Joint Commissioning Plan of the Health and Social Care Board and the Public Health Agency: 2010-2011

Legislation enacted on 1 April 2009 created a new Commissioning system with the establishment of a region-wide Health and Social Care Board, including 5 Local Commissioning Groups (LCGs), and a Public Health Agency. In line with Departmental direction and guidance the objectives of the new commissioning arrangements were to: - Approach the future delivery of Health and Social Care from a region-wide perspective focused on outcomes. - Ensure local sensitivity through the creation of five Local Commissioning Groups reflective of their areas. - Give appropriate weight to the public health agenda to ensure that commissioning reflects the drive to reduce health inequalities in our society and works in partnership with others to improve health and wellbeing. In this regard the legislation signalled a new way forward which would first be expressed in a Commissioning Plan for 2010/11 and beyond. This plan outlines how the Health and Social Care Board and the Public Health Agency are approaching that task. It is our aim that this plan is straightforward and written in a manner which will encourage public engagement and understanding. We wish to show clearly how the commissioning task is to be approached and to signal the decisions necessary to ensure the maintenance of a health and social care system in Northern Ireland which responds to the population it serves.

Health Promoting Hospitals and Health Services network in Northern Ireland - Update report 2008-2009

The third annual report from the World Health Organisation’s (WHO) Healthy Promoting Hospitals (HPH) and Healthy Services network highlights a rich selection of the innovative developments and team-working achievements across services in Northern Ireland. The report provides a platform to showcase the five Health and Social Care Trusts and Cooperation and Working Together (CAWT)’s commitment to health and wellbeing to the population and shows how hospitals can have an impact on the determinants of health as they are explained in the context of people’s daily lives. The Public Health Agency continues to support the network both locally and nationally as this report gives hospitals and other health services a chance to be recognised as health enhancing organisations. The HPH and Healthy Services concept recognises that a hospital is much more than a place where people go for treatment and cure from sickness. It identifies the huge opportunities for the promotion of good health among the many thousands of people, patients and staff who have daily contact with hospitals and also with the wider community which the hospitals serve. In recent years much progress has been made in addressing health improvement in the hospital setting by looking at the broader cultural, social and environmental issues which can support health and wellbeing. The Northern Ireland HPH network continues to embrace change across services and to drive action to ensure that health improvement is embedded in the new health and social care systems.

Performance of an ICU ventilator and two turbin-based ventilators dedicated to non invasive ventilation (NIV) in simulated high inspiratory effort and rate: a NIV-bench-study.

INTRODUCTION. The role of turbine-based NIV ventilators (TBV) versus ICU ventilators with NIV mode activated (ICUV) to deliver NIV in case of severe respiratory failure remains debated. OBJECTIVES. To compare the response time and pressurization capacity of TBV and ICUV during simulated NIV with normal and increased respiratory demand, in condition of normal and obstructive respiratory mechanics. METHODS. In a two-chamber lung model, a ventilator simulated normal (P0.1 = 2 mbar, respiratory rate RR = 15/min) or increased (P0.1 = 6 mbar, RR = 25/min) respiratory demand. NIV was simulated by connecting the lung model (compliance 100 ml/mbar; resistance 5 or 20 l/mbar) to a dummy head equipped with a naso-buccal mask. Connections allowed intentional leaks (29 ± 5 % of insufflated volume). Ventilators to test: Servo-i (Maquet), V60 and Vision (Philips Respironics) were connected via a standard circuit to the mask. Applied pressure support levels (PSL) were 7 mbar for normal and 14 mbar for increased demand. Airway pressure and flow were measured in the ventilator circuit and in the simulated airway. Ventilator performance was assessed by determining trigger delay (Td, ms), pressure time product at 300 ms (PTP300, mbar s) and inspiratory tidal volume (VT, ml) and compared by three-way ANOVA for the effect of inspiratory effort, resistance and the ventilator. Differences between ventilators for each condition were tested by oneway ANOVA and contrast (JMP 8.0.1, p\0.05). RESULTS. Inspiratory demand and resistance had a significant effect throughout all comparisons. Ventilator data figure in Table 1 (normal demand) and 2 (increased demand): (a) different from Servo-i, (b) different from V60.CONCLUSION. In this NIV bench study, with leaks, trigger delay was shorter for TBV with normal respiratory demand. By contrast, it was shorter for ICUV when respiratory demand was high. ICUV afforded better pressurization (PTP 300) with increased demand and PSL, particularly with increased resistance. TBV provided a higher inspiratory VT (i.e., downstream from the leaks) with normal demand, and a significantly (although minimally) lower VT with increased demand and PSL.

