The identification of chronic liver disease in primary care using non-invasive diagnostics within a novel pathway

Introduction: Deaths due to chronic liver disease have increased significantly in recent decades. This is due to increases in alcohol consumption and obesity during this time period, and insensitive screening tests (liver function blood tests) utilised in primary care. This thesis describes a new liver disease community diagnostic pathway which focussed upon defined risk factors for chronic liver disease and uses Transient Elastography (TE) as the primary investigation modality. The aims of the thesis are to assess the feasibility of this pathway for detecting liver disease due to alcohol or non-alcoholic fatty liver disease within the United Kingdom healthcare system, to quantify the number of new cases detected with this approach and to evaluate patient experience of these investigations. Methods: Following a systematic review of the literature, an investigation pathway was derived and piloted in 4 general practice sites in Nottinghamshire in two phases between February 2012 and September 2014. Patients with hazardous alcohol use, type 2 diabetes or persistently raised alanine aminotransferase (ALT) level and negative liver serology were eligible for study. TE was performed in the community; a liver stiffness reading of ≥8 kilopascals defined clinically significant liver disease and subsequent review in a consultant led community clinic. Risk factors for new diagnoses of liver disease and cirrhosis were identified and the association with obesity investigated. A qualitative interview substudy was conducted to explore the experiences of 20 patients undergoing investigation. Results: In a total adult population of 20,868 patients, 2,022 patients were eligible for study of whom 909 (45%) underwent TE. Valid liver stiffness measurements were possible in 98% of patients. Overall, 230 cases of elevated liver stiffness and 27 new cases of cirrhosis were identified. Minimum cirrhosis prevalence in patients with type 2 diabetes was 2%. Obesity was significantly associated with diagnosis of cirrhosis in type 2 diabetics (odds ratio 9.4 (95% CI 2.2-40.9)) and hazardous alcohol users (OR 5.6 (95% CI 1.6-19.7)). The majority of new cases of liver disease had normal ALT levels. From the initial pilot phase in two general practices in Rushcliffe (Nottingham), in which liver function test data from 378 patients undergoing TE was analysed, 72.4% with elevated liver stiffness measurement, 60% with biopsy proven cirrhosis and 90% with cirrhosis diagnosis had normal ALT. Patients felt that TE was a useful adjunct to lifestyle change and described a positive experience of liver disease investigation. Conclusion: A new non-invasive diagnostic pathway for liver disease was feasible to implement in Nottinghamshire primary care and resulted in significantly increased diagnosis of chronic liver disease and cirrhosis. These findings warrant exploration of the pathway in a larger primary care population

Introduction to the themed issue - Corporate power : agency, communication, influence and social policy

This paper introduces this themed issue of Critical Social Policy on the question of corporate power. Corporate power is recognized as an important agent in social policy making and delivery. However, to date there has been comparatively little attention to the crucial role that lobbying and corporate 'spin' play in helping to shape policy making contexts. This special issue of Critical Social Policy is concerned to bring such issues to the mainstream of social policy analysis. It is argued here that the rise of spin and public relations is a key feature of neoliberalism in the past two decades. These have worked to reshape policy making, resulting in pronounced changes in the content and process of policy making and it is argued that these have tended to marginalize or undermine democratic processes

Development of an Objective Structured Clinical Examination as a Component of Assessment for Initial Board Certification in Anesthesiology.

With its first administration of an Objective Structured Clinical Examination (OSCE) in 2018, the American Board of Anesthesiology (ABA) became the first US medical specialty certifying board to incorporate this type of assessment into its high-stakes certification examination system. The fundamental rationale for the ABA's introduction of the OSCE is to include an assessment that allows candidates for board certification to demonstrate what they actually "do" in domains relevant to clinical practice. Inherent in this rationale is that the OSCE will capture competencies not well assessed in the current written and oral examinations-competencies that will allow the ABA to judge whether a candidate meets the standards expected for board certification more properly. This special article describes the ABA's journey from initial conceptualization through first administration of the OSCE, including the format of the OSCE, the process for scenario development, the standardized patient program that supports OSCE administration, examiner training, scoring, and future assessment of reliability, validity, and impact of the OSCE. This information will be beneficial to both those involved in the initial certification process, such as residency graduate candidates and program directors, and others contemplating the use of high-stakes summative OSCE assessments

A comparison of chemical and electrochemical synthesis of PEDOT: Dextran sulphate for bio-application

