Techno-Economic and life cycle assessment of standalone Single-Stream material recovery facilities in the United states.

Material Recovery Facilities (MRFs) are crucial players in achieving a circular economy. MRFs receive complex waste streams and separate valuable recyclables from these mixtures. This study conducts techno-economic analysis (TEA) to estimate the net present value (NPV) and life cycle assessment (LCA) to estimate different environmental impacts of a commercial scale standalone, single-stream MRF to assess the economic feasibility and environmental impacts of recovering valuable recyclables from an MRF processing 120,000 tonnes per year (t/y). The TEA employs a discounted cash flow rate of return (DCFROR) analysis over a 20-year facility lifetime, along with a sensitivity analysis on the impact of different operating and economic parameters. Results show that the total fixed cost of building the MRF facility is $23 MM, and the operating cost is $45.48/tonne. The NPV of the MRF can vary from $3.57 MM to $60 MM, while 100-year global warming potential can range from 5.98 to 8.53 kg carbon dioxide equivalents (CO2-eq) per tonne of MSW. We have also found that MSW composition (arising from regional effects) significantly impacts costs, 100-year global warming potential, and other impact categories such as acidification potential, eutrophication potential, ecotoxicity, ozone depletion, photochemical oxidation, carcinogenic effects, and non-carcinogenic effects. Sensitivity and uncertainty analysis indicate that waste composition and market prices significantly impact the profitability of the MRF, and the waste composition mostly impacts global warming potential. Our analysis also indicates that facility capacity, fixed capital cost, and waste tipping fees are vital parameters that affect the economic viability of MRF operations.

Techno-economic and life cycle analysis of a farm-scale anaerobic digestion plant in Iowa.

There is growing interest in the use of anaerobic digestion to increase revenues in rural areas and reduce greenhouse gas emissions. This study evaluates the economic and environmental feasibility of a farm-scale anaerobic digestion (AD) combined heat and power (CHP) plant co-located with a cattle feedlot. The study evaluates two different scenarios with six cases - Biomass Only (BO) scenario and Biomass and Glycerin (BG) scenario, targeting a power capacity of 950 kWe using combinations of manure, biomass, and crude glycerin. Beef cattle manure with approximately 10.15 wt% of biomass and 10 wt% of glycerin is added into the system. The internal rate of return (IRR) and greenhouse gas emissions (GHG) were calculated for six cases. The IRR ranges between 3.51% and 5.57%, and the GHG emissions range between -82.6 and 498.52 g CO2e/kWh. Glycerin reduces the operating cost by 32%. These results indicate that AD CHP could be profitable at the farm-scale depending on various parameters. Sensitivity analysis indicates that power efficiency, operating capacity and waste generation per cattle have the strongest impact on the IRR, affecting it by over 40%, while glycerin and manure emission factors are the most important for GHG emissions affecting it by over 15%. Uncertainty analysis describes the role of feedstock choice and process performance on minimizing commercialization risks.

Electronically delivered interventions to reduce antibiotic prescribing for respiratory infections in primary care: cluster RCT using electronic health records and cohort study.