Improving Outcomes: A Strategy for Cancer: Third Annual Report

The third annual Improving Outcomes: A Strategy for Cancer report, in partnership with NHS England and Public Health England, reports on: significant developments in cancer screening - particularly on the first phase of introducing Bowel Scope Screening (BSS) activity to promote earlier diagnosis of symptomatic cancers through the Be Clear on Cancer campaigns and the associated work with primary and secondary care progress in ensuring better access for all to the best possible treatment significant developments in the collection and reporting of new datasets and the analysis of information to drive improvements and inform patients

The fine-scale architecture of structural variants in 17 mouse genomes.

BACKGROUND: Accurate catalogs of structural variants (SVs) in mammalian genomes are necessary to elucidate the potential mechanisms that drive SV formation and to assess their functional impact. Next generation sequencing methods for SV detection are an advance on array-based methods, but are almost exclusively limited to four basic types: deletions, insertions, inversions and copy number gains. RESULTS: By visual inspection of 100 Mbp of genome to which next generation sequence data from 17 inbred mouse strains had been aligned, we identify and interpret 21 paired-end mapping patterns, which we validate by PCR. These paired-end mapping patterns reveal a greater diversity and complexity in SVs than previously recognized. In addition, Sanger-based sequence analysis of 4,176 breakpoints at 261 SV sites reveal additional complexity at approximately a quarter of structural variants analyzed. We find micro-deletions and micro-insertions at SV breakpoints, ranging from 1 to 107 bp, and SNPs that extend breakpoint micro-homology and may catalyze SV formation. CONCLUSIONS: An integrative approach using experimental analyses to train computational SV calling is essential for the accurate resolution of the architecture of SVs. We find considerable complexity in SV formation; about a quarter of SVs in the mouse are composed of a complex mixture of deletion, insertion, inversion and copy number gain. Computational methods can be adapted to identify most paired-end mapping patterns.

Addiction and Change: How Aaddictions Develop and Addicted People Recover

Contents: 1. Models of addiction and change 2. The process of human intentional behavior change 3. The well maintained addiction : an ending and a beginning 4. Exploring precontemplation, contemplation, and preparation stages of becoming addicted 5. Repeated and regular use : moving from preparation to action on the road to addiction 6. Precontemplation for recovery : cultivating seeds for change 7. The decision to change : moving from the contemplation to the preparation stage of recovery 8. Preparing for action : creating a plan 9. Taking action to change an addiction 10. The long haul : well-maintained recovery 11. Prevention : interfering with the process of becoming addicted 12. Designing interventions for recovery 13. Research on addiction and change. "The stages-of-change model has become widely known as a framework for conceptualizing recovery. Less well known are the processes that drive movement through the stages or how the stages apply to becoming addicted. From Carlo DiClemente, codeveloper of the Transtheoretical Model, this book offers a panoramic view of the entire continuum of addictive behavior change. Illuminated is the common path that individuals travel as they establish and reinforce new patterns of behavior, whether they are developing an addiction or struggling to free themselves from one, and regardless of the specific addictive behavior. Presenting cutting-edge research with significant clinical implications, the book addresses crucial questions of why, when, and how to intervene to bolster recovery in those already addicted and reach out effectively to people at risk. It is essential reading for clinicians, prevention specialists, and policymakers." [from Book Jacket]This resource was contributed by The National Documentation Centre on Drug Use.

Sleep loss reduces the DNA-binding of BMAL1, CLOCK, and NPAS2 to specific clock genes in the mouse cerebral cortex.

