Disease burden and economic impact of diagnosed non-alcoholic steatohepatitis (NASH) in the United Kingdom (UK) in 2018

BACKGROUNDS AND AIMS: Non-alcoholic steatohepatitis (NASH) – a progressive subset of non-alcoholic fatty liver disease (NAFLD) – is a chronic liver disease that can progress to advanced fibrosis, cirrhosis, and end-stage liver disease (ESLD) if left untreated. Early-stage NASH is usually asymptomatic, meaning a large proportion of the prevalent population are undiagnosed. Receiving a NASH diagnosis increases the probability that a patient will receive interventions for the purpose of managing their condition. The purpose of this study was to estimate the disease burden and economic impact of diagnosed NASH in the United Kingdom (UK) adult population in 2018. METHODS: The socioeconomic burden of diagnosed NASH from a societal perspective was estimated using cost-of-illness methodology applying a prevalence approach. This involved estimating the number of adults with diagnosed NASH in the UK in a base period (2018) and the economic and wellbeing costs attributable to diagnosed NASH in that period. The analysis was based on a targeted review of the scientific literature, existing databases and consultation with clinical experts, health economists and patient groups. RESULTS: Of the prevalent NASH population in the UK in 2018, an estimated 79.8% were not diagnosed. In particular, of the prevalent population in disease stages F0 to F2, only 2.0% (F0), 2.0% (F1) and 16.5% (F2), respectively, were diagnosed. Total economic costs of diagnosed NASH in the UK ranged from £2.3 billion (lower prevalence scenario, base probability of diagnosis scenario) to £4.2 billion (higher prevalence scenario, base probability of diagnosis scenario). In 2018, people with NASH in the UK were estimated to experience 94,094 to 174,564 disability-adjusted life years (DALYs) overall. Total wellbeing costs associated with NASH in 2018 were estimated to range between £5.6 to £10.5 billion. CONCLUSIONS: The prevention and appropriate management of adult NASH patients could result in reduced economic costs and improvements in wellbeing

Differential effects of saturated and unsaturated fatty acids on autophagy in pancreatic β-cells

Long-chain saturated fatty acids are lipotoxic to pancreatic β-cells, whereas most unsaturates are better tolerated and some may even be cytoprotective. Fatty acids alter autophagy in β-cells and there is increasing evidence that such alterations can impact directly on the regulation of viability. Accordingly, we have compared the effects of palmitate (C16:0) and palmitoleate (C16:1) on autophagy in cultured β-cells and human islets. Treatment of BRIN-BD11 β-cells with palmitate led to enhanced autophagic activity, as judged by cleavage of microtubule-associated protein 1 light chain 3-I (LC3-I) and this correlated with a marked loss of cell viability in the cells. In addition, transfection of these cells with an mCherry-YFP-LC3 reporter construct revealed the accumulation of autophagosomes in palmitate-treated cells, indicating an impairment of autophagosome-lysosome fusion. This was also seen upon addition of the vacuolar ATPase inhibitor, bafilomycin A1. Exposure of BRIN-BD11 cells to palmitoleate (C16:1) did not lead directly to changes in autophagic activity or flux, but it antagonised the actions of palmitate. In parallel, palmitoleate also improved the viability of palmitate-treated BRIN-BD11 cells. Equivalent responses were observed in INS-1E cells and in isolated human islets. Taken together, these data suggest that palmitate may cause an impairment of autophagosome-lysosome fusion. These effects were not reproduced by palmitoleate which, instead, antagonised the responses mediated by palmitate suggesting that attenuation of β-cell stress may contribute to the improvement in cell viability caused by the mono-unsaturated fatty acid.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.The authors are grateful to Diabetes UK for financial support via project grants 14/0005093 and 15/0005156 (to N G M) and a PhD studentship (14/0005093) to Patricia Thomas. They also thank Dr Jon Lane (University of Bristol) for the kind gift of a dual-fluorescence LC3 reporter construct.accepted version (12 month embargo), submitted versio

Cross-polarized photon-pair generation and bi-chromatically pumped optical parametric oscillation on a chip