BACKGROUND: Unnecessary prescribing of antibiotics in primary care is contributing to the emergence of antimicrobial drug resistance. OBJECTIVES: To develop and evaluate a multicomponent intervention for antimicrobial stewardship in primary care, and to evaluate the safety of reducing antibiotic prescribing for self-limiting respiratory infections (RTIs). INTERVENTIONS: A multicomponent intervention, developed as part of this study, including a webinar, monthly reports of general practice-specific data for antibiotic prescribing and decision support tools to inform appropriate antibiotic prescribing. DESIGN: A parallel-group, cluster randomised controlled trial. SETTING: The trial was conducted in 79 general practices in the UK Clinical Practice Research Datalink (CPRD). PARTICIPANTS: All registered patients were included. MAIN OUTCOME MEASURES: The primary outcome was the rate of antibiotic prescriptions for self-limiting RTIs over the 12-month intervention period. COHORT STUDY: A separate population-based cohort study was conducted in 610 CPRD general practices that were not exposed to the trial interventions. Data were analysed to evaluate safety outcomes for registered patients with 45.5 million person-years of follow-up from 2005 to 2014. RESULTS: There were 41 intervention trial arm practices (323,155 patient-years) and 38 control trial arm practices (259,520 patient-years). There were 98.7 antibiotic prescriptions for RTIs per 1000 patient-years in the intervention trial arm (31,907 antibiotic prescriptions) and 107.6 per 1000 patient-years in the control arm (27,923 antibiotic prescriptions) [adjusted antibiotic-prescribing rate ratio (RR) 0.88, 95% confidence interval (CI) 0.78 to 0.99; p = 0.040]. There was no evidence of effect in children aged < 15 years (RR 0.96, 95% CI 0.82 to 1.12) or adults aged ≥ 85 years (RR 0.97, 95% CI 0.79 to 1.18). Antibiotic prescribing was reduced in adults aged between 15 and 84 years (RR 0.84, 95% CI 0.75 to 0.95), that is, one antibiotic prescription was avoided for every 62 patients (95% CI 40 to 200 patients) aged 15-84 years per year. Analysis of trial data for 12 safety outcomes, including pneumonia and peritonsillar abscess, showed no evidence that these outcomes might be increased as a result of the intervention. The analysis of data from non-trial practices showed that if a general practice with an average list size of 7000 patients reduces the proportion of RTI consultations with antibiotics prescribed by 10%, then 1.1 (95% CI 0.6 to 1.5) more cases of pneumonia per year and 0.9 (95% CI 0.5 to 1.3) more cases of peritonsillar abscesses per decade may be observed. There was no evidence that mastoiditis, empyema, meningitis, intracranial abscess or Lemierre syndrome were more frequent at low-prescribing practices. LIMITATIONS: The research was based on electronic health records that may not always provide complete data. The number of practices included in the trial was smaller than initially intended. CONCLUSIONS: This study found evidence that, overall, general practice antibiotic prescribing for RTIs was reduced by this electronically delivered intervention. Antibiotic prescribing rates were reduced for adults aged 15-84 years, but not for children or the senior elderly. FUTURE WORK: Strategies for antimicrobial stewardship should employ stratified interventions that are tailored to specific age groups. Further research into the safety of reduced antibiotic prescribing is also needed. TRIAL REGISTRATION: Current Controlled Trials ISRCTN95232781. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 11. See the NIHR Journals Library website for further project information.

The overuse of antibiotics to treat infections is contributing to the rise of antibiotic resistance in bacteria. A trial was carried out to evaluate whether or not interventions delivered through general practice computer systems may be used to reduce antibiotic prescribing for self-limiting respiratory tract infections (RTIs). The study was carried out in 79 UK general practices. The study tested the effect of a webinar to introduce the trial interventions, which included monthly feedback reports of data for respiratory consultations and antibiotic prescriptions, as well as computer-delivered decision support tools. These interventions were specially developed for this study and were pre-tested with general practitioners and practice nurses. Over the 12-month intervention period, the antibiotic-prescribing rate was about 12% lower in the intervention trial arm than in the control arm. There was no effect of intervention in children aged < 15 years or adults aged ≥ 85 years, but antibiotic prescribing was reduced by about 16% in adults aged between 15 and 84 years. Assuming this was caused by the intervention, one antibiotic prescription was avoided per year for every 62 patients aged between 15 and 84 years and registered with a trial practice. The study found no evidence that the intervention might increase the risk of 12 bacterial infections. In addition, a follow-up study of 610 UK general practices not included in the trial was conducted. The study found that if a general practice with an average list size of 7000 patients reduces the proportion of RTI consultations with antibiotics prescribed by 10%, then it may be possible to observe about one more case of pneumonia per year and one more case of peritonsillar abscess per decade, but no increase in other infections is likely. It can be concluded that electronically delivered interventions, including feedback of antibiotic-prescribing data for specific indications, may have the potential to reduce unnecessary antibiotic prescribing; however, antimicrobial stewardship interventions need to be tailored to particular age groups.

Cost-Efficient and Easy to Perform PCR-Based Assay to Identify Met Exon 14 Skipping in Formalin-Fixed Paraffin-Embedded (FFPE) Non-Small Cell Lung Cancer (NSCLC) Samples.

