Fibrosis Evaluation by Transient Elastography in Patients With Long-Term Sustained HCV Clearance

BACKGROUND: Reversibility of advanced fibrosis after HCV-clearance is an important goal of therapy. OBJECTIVES: Measuring liver stiffness (LS) by transient elastography (TE) might be helpful in this setting. PATIENTS AND METHODS: We evaluated 104 patients with biopsy-proven chronic hepatitis C (CHC) and sustained virological response (SVR) after Peg-Interferon (IFN) plus ribavirin since at least 18 months. HCV-eradication was confirmed searching for serum HCV-RNA (TMA® sensitivity > 5-10 IU/ml). Data from literature reported the best LS cut-off values for different stages of liver fibrosis were 7.1 kPa for Metavir stage 2 (F2), 9.5 kPa for F3 and 12.5 for cirrhosis (F4). RESULTS: TE was not reliable in four SVR obese patients. Metavir-stage of biopsy was F0-1 in 28, F2 in 47, F3 in 17 and F4 in eight patients. The median interval elapsed since achieving SVR was 36 months (range: 18-77, SD¬¬:18). Stratifying patients according to the histological stage assessed before treatment, a clear-cut gradient of LS values was observed from F0-1: median: 3.8 kPa (range: 3.5-4.9) to F2: 4.6 kPa (3.8-6.0), F3: 6.2 kPa (4.8-8.6) and F4: 8.4 kPa (6.2-9.2) (P = 0.001). Overall, 86 patients had lower values of LS than the expected LS values according to Metavir-stage. At multivariate logistic analysis γ-GT and histological steatosis were independently associated with persistence of higher values of LS. CONCLUSION: Long term responders to IFN-based therapies have lower LS values than those who are untreated and still viraemic. High levels of γ-GT and liver steatosis, all markers of insulin resistance, may hamper reduction of liver stiffness after HCV-clearance

The SCottish Alcoholic Liver disease Evaluation: a population-level matched cohort study of hospital-based costs, 1991-2011

Studies assessing the costs of alcoholic liver disease are lacking. We aimed to calculate the costs of hospitalisations before and after diagnosis compared to population controls matched by age, sex and socio-economic deprivation. We aimed to use population level data to identify a cohort of individuals hospitalised for the first time with alcoholic liver disease in Scotland between 1991 and 2011.Incident cases were classified by disease severity, sex, age group, socio-economic deprivation and year of index admission. 5 matched controls for every incident case were identified from the Scottish population level primary care database. Hospital costs were calculated for both cases and controls using length of stay from morbidity records and hospital-specific daily rates by specialty. Remaining lifetime costs were estimated using parametric survival models and predicted annual costs. 35,208 incident alcoholic liver disease hospitalisations were identified. Mean annual hospital costs for cases were 2.3 times that of controls pre diagnosis (£804 higher) and 10.2 times (£12,774 higher) post diagnosis. Mean incident admission cost was £6,663. Remaining lifetime cost for a male, 50-59 years old, living in the most deprived area diagnosed with acoholic liver disease was estimated to be £65,999 higher than the matched controls (£12,474 for 7.43 years remaining life compared to £1,224 for 21.8 years). In Scotland, alcoholic liver disease diagnosis is associated with significant increases in admissions to hospital both before and after diagnosis. Our results provide robust population level estimates of costs of alcoholic liver disease for the purposes of health-care delivery, planning and future cost-effectiveness analyses

Interpersonal and affective dimensions of psychopathic traits in adolescents : development and validation of a self-report instrument

We report the development and psychometric evaluations of a self-report instrument designed to screen for psychopathic traits among mainstream community adolescents. Tests of item functioning were initially conducted with 26 adolescents. In a second study the new instrument was administered to 150 high school adolescents, 73 of who had school records of suspension for antisocial behavior. Exploratory factor analysis yielded a 4-factor structure (Impulsivity α = .73, Self-Centredness α = .70, Callous-Unemotional α = .69, and Manipulativeness α = .83). In a third study involving 328 high school adolescents, 130 with records of suspension for antisocial behaviour, competing measurement models were evaluated using confirmatory factor analysis. The superiority of a first-order model represented by four correlated factors that was invariant across gender and age was confirmed. The findings provide researchers and clinicians with a psychometrically strong, self-report instrument and a greater understanding of psychopathic traits in mainstream adolescents

