Design and Synthesis of Carbohydrate Based Derivatives as Antimicrobial Compounds

Investigations into the design of analogues of GlcNAc-Ins, the substrate for the enzyme GlcNAc-Ins deacetylase (mshB), a therapeutic target on the pathway to mycothiol biosynthesis in Mycobacterium tuberculosis are described. Initial studies directed towards the design of a substrate analogue were based on the 3-D structure and a proposed mechanism of action of mshB (deduced by Dr. Andrew McCarthy, EMBL). The compounds were designed with the aim to produce an analogue which could better mimic the natural substrate for mshB (GlcNAc-Ins) for crystallisation and mechanistic studies to further improve the knowledge of this enzyme. A series of fatty acid ester and ether derivatives were designed and synthesised based on carbohydrate and non-carbohydrate polyhydroxylated scaffolds with a view to testing their antimicrobial activity against microorganisms of concern to the food and healthcare industries. The synthesised compounds, along with their corresponding fatty acid monoglyceride antimicrobials, were evaluated for antimicrobial activity against Staphylococcus aureus and Escherichia coli. Of the derivatives synthesised several of the carbohydrate based compounds have antimicrobial efficacy comparable with commercially available antimicrobials. The results suggest that the nature of the carbohydrate core plays a role in the efficacy of carbohydrate fatty acid derivatives as antimicrobials

Economic Evaluation of Palliative Care in Ireland

This report examines the cost of providing palliative care in Ireland for individuals facing life-threatening illnesses, outcomes for patients and families resulting from that care, and the patterns and variations among the measures studied. Focusing their examination on three regional areas, researchers found:Wide variations in the availability of palliative care services across the regions.Significant differences in how those services are resourced and models of care.Despite the variation in availability and models of care, costs remain broadly the same across regions.Among the conclusions from examination of key outcomes for the patients:High patient satisfaction with palliative care services across all regions.Where available, hospice care is easier to access and rated more highly on every quality measure than in-hospital care.The ability to access in-hospice services in the last three months of life would be preferable for patients and may provide savings within hospitals

Evidence on the Cost and Cost-effectiveness of Palliative Care: A Literature Review

In the context of limited resources, evidence on costs and cost-effectiveness of alternative methods of delivering health-care services is increasingly important to facilitate appropriate resource allocation. Palliative care services have been expanding worldwide with the aim of improving the experience of patients with terminal illness at the end of life through better symptom control, coordination of care and improved communication between professionals and the patient and family.The aim of this paper is to present results from a comprehensive literature review of available international evidence on the costs and cost-effectiveness of palliative care interventions in any setting (e.g. hospital-based, home-based and hospice care) over the period 2002 -- 2011. Key bibliographic and review databases were searched and the quality of retrieved papers was assessed against a set of 31 indicators developed for this review.A total of 46 papers met the criteria for inclusion in the review, examining the cost and/or utilisation implications of a palliative care intervention with some form of comparator. The main focus of these studies was on direct costs with little focus on informal care or out-of-pocket costs. The overall quality of the studies is mixed, although a number of cohort studies do undertake multivariate regression analysis.Despite wide variation in study type, characteristic and study quality, there are consistent patterns in the results. Palliative care is most frequently found to be less costly relative to comparator groups, and in most cases, the difference in cost is statistically significant

Community and functional shifts in ammonia oxidizers across terrestrial and marine (soil/sediment) boundaries in two coastal Bay ecosystems

Terrestrial–marine boundaries are significant sites of biogeochemical activity with delineated gradients from land to sea. While niche differentiation of ammonia‐oxidizing archaea (AOA) and bacteria (AOB) driven by pH and nitrogen is well known, the patterns and environmental drivers of AOA and AOB community structure and activity across soil‐sediment boundaries have not yet been determined. In this study, nitrification potential rate, community composition and transcriptional activity of AOA and AOB in soil, soil/sediment interface and sediments of two coastal Bays were characterized using a combination of field investigations and microcosm incubations. At DNA level, amoA gene abundances of AOA were significantly greater than AOB in soil, while in sediments AOB were significantly more abundant than AOA, but at the soil/sediment interface there were equal numbers of AOA and AOB amoA genes. Microcosm incubations provided further evidence, through qPCR and DGGE‐sequencing analysis of amoA transcripts, that AOA were active in soil, AOB in sediment and both AOA and AOB were active at the soil/sediment interface. The AOA and AOB community composition shifted across the coastal soil‐interface‐sediment gradient with salinity and pH identified as major environmental drivers