MET is a receptor tyrosine kinase (RTK) that plays important roles in carcinogenesis. Despite being frequently overexpressed in cancer, clinical responses to targeting this receptor have been limited. Recently novel splicing mutations involving the loss of exon 14 (called METex14 skipping) have emerged as potential biomarkers to predict for responsiveness to targeted therapies with Met inhibitors in non-small cell lung cancer (NSCLC). Currently, the diverse genomic alterations responsible for METex14 skipping pose a challenge for routine clinical diagnostic testing. In this report, we examine three different methodologies to detect METex14 and assess their potential utility for use as a diagnostic assay for both the identification of METex14 and intra-tumoural distribution in NSCLC.

Performance of Bacillus subtilis on fibrous biomass sugar hydrolysates in producing biosurfactants and techno-economic comparison.

Surfactin and fatty acetyl glutamate (FA-Glu) were produced by Bacillus subtilis in 5-L fermentor. In a previous 50-mL shake flask study, sugar hydrolysates from soy hull, alfalfa and switchgrass were shown to support the growth of Bacillus strains. It was observed that glucose content and availability of hexose and pentose sugars in the hydrolysates played an important role in determining growth and product concentration. Growth, economic efficiency and product concentration of biosurfactants was compared in fermentations conducted in 5-L stirred tank bioreactor, on biomass hydrolysate-based growth media. Highest bacterial growth absorbance for surfactin and FA-Glu producing strains were at 3.5 and 3.3 absorbance units, respectively, for switchgrass hydrolysate media. Highest concentrations of products were observed in soy hull hydrolysate media (2.9 g/L and 0.28 g/L for surfactin and FA-Glu). Techno-economic analysis of the 5-L fermentations on the three biomasses showed surfactin cost estimate to be $6.63/kg for 97% pure product.

The impact of rifaximin-α on the hospital resource use associated with the management of patients with hepatic encephalopathy: a retrospective observational study (IMPRESS).

OBJECTIVE: To compare all-cause and liver-related hospital resource use in the 6 and 12 months pre-rifaximin-α and post-rifaximin-α initiation in UK patients with hepatic encephalopathy (HE). DESIGN: A UK multicentre, retrospective, observational study. Patients' medical records were reviewed for demographics, clinical outcomes and adverse events (AEs) to rifaximin-α. Details of hospital admissions/attendances in the 6 and 12 months pre-rifaximin-α and post-rifaximin-α initiation were extracted from hospital electronic databases. SETTING: 13 National Health Service centres. PATIENTS: 207 patients with HE who initiated rifaximin-α between July 2008 and May 2014. Hospital resource use data were available for 145/207 patients. MAIN OUTCOME MEASURE: Change in mean number of liver-related hospital bed days/patient (total and critical care) between the 6 months pre-rifaximin-α and post-rifaximin-α initiation. RESULTS: Comparing the 6 months pre-rifaximin-α and post-rifaximin-α initiation in alive patients at the end of the observation period (N=114): there were significant reductions in the mean number of hospitalisations/patient (liver-related 1.3 to 0.5, p<0.001; all-cause 1.9 to 0.9, p<0.001), hospital bed days/patient (liver-related 17.8 to 6.8, p<0.001; all-cause 25.4 to 10.6, p<0.001), 30-day hospital readmissions/patient (liver-related 0.5 to 0.2, p=0.039; all-cause 0.8 to 0.4, p=0.024) and emergency department (ED) attendances/patient (all-cause, 1.0 to 0.5, p<0.001). The mean critical care bed days/patient reduced significantly for all-cause admissions (1.3 to 0.3, p=0.049); non-significant reduction for liver-related admissions. 4% of patients (9/207) developed AEs. CONCLUSIONS: In UK clinical practice, treatment with rifaximin-α for HE is well-tolerated and associated with significant reductions in hospitalisations, bed days (including critical care), ED attendances and 30-day readmissions.

Assessing Probabilistic Risk Assessment Approaches for Insect Biological Control Introductions.