Poly(3,4-ethylenedioxythiophene) (PEDOT) is an organic conducting polymer that has been the focus of significant research over the last decade, in both energy and biological applications. Most commonly, PEDOT is doped by the artificial polymer polystyrene sulfonate due to the excellent electrical characteristics yielded by this pairing. The biopolymer dextran sulphate (DS) has been recently reported as a promising alternative to PEDOT: PSS for biological application, having electrical properties rivaling PEDOT: PSS, complimented by the potential bioactivity of the polysaccharide. In this work we compared chemical and electrochemical polymerisations of PEDOT: DS in terms of their impact on the electrical, morphological and biological properties of the resultant PEDOT: DS films. Post-growth cyclic voltammograms and UV-Vis analyses revealed comparable redox behaviour and absorbance profiles for the two synthesis approaches. Despite good intrinsic conductivity of particles, the addition of chemically produced PEDOT: DS did not markedly enhance the bulk conductivity of aqueous solutions due to the lack of interConnectivity between adjacent PEDOT: DS particles at achievable concentrations. Scanning electron microscopy revealed significantly greater roughness in films cast from chemically produced PEDOT: DS compared to electropolymerised samples, attributable to the formation of solution phase nanoparticles prior to casting. In cell studies with the L929 cell line, electrochemical polymerisation of PEDOT: DS afforded better integrity of resultant films for surface seeding, whilst chemically polymerised PEDOT: DS appeared to localised at the proliferating cells, suggesting possible applications in drug delivery

Economic evaluation of a community-based diagnostic pathway to stratify adults for non-alcoholic fatty liver disease: a Markov model informed by a feasibility study

Objectives: To assess the long-term cost-effectiveness of a risk stratification pathway, compared with standard care, for detecting non-alcoholic fatty liver disease (NAFLD) in primary care. Setting: Primary care general practices in England. Participants: Adults who have been identified in primary care to have a risk factor for developing NAFLD, that is, type 2 diabetes without a history of excessive alcohol use. Intervention: A community-based pathway, which utilises transient elastography and hepatologists to stratify patients at risk of NAFLD, has been implemented and demonstrated to be feasible (NCT02037867). Earlier identification could mean earlier treatments, referral to specialist, and enrolment into surveillance programmes. Design: The impact of earlier detection and treatment with the risk stratification pathway on progression to later stages of liver disease was examined using decision modelling with Markov chains to estimate lifetime health and economic effects of the two comparators. Data sources: Data from a prospective cross-sectional feasibility study indicating risk stratification pathway and standard care diagnostic accuracies, were combined with a Markov model that comprised the following states: no/mild liver disease, significant liver disease, compensated cirrhosis; decompensated cirrhosis, hepatocellular carcinoma, liver transplant and death. The model data were chosen from up-to-date UK sources, published literature and an expert panel. Outcome measure: An incremental cost-effectiveness ratio (ICER) indicating cost per quality adjusted life year (QALY) of the risk stratification pathway compared with standard care was estimated. Results: The risk stratification pathway was more effective than standard care, and cost ￡2,138 per QALY gained. The ICER was most sensitive to estimates of the rate of fibrosis progression and the effect of treatment on reducing this, and ranged from -￡1,895 to ￡7,032/QALY. The risk stratification pathway demonstrated an 85% probability of cost-effectiveness at the UK willingness-to-pay threshold of ￡20,000/QALY. Conclusions: Implementation of a community-based risk stratification pathway is likely to be cost effective

Validation of a Model for Identification of Patients With Compensated Cirrhosis at High Risk of Decompensation

Background & Aims: It is important to rapidly identify patients with advanced liver disease. Routine tests to assess liver function and fibrosis provide data that can be used to determine patients’ prognoses. We tested the validated the ability of combined data from the ALBI and FIB-4 scoring systems to identify patients with compensated cirrhosis at highest risk for decompensation.Methods: We collected data from 145 patients with compensated cirrhosis (91% Child A cirrhosis and median MELD scores below 8) from a cohort in Nottingham, United Kingdom, followed for a median 4.59 years (development cohort). We collected baseline clinical features and recorded decompensation events. We used these data to develop a model based on liver function (assessed by the ALBI score) and extent of fibrosis (assessed by the FIB-4 index) to determine risk of decompensation. We validated the model in 2 independent external cohorts (1 in Dublin, Ireland and 1 in Menoufia, Egypt) comprising 234 patients.Results: In the development cohort, 19.3% of the patients developed decompensated cirrhosis. Using a combination of ALBI and FIB-4 scores, we developed a model that identified patients at low vs high risk of decompensation (hazard ratio [HR] for decompensation in patients with high risk score was 7.10). When we tested the scoring system in the validation cohorts, the HR for decompensation in patients with a high-risk score was 12.54 in the Ireland cohort and 5.10 in the Egypt cohort.Conclusion: We developed scoring system, based on a combination of ALBI and FIB-4 scores, that identifies patients at risk for liver decompensation. We validated the scoring system in 2 independent international cohorts (Europe and the Middle East), so it appears to apply to diverse populations

A One Health overview, facilitating advances in comparative medicine and translational research.