We have previously demonstrated that clock genes contribute to the homeostatic aspect of sleep regulation. Indeed, mutations in some clock genes modify the markers of sleep homeostasis and an increase in homeostatic sleep drive alters clock gene expression in the forebrain. Here, we investigate a possible mechanism by which sleep deprivation (SD) could alter clock gene expression by quantifying DNA-binding of the core-clock transcription factors CLOCK, NPAS2, and BMAL1 to the cis-regulatory sequences of target clock genes in mice. Using chromatin immunoprecipitation (ChIP), we first showed that, as reported for the liver, DNA-binding of CLOCK and BMAL1 to target clock genes changes in function of time-of-day in the cerebral cortex. Tissue extracts were collected at ZT0 (light onset), -6, -12, and -18, and DNA enrichment of E-box or E'-box containing sequences was measured by qPCR. CLOCK and BMAL1 binding to Cry1, Dbp, Per1, and Per2 depended on time-of-day, with maximum values reached at around ZT6. We then observed that SD, performed between ZT0 and -6, significantly decreased DNA-binding of CLOCK and BMAL1 to Dbp, consistent with the observed decrease in Dbp mRNA levels after SD. The DNA-binding of NPAS2 and BMAL1 to Per2 was also decreased by SD, although SD is known to increase Per2 expression in the cortex. DNA-binding to Per1 and Cry1 was not affected by SD. Our results show that the sleep-wake history can affect the clock molecular machinery directly at the level of chromatin binding thereby altering the cortical expression of Dbp and Per2 and likely other targets. Although the precise dynamics of the relationship between DNA-binding and mRNA expression, especially for Per2, remains elusive, the results also suggest that part of the reported circadian changes in DNA-binding of core clock components in tissues peripheral to the suprachiasmatic nuclei could, in fact, be sleep-wake driven.

Whole-person care: from rhetoric to reality. Achieving parity between mental and physical health.

The report presents evidence on a range of factors affecting disparity between mental and physical health, and includes case studies and examples of good practice to illustrate some of the key issues and solutions. It should be seen as the first stage of an on-going process over the next 5"10 years that will deliver parity for mental health and make whole-person care a reality. It builds on the Implementation Framework for the Mental Health Strategy in providing further analysis of why parity does not currently exist, and the actions required to bring it about. A parity approach should enable NHS and local authority health and social care services to provide a holistic, whole person response to each individual, whatever their needs, and should ensure that all publicly funded services, including those provided by private organisations, give people's mental health equal status to their physical health needs. Central to this approach is the fact that there is a strong relationship between mental health and physical health, and that this influence works in both directions. Poor mental health is associated with a greater risk of physical health problems, and poor physical health is associated with a greater risk of mental health problems. Mental health affects physical health and vice versa. The report makes a series of key recommendations for the UK government, policy-makers and health professionals. Recommendations include: The government and the NHS Commissioning Board should work together to give people equivalent levels of access to treatment for mental health problems as for physical health problems, agreed standards for waiting times, and agreed standards for emergency/crisis mental healthcare. Action to promote good mental health and to address mental health problems needs to start at the earliest stage of a person's life and continue throughout the life course. Preventing premature mortality " there must be a major focus on improving the physical health of people with mental health problems. Public health programmes must include a focus on the mental health dimension of issues commonly considered as physical health concerns, such as smoking, obesity and substance misuse. Commissioners need to regard liaison doctors (who work across physical and mental healthcare) as an absolute necessity rather than an optional luxury. NHS and social care commissioners should commission liaison psychiatry and liaison physician services to drive a whole-person, integrated approach to healthcare in acute, secure, primary care and community settings, for all ages. Mental health services and mental health research must receive funding that reflects the prevalence of mental health problems and their cost to society. Mental illness is responsible for the largest proportion of the disease burden in the UK (22.8%), larger than that of cardiovascular disease (16.2%) or cancer (15.9%). However, only 11% of the NHS budget was spent on NHS services to treat mental health problems for all ages during 2010/11. Culture, attitudes and stigma " zero-tolerance policies in relation to discriminatory attitudes or behaviours should be introduced in all health settings to help combat the stigma that is still attached to mental illness within medicine. Political and managerial leadership is required at all levels. There should be a mechanism at national level for driving a parity approach to relevant policy areas across government; all local councils should have a lead councillor for mental health; all providers of specialist mental health services should have a board-level lead for physical health and all providers of physical healthcare services should have a board-level lead for mental health. The General Medical Council (GMC) and Nursing and Midwifery Council (NMC) should consider how medical and nursing study and training could give greater emphasis to mental health. Mental and physical health should be integrated within undergraduate medical education.This resource was contributed by The National Documentation Centre on Drug Use.

