81 research outputs found

    A cost effectiveness analysis of the preferred antidotes for acute paracetamol poisoning patients in Sri Lanka

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    Background: Acute paracetamol poisoning is a rapidly increasing problem in Sri Lanka. The antidotes are expensive and yet no health economic evaluation has been done on the therapy for acute paracetamol poisoning in the developing world. The aim of this study is to determine the cost effectiveness of using N-acetylcysteine over methionine in the management of acute paracetamol poisoning in Sri Lanka. Methods:Economic analysis was applied using public healthcare system payer perspective. Costs were obtained from a series of patients admitted to the National Hospital of Sri Lanka with a history of acute paracetamol overdose. Evidence on effectiveness was obtained from a systematic review of the literature. Death due to hepatotoxicity was used as the primary outcome of interest. Analysis and development of decision tree models was done using Tree Age Pro 2008. Results: An affordable treatment threshold of Sri Lankan rupees 1,537,120/death prevented was set from the expected years of productive life gained and the average contribution to GDP. A cost-minimisation analysis was appropriate for patients presenting within 10 hours and methionine was the least costly antidote. For patients presenting 10-24 hours after poisoning, n-acetylcysteine was more effective and the incremental cost effectiveness ratio of Sri Lankan rupees 316,182/life saved was well under the threshold. One-way and multi-way sensitivity analysis also supported methionine for patients treated within 10 hours and n-acetylcysteine for patients treated within 10-24 hours as preferred antidotes.Conclusions: Post ingestion time is an important determinant of preferred antidotal therapy for acute paracetamol poisoning patients in Sri Lanka. Using n-acetylcysteine in all patients is not cost effective. On economic grounds, methionine should become the preferred antidote for Sri Lankan patients treated within 10 hours of the acute ingestion and n-acetylcysteine should continue to be given to patients treated within 10-24 hours

    Primary biliary cirrhosis

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    Primary biliary cirrhosis (PBC) is a chronic and slowly progressive cholestatic liver disease of autoimmune etiology characterized by injury of the intrahepatic bile ducts that may eventually lead to liver failure. Affected individuals are usually in their fifth to seventh decades of life at time of diagnosis, and 90% are women. Annual incidence is estimated between 0.7 and 49 cases per million-population and prevalence between 6.7 and 940 cases per million-population (depending on age and sex). The majority of patients are asymptomatic at diagnosis, however, some patients present with symptoms of fatigue and/or pruritus. Patients may even present with ascites, hepatic encephalopathy and/or esophageal variceal hemorrhage. PBC is associated with other autoimmune diseases such as Sjogren's syndrome, scleroderma, Raynaud's phenomenon and CREST syndrome and is regarded as an organ specific autoimmune disease. Genetic susceptibility as a predisposing factor for PBC has been suggested. Environmental factors may have potential causative role (infection, chemicals, smoking). Diagnosis is based on a combination of clinical features, abnormal liver biochemical pattern in a cholestatic picture persisting for more than six months and presence of detectable antimitochondrial antibodies (AMA) in serum. All AMA negative patients with cholestatic liver disease should be carefully evaluated with cholangiography and liver biopsy. Ursodeoxycholic acid (UDCA) is the only currently known medication that can slow the disease progression. Patients, particularly those who start UDCA treatment at early-stage disease and who respond in terms of improvement of the liver biochemistry, have a good prognosis. Liver transplantation is usually an option for patients with liver failure and the outcome is 70% survival at 7 years. Recently, animal models have been discovered that may provide a new insight into the pathogenesis of this disease and facilitate appreciation for novel treatment in PBC