Mathematical modelling of polyamine metabolism in bloodstream-form trypanosoma brucei: An application to drug target identification

© 2013 Gu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedThis article has been made available through the Brunel Open Access Publishing Fund.We present the first computational kinetic model of polyamine metabolism in bloodstream-form Trypanosoma brucei, the causative agent of human African trypanosomiasis. We systematically extracted the polyamine pathway from the complete metabolic network while still maintaining the predictive capability of the pathway. The kinetic model is constructed on the basis of information gleaned from the experimental biology literature and defined as a set of ordinary differential equations. We applied Michaelis-Menten kinetics featuring regulatory factors to describe enzymatic activities that are well defined. Uncharacterised enzyme kinetics were approximated and justified with available physiological properties of the system. Optimisation-based dynamic simulations were performed to train the model with experimental data and inconsistent predictions prompted an iterative procedure of model refinement. Good agreement between simulation results and measured data reported in various experimental conditions shows that the model has good applicability in spite of there being gaps in the required data. With this kinetic model, the relative importance of the individual pathway enzymes was assessed. We observed that, at low-to-moderate levels of inhibition, enzymes catalysing reactions of de novo AdoMet (MAT) and ornithine production (OrnPt) have more efficient inhibitory effect on total trypanothione content in comparison to other enzymes in the pathway. In our model, prozyme and TSHSyn (the production catalyst of total trypanothione) were also found to exhibit potent control on total trypanothione content but only when they were strongly inhibited. Different chemotherapeutic strategies against T. brucei were investigated using this model and interruption of polyamine synthesis via joint inhibition of MAT or OrnPt together with other polyamine enzymes was identified as an optimal therapeutic strategy.The work was carried out under a PhD programme partly funded by Prof. Ray Welland, School of Computing Science, University of Glasgo

Cost-effectiveness of HBV and HCV screening strategies:a systematic review of existing modelling techniques

Introduction: Studies evaluating the cost-effectiveness of screening for Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) are generally heterogeneous in terms of risk groups, settings, screening intervention, outcomes and the economic modelling framework. It is therefore difficult to compare cost-effectiveness results between studies. This systematic review aims to summarise and critically assess existing economic models for HBV and HCV in order to identify the main methodological differences in modelling approaches. Methods: A structured search strategy was developed and a systematic review carried out. A critical assessment of the decision-analytic models was carried out according to the guidelines and framework developed for assessment of decision-analytic models in Health Technology Assessment of health care interventions. Results: The overall approach to analysing the cost-effectiveness of screening strategies was found to be broadly consistent for HBV and HCV. However, modelling parameters and related structure differed between models, producing different results. More recent publications performed better against a performance matrix, evaluating model components and methodology. Conclusion: When assessing screening strategies for HBV and HCV infection, the focus should be on more recent studies, which applied the latest treatment regimes, test methods and had better and more complete data on which to base their models. In addition to parameter selection and associated assumptions, careful consideration of dynamic versus static modelling is recommended. Future research may want to focus on these methodological issues. In addition, the ability to evaluate screening strategies for multiple infectious diseases, (HCV and HIV at the same time) might prove important for decision makers

Temporal and Geographic variation in the validity and internal consistency of the Nursing Home Resident Assessment Minimum Data Set 2.0