Public Policy and Ageing in Northern Ireland: Identifying Levers for Change

Public Policy and Ageing in Northern Ireland: Identifying Levers for Change Judith Cross, Policy Officer with the Centre for Ageing Research Development in Ireland (CARDI)��������Introduction Identifying a broad range of key public policy initiatives as they relate to age can facilitate discussion and create new knowledge within and across government to maximise the opportunities afforded by an ageing population. This article looks at how examining the current public policy frameworks in Northern Ireland can present opportunities for those working in this field for the benefit of older people. Good policy formulation needs to be evidence-based, flexible, innovative and look beyond institutional boundaries. Bringing together architects and occupational therapists, for example, has the potential to create better and more effective ways relevant to health, housing, social services and government departments. Traditional assumptions of social policy towards older people have tended to be medically focused with an emphasis on care and dependency. This in turn has consequences for the design and delivery of services for older people. It is important that these assumptions are challenged as changes in thinking and attitudes can lead to a redefinition of ageing, resulting in policies and practices that benefit older people now and in the future. Older people, their voices and experiences, need to be central to these developments. The Centre for Ageing Research and Development in Ireland The Centre for Ageing Research and Development in Ireland (CARDI) (1) is a not for profit organisation developed by leaders from the ageing field across Ireland (North and South) including age sector focused researchers and academics, statutory and voluntary, and is co-chaired by Professor Robert Stout and Professor Davis Coakley. CARDI has been established to provide a mechanism for greater collaboration among age researchers, for wider dissemination of ageing research information and to advance a research agenda relevant to the needs of older people in Ireland, North and South. Operating at a strategic level and in an advisory capacity, CARDI�۪s work focuses on promoting research co-operation across sectors and disciplines and concentrates on influencing the strategic direction of research into older people and ageing in Ireland. It has been strategically positioned around the following four areas: Identifying and establishing ageing research priorities relevant to policy and practice in Ireland, North and South;Promoting greater collaboration and co-operation on ageing research in order to build an ageing research community in Ireland, North and South;Stimulating research in priority areas that can inform policy and practice relating to ageing and older people in Ireland, North and South;Communicating strategic research issues on ageing to raise the profile of ageing research in Ireland, North and South, and its role in informing policy and practice. Context of Ageing in Ireland Ireland �۪s population is ageing. One million people aged 60 and over now live on the island of Ireland. By 2031, it is expected that Northern Ireland�۪s percentage of older people will increase to 28% and the Republic of Ireland�۪s to 23%. The largest increase will be in the older old; the number aged 80+ is expected to triple by the same date. However while life expectancy has increased, it is not clear that life without disability and ill health has increased to the same extent. A growing number of older people may face the combined effects of a decline in physical and mental function, isolation and poverty. Policymakers, service providers and older people alike recognise the need to create a high quality of life for our ageing population. This challenge can be meet by addressing the problems relating to healthy ageing, reducing inequalities in later life and creating services that are shaped by, and appropriate for, older people. Devolution and Structures of Government in Northern Ireland The Agreement (2) reached in the Multi-Party Negotiations in Belfast 1998 established the Northern Ireland Assembly which has full legislative authority for all transferred matters. The majority of social and economic public policy such as; agriculture, arts, education, health, environment and planning is determined by the Northern Ireland Assembly at Stormont. There are 11 Government Departments covering the main areas of responsibility with 108 elected Members of the Legislative Assembly (MLA�۪s). The powers of the Northern Ireland Assembly do not cover ��� reserved�۪ matters or ��� excepted�۪ matters . These are the responsibility of Westminster and include issues such as, tax, social security, policing, justice, defence, immigration and foreign