Nonlinear optical processes are one of the most important tools in modern optics with a broad spectrum of applications in, for example, frequency conversion, spectroscopy, signal processing and quantum optics. For practical and ultimately widespread implementation, on-chip devices compatible with electronic integrated circuit technology offer great advantages in terms of low cost, small footprint, high performance and low energy consumption. While many on-chip key components have been realized, to date polarization has not been fully exploited as a degree of freedom for integrated nonlinear devices. In particular, frequency conversion based on orthogonally polarized beams has not yet been demonstrated on chip. Here we show frequency mixing between orthogonal polarization modes in a compact integrated microring resonator and demonstrate a bi-chromatically pumped optical parametric oscillator. Operating the device above and below threshold, we directly generate orthogonally polarized beams, as well as photon pairs, respectively, that can find applications, for example, in optical communication and quantum optics

Effects of ecstasy/polydrug use on memory for associative information

Rationale Associative learning underpins behaviours that are fundamental to the everyday functioning of the individual. Evidence pointing to learning deficits in recreational drug users merits further examination. Objectives A word pair learning task was administered to examine associative learning processes in ecstasy/polydrug users. Methods After assignment to either single or divided attention conditions, 44 ecstasy/polydrug users and 48 non-users were presented with 80 word pairs at encoding. Following this, four types of stimuli were presented at the recognition phase: the words as originally paired (old pairs), previously presented words in different pairings (conjunction pairs), old words paired with new words, and pairs of new words (not presented previously). The task was to identify which of the stimuli were intact old pairs. Results Ecstasy/ploydrug users produced significantly more false-positive responses overall compared to non-users. Increased long-term frequency of ecstasy use was positively associated with the propensity to produce false-positive responses. It was also associated with a more liberal signal detection theory decision criterion value. Measures of long term and recent cannabis use were also associated with these same word pair learning outcome measures. Conjunction word pairs, irrespective of drug use, generated the highest level of false-positive responses and significantly more false-positive responses were made in the divided attention condition compared to the single attention condition. Conclusions Overall, the results suggest that long-term ecstasy exposure may induce a deficit in associative learning and this may be in part a consequence of users adopting a more liberal decision criterion value

ERP evidence suggests executive dysfunction in ecstasy polydrug users

Background: Deficits in executive functions such as access to semantic/long-term memory have been shown in ecstasy users in previous research. Equally, there have been many reports of equivocal findings in this area. The current study sought to further investigate behavioural and electro-physiological measures of this executive function in ecstasy users. Method: Twenty ecstasy–polydrug users, 20 non-ecstasy–polydrug users and 20 drug-naïve controls were recruited. Participants completed background questionnaires about their drug use, sleep quality, fluid intelligence and mood state. Each individual also completed a semantic retrieval task whilst 64 channel Electroencephalography (EEG) measures were recorded. Results: Analysis of Variance (ANOVA) revealed no between-group differences in behavioural performance on the task. Mixed ANOVA on event-related potential (ERP) components P2, N2 and P3 revealed significant between-group differences in the N2 component. Subsequent exploratory univariate ANOVAs on the N2 component revealed marginally significant between-group differences, generally showing greater negativity at occipito-parietal electrodes in ecstasy users compared to drug-naïve controls. Despite absence of behavioural differences, differences in N2 magnitude are evidence of abnormal executive functioning in ecstasy–polydrug users

High Level of Pyrethroid Resistance in an Anopheles funestus Population of the Chokwe District in Mozambique

Background Although Anopheles funestus is difficult to rear, it is crucial to analyse field populations of this malaria vector in order to successfully characterise mechanisms of insecticide resistance observed in this species in Africa. In this study we carried out a large-scale field collection and rearing of An. funestus from Mozambique in order to analyse its susceptibility status to insecticides and to broadly characterise the main resistance mechanisms involved in natural populations. Methodology/Principal Findings 3,000 F1 adults were obtained through larval rearing. WHO susceptibility assays indicated a very high resistance to pyrethroids with no mortality recorded after 1h30min exposure and less than 50% mortality at 3h30min. Resistance to the carbamate, bendiocarb was also noted, with 70% mortality after 1h exposure. In contrast, no DDT resistance was observed, indicating that no kdr-type resistance was involved. The sequencing of the acetylcholinesterase gene indicated the absence of the G119S and F455W mutations associated with carbamate and organophosphate resistance. This could explain the absence of malathion resistance in this population. Both biochemical assays and quantitative PCR implicated up-regulated P450 genes in pyrethroid resistance, with GSTs playing a secondary role. The carbamate resistance observed in this population is probably conferred by the observed altered AChE with esterases also involved. Conclusion/Significance The high level of pyrethroid resistance in this population despite the cessation of pyrethroid use for IRS in 1999 is a serious concern for resistance management strategies such as rotational use of insecticides. As DDT has now been re-introduced for IRS, susceptibility to DDT needs to be closely monitored to prevent the appearance and spread of resistance to this insecticide