The introduction of biological control agents to new environments requires host specificity tests to estimate potential non-target impacts of a prospective agent. Currently, the approach is conservative, and is based on physiological host ranges determined under captive rearing conditions, without consideration for ecological factors that may influence realized host range. We use historical data and current field data from introduced parasitoids that attack an endemic Lepidoptera species in Hawaii to validate a probabilistic risk assessment (PRA) procedure for non-target impacts. We use data on known host range and habitat use in the place of origin of the parasitoids to determine whether contemporary levels of non-target parasitism could have been predicted using PRA. Our results show that reasonable predictions of potential non-target impacts may be made if comprehensive data are available from places of origin of biological control agents, but scant data produce poor predictions. Using apparent mortality data rather than marginal attack rate estimates in PRA resulted in over-estimates of predicted non-target impact. Incorporating ecological data into PRA models improved the predictive power of the risk assessments.

The impacts of biomass properties on pyrolysis yields, economic and environmental performance of the pyrolysis-bioenergy-biochar platform to carbon negative energy.

This study evaluated the impact of biomass properties on the pyrolysis product yields, economic and environmental performance for the pyrolysis-biochar-bioenergy platform. We developed and applied a fast pyrolysis, feedstock-sensitive, regression-based chemical process model to 346 different feedstocks, which were grouped into five types: woody, stalk/cob/ear, grass/plant, organic residue/product and husk/shell/pit. The results show that biomass ash content of 0.3-7.7wt% increases biochar yield from 0.13 to 0.16kg/kg of biomass, and decreases biofuel yields from 87.3 to 40.7 gallons per tonne. Higher O/C ratio (0.88-1.12) in biomass decreases biochar yield and increases biofuel yields within the same ash content level. Higher ash content of biomass increases minimum fuel selling price (MFSP), while higher O/C ratio of biomass decreases MFSP within the same ash content level. The impact of ash and O/C ratio of biomass on GHG emissions are not consistent for all feedstocks.

The clinical effectiveness and cost-effectiveness of STeroids Or Pentoxifylline for Alcoholic Hepatitis (STOPAH): a 2 × 2 factorial randomised controlled trial.

BACKGROUND: Alcoholic hepatitis (AH) is a distinct presentation of alcoholic liver disease arising in patients who have been drinking to excess for prolonged periods, which is characterised by jaundice and liver failure. Severe disease is associated with high short-term mortality. Prednisolone and pentoxifylline (PTX) are recommended in guidelines for treatment of severe AH, but trials supporting their use have given heterogeneous results and controversy persists about their benefit. OBJECTIVES: The aim of the clinical effectiveness and cost-effectiveness of STeroids Or Pentoxifylline for Alcoholic Hepatitis trial was to resolve the clinical dilemma on the use of prednisolone or PTX. DESIGN: The trial was a randomised, double-blind, 2 × 2 factorial, multicentre design. SETTING: Sixty-five gastroenterology and hepatology inpatient units across the UK. PARTICIPANTS: Patients with a clinical diagnosis of AH who had a Maddrey's discriminant function value of ≥ 32 were randomised into four arms: A, placebo/placebo; B, placebo/prednisolone; C, PTX/placebo; and D, PTX/prednisolone. Of the 5234 patients screened for the trial, 1103 were randomised and after withdrawals, 1053 were available for primary end-point analysis. INTERVENTIONS: Those allocated to prednisolone were given 40 mg daily for 28 days and those allocated to PTX were given 400 mg three times per day for 28 days. OUTCOMES: The primary outcome measure was mortality at 28 days. Secondary outcome measures included mortality or liver transplant at 90 days and at 1 year. Rates of recidivism among survivors and the impact of recidivism on mortality were assessed. RESULTS: At 28 days, in arm A, 45 of 269 (16.7%) patients died; in arm B, 38 of 266 (14.3%) died; in arm C, 50 of 258 (19.4%) died; and in arm D, 35 of 260 (13.5%) died. For PTX, the odds ratio for 28-day mortality was 1.07 [95% confidence interval (CI) 0.77 to 1.40; p = 0.686)] and for prednisolone the odds ratio was 0.72 (95% CI 0.52 to 1.01; p = 0.056). In the logistic regression analysis, accounting for indices of disease severity and prognosis, the odds ratio for 28-day mortality in the prednisolone-treated group was 0.61 (95% CI 0.41 to 0.91; p = 0.015). At 90 days and 1 year there were no significant differences in mortality rates between the treatment groups. Serious infections occurred in 13% of patients treated with prednisolone compared with 7% of controls (p = 0.002). At the 90-day follow-up, 45% of patients reported being completely abstinent, 9% reported drinking within safety limits and 33% had an unknown level of alcohol consumption. At 1 year, 37% of patients reported being completely abstinent, 10% reported drinking within safety limits and 39% had an unknown level of alcohol consumption. Only 22% of patients had attended alcohol rehabilitation treatment at 90 days and 1 year. CONCLUSIONS: We conclude that prednisolone reduces the risk of mortality at 28 days, but this benefit is not sustained beyond 28 days. PTX had no impact on survival. Future research should focus on interventions to promote abstinence and on treatments that suppress the hepatic inflammation without increasing susceptibility to infection. TRIAL REGISTRATION: This trial is registered as EudraCT 2009-013897-42 and Current Controlled Trials ISRCTN88782125. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 102. See the NIHR Journals Library website for further project information. The NIHR Clinical Research Network provided research nurse support and the Imperial College Biomedical Research Centre also provided funding.