affairs. Northern Ireland has 18 elected Members of Parliament (MP�۪s) to the House of Commons. Public Policy Context in Northern Ireland The economic, social and political consequence of an ageing population is a challenge for policy makers across government. Considering the complex and diverse causal factors that contribute to ageing in Northern Ireland, there are a number of areas of government policy at regional, national and international levels that are likely to impact in this area. International The Madrid International Plan of Action on Ageing (3) and the Research Agenda on Ageing for the 21st Century (4) provide important mechanisms for furthering research into ageing. The United Kingdom has signed up to these. The Madrid International Plan of Action on Ageing commits member states to a systematic review of the Plan of Action through Regional Implementation Strategies. The United Kingdom�۪s Regional Implementation Strategy covers Northern Ireland. National At National level, pension and social security are high on the agenda. The Pensions Act (5) became law in 2007 and links pensions increases with earnings as opposed to prices from 2012. Additional credits for people raising children and caring for older people to boost their pensions were introduced. Some protections are included for those who lost occupational pensions as a result of underfunded schemes being wound up before April 2005. In relation to State Pensions and benefits, this Act will bring changes to state pensions in future. The Act now places the Pension Credit element which is up-rated in line with or above earnings, on a permanent, statutory footing. Regional At regional level there are a number of age related public policy initiatives that have the potential to impact positively on the lives of older people in Northern Ireland. Some are specific to ageing such as the Ageing in an Inclusive Society (6) and others by their nature are cross-cutting such as Lifetime Opportunities: Governments Anti-Poverty Strategy for Northern Ireland (7). The main public policy framework in Northern Ireland is the Programme for Government: Building a Better Future, 2008-2011(PfG) (8) . The PfG, is the overarching high level policy framework for Northern Ireland and provides useful principles for ageing research and public policy in Northern Ireland. The PfG vision is to build a peaceful, fair and prosperous society in Northern Ireland, with respect for the rule of law. A number of Public Service Agreements (PSA) aligned to the PfG confirm key actions that will be taken to support the priorities that the Government aim to achieve over the next three years. For example objective 2 of PSA 7: Making Peoples�۪ Lives Better: Drive a programme across Government to reduce poverty and address inequality and disadvantage, refers to taking forward strategic action to promote social inclusion for older people; and to deliver a strong independent voice for older people. The Office of the First Minister and deputy First Minister (OFMDFM) have recently appointed an Interim Older People�۪s Advocate, Dame Joan Harbison to provide a focus for older peoples issues across Government. Ageing in an Inclusive Society is the cross-departmental strategy for older people in Northern Ireland and was launched in March 2005. It sets out the approach to be taken across Government to promote and support the inclusion of older people. The vision coupled with six strategic objectives form the basis of the action plans accompanying the strategy. The vision is: ���To ensure that age related policies and practices create an enabling environment, which offers everyone the opportunity to make informed choices so that they may pursue healthy, active and positive ageing.�۝ (Ageing in an Inclusive Society, Office of the First Minister and Deputy First Minister, 2005) Action planning and maintaining momentum across government in relation to this strategy has proved to be slower than anticipated. It is proposed to refresh this Strategy in line with Opportunity Age ��� meeting the challenges of ageing in the 21st Century (9). There are a number of policy levers elsewhere which can also be used to promote the positive aspects of an ageing society. The Investing for Health (10) and A Healthier Future:A 20 Year Vision for Health and Well-being in Northern Ireland (11), seek to ensure that the overall vision for health and wellbeing is achievable and provides a useful framework for ageing policy and research in the health area. These health initiatives have the potential to positively impact on the quality of life of older people and provide a useful framework for improving current policy and practice. In addition to public policy initiatives, the anti-discrimination frameworks in terms of employment in Northern Ireland cover age as well as a range of