    Primary biliary cirrhosis

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    Primary biliary cirrhosis (PBC) is an immune-mediated chronic cholestatic liver disease with a slowly progressive course. Without treatment, most patients eventually develop fibrosis and cirrhosis of the liver and may need liver transplantation in the late stage of disease. PBC primarily affects women (female preponderance 9–10:1) with a prevalence of up to 1 in 1,000 women over 40 years of age. Common symptoms of the disease are fatigue and pruritus, but most patients are asymptomatic at first presentation. The diagnosis is based on sustained elevation of serum markers of cholestasis, i.e., alkaline phosphatase and gamma-glutamyl transferase, and the presence of serum antimitochondrial antibodies directed against the E2 subunit of the pyruvate dehydrogenase complex. Histologically, PBC is characterized by florid bile duct lesions with damage to biliary epithelial cells, an often dense portal inflammatory infiltrate and progressive loss of small intrahepatic bile ducts. Although the insight into pathogenetic aspects of PBC has grown enormously during the recent decade and numerous genetic, environmental, and infectious factors have been disclosed which may contribute to the development of PBC, the precise pathogenesis remains enigmatic. Ursodeoxycholic acid (UDCA) is currently the only FDA-approved medical treatment for PBC. When administered at adequate doses of 13–15 mg/kg/day, up to two out of three patients with PBC may have a normal life expectancy without additional therapeutic measures. The mode of action of UDCA is still under discussion, but stimulation of impaired hepatocellular and cholangiocellular secretion, detoxification of bile, and antiapoptotic effects may represent key mechanisms. One out of three patients does not adequately respond to UDCA therapy and may need additional medical therapy and/or liver transplantation. This review summarizes current knowledge on the clinical, diagnostic, pathogenetic, and therapeutic aspects of PBC

    The role of ETG modes in JET-ILW pedestals with varying levels of power and fuelling

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    We present the results of GENE gyrokinetic calculations based on a series of JET-ITER-like-wall (ILW) type I ELMy H-mode discharges operating with similar experimental inputs but at different levels of power and gas fuelling. We show that turbulence due to electron-temperature-gradient (ETGs) modes produces a significant amount of heat flux in four JET-ILW discharges, and, when combined with neoclassical simulations, is able to reproduce the experimental heat flux for the two low gas pulses. The simulations plausibly reproduce the high-gas heat fluxes as well, although power balance analysis is complicated by short ELM cycles. By independently varying the normalised temperature gradients (omega(T)(e)) and normalised density gradients (omega(ne )) around their experimental values, we demonstrate that it is the ratio of these two quantities eta(e) = omega(Te)/omega(ne) that determines the location of the peak in the ETG growth rate and heat flux spectra. The heat flux increases rapidly as eta(e) increases above the experimental point, suggesting that ETGs limit the temperature gradient in these pulses. When quantities are normalised using the minor radius, only increases in omega(Te) produce appreciable increases in the ETG growth rates, as well as the largest increases in turbulent heat flux which follow scalings similar to that of critical balance theory. However, when the heat flux is normalised to the electron gyro-Bohm heat flux using the temperature gradient scale length L-Te, it follows a linear trend in correspondence with previous work by different authors

    Spectroscopic camera analysis of the roles of molecularly assisted reaction chains during detachment in JET L-mode plasmas

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    The roles of the molecularly assisted ionization (MAI), recombination (MAR) and dissociation (MAD) reaction chains with respect to the purely atomic ionization and recombination processes were studied experimentally during detachment in low-confinement mode (L-mode) plasmas in JET with the help of experimentally inferred divertor plasma and neutral conditions, extracted previously from filtered camera observations of deuterium Balmer emission, and the reaction coefficients provided by the ADAS, AMJUEL and H2VIBR atomic and molecular databases. The direct contribution of MAI and MAR in the outer divertor particle balance was found to be inferior to the electron-atom ionization (EAI) and electron-ion recombination (EIR). Near the outer strike point, a strong atom source due to the D+2-driven MAD was, however, observed to correlate with the onset of detachment at outer strike point temperatures of Te,osp = 0.9-2.0 eV via increased plasma-neutral interactions before the increasing dominance of EIR at Te,osp < 0.9 eV, followed by increasing degree of detachment. The analysis was supported by predictions from EDGE2D-EIRENE simulations which were in qualitative agreement with the experimental observations

    Shattered pellet injection experiments at JET in support of the ITER disruption mitigation system design

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    A series of experiments have been executed at JET to assess the efficacy of the newly installed shattered pellet injection (SPI) system in mitigating the effects of disruptions. Issues, important for the ITER disruption mitigation system, such as thermal load mitigation, avoidance of runaway electron (RE) formation, radiation asymmetries during thermal quench mitigation, electromagnetic load control and RE energy dissipation have been addressed over a large parameter range. The efficiency of the mitigation has been examined for the various SPI injection strategies. The paper summarises the results from these JET SPI experiments and discusses their implications for the ITER disruption mitigation scheme