Table of contentsA1 One health advances and successes in comparative medicine and translational researchCheryl StroudA2 Dendritic cell-targeted gorilla adenoviral vector for cancer vaccination for canine melanomaIgor Dmitriev, Elena Kashentseva, Jeffrey N. Bryan, David T. CurielA3 Viroimmunotherapy for malignant melanoma in the companion dog modelJeffrey N. Bryan, David Curiel, Igor Dmitriev, Elena Kashentseva, Hans Rindt, Carol Reinero, Carolyn J. HenryA4 Of mice and men (and dogs!): development of a commercially licensed xenogeneic DNA vaccine for companion animals with malignant melanomaPhilip J. BergmanA5 Successful immunotherapy with a recombinant HER2-expressing Listeria monocytogenes in dogs with spontaneous osteosarcoma paves the way for advances in pediatric osteosarcomaNicola J. Mason, Josephine S. Gnanandarajah, Julie B. Engiles, Falon Gray, Danielle Laughlin, Anita Gaurnier-Hausser, Anu Wallecha, Margie Huebner, Yvonne PatersonA6 Human clinical development of ADXS-HER2Daniel O'ConnorA7 Leveraging use of data for both human and veterinary benefitLaura S. TremlA8 Biologic replacement of the knee: innovations and early clinical resultsJames P. StannardA9 Mizzou BioJoint Center: a translational success storyJames L. CookA10 University and industry translational partnership: from the lab to commercializationMarc JacobsA11 Beyond docking: an evolutionarily guided OneHealth approach to drug discoveryGerald J. Wyckoff, Lee Likins, Ubadah Sabbagh, Andrew SkaffA12 Challenges and opportunities for data applications in animal health: from precision medicine to precision husbandryAmado S. GuloyA13 A cloud-based programmable platform for healthHarlen D. HaysA14 Comparative oncology: One Health in actionAmy K. LeBlancA15 Companion animal diseases bridge the translational gap for human neurodegenerative diseaseJoan R. Coates, Martin L. Katz, Leslie A. Lyons, Gayle C. Johnson, Gary S. Johnson, Dennis P. O'BrienA16 Duchenne muscular dystrophy gene therapyDongsheng DuanA17 Polycystic kidney disease: cellular mechanisms to emerging therapiesJames P. CalvetA18 The domestic cat as a large animal model for polycystic kidney diseaseLeslie A. Lyons, Barbara GandolfiA19 The support of basic and clinical research by the Polycystic Kidney Disease FoundationDavid A. BaronA20 Using naturally occurring large animal models of human disease to enable clinical translation: treatment of arthritis using autologous stromal vascular fraction in dogsMark L. WeissA21 Regulatory requirements regarding clinical use of human cells, tissues, and tissue-based productsDebra A. WebsterA22 Regenerative medicine approaches to Type 1 diabetes treatmentFrancis N. KaranuA23 The zoobiquity of canine diabetes mellitus, man's best friend is a friend indeed-islet transplantationEdward J. RobbA24 One Medicine: a development model for cellular therapy of diabetesRobert J. Harman

Advanced cognitive networked radar surveillance

The concept of a traditional monostatic radar with co-located transmit and receive antennas naturally imposes performance limits that can adversely impact applications. Using a multiplicity of transmit and receive antennas and exploiting spatial diversity provides additional degrees of design freedom that can help overcome such limitations. Further, when coupled with cognitive signal processing, such advanced systems offer significant improvement in performance over their monostatic counterparts. This will also likely lead to new applications for radar sensing. In this paper we explore the fundamentals of multistatic network radar highlighting both potential and constraints whilst identifying future research needs and applications. Initial experimental results are presented for a 2-node networked staring radar

“A very orderly retreat”: Democratic transition in East Germany, 1989-90

East Germany's 1989-90 democratisation is among the best known of East European transitions, but does not lend itself to comparative analysis, due to the singular way in which political reform and democratic consolidation were subsumed by Germany's unification process. Yet aspects of East Germany's democratisation have proved amenable to comparative approaches. This article reviews the comparative literature that refers to East Germany, and finds a schism between those who designate East Germany's transition “regime collapse” and others who contend that it exemplifies “transition through extrication”. It inquires into the merits of each position and finds in favour of the latter. Drawing on primary and secondary literature, as well as archival and interview sources, it portrays a communist elite that was, to a large extent, prepared to adapt to changing circumstances and capable of learning from “reference states” such as Poland. Although East Germany was the Soviet state in which the positions of existing elites were most threatened by democratic transition, here too a surprising number succeeded in maintaining their position while filing across the bridge to market society. A concluding section outlines the alchemy through which their bureaucratic power was transmuted into property and influence in the “new Germany”