Ultra-Low Carbon Emissions from Coal-Fired Power Plants through Bio-Oil Co-Firing and Biochar Sequestration.

This study investigates a novel strategy of reducing carbon emissions from coal-fired power plants through co-firing bio-oil and sequestering biochar in agricultural lands. The heavy end fraction of bio-oil recovered from corn stover fast pyrolysis is blended and co-fired with bituminous coal to form a bio-oil co-firing fuel (BCF). Life-cycle greenhouse gas (GHG) emissions per kWh electricity produced vary from 1.02 to 0.26 kg CO2-eq among different cases, with BCF heavy end fractions ranging from 10% to 60%, which corresponds to a GHG emissions reduction of 2.9% to 74.9% compared with that from traditional bituminous coal power plants. We found a heavy end fraction between 34.8% and 37.3% is required to meet the Clean Power Plan's emission regulation for new coal-fired power plants. The minimum electricity selling prices are predicted to increase from 8.8 to 14.9 cents/kWh, with heavy end fractions ranging from 30% to 60%. A minimum carbon price of $67.4 ± 13 per metric ton of CO2-eq was estimated to make BCF power commercially viable for the base case. These results suggest that BCF co-firing is an attractive pathway for clean power generation in existing power plants with a potential for significant reductions in carbon emissions.

Techno-economic and uncertainty analysis of in situ and ex situ fast pyrolysis for biofuel production.

This study evaluates the techno-economic uncertainty in cost estimates for two emerging technologies for biofuel production: in situ and ex situ catalytic pyrolysis. The probability distributions for the minimum fuel-selling price (MFSP) indicate that in situ catalytic pyrolysis has an expected MFSP of $1.11 per liter with a standard deviation of 0.29, while the ex situ catalytic pyrolysis has a similar MFSP with a smaller deviation ($1.13 per liter and 0.21 respectively). These results suggest that a biorefinery based on ex situ catalytic pyrolysis could have a lower techno-economic uncertainty than in situ pyrolysis compensating for a slightly higher MFSP cost estimate. Analysis of how each parameter affects the NPV indicates that internal rate of return, feedstock price, total project investment, electricity price, biochar yield and bio-oil yield are parameters which have substantial impact on the MFSP for both in situ and ex situ catalytic pyrolysis.

Prednisolone or pentoxifylline for alcoholic hepatitis.