    New H-mode regimes with small ELMs and high thermal confinement in the Joint European Torus

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    New H-mode regimes with high confinement, low core impurity accumulation, and small edge-localized mode perturbations have been obtained in magnetically confined plasmas at the Joint European Torus tokamak. Such regimes are achieved by means of optimized particle fueling conditions at high input power, current, and magnetic field, which lead to a self-organized state with a strong increase in rotation and ion temperature and a decrease in the edge density. An interplay between core and edge plasma regions leads to reduced turbulence levels and outward impurity convection. These results pave the way to an attractive alternative to the standard plasmas considered for fusion energy generation in a tokamak with a metallic wall environment such as the ones expected in ITER.& nbsp;Published under an exclusive license by AIP Publishing

    Peripheral temperature gradient screening of high-Z impurities in optimised 'hybrid' scenario H-mode plasmas in JET-ILW

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    Screening of high-Z (W) impurities from the confined plasma by the temperature gradient at the plasma periphery of fusion-grade H-mode plasmas has been demonstrated in the JET-ILW (ITER-like wall) tokamak. Through careful optimisation of the hybrid-scenario, deuterium plasmas with sufficient heating power (greater than or similar to 32 MW), high enough ion temperature gradients at the H-mode pedestal top can be achieved for the collisional, neo-classical convection of the W impurities to be directed outwards, expelling them from the confined plasma. Measurements of the W impurity fluxes between and during edge-localised modes (ELMs) based on fast bolometry measurements show that in such plasmas there is a net efflux (loss) between ELMs but that ELMs often allow some W back into the confined plasma. Provided steady, high-power heating is maintained, this mechanism allows such plasmas to sustain high performance, with an average D-D neutron rate of similar to 3.2 x 10(16) s(-1) over a period of similar to 3 s, after an initial overshoot (equivalent to a D-T fusion power of similar to 9.4 MW), without an uncontrolled rise in W impurity radiation, giving added confidence that impurity screening by the pedestal may also occur in ITER, as has previously been predicted (Dux et al 2017 Nucl. Mater. Energy 12 28-35)

    Testing a prediction model for the H-mode density pedestal against JET-ILW pedestals

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    The neutral ionisation model proposed by Groebner et al (2002 Phys. Plasmas 9 2134) to determine the plasma density profile in the H-mode pedestal, is extended to include charge exchange processes in the pedestal stimulated by the ideas of Mahdavi et al (2003 Phys. Plasmas 10 3984). The model is then tested against JET H-mode pedestal data, both in a 'standalone' version using experimental temperature profiles and also by incorporating it in the Europed version of EPED. The model is able to predict the density pedestal over a wide range of conditions with good accuracy. It is also able to predict the experimentally observed isotope effect on the density pedestal that eludes simpler neutral ionization models

    Disruption prediction at JET through deep convolutional neural networks using spatiotemporal information from plasma profiles

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    In view of the future high power nuclear fusion experiments, the early identification of disruptions is a mandatory requirement, and presently the main goal is moving from the disruption mitigation to disruption avoidance and control. In this work, a deep-convolutional neural network (CNN) is proposed to provide early detection of disruptive events at JET. The CNN ability to learn relevant features, avoiding hand-engineered feature extraction, has been exploited to extract the spatiotemporal information from 1D plasma profiles. The model is trained with regularly terminated discharges and automatically selected disruptive phase of disruptions, coming from the recent ITER-like-wall experiments. The prediction performance is evaluated using a set of discharges representative of different operating scenarios, and an in-depth analysis is made to evaluate the performance evolution with respect to the considered experimental conditions. Finally, as real-time triggers and termination schemes are being developed at JET, the proposed model has been tested on a set of recent experiments dedicated to plasma termination for disruption avoidance and mitigation. The CNN model demonstrates very high performance, and the exploitation of 1D plasma profiles as model input allows us to understand the underlying physical phenomena behind the predictor decision
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