Management of infections pre- and post-liver transplantation: Report of an AISF consensus conference

The burden of infectious diseases both before and after liver transplantation is clearly attributable to the dysfunction of defensive mechanisms of the host, both as a result of cirrhosis, as well as the use of immunosuppressive agents. The present document represents the recommendations of an expert panel commended by the Italian Association for the Study of the Liver (AISF), on the prevention and management of infectious complications excluding hepatitis B, D, C, and HIV in the setting of liver transplantation. Due to a decreased response to vaccinations in cirrhosis as well as within the first six months after transplantation, the best timing for immunization is likely before transplant and early in the course of disease. Before transplantation, a vaccination panel including inactivated as well as live attenuated vaccines is recommended, while oral polio vaccine, Calmette-Guerin's bacillus, and Smallpox are contraindicated, whereas after transplantation, live attenuated vaccines are contraindicated. Before transplant, screening protocols should be divided into different levels according to the likelihood of infection, in order to reduce costs for the National Health Service. Recommended preoperative and postoperative prophylaxis varies according to the pathologic agent to which it is directed (bacterial vs. viral vs. fungal). Timing after transplantation greatly determines the most likely agent involved in post-transplant infections, and specific high-risk categories of patients have been identified that warrant closer surveillance. Clearly, specifically targeted treatment protocols are needed upon diagnosis of infections in both the pre- as well as the post-transplant scenarios, not without considering local microbiology and resistance patterns

The economic impact of alcohol consumption: a systematic review

<p>Abstract</p> <p>Background</p> <p>Information on the economic impact of alcohol consumption can provide important evidence in supporting policies to reduce its associated harm. To date, several studies on the economic costs of alcohol consumption have been conducted worldwide. This study aims to review the economic impact of alcohol worldwide, summarizing the state of knowledge with regard to two elements: (1) cost components included in the estimation; (2) the methodologies employed in works conducted to date.</p> <p>Methods</p> <p>Relevant publications concerning the societal cost of alcohol consumption published during the years 1990-2007 were identified through MEDLINE. The World Health Organization's global status report on alcohol, bibliographies and expert communications were also used to identify additional relevant studies.</p> <p>Results</p> <p>Twenty studies met the inclusion criteria for full review while an additional two studies were considered for partial review. Most studies employed the human capital approach and estimated the gross cost of alcohol consumption. Both direct and indirect costs were taken into account in all studies while intangible costs were incorporated in only a few studies. The economic burden of alcohol in the 12 selected countries was estimated to equate to 0.45 - 5.44% of Gross Domestic Product (GDP).</p> <p>Conclusion</p> <p>Discrepancies in the estimation method and cost components included in the analyses limit a direct comparison across studies. The findings, however, consistently confirmed that the economic burden of alcohol on society is substantial. Given the importance of this issue and the limitation in generalizing the findings across different settings, further well-designed research studies are warranted in specific countries to support the formulation of alcohol-related policies.</p

An exploratory randomised controlled trial of a premises-level intervention to reduce alcohol-related harm including violence in the United Kingdom

&lt;b&gt;Background&lt;/b&gt;&lt;p&gt;&lt;/p&gt; To assess the feasibility of a randomised controlled trial of a licensed premises intervention to reduce severe intoxication and disorder; to establish effect sizes and identify appropriate approaches to the development and maintenance of a rigorous research design and intervention implementation.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt;&lt;p&gt;&lt;/p&gt; An exploratory two-armed parallel randomised controlled trial with a nested process evaluation. An audit of risk factors and a tailored action plan for high risk premises, with three month follow up audit and feedback. Thirty-two premises that had experienced at least one assault in the year prior to the intervention were recruited, match paired and randomly allocated to control or intervention group. Police violence data and data from a street survey of study premises’ customers, including measures of breath alcohol concentration and surveyor rated customer intoxication, were used to assess effect sizes for a future definitive trial. A nested process evaluation explored implementation barriers and the fidelity of the intervention with key stakeholders and senior staff in intervention premises using semi-structured interviews.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt;&lt;p&gt;&lt;/p&gt; The process evaluation indicated implementation barriers and low fidelity, with a reluctance to implement the intervention and to submit to a formal risk audit. Power calculations suggest the intervention effect on violence and subjective intoxication would be raised to significance with a study size of 517 premises.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt;&lt;p&gt;&lt;/p&gt; It is methodologically feasible to conduct randomised controlled trials where licensed premises are the unit of allocation. However, lack of enthusiasm in senior premises staff indicates the need for intervention enforcement, rather than voluntary agreements, and on-going strategies to promote sustainability

