis was performed using the Cochrane-Armitage and linear regression tests as implemented in PLINK, for dichotomous and quantitative variables, respectively. Gene expression profile was carried out using Illumina HT-12 Whole-Genome Expression BeadChips and candidate genes were validated using qPCR-based TaqMan Low Density Arrays (TLDAs). Results: A total of 369 patients (62.3% male; mean age 45.4±13.2 years; mean disease duration 11.4±10.5 years), were included. Regarding clinical disease pattern, at the time of assessment, 49.9% had axial disease, 2.4% peripheral disease, 40.9% mixed disease and 7.1% isolated enthesopathic disease. Acute anterior uveitis (33.6%) was the most common extra-articular manifestation. 80.3% of AS patients were HLA-B27 positive. The haplotype A*02/B*27/Cw*02/DRB1*01/DQB1*05 seems to confer susceptibility to AS, whereas A*02/B*27/Cw*01/DRB1*08/DQB1*04 seems to provide protection in terms of disease activity, functional and radiological repercussion. Three markers (two for IL23R and one for ERAP1) showed significant single-locus disease associations. Association of these genes with AS in the Portuguese population was confirmed, whereas ANKH markers studied did not show an association with AS. No association was seen between non-MHC genes and clinical manifestations of AS. A gene expression signature for AS was established; among the fourteen validated genes, a number of them have a well-documented inflammatory role or in modulation of cartilage and bone metabolism. Conclusions: A demographic and clinical profile of patients with AS in Portugal was established. Identification of genetic variants of target genes as well as gene expression signatures could provide a better understanding of AS pathophysiology and could be useful to establish models with relevance in terms of susceptibility, prognosis, and potential therapeutic guidance.

The impact of Ireland’s current Mental Health Policy on the profile of community mental Health Services

RESUMO: Em 2006, foi aprovada uma nova política governamental para a saúde mental intitulada “Uma Visão para a Mudança”, a qual está neste momento no sétimo ano de implementação. A política descreve um enquadramento para o desenvolvimento e promoção da saúde mental positiva para toda a Comunidade e para a prestação de serviços acessíveis, baseados na comunidade, serviços especializados para pessoas com doença mental. A implementação da política e o tornar a “Vision for Change” uma realidade têm sido problemáticos, com críticas consideráveis por parte dos intervenientes, relativas à lenta e desconexa implementação. Este estudo fornece informação sobre as características dos serviços de três importantes tipos de instituições de saúde mental comunitária a nível nacional, nomeadamente Hospitais de Dia, Centros de Dia e residências comunitárias operantes 24 horas. A pesquisa analisa objetivos e funções, perfis dos pacientes, atividades terapêuticas, a eficácia das redes de comunicação e beneficia da perspectiva dos funcionários sobre o que mudou no terreno ao longo dos últimos sete anos. As questões identificadas a partir das características dos três serviços dizem respeito a todos. Os participantes indicaram que o ethos da recuperação parece ter alcançado um papel mais central no tratamento do paciente na comunidade mas reconheceram que o desafio de integrar os princípios de recuperação na prática clínica se mantém presente. Parece ser reconhecida a importância da planificação do cuidado individual nos serviços comunitários e os entrevistados indicaram que existe um empenho para garantir o envolvimento do usuário do serviço. Há diferenças entre os „pontos de vista do pessoal‟ e os „pontos de vista dos representantes‟ sobre uma série de aspetos da prestação de serviços. Este é o primeiro estudo irlandês deste género a examinar a prestação de serviços das três principais instituições comunitárias de saúde mental num só estudo. Estes serviços representam um enorme investimento em recursos, quer a nível monetário, quer humano. O estudo examinou os desafios e as questões fundamentais que lhe são aplicáveis e que têm impacto nestes três tipos de prestação de serviços. Também forneceu informações sobre os elementos de mudança positiva, os quais se começam a focar lentamente na prestação do serviço, assim como na importância da centralidade do utilizador do serviço e na promoção de um ethos da recuperação.----------ABSTRACT: In 2006, a new Government policy for mental health “A Vision for Change” was endorsed and is currently in the seventh year of implementation. The policy describes a comprehensive framework for building and fostering positive mental health across the entire community and for providing accessible, community based, specialist services for people with mental illness. The implementation of the policy and turning “Vision for Change” into reality has been problematic with considerable criticism from stakeholders concerning slow and disjointed implementation. This study provides information on three key community mental health service settings, namely Day Hospitals, Day Centres and 24 Hour Community Residences at a national level. The research looks at aims and functions, patient profiles, therapeutic activities, effectiveness of key communication networks and gains an insight from staff on what has changed on the ground over the past seven years. Issues identified from the three service settings pertain to all. Participants indicated that the recovery ethos appears to have moved to a more central role in patient care in the community but acknowledged that the challenge of integrating recovery principles in clinical practice remains present. The importance of individual care planning appears to be recognised in community services and respondents indicated that efforts are being made to ensure service user involvement. There were differences between „staff views‟ and „advocate views‟ on a number of aspects of service provision. This is the first Irish study of its kind to examine service provision across the three main community mental health settings in one study. These services represent a huge investment in resources both on a monetary and human level. This study has examined the challenges and key issues which are applicable and impacting on all three types of service provision. It has also provided information on the elements of positive change, which are slowly embedding themselves in service provision such as the importance of the centricity of the service user and the promotion of a recovery ethos.