other grounds. Goods facilitates and services are currently excluded from the Employment Equality (age) Regulations (NI) 2006 (12). Supplementing the anti-discrimination measures, Section 75 of the Northern Ireland Act 1998 (13), unique to Northern Ireland, places a statutory obligation on public authorities in fulfilling their functions to promote equality of opportunity across nine grounds, one of which is age(14). This positive duty has the potential to make a real difference to the lives of older people in Northern Ireland. Those affected by policy decisions must be consulted and their interests taken into account. This provides an opportunity for older people and their representatives to participate in public policy-making, right from the start of the process. Policy and Research Interface ���Ageing research is vital as decisions in relation to policy and practice and resource allocation will be made on the best available information�۝. (CARDI�۪s Strategic Plan 2008-2011) As outlined earlier, CARDI has been established to bridge the gap to ensure that research reaches those involved in making policy decisions. CARDI is stimulating the ageing research agenda in Ireland through a specific research fund that has a policy and practice focus. My work is presently focusing on helping to build a greater awareness of the key policy levers and providing opportunities for those within research and policy to develop closer links. The development of this shared understanding by establishing these links between researchers and policy makers is seen as the best predictor for research utilization. It is important to acknowledge and recognise that researchers and policy makers operate in different institutional, political and cultural contexts. Research however needs to ���resonate�۪ with the contextual factors in which policy makers operate. Conclusions Those working within the public policy field recognise all too often that the development of government policies and initiatives in respect of age does not guarantee that they will result in changes in actual provision of services, despite Government recommendations and commitments. The identification of public policy initiatives as they relate to age has the potential to highlight persistent and entrenched difficulties that social policy has previously failed to address. Furthermore, the identification of these difficulties can maximise the opportunities for progressing these across government. A focus on developing effective and meaningful targets to ensure measurable outcomes in public policy for older people can assist in this. Access to sound, credible and up-to-date evidence will be vital in this respect. As well as a commitment to working across departmental boundaries to effect change. Further details: If you would like to discuss this paper or for further information about CARDI please contact: Judith Cross, Policy Officer, Centre for Ageing Research and Development in Ireland CARDI). t: +44 (0) 28 9069 0066; m: +353 (0) 867 904 171; e: judith@cardi.ie ; or visit our website at: www.cardi.ie References 1) Centre for Ageing Research and Development in Ireland (2008) Strategic Plan 2008-2011. Belfast. CARDI 2) The Agreement: Agreement Reached in the Multi-Party Negotiations. Belfast 1998 3) Madrid International Plan of Action on Ageing. http://www.un.org/ageing/ 4) UN Programme on Ageing (2007) Research Agenda on Ageing for the 21st Century: 2007 Update. New York. New York. UN Programme on Ageing and the International Association of Gerontology and Geriatrics. 5) The Pensions Act 2007 Chapter 22 6) Office of the First Minister and deputy First Minister (2005). Ageing in an Inclusive Society. Belfast. OFMDFM Central Anti-Poverty Unit. 7) Office of the First Minister and deputy First Minister (2005). Lifetime Opportunities: Government�۪s Anti-Poverty and Social Inclusion Strategy for Northern Ireland. Belfast. OFMDFM Central Anti-Poverty Unit. 8) Northern Ireland Executive (2008) Building a Better Future: Programme for Government 2008-2011. Belfast. OFMDFM Economic Policy Unit. 9) Department for Work and Pensions, (2005) Opportunity Age: Meeting the Challenges of Ageing in the 21 st Century. London. DWP. 10) Department of Health, Social Services and Public Safety (DHSS&PS) (2002) Investing for Health. Belfast. DHSS&PS. 11) Department of Health, Social Services and Public Safety (DHSS&PS) (2005) A Healthier Future:A 20 Year Vision for Health and Well-being in Northern Ireland Belfast. DHSS&PS. �� 12) The Employment Equality (Age) Regulations (Northern Ireland) 2006 SR2006 No.261 13) The Northern Ireland Act 1998, Part VII, S75 14) The nine grounds covered under S75 of the Northern Ireland Act are: gender, religion, race, sexual orientation, those with dependents, disability, political opinion, marital status and age.

