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

Informing investment to reduce inequalities: a modelling approach

Background: Reducing health inequalities is an important policy objective but there is limited quantitative information about the impact of specific interventions. Objectives: To provide estimates of the impact of a range of interventions on health and health inequalities. Materials and methods: Literature reviews were conducted to identify the best evidence linking interventions to mortality and hospital admissions. We examined interventions across the determinants of health: a ‘living wage’; changes to benefits, taxation and employment; active travel; tobacco taxation; smoking cessation, alcohol brief interventions, and weight management services. A model was developed to estimate mortality and years of life lost (YLL) in intervention and comparison populations over a 20-year time period following interventions delivered only in the first year. We estimated changes in inequalities using the relative index of inequality (RII). Results: Introduction of a ‘living wage’ generated the largest beneficial health impact, with modest reductions in health inequalities. Benefits increases had modest positive impacts on health and health inequalities. Income tax increases had negative impacts on population health but reduced inequalities, while council tax increases worsened both health and health inequalities. Active travel increases had minimally positive effects on population health but widened health inequalities. Increases in employment reduced inequalities only when targeted to the most deprived groups. Tobacco taxation had modestly positive impacts on health but little impact on health inequalities. Alcohol brief interventions had modestly positive impacts on health and health inequalities only when strongly socially targeted, while smoking cessation and weight-reduction programmes had minimal impacts on health and health inequalities even when socially targeted. Conclusions: Interventions have markedly different effects on mortality, hospitalisations and inequalities. The most effective (and likely cost-effective) interventions for reducing inequalities were regulatory and tax options. Interventions focused on individual agency were much less likely to impact on inequalities, even when targeted at the most deprived communities

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

Towards transforming community eye care: an observational study and time-series analysis of optometrists' prescribing for eye disorders

Objectives: This study aimed to provide evidence on the therapeutic prescribing activity by community optometrists in Scotland and to determine its impact on workload in general practice and ophthalmology clinics. Study design: Scottish administrative healthcare data for a 53-month period (November 2013–April 2018) were used to analyse non-medical prescribing practice by optometrists. Methods: Using interrupted time-series regression (Autoregressive Integrated Moving Average), we assessed the impact of optometrist prescribing on ophthalmology outpatient attendances and general practice prescribing for eye disorders. Results: A total of 54,246 items were prescribed by 205 optometrists over the study period. Since the commencement of data recording, optometrist prescribing activity increased steadily from a baseline of zero to 1.2% of all ophthalmic items prescribed. Neither the monthly number of items prescribed nor the size of optometric workforce were associated with a reduction in ophthalmology outpatient appointments over time. Conclusions: Optometrists increasingly contribute to community ophthalmic prescribing in Scotland, releasing capacity and lessening general practice, but not secondary care workload. There appears to be an underutilisation of optometrists related to the management of dry eye, which represents an opportunity to release further capacity

Influence of Levulinoyl Protecting Groups on Glycosylation Stereoselectivity and Glycosyl Cation Structure

The stereoselective synthesis of 1,2-cis glycosidic bonds is historically challenging, and a common synthetic approach is based on the participation of remote protecting ester groups. Common intermediates of glycosylation reactions are glycosyl cations, whose structures are difficult to characterize. Here, the glycosylation reactions and structure of the glycosyl cations of galactose and mannose are investigated when protected with levulinic acid (Lev) at C4 and/or C6, respectively. The glycosyl cations can be assigned to rearranged structures as a consequence of ring opening, as well as dioxolenium ions that suggest remote participation. Some evidence for the long-range interaction of the Lev keto group is found as previously proposed, which could explain unusual solution-phase stereoselectivities observed

Influence of levulinoyl protecting groups on glycosylation stereoselectivity and glycosyl cation structure

The stereoselective synthesis of 1,2-cis glycosidic bonds is historically challenging, and a common synthetic approach is based on the participation of remote protecting ester groups. A common intermediate of glycosylation reactions are glycosyl cations, whose structures are difficult to characterise. Here, we investigate the glycosylation reactions and structure of the glycosyl cations of galactose and mannose when protected with levulinic acid (Lev) at C4 and/or C6, respectively. The glycosyl cations can be assigned to rearranged structures as a consequence of ring opening, and dioxolenium ions that suggest remote participation, respectively. Some evidence for the long-range interaction of the Lev keto group was found as previously proposed, which could explain certain unusual solution-phase stereoselectivities observed

Hexanuclear Ln6L6 Complex Formation by using an Unsymmetric Ligand

Multinuclear, self‐assembled lanthanide complexes present clear opportunities as sensors and imaging agents. Despite the widely acknowledged potential of this class of supramolecule, synthetic and characterization challenges continue to limit systematic studies into their self‐assembly restricting the number and variety of lanthanide architectures reported relative to their transition metal counterparts. Here we present the first study evaluating the effect of ligand backbone symmetry on multinuclear lanthanide complex self‐assembly. Replacement of a symmetric ethylene linker with an unsymmetric amide at the centre of a homoditopic ligand governs formation of an unusual Ln6L6 complex with coordinatively unsaturated metal centres. The choice of triflate as a counterion, and the effect of ionic radii are shown to be critical for formation of the Ln6L6 complex. The atypical Ln6L6 architecture is characterized using a combination of mass spectrometry, luminescence, DOSY NMR and EPR spectroscopy measurements. Luminescence experiments support clear differences between comparable Eu6L6 and Eu2L3 complexes, with relatively short luminescent lifetimes and low quantum yields observed for the Eu6L6 structure indicative of non‐radiative decay processes. Synthesis of the Gd6L6analogue allows three distinct Gd···Gd distance measurements to be extracted using homo‐RIDME EPR experiments