BioTorrents: A File Sharing Service for Scientific Data

The transfer of scientific data has emerged as a significant challenge, as datasets continue to grow in size and demand for open access sharing increases. Current methods for file transfer do not scale well for large files and can cause long transfer times. In this study we present BioTorrents, a website that allows open access sharing of scientific data and uses the popular BitTorrent peer-to-peer file sharing technology. BioTorrents allows files to be transferred rapidly due to the sharing of bandwidth across multiple institutions and provides more reliable file transfers due to the built-in error checking of the file sharing technology. BioTorrents contains multiple features, including keyword searching, category browsing, RSS feeds, torrent comments, and a discussion forum. BioTorrents is available at http://www.biotorrents.net

Psychiatric and medical admissions observed among elderly patients with new-onset epilepsy

<p>Abstract</p> <p>Background</p> <p>Inpatient utilization associated with incidence of geriatric new-onset epilepsy has not been characterized in any large study, despite recognized high levels of risk factors (comorbidity).</p> <p>Methods</p> <p>Retrospective study using administrative data (Oct '01-Sep '05) from the Veterans Health Administration from a nationwide sample of 824,483 patients over age 66 in the retrospective observational Treatment In Geriatric Epilepsy Research (TIGER) study. Psychiatric and medical hospital admissions were analyzed as a function of patient demographics, comorbid psychiatric, neurological, and other medical conditions, and new-onset epilepsy.</p> <p>Results</p> <p>Elderly patients experienced a 15% hospitalization rate in FY00 overall, but the subset of new-onset epilepsy patients (n = 1,610) had a 52% hospitalization rate. New-onset epilepsy was associated with three-fold increased relative odds of psychiatric admission and nearly five-fold increased relative odds of medical admission. Among new-onset epilepsy patients, alcohol dependence was most strongly associated with psychiatric admission during the first year after epilepsy onset (odds ratio = 5.2; 95% confidence interval 2.6-10.0), while for medical admissions the strongest factor was myocardial infarction (odds ratio = 4.7; 95% confidence interval 2.7-8.3).</p> <p>Conclusion</p> <p>From the patient point of view, new-onset epilepsy was associated with an increased risk of medical admission as well as of psychiatric admission. From an analytic perspective, omitting epilepsy and other neurological conditions may lead to overestimation of the risk of admission attributable solely to psychiatric conditions. Finally, from a health systems perspective, the emerging picture of the epilepsy patient with considerable comorbidity and demand for healthcare resources may merit development of practice guidelines to improve coordinated delivery of care.</p

Pyrethroid Resistance in an Anopheles funestus Population from Uganda

Background: The susceptibility status of Anopheles funestus to insecticides remains largely unknown in most parts of Africa because of the difficulty in rearing field-caught mosquitoes of this malaria vector. Here we report the susceptibility status of the An. funestus population from Tororo district in Uganda and a preliminary haracterisation of the putative resistance mechanisms involved. Methodology/Principal Findings: A new forced egg laying technique used in this study significantly increased the numbers of field-caught females laying eggs and generated more than 4000 F1 adults. WHO bioassays indicated that An. funestus in Tororo is resistant to pyrethroids (62% mortality after 1 h exposure to 0.75% permethrin and 28% mortality to 0.05% deltamethrin). Suspected DDT resistance was also observed with 82% mortality. However this population is fully susceptible to bendiocarb (carbamate), malathion (organophosphate) and dieldrin with 100% mortality observed after exposure to each of these insecticides. Sequencing of a fragment of the sodium channel gene containing the 1014 codon conferring pyrethroid/DDT resistance in An. gambiae did not detect the L1014F kdr mutation but a correlation between haplotypes and resistance phenotype was observed indicating that mutations in other exons may be conferring the knockdown resistance in this species. Biochemical assays suggest that resistance in this population is mediated by metabolic resistance with elevated level of GSTs, P450s and pNPA compared to a susceptible strain of Anopheles gambiae. RT-PCR further confirmed the involvement of P450s with a 12-fold over-expression of CYP6P9b in the Tororo population compared to the fully susceptible laboratory colony FANG. Conclusion: This study represents the first report of pyrethroid/DDT resistance in An. funestus from East Africa. With resistance already reported in southern and West Africa, this indicates that resistance in An. funestus may be more widespread than previously assumed and therefore this should be taken into account for the implementation and management of vector control programs in Africa