Delivering Choosing Health: Making healthier choices easier

This delivery plan outlines the key steps that will be taken over the next three years to deliver the Governnment White Paper Choosing Health: making healthier choices easier. This delivery plan highlights how the DH and the NHS, within the framework of government policies, will help more people make more healthy choices and reduce health inequalities. It outlines clearly the priorities for delivery at national, regional and local levels and what will be done by whom and when. It brings into one place all of the actions on the White Paper commitments, alongside related Public Service Agreements and local targets to improve health. It lists 45 'big wins' - key interventions which the evidence and expert advice suggest will make the greatest impact on health in the shortest period of time It explains how new policies and programmes will be developed and implemented. It describes how Government will drive forward delivery through Government targets to improve health new partnerships

Fully engaged: tackling health inequalities through public health interventions

The evolving role of Primary Care Trusts (PCTs) is currently centre stage, with fundamental debate emerging from Commissioning a patient-led NHS and Our health, our care, our say a new direction for community services. This paper argues that PCTs have a crucial role to play in the public health agenda, specifically tackling health inequalities. This responsibility will become even stronger as the present wave of reforms gains momentum. There is also a lively debate on whether these reforms will make inroads into the persistent problem of health inequality or will exacerbate them even further unless robust, additional intervention levers and mechanisms are introduced. This paper suggests that PCTs will be central to ensuring the balance of reforms is tilted towards a more rather than a less equitable NHS. One of the key responsibilities for PCTs outlined by the Department of Health1 will be to act as the anchor at local level to the increasingly diverse and potentially3fragmented NHS. By using their crucial commissioning role to provide overall coherence to the health system, acting as leading local champions of the NHS and continuing the drive for improvement in access and quality, PCTs will have to act as enforcer and guardian of the equity of the NHS at local level. There is widespread evidence of the tenacity of health inequalities in Great Britain. This report looks at the measures that a fully engaged۝3 PCT has taken to grapple with the issues and draws some conclusions as to their possible wider application.refer to the resource

Increased efflux of amyloid-β peptides through the blood-brain barrier by muscarinic acetylcholine receptor inhibition reduces pathological phenotypes in mouse models of brain amyloidosis.

The formation and accumulation of toxic amyloid-β peptides (Aβ) in the brain may drive the pathogenesis of Alzheimer's disease. Accordingly, disease-modifying therapies for Alzheimer's disease and related disorders could result from treatments regulating Aβ homeostasis. Examples are the inhibition of production, misfolding, and accumulation of Aβ or the enhancement of its clearance. Here we show that oral treatment with ACI-91 (Pirenzepine) dose-dependently reduced brain Aβ burden in AβPPPS1, hAβPPSL, and AβPP/PS1 transgenic mice. A possible mechanism of action of ACI-91 may occur through selective inhibition of muscarinic acetylcholine receptors (AChR) on endothelial cells of brain microvessels and enhanced Aβ peptide clearance across the blood-brain barrier. One month treatment with ACI-91 increased the clearance of intrathecally-injected Aβ in plaque-bearing mice. ACI-91 also accelerated the clearance of brain-injected Aβ in blood and peripheral tissues by favoring its urinal excretion. A single oral dose of ACI-91 reduced the half-life of interstitial Aβ peptide in pre-plaque mhAβPP/PS1d mice. By extending our studies to an in vitro model, we showed that muscarinic AChR inhibition by ACI-91 and Darifenacin augmented the capacity of differentiated endothelial monolayers for active transport of Aβ peptide. Finally, ACI-91 was found to consistently affect, in vitro and in vivo, the expression of endothelial cell genes involved in Aβ transport across the Blood Brain Brain (BBB). Thus increased Aβ clearance through the BBB may contribute to reduced Aβ burden and associated phenotypes. Inhibition of muscarinic AChR restricted to the periphery may present a therapeutic advantage as it avoids adverse central cholinergic effects.