Alternative splicing substantially diversifies the transcriptome during early photomorphogenesis and correlates with the energy availability in arabidopsis

Plants use light as source of energy and information to detect diurnal rhythms and seasonal changes. Sensing changing light conditions is critical to adjust plant metabolism and to initiate developmental transitions. Here we analyzed transcriptome-wide alterations in gene expression and alternative splicing (AS) of etiolated seedlings undergoing photomorphogenesis upon exposure to blue, red, or white light. Our analysis revealed massive transcriptome reprograming as reflected by differential expression of ~20% of all genes and changes in several hundred AS events. For more than 60% of all regulated AS events, light promoted the production of a presumably protein-coding variant at the expense of an mRNA with nonsense-mediated decay-triggering features. Accordingly, AS of the putative splicing factor REDUCED RED-LIGHT RESPONSES IN CRY1CRY2 BACKGROUND 1 (RRC1), previously identified as a red light signaling component, was shifted to the functional variant under light. Downstream analyses of candidate AS events pointed at a role of photoreceptor signaling only in monochromatic but not in white light. Furthermore, we demonstrated similar AS changes upon light exposure and exogenous sugar supply, with a critical involvement of kinase signaling. We propose that AS is an integration point of signaling pathways that sense and transmit information regarding the energy availability in plants

Evaluating the effect of inequalities in oral anti-coagulant prescribing on outcomes in people with atrial fibrillation

Background: Whilst anti-coagulation is typically recommended for thromboprophylaxis in atrial fibrillation (AF), it is often never prescribed, or prematurely discontinued. The aim of this study was to evaluate the effect of inequalities in anti-coagulant prescribing by assessing stroke/systemic embolism (SSE) and bleeding risk in people with AF who continue anticoagulation compared with those who stop transiently, permanently, or never start. Methods: This retrospective cohort study utilised linked Scottish healthcare data to identify adults diagnosed with AF between January 2010 and April 2016, with a CHA2DS2-VASC score of ≥2. They were sub-categorised based on anti-coagulant exposure: never started, continuous, discontinuous, and cessation. Inverse probability of treatment weighting-adjusted Cox regression and competing-risks regression were utilised to compare SSE and bleeding risks between cohorts during five year follow-up. Results: Of an overall cohort of 47,427 people, 26,277 (55.41%) were never anti-coagulated, 7,934 (16.72%) received continuous anti-coagulation, 9,107 (19.2%) temporarily discontinued and 4,109 (8.66%) permanently discontinued. Lower socio-economic status, elevated frailty score, and age ≥75 were associated with a reduced likelihood of initiation and continuation of anti-coagulation. SSE risk was significantly greater in those with discontinuous anti-coagulation, compared to continuous (SHR: 2.65; 2.39-2.94). In the context of a major bleeding event, there was no significant difference in bleeding risk between the cessation and continuous cohorts (SHR 0.94; 0.42-2.14). Conclusion: Our data suggest significant inequalities in anti-coagulation prescribing, with substantial opportunity to improve initiation and continuation. Decision-making should be patient-centered and must recognise that discontinuation or cessation is associated with considerable thromboembolic risk not offset by mitigated bleeding risk

Faecal Escherichia coli as biological indicator of spatial interaction between domestic pigs and wild boar (Sus scrofa) in Corsica

On the Mediterranean island of Corsica, cohabitation between sympatric domestic pigs and Eurasian wild boar (Sus scrofa) is common and widespread and can facilitate the maintenance and dissemination of several pathogens detrimental for the pig industry or human health. In this study, we monitored a population of free-ranging domestic pigs reared in extensive conditions within a 800-ha property located in Central Corsica which was frequently visited by a sympatric population of wild boar between 2013 and 2015. We used GPS collars to assess evidence of a spatially shared environment. Subsequently, we analysed by PFGE of XbaI-restricted DNA if those populations shared faecal Escherichia coli clones that would indicate contact and compared these results with those collected in a distant (separated by at least 50 km) population of wild boar used as control. Results showed that one of eight wild boars sampled in the study area shed E. coli XbaI clones identical to clones isolated from domestic pig sounders from the farm, while wild boar populations sampled in distant parts of the study area shared no identical clone with the domestic pigs monitored. Interestingly, within the sampled pigs, two identical clones were found in 2013 and in 2015, indicating a long-time persisting colonization type. Although the method of isolation of E. coli and PFGE typing of the isolates requires intensive laboratory work, it is applicable under field conditions to monitor potential infectious contacts. It also provides evidence of exchange of microorganisms between sympatric domestic pigs and wild boar populations. (Résumé d'auteur