<p>Abstract</p> <p>Background</p> <p>The Minimum Data Set (MDS) for nursing home resident assessment has been required in all U.S. nursing homes since 1990 and has been universally computerized since 1998. Initially intended to structure clinical care planning, uses of the MDS expanded to include policy applications such as case-mix reimbursement, quality monitoring and research. The purpose of this paper is to summarize a series of analyses examining the internal consistency and predictive validity of the MDS data as used in the "real world" in all U.S. nursing homes between 1999 and 2007.</p> <p>Methods</p> <p>We used person level linked MDS and Medicare denominator and all institutional claim files including inpatient (hospital and skilled nursing facilities) for all Medicare fee-for-service beneficiaries entering U.S. nursing homes during the period 1999 to 2007. We calculated the sensitivity and positive predictive value (PPV) of diagnoses taken from Medicare hospital claims and from the MDS among all new admissions from hospitals to nursing homes and the internal consistency (alpha reliability) of pairs of items within the MDS that logically should be related. We also tested the internal consistency of commonly used MDS based multi-item scales and examined the predictive validity of an MDS based severity measure viz. one year survival. Finally, we examined the correspondence of the MDS discharge record to hospitalizations and deaths seen in Medicare claims, and the completeness of MDS assessments upon skilled nursing facility (SNF) admission.</p> <p>Results</p> <p>Each year there were some 800,000 new admissions directly from hospital to US nursing homes and some 900,000 uninterrupted SNF stays. Comparing Medicare enrollment records and claims with MDS records revealed reasonably good correspondence that improved over time (by 2006 only 3% of deaths had no MDS discharge record, only 5% of SNF stays had no MDS, but over 20% of MDS discharges indicating hospitalization had no associated Medicare claim). The PPV and sensitivity levels of Medicare hospital diagnoses and MDS based diagnoses were between .6 and .7 for major diagnoses like CHF, hypertension, diabetes. Internal consistency, as measured by PPV, of the MDS ADL items with other MDS items measuring impairments and symptoms exceeded .9. The Activities of Daily Living (ADL) long form summary scale achieved an alpha inter-consistency level exceeding .85 and multi-item scale alpha levels of .65 were achieved for well being and mood, and .55 for behavior, levels that were sustained even after stratification by ADL and cognition. The Changes in Health, End-stage disease and Symptoms and Signs (CHESS) index, a summary measure of frailty was highly predictive of one year survival.</p> <p>Conclusion</p> <p>The MDS demonstrates a reasonable level of consistency both in terms of how well MDS diagnoses correspond to hospital discharge diagnoses and in terms of the internal consistency of functioning and behavioral items. The level of alpha reliability and validity demonstrated by the scales suggest that the data can be useful for research and policy analysis. However, while improving, the MDS discharge tracking record should still not be used to indicate Medicare hospitalizations or mortality. It will be important to monitor the performance of the MDS 3.0 with respect to consistency, reliability and validity now that it has replaced version 2.0, using these results as a baseline that should be exceeded.</p

Self-adjustment mechanisms and their application for orthosis design

Medical orthoses aim at guiding anatomical joints along their natural trajectories while preventing pathological movements, especially in case of trauma or injuries. The motions that take place between bone surfaces have complex kinematics. These so-called arthrokinematic motions exhibit axes that move both in translation and rotation. Traditionally, orthoses are carefully adjusted and positioned such that their kinematics approximate the arthrokinematic movements as closely as possible in order to protect the joint. Adjustment procedures are typically long and tedious. We suggest in this paper another approach. We propose mechanisms having intrinsic self-aligning properties. They are designed such that their main axis self-adjusts with respect to the joint’s physiological axis during motion. When connected to a limb, their movement becomes homokinetic and they have the property of automatically minimizing internal stresses. The study is performed here in the planar case focusing on the most important component of the arthrokinematic motions of a knee joint

Septic cardiomyopathy

Depression of left ventricular (LV) intrinsic contractility is constant in patients with septic shock. Because most parameters of cardiac function are strongly dependent on afterload, especially in this context, the cardiac performance evaluated at the bedside reflects intrinsic contractility, but also the degree of vasoplegia. Recent advances in echocardiography have allowed better characterization of septic cardiomyopathy. It is always reversible providing the patient's recovery. Unlike classic cardiomyopathy, it is not associated with high filling pressures, for two reasons: improvement in LV compliance and associated right ventricular dysfunction. Although, it is unclear to which extent it affects prognosis, a hyperkinetic state is indicative of a profound and persistent vasoplegia associated with a high mortality rate. Preliminary data suggest that the hemodynamic response to a dobutamine challenge has a prognostic value, but large studies are required to establish whether inotropic drugs should be used to treat this septic cardiac dysfunction

Development time and new product sales: A contingency analysis of product innovativeness and price

Opposing theories and conflicting empirical results with regard to the effect of development time on new product sales suggest the need for a contingency analysis into factors affecting this relationship. This study uses a unique combination of accounting and perceptual data from 129 product development projects to test the combined contingency effect of product innovativeness and new product price on the relationship between development time and new product sales. The results show that for radically new products with short development times, price has no effect on new product sales. When the development time is long, price has a negative effect on the sales of radical new products. The findings additionally show that price has no effect on sales for incremental new products with short development times and a negative effect for incremental new products with long development times. Together, these findings shed new light on the relationship between development time and new product sales