RESOURCE ALLOCATION, FINANCING AND SUSTAINABILITY IN THE HEALTH SECTOR. ESRI Research Bulletin 2010/3/1

The focus on acute, episodic care in the conventional health-care model fails to provide adequately for changing health-care needs arising from increased longevity and increasing prevalence of chronic disease. Integrated care involves coherent and co-ordinated delivery of health-care services across a broad range of health and social care providers. A principal aim of integrated health care is to improve the patient’s journey through the system by co-ordinating care among providers and by strengthening the role of primary care. Effective resource allocation mechanisms, supported by appropriate financing arrangements, have an important role to play in delivering integrated health care. In addition, more efficient use of scarce health-care resources is required, and can be influenced by the resource allocation and financing mechanisms. This article summarises research undertaken by the ESRI to provide evidence for the Expert Group on Resource Allocation and Financing in Health Care, which reported in July 2010 (Brick et al., 2010a, b; Ruane, 2010). The research: • reviewed the theoretical and international empirical literature on resource allocation, financing and sustainability in health care (focusing on eight comparator countries – Australia, Canada, Germany, Netherlands, New Zealand, Sweden, UK, USA); • evaluated current Irish systems of resource allocation and financing and issues associated with sustainability; • proposed a framework for health-care entitlements and user fees that would support the delivery of integrated health care in Ireland

The Antimicrobial Efficacy and Structure Activity Relationship of Novel Carbohydrate Fatty Acid Derivatives Against Listera spp. and Food Spoilage Microorganisms

Novel mono-substituted carbohydrate fatty acid (CFA) esters and ethers were investigated for their antibacterial activity against a range of pathogenic and spoilage bacteria focussing on Listeria monocytogenes. Carbohydrate derivatives with structural differences enable comparative studies on the structure/activity relationship for antimicrobial efficacy and mechanism of action. The antimicrobial efficacy of the synthesized compounds was compared with commercially available compounds such as monolaurin and monocaprylin, as well as the pure free fatty acids, lauric acid and caprylic acid, which have proven antimicrobial activity. Compound efficacy was compared using an absorbance based broth microdilution assay to determine the minimum inhibitory concentration (MIC), increase in lag phase and decrease in maximum growth rate. Among the carbohydrate derivatives synthesized, lauric ether of methyl α-d-glucopyranoside and lauric ester of methyl α-d-mannopyranoside showed the highest growth-inhibitory effect with MIC values of 0.04 mM, comparable to monolaurin. CFA derivatives were generally more active against Gram positive bacteria than Gram negative bacteria. The analysis of both ester and ether fatty acid derivatives of the same carbohydrate, in tandem with alpha and beta configuration of the carbohydrate moiety suggest that the carbohydrate moiety is involved in the antimicrobial activity of the fatty acid derivatives and that the nature of the bond also has a significant effect on efficacy, which requires further investigation. This class of CFA derivatives has great potential for developing antibacterial agents relevant to the food industry, particularly for control of Listeria or other Gram-positive pathogens

The CONSENSUS study: protocol for a mixed methods study to establish which outcomes should be included in a core outcome set for oropharyngeal cancer

BACKGROUND: The incidence of oropharyngeal cancer is increasing in the developed world. This has led to a large rise in research activity and clinical trials in this area, yet there is no consensus on which outcomes should be measured. As a result, the outcomes measured often differ between trials of comparable interventions, making the combination or comparison of results between trials impossible. Outcomes may also be ‘cherry-picked’, such that favourable results are reported, and less favourable results withheld. The development of a minimum outcome reporting standard, known as a core outcome set, goes some way to addressing these problems. Core outcome sets are ideally developed using a patient-centred approach so that the outcomes measured are relevant to patients and clinical practice. Core outcome sets drive up the quality and relevance of research by ensuring that the right outcomes are consistently measured and reported in trials in specific areas of health or healthcare. METHODS/DESIGN: This is a mixed methods study involving three phases to develop a core outcome set for oropharyngeal cancer clinical trials. Firstly, a systematic review will establish which outcomes are measured in published oropharyngeal cancer randomised controlled trials (RCTs). Secondly, qualitative interviews with patients and carers in the UK and the USA will aim to establish which outcomes are important to these stakeholders. Data from these first two stages will be used to develop a comprehensive list of outcomes to be considered for inclusion in the core outcome set. In the third stage, patients and clinicians will participate in an iterative consensus exercise known as a Delphi study to refine the contents of the core outcome set. This protocol lays out the methodology to be implemented in the CONSENSUS study. DISCUSSION: A core outcome set defines a minimum outcome reporting standard for clinical trials in a particular area of health or healthcare. Its consistent implementation in oropharyngeal cancer clinical trials will improve the quality and relevance of research. TRIALS AND REGISTRATION: This study is registered at the National Institute for Health Research (NIHR) Clinical Research Network (CRN) portfolio, ID 13823 (17 January 2013)

Do mass participation sporting events have a role in making populations more active?

Mass sporting events are becoming increasingly popular worldwide and may have health benefits as they foster low intensity participation in a non competitive, fun environment. We know little, however, about their long term effect, if any, on physical activity levels. This report describes the initial impact of three women only mass events in Ireland as well as the effectiveness of a series of initiatives designed to boost activity among the least active participants. It also presents key lessons and recommendations for all those charged with promoting physical activity in Ireland