The economic costs of alcohol consumption in Thailand, 2006

<p>Abstract</p> <p>Background</p> <p>There is evidence that the adverse consequences of alcohol impose a substantial economic burden on societies worldwide. Given the lack of generalizability of study results across different settings, many attempts have been made to estimate the economic costs of alcohol for various settings; however, these have mostly been confined to industrialized countries. To our knowledge, there are a very limited number of well-designed studies which estimate the economic costs of alcohol consumption in developing countries, including Thailand. Therefore, this study aims to estimate these economic costs, in Thailand, 2006.</p> <p>Methods</p> <p>This is a prevalence-based, cost-of-illness study. The estimated costs in this study included both direct and indirect costs. Direct costs included health care costs, costs of law enforcement, and costs of property damage due to road-traffic accidents. Indirect costs included costs of productivity loss due to premature mortality, and costs of reduced productivity due to absenteeism and presenteeism (reduced on-the-job productivity).</p> <p>Results</p> <p>The total economic cost of alcohol consumption in Thailand in 2006 was estimated at 156,105.4 million baht (9,627 million US$PPP) or about 1.99$ PPP), followed by cost of productivity loss due to reduced productivity (45,464.6 million baht/2,804 million US$PPP), health care cost (5,491.2 million baht/339 million US$ PPP), cost of property damage as a result of road traffic accidents (779.4 million baht/48 million US$PPP), and cost of law enforcement (242.4 million baht/15 million US$ PPP), respectively. The results from the sensitivity analysis revealed that the cost ranges from 115,160.4 million baht to 214,053.0 million baht (7,102.1 - 13,201 million US$ PPP) depending on the methods and assumptions employed.</p> <p>Conclusions</p> <p>Alcohol imposes a substantial economic burden on Thai society, and according to these findings, the Thai government needs to pay significantly more attention to implementing more effective alcohol policies/interventions in order to reduce the negative consequences associated with alcohol.</p

Copy Number Variation of KIR Genes Influences HIV-1 Control

The authors that the number of activating and inhibitory KIR genes varies between individuals and plays a role in the regulation of immune mechanisms that determine HIV-1 control

Apoptosis assays with lymphoma cell lines: problems and pitfalls

Much attention has been focused on the manner in which tumour cells die after treatment with cytotoxic agents. The basic question is whether cells die via apoptosis or via direct damage from the toxic agent. Various assays have been used to make this distinction. However, we show herein that some of the widely used assays for apoptosis do not in fact distinguish between apoptosis and other forms of cell death. More specifically: (1) A sub-G1 DNA content, identified by propidium iodide staining, does not distinguish between apoptotic and necrotic cells; (2) loss of mitochondrial membrane potential does not distinguish between apoptotic and necrotic cells, unless combined with an assay for an intact cell membrane; (3) subcellular fragments that arise from dead cells or from apoptotic bodies can interfere with some assays for apoptosis such as annexin V staining, as they may be close to the size of intact cells, making it difficult to decide where to set the size threshold; (4) irradiated cells display a large increase in nonspecific Ab binding. This may be partly due to an increase in cell size, but, regardless of the cause, it can lead to a mistaken conclusion that there is an increase in a particular antigen if appropriate control reagents are not tested; and (5) experiments utilising Ab crosslinking have neglected the role of cell aggregation, which can cause multiple problems including death from mechanical stress when cells are handled. Consideration of these factors will improve our ability to determine the mode of cell death

Distributed Dendritic Processing Facilitates Object Detection: A Computational Analysis on the Visual System of the Fly