New insights into the anti-inflammatory actions of aspirin- induction of nitric oxide through the generation of epi-lipoxins

Aspirin has always remained an enigmatic drug. Not only does it present with new benefits for treating an ever-expanding list of apparently unrelated diseases at an astounding rate but also because aspirin enhances our understanding of the nature of these diseases processe. Originally, the beneficial effects of aspirin were shown to stem from its inhibition of cyclooxygenase-derived prostaglandins, fatty acid metabolites that modulate host defense. However, in addition to inhibiting cyclooxygenase activity aspirin can also inhibit pro-inflammatory signaling pathways, gene expression and other factors distinct from eicosanoid biosynthesis that drive inflammation as well as enhance the synthesis of endogenous protective anti-inflammatory factors. Its true mechanism of action in anti-inflammation remains unclear. Here the data from a series of recent experiments proposing that one of aspirin's predominant roles in inflammation is the induction of nitric oxide, which potently inhibits leukocyte/endothelium interaction during acute inflammation, will be discussed. It will be argued that this nitric oxide-inducing effects are exclusive to aspirin due to its unique ability, among the family of traditional anti-inflammatory drugs, to acetylate the active site of inducible cyclooxygenase and generate a family of lipid mediators called the epi-lipoxins that are increasingly being shown to have profound roles in a range of host defense responses.

Neutrophil transepithelial migration: role of toll-like receptors in mucosal inflammation

The symptomatic phases of many inflammatory diseases are characterized by migration of large numbers of neutrophils (PMN) across a polarized epithelium and accumulation within a lumen. For example, acute PMN influx is common in diseases of the gastrointestinal system (ulcerative colitis, Crohn's disease, bacterial enterocolitis, gastritis), hepatobiliary system (cholangitis, acute cholecystitis), respiratory tract (bronchial pneumonia, bronchitis, cystic fibrosis, bronchiectasis), and urinary tract (pyelonephritis, cystitis). Despite these observations, the molecular basis of leukocyte interactions with epithelial cells is incompletely understood. In vitro models of PMN transepithelial migration typically use N-formylated bacterial peptides such as fMLP in isolation to drive human PMNs across epithelial monolayers. However, other microbial products such as lipopolysaccharide (LPS) are major constituents of the intestinal lumen and have potent effects on the immune system. In the absence of LPS, we have shown that transepithelial migration requires sequential adhesive interactions between the PMN beta2 integrin CD11b/CD18 and JAM protein family members. Other epithelial ligands appear to be abundantly represented as fucosylated proteoglycans. Further studies indicate that the rate of PMN migration across mucosal surfaces can be regulated by the ubiquitously expressed transmembrane protein CD47 and microbial-derived factors, although many of the details remain unclear. Current data suggests that Toll-like receptors (TLR), which recognize specific pathogen-associated molecular patterns (PAMPs), are differentially expressed on both leukocytes and mucosal epithelial cells while serving to modulate leukocyte-epithelial interactions. Exposure of epithelial TLRs to microbial ligands has been shown to result in transcriptional upregulation of inflammatory mediators whereas ligation of leukocyte TLRs modulate specific antimicrobial responses. A better understanding of these events will hopefully provide new insights into the mechanisms of epithelial responses to microorganisms and ideas for therapies aimed at inhibiting the deleterious consequences of mucosal inflammation.

Diabetes in pregnancy: are we providing the best care?

This third and final report of the CEMACH national diabetes programme comes at an important time in the national drive to improve services for women with diabetes in pregnancy. The National Service Framework (NSF) for Diabetes requires the NHS to develop, implement and monitor policies that seek to empower and support women with diabetes to optimise the outcomes of their pregnancy. The CEMACH report shows that, whilst progress has been made in improving services for women with diabetes and their babies, there is much still to be done to meet the standards recommended by the NSF. Too many women continue to be poorly prepared for pregnancy in the critical areas of glycaemic control and folic acid supplementation. The report underlines the need for an increased focus on diabetes preconception care services and the development of strategies to educate women with diabetes of childbearing age. The growing proportion of women with type 2 diabetes during pregnancy, many of whom are from minority ethnic groups, presents an additional challenge for health services in developing responsive and accessible services.This CEMACH report has identifi ed several areas of good clinical practice during pregnancy in women with pre-existing diabetes. However, there continue to be areas where there is room for improvement, including antenatal fetal surveillance, glycaemic control during labour and delivery and postnatal diabetes care. The National Institute for Health and Clinical Excellence (NICE) is currently in the fi nal stages of development of its new guideline for the management of diabetes in pregnancy. This guideline, when taken together with the CEMACH report, will provide local health services with an unprecedented wealth of material on which to base their development of improved services for women with diabetes in pregnancy.��