Investigating the long term planning framework for the Galway Bay community from climate change.

This research looked at the scientific evidence available on climate change and in particular, projections on sea level rise which ranged from 0.5m to 2m by the end of the century. These projections were then considered in an Irish context. A review of current policy in Ireland revealed that there was no dedicated Government policy on climate change or coastal zone management. In terms of spatial planning policy, it became apparent that there was little or no guidance on climate change either at a national, regional or local level. Therefore, to determine the likely impacts of sea level rise in Ireland based on current spatial planning practice and policy, a scenario-building exercise was carried out for two case study areas in Galway Bay. The two case study areas were: Oranmore, a densely populated town located to the east of Inner Galway Bay; and Tawin Island, a rural dispersed community, located to the south east of Inner Galway Bay. A ‘best’ and ‘worse’ case scenario was envisaged for both areas in terms of sea level rise. In the absence of specific climate change policies it was projected that in the ‘best’ case scenario of 0.5m sea level rise, Tawin Island would suffer serious and adverse impacts while Oranmore was likely to experience slight to moderate impacts. However, in the ‘worse’ case scenario of a 2m sea level rise, it was likely that Tawin Island would be abandoned while many houses, businesses and infrastructure built within the floodplain of Oranmore Bay would be inundated and permanently flooded. In this regard, it was the author’s opinion that a strategic and integrated climate change policy and adaptation plan is vital for the island of Ireland that recognises the importance of integrated land use and spatial planning in terms of mitigation and adaptation to climate change.

IPH response to Health and Social Care Board and Public Health Agency Community Development Strategy

The Health and Social Care Board (HSCB) and the Public Health Agency (PHA) launched a new Community Development Strategy for public consultation.  The HSCB and PHA want to see strong, resilient communities where everyone has good health and wellbeing, places where people look out for each other and have community pride in where they live. The HSCB and PHA seek a number of benefits from implementing this strategy including; a reduction in health and wellbeing inequalities, which also means addressing the social factors that affect health; strengthening partnership working with service users, the community and voluntary sectors and other organisations; strengthening families and communities; supporting volunteering and making best use of our resources. Key points from the IPH summary include IPH welcome the Community Development Strategy as an approach to enhance health and wellbeing and tackle health inequalities in Northern Ireland.   IPH recommend the current three strategy documents (Full and summary versions and the Performance Management Framework) are merged into one document for greater clarity. Reference to the Performance Management Framework is required in the main body of the text is to ensure good practice is implemented. IPH welcome the focus on tackling health inequalities using community development approaches however the contribution of community development approaches needs to be highlighted. HIA is a tool to support community engagement and provides a mechanism for HSCB and PHA to support the implementation of this strategy.

Causeway HSS Trust - Public Health Practice Development Pilot Report (PDF 257 KB)

Final Causeway HSS Trust Report on its Public Health Practice Development Pilot, part of the Department's redesign of community nursing project

Our Duty to Care : the principles of good practice for the protection of children and young people

This document, which has been named Our Duty to Care, is aimed at community and voluntary organisations of any size or type that provide services for children. It offers guidance on the promotion of child welfare and the development of safe practices in work with children. It also gives information on how to recognise signs of child abuse and the correct steps to take within organisations if it is suspected, witnessed or disclosed. The process of reporting suspected or actual child abuse to the health board is described step by step, and guidance is given on how to handle sensitive areas. Download document here

Community Development Health Network

The Community Development and Health Network (CDHN) aim to end health inequalities using a community development approach - campaigning, influencing policy and developing best practice work which shows that communities, both geographical and of interest & identity, can define their own health needs and design and implement preventative and radical solutions. It believes that health is affected by more than access to health services, individual lifestyle choices and our own genetic make-up. These other factors can include poverty, the environment, education, living and working conditions, housing, access to food and social and community networks. This resource is part of the Public Health Advocacy Website Collection.

Good Practice Guides

This series of Good Practice Guides is designed to share important information about health inequalities and some of the evidence-based measures that can be taken to reduce the stark differences in health and wellbeing within populations. It is recognised that leadership and coordinated, effective action at a number of levels can reduce this gap. Ensuring concerted, evidence-based action on health and wellbeing inequalities demands the efforts of government, statutory organisations and the community, voluntary and private sectors. The Good Practice Guides were developed to inform and support joined-up working across these sectors. It is known that health inequalities are closely linked with degrees of social disadvantage and with the unequal distribution of power, income, goods and services. According to the World Health Organization, there are also powerful social and psychological factors and life circumstances that can serve to compound health and wellbeing inequalities. The topics included in the Good Practice Guide series reflect the wider determinants of health and the range of approaches necessary to reduce health inequalities. This first set of three guides is designed, in part, to test their usefulness. There are many other issues and areas where evidence of what works may be needed. It is envisaged that further guides will follow on other issues. All of the guides will be kept under review and amended in light of experience.