Hennig P, Möller R, Egelhaaf M. Distributed Dendritic Processing Facilitates Object Detection: A Computational Analysis on the Visual System of the Fly. PLoS ONE. 2008;3(8): e3092.Background: Detecting objects is an important task when moving through a natural environment. Flies, for example, may land on salient objects or may avoid collisions with them. The neuronal ensemble of Figure Detection cells (FD-cells) in the visual system of the fly is likely to be involved in controlling these behaviours, as these cells are more sensitive to objects than to extended background structures. Until now the computations in the presynaptic neuronal network of FD-cells and, in particular, the functional significance of the experimentally established distributed dendritic processing of excitatory and inhibitory inputs is not understood. Methodology/Principal Findings: We use model simulations to analyse the neuronal computations responsible for the preference of FD-cells for small objects. We employed a new modelling approach which allowed us to account for the spatial spread of electrical signals in the dendrites while avoiding detailed compartmental modelling. The models are based on available physiological and anatomical data. Three models were tested each implementing an inhibitory neural circuit, but differing by the spatial arrangement of the inhibitory interaction. Parameter optimisation with an evolutionary algorithm revealed that only distributed dendritic processing satisfies the constraints arising from electrophysiological experiments. In contrast to a direct dendro-dendritic inhibition of the FD-cell (Direct Distributed Inhibition model), an inhibition of its presynaptic retinotopic elements (Indirect Distributed Inhibition model) requires smaller changes in input resistance in the inhibited neurons during visual stimulation. Conclusions/Significance: Distributed dendritic inhibition of retinotopic elements as implemented in our Indirect Distributed Inhibition model is the most plausible wiring scheme for the neuronal circuit of FD-cells. This microcircuit is computationally similar to lateral inhibition between the retinotopic elements. Hence, distributed inhibition might be an alternative explanation of perceptual phenomena currently explained by lateral inhibition networks

Methodologies used to estimate tobacco-attributable mortality: a review

<p>Abstract</p> <p>Background</p> <p>One of the most important measures for ascertaining the impact of tobacco on a population is the estimation of the mortality attributable to its use. To measure this, a number of indirect methods of quantification are available, yet there is no consensus as to which furnishes the best information. This study sought to provide a critical overview of the different methods of attribution of mortality due to tobacco consumption.</p> <p>Method</p> <p>A search was made in the Medline database until March 2005 in order to obtain papers that addressed the methodology employed for attributing mortality to tobacco use.</p> <p>Results</p> <p>Of the total of 7 methods obtained, the most widely used were the prevalence methods, followed by the approach proposed by Peto et al, with the remainder being used in a minority of studies.</p> <p>Conclusion</p> <p>Different methodologies are used to estimate tobacco attributable mortality, but their methodological foundations are quite similar in all. Mainly, they are based on the calculation of proportional attributable fractions. All methods show limitations of one type or another, sometimes common to all methods and sometimes specific.</p

Alcohol use and misuse: What are the contributions of occupation and work organization conditions?

<p>Abstract</p> <p>Background</p> <p>This research examines the specific contribution of occupation and work organization conditions to alcohol use and misuse. It is based on a social-action model that takes into account agent personality, structures of daily life, and macro social structures.</p> <p>Methods</p> <p>Data come from a representative sample of 10,155 workers in Quebec, Canada. Multinomial regression models corrected for sample design effect have been used to predict low-risk and high-risk drinking compared to non-drinkers. The contribution of occupation and work organization conditions (skill used, decision authority, physical and psychological demands, hours worked, irregular work schedule, harassment, unionization, job insecurity, performance pay, prestige) have been adjusted for family situation, social network outside the workplace, and individual characteristics.</p> <p>Results</p> <p>Compared to non-qualified blue-collars, both low-risk and high-risk drinking are associated with qualified blue-collars, semi-qualified white-collars, and middle managers; high-risk drinking is associated with upper managers. For constraints-resources related to work organization conditions, only workplace harassment is an important determinant of both low-risk and high-risk drinking, but it is modestly moderated by occupation. Family situation, social support outside work, and personal characteristics of individuals are also associated with alcohol use and misuse. Non-work factors mediated/suppressed the role of occupation and work organization conditions.</p> <p>Conclusion</p> <p>Occupation and workplace harassment are important factors associated with alcohol use and misuse. The results support the theoretical model conceptualizing alcohol use and misuse as being the product of stress caused by constraints and resources brought to bear simultaneously by agent personality, structures of daily life, and macro social structures. Occupational alcohol researchers must expand their theoretical perspectives to avoid erroneous conclusions about the specific role of the workplace.</p