Management goals for type 1 Gaucher disease: An expert consensus document from the European working group on Gaucher disease

AbstractGaucher Disease type 1 (GD1) is a lysosomal disorder that affects many systems. Therapy improves the principal manifestations of the condition and, as a consequence, many patients show a modified phenotype which reflects manifestations of their disease that are refractory to treatment. More generally, it is increasingly recognised that information as to how a patient feels and functions [obtained by patient- reported outcome measurements (PROMs)] is critical to any comprehensive evaluation of treatment. A new set of management goals for GD1 in which both trends are reflected is needed. To this end, a modified Delphi procedure among 25 experts was performed. Based on a literature review and with input from patients, 65 potential goals were formulated as statements. Consensus was considered to be reached when ≥75% of the participants agreed to include that specific statement in the management goals. There was agreement on 42 statements. In addition to the traditional goals concerning haematological, visceral and bone manifestations, improvement in quality of life, fatigue and social participation, as well as early detection of long-term complications or associated diseases were included. When applying this set of goals in medical practice, the clinical status of the individual patient should be taken into account

Increased Levels of Inflammatory Cytokines and Endothelin-1 in Alveolar Macrophages from Patients with Chronic Heart Failure

BACKGROUND: Pathophysiological interactions between heart and lungs in heart failure (HF) are well recognized. We investigated whether expression of different factors known to be increased in the myocardium and/or the circulation in HF is also increased in alveolar macrophages in HF. METHODOLOGY/PRINCIPAL FINDINGS: Lung function, hemodynamic parameters, gene expression in alveolar macrophages, and plasma levels in the pulmonary and femoral arteries of HF patients (n = 20) were compared to control subjects (n = 16). Our principal findings were: (1) Lung function was significantly lower in HF patients compared to controls (P<0.05). (2) mRNA levels of ET-1, tumor necrosis factor (TNF)-α and interleukin-6 (IL-6) were increased in alveolar macrophages from HF patients. (3) Plasma levels of ET-1, TNFα, IL-6 and MCP-1 were significantly increased in HF patients, whereas our data indicate a net pulmonary release of MCP-1 into the circulation in HF. CONCLUSIONS/SIGNIFICANCE: Several important cytokines and ET-1 are induced in alveolar macrophages in human HF. Further studies should clarify whether increased synthesis of these factors affects pulmonary remodeling and, directly or indirectly, adversely affects the failing myocardium

Limits on the production of scalar leptoquarks from Z (0) decays at LEP

A search has been made for pairs and for single production of scalar leptoquarks of the first and second generations using a data sample of 392000 Z0 decays from the DELPHI detector at LEP 1. No signal was found and limits on the leptoquark mass, production cross section and branching ratio were set. A mass limit at 95% confidence level of 45.5 GeV/c2 was obtained for leptoquark pair production. The search for the production of a single leptoquark probed the mass region above this limit and its results exclude first and second generation leptoquarks D0 with masses below 65 GeV/c2 and 73 GeV/c2 respectively, at 95% confidence level, assuming that the D0lq Yukawa coupling alpha(lambda) is equal to the electromagnetic one. An upper limit is also given on the coupling alpha(lambda) as a function of the leptoquark mass m(D0)

Community hospitals and their services in the NHS: identifying transferable learning from international developments - scoping review, systematic review, country reports and case studies

Background: The notion of a community hospital in England is evolving from the traditional model of a local hospital staffed by general practitioners and nurses and serving mainly rural populations. Along with the diversification of models, there is a renewed policy interest in community hospitals and their potential to deliver integrated care. However, there is a need to better understand the role of different models of community hospitals within the wider health economy and an opportunity to learn from experiences of other countries to inform this potential. Objectives This study sought to (1) define the nature and scope of service provision models that fit under the umbrella term ‘community hospital’ in the UK and other high-income countries, (2) analyse evidence of their effectiveness and efficiency, (3) explore the wider role and impact of community engagement in community hospitals, (4) understand how models in other countries operate and asses their role within the wider health-care system, and (5) identify the potential for community hospitals to perform an integrative role in the delivery of health and social care. Methods A multimethod study including a scoping review of community hospital models, a linked systematic review of their effectiveness and efficiency, an analysis of experiences in Australia, Finland, Italy, Norway and Scotland, and case studies of four community hospitals in Finland, Italy and Scotland. Results The evidence reviews found that community hospitals provide a diverse range of services, spanning primary, secondary and long-term care in geographical and health system contexts. They can offer an effective and efficient alternative to acute hospitals. Patient experience was frequently reported to be better at community hospitals, and the cost-effectiveness of some models was found to be similar to that of general hospitals, although evidence was limited. Evidence from other countries showed that community hospitals provide a wide spectrum of health services that lie on a continuum between serving a ‘geographic purpose’ and having a specific population focus, mainly older people. Structures continue to evolve as countries embark on major reforms to integrate health and social care. Case studies highlighted that it is important to consider local and national contexts when looking at how to transfer models across settings, how to overcome barriers to integration beyond location and how the community should be best represented. Limitations The use of a restricted definition may have excluded some relevant community hospital models, and the small number of countries and case studies included for comparison may limit the transferability of findings for England. Although this research provides detailed insights into community hospitals in five countries, it was not in its scope to include the perspective of patients in any depth. Conclusions At a time when emphasis is being placed on integrated and community-based care, community hospitals have the potential to assume a more strategic role in health-care delivery locally, providing care closer to people’s homes. There is a need for more research into the effectiveness and cost-effectiveness of community hospitals, the role of the community and optimal staff profile(s). Funding: The National Institute for Health Research Health Services and Delivery Research programme