Planning Practice Guidance

The Department for Communities and Local Government has published National Planning Practice Guidance which recognises the importance of local infrastructure planning in the development of healthy communities. The guidance supports the National Planning Policy Framework and now includes a section on health and wellbeing. This guidance sets out the government’s planning policies for England and how these are expected to be applied by local authorities. A significant development in the guidance is the recognition of the important role the planning system can play in facilitating social interaction and creating healthy, inclusive communities. Local planning authorities should ensure that health and wellbeing, and health infrastructure are considered in local and neighbourhood plans and in planning decision making.

A good practice guide for school food initiatives

This Guide was developed through extensive consultation with schools, community groups, health professionals and suppliers who are currently involved in providing food in school. Research was also conducted on approaches in Northern Ireland and in other countries. Finally, we consulted with Government and social partner stakeholders at national level to get their views as to the main issues to be addressed.

Good Practice Guides: Reducing young people's drinking

Actions to tackle health inequalities demand the efforts of government, statutory organisations, and community, voluntary and private sectors. This Good Practice Guide to reducing young people's drinking is one of a series designed to capture information about health inequalities and highlight evidence-based interventions and key actions for improvement across sectors.This resource was contributed by The National Documentation Centre on Drug Use.

Portland Row Community Café

Our Vision is that each individual accessing these service’s be provided with a choice of affordable, nutritious meals in a safe, warm and attractive environment.  We achieve this through the following best practice standards: – Quality service – Maintaining a high quality environment – The highest quality food standard (with choice of meals) Cafes are open to the public from 8am serving breakfast until 11.30 and lunch/dinner from 12-4pm. (open Monday – Friday) Telephone: (01) 8555577 Initiative Type Community Cafés Location Dublin 1

Holles Row Community Café

Our Vision is that each individual accessing these service’s be provided with a choice of affordable, nutritious meals in a safe, warm and attractive environment.  We achieve this through the following best practice standards: – Quality service – Maintaining a high quality environment – The highest quality food standard (with choice of meals) Cafes are open to the public from 8am serving breakfast until 11.30 and lunch/dinner from 12-4pm.(open Monday - Saturday) Telephone: (01) 5515916 Initiative Type Community Cafés Location Dublin 2

Substance Misuse Among People Over 55 - Perspectives from the Community and Voluntary sector in Belfast

The Belfast Health Development Unit (BHDU) was established as a Ministerial priority in March 2010, co-locating staff from The Public Health Agency (PHA), Belfast Health and Social Care Trust (BHSCT) and Belfast City Council (BCC). One of the strategic priorities for the BHDU is: an integrated approach to planning and delivery of services for older people in the city.The PHA and the BHDU had identified a need to examine the extent of substance misuse issues within the older population of the city of Belfast and to explore early intervention programmes targeting this population. It is envisioned that this piece of work will inform and support the Belfast Healthy Ageing Strategic Partnership on older people and its multi-sectoral action plan and will influence the work and priorities of the Belfast Strategic Partnership and its constituent stakeholders in taking drug and alcohol work forward in Belfast.The aim of this research was to review knowledge, awareness and evidence of the impact of substance misuse on the older population (aged 55+) and to review good practice in reducing substance related harm within this population which has been done by undertaking a review of available research, data and information sources. However, the main focus of the research involved consulting with a broad range of community and voluntary sector organisations working in the Belfast area to assess their views and perceptions of the prevalence and extent of substance misuse within the older population and the services currently in place to address this issue.�

The development of the Quality Indicator for Rehabilitative Care (QuIRC): a measure of best practice for facilities for people with longer term mental health problems

BACKGROUND: Despite the progress over recent decades in developing community mental health services internationally, many people still receive treatment and care in institutional settings. Those most likely to reside longest in these facilities have the most complex mental health problems and are at most risk of potential abuses of care and exploitation. This study aimed to develop an international, standardised toolkit to assess the quality of care in longer term hospital and community based mental health units, including the degree to which human rights, social inclusion and autonomy are promoted. METHOD: The domains of care included in the toolkit were identified from a systematic literature review, international expert Delphi exercise, and review of care standards in ten European countries. The draft toolkit comprised 154 questions for unit managers. Inter-rater reliability was tested in 202 units across ten countries at different stages of deinstitutionalisation and development of community mental health services. Exploratory factor analysis was used to corroborate the allocation of items to domains. Feedback from those using the toolkit was collected about its usefulness and ease of completion. RESULTS: The toolkit had excellent inter-rater reliability and few items with narrow spread of response. Unit managers found the content highly relevant and were able to complete it in around 90 minutes. Minimal refinement was required and the final version comprised 145 questions assessing seven domains of care. CONCLUSIONS: Triangulation of qualitative and quantitative evidence directed the development of a robust and comprehensive international quality assessment toolkit for units in highly variable socioeconomic and political contexts