BACKGROUND: Alcoholic hepatitis is a clinical syndrome characterized by jaundice and liver impairment that occurs in patients with a history of heavy and prolonged alcohol use. The short-term mortality among patients with severe disease exceeds 30%. Prednisolone and pentoxifylline are both recommended for the treatment of severe alcoholic hepatitis, but uncertainty about their benefit persists. METHODS: We conducted a multicenter, double-blind, randomized trial with a 2-by-2 factorial design to evaluate the effect of treatment with prednisolone or pentoxifylline. The primary end point was mortality at 28 days. Secondary end points included death or liver transplantation at 90 days and at 1 year. Patients with a clinical diagnosis of alcoholic hepatitis and severe disease were randomly assigned to one of four groups: a group that received a pentoxifylline-matched placebo and a prednisolone-matched placebo, a group that received prednisolone and a pentoxifylline-matched placebo, a group that received pentoxifylline and a prednisolone-matched placebo, or a group that received both prednisolone and pentoxifylline. RESULTS: A total of 1103 patients underwent randomization, and data from 1053 were available for the primary end-point analysis. Mortality at 28 days was 17% (45 of 269 patients) in the placebo-placebo group, 14% (38 of 266 patients) in the prednisolone-placebo group, 19% (50 of 258 patients) in the pentoxifylline-placebo group, and 13% (35 of 260 patients) in the prednisolone-pentoxifylline group. The odds ratio for 28-day mortality with pentoxifylline was 1.07 (95% confidence interval [CI], 0.77 to 1.49; P=0.69), and that with prednisolone was 0.72 (95% CI, 0.52 to 1.01; P=0.06). At 90 days and at 1 year, there were no significant between-group differences. Serious infections occurred in 13% of the patients treated with prednisolone versus 7% of those who did not receive prednisolone (P=0.002). CONCLUSIONS: Pentoxifylline did not improve survival in patients with alcoholic hepatitis. Prednisolone was associated with a reduction in 28-day mortality that did not reach significance and with no improvement in outcomes at 90 days or 1 year. (Funded by the National Institute for Health Research Health Technology Assessment program; STOPAH EudraCT number, 2009-013897-42 , and Current Controlled Trials number, ISRCTN88782125 ).

Developing and enhancing biodiversity monitoring programmes: a collaborative assessment of priorities.

Biodiversity is changing at unprecedented rates, and it is increasingly important that these changes are quantified through monitoring programmes. Previous recommendations for developing or enhancing these programmes focus either on the end goals, that is the intended use of the data, or on how these goals are achieved, for example through volunteer involvement in citizen science, but not both. These recommendations are rarely prioritized.We used a collaborative approach, involving 52 experts in biodiversity monitoring in the UK, to develop a list of attributes of relevance to any biodiversity monitoring programme and to order these attributes by their priority. We also ranked the attributes according to their importance in monitoring biodiversity in the UK. Experts involved included data users, funders, programme organizers and participants in data collection. They covered expertise in a wide range of taxa.We developed a final list of 25 attributes of biodiversity monitoring schemes, ordered from the most elemental (those essential for monitoring schemes; e.g. articulate the objectives and gain sufficient participants) to the most aspirational (e.g. electronic data capture in the field, reporting change annually). This ordered list is a practical framework which can be used to support the development of monitoring programmes.People's ranking of attributes revealed a difference between those who considered attributes with benefits to end users to be most important (e.g. people from governmental organizations) and those who considered attributes with greatest benefit to participants to be most important (e.g. people involved with volunteer biological recording schemes). This reveals a distinction between focussing on aims and the pragmatism in achieving those aims. Synthesis and applications. The ordered list of attributes developed in this study will assist in prioritizing resources to develop biodiversity monitoring programmes (including citizen science). The potential conflict between end users of data and participants in data collection that we discovered should be addressed by involving the diversity of stakeholders at all stages of programme development. This will maximize the chance of successfully achieving the goals of biodiversity monitoring programmes.

Trans-jugular intrahepatic porto-systemic shunt placement for refractory ascites: a 'real-world' UK health economic evaluation.

OBJECTIVE: To assess the benefit of trans-jugular intrahepatic porto-systemic shunt (TIPS) placement for refractory ascites. DESIGN: A retrospective observational study of all patients undergoing TIPS for refractory ascites in our hospital between 2003 and 2012. SETTING: Secondary care. PATIENTS: Cirrhotic patients with refractory ascites. MAIN OUTCOME MEASURES: We examined direct real-world (National Health Service) health related costs in the year before and after the TIPS procedure took place. Data were collected relating to the need for reintervention and hepatic encephalopathy. RESULTS: Data were available for 24 patients who underwent TIPS for refractory ascites (86% of eligible patients). TIPS was technically successful in all cases. Mean number of bed days in the year prior to TIPS was 30.3 and 14.3 in the year following (p=0.005). No patient had ascites at the end of the year after the TIPS with less requirement for paracentesis over the course of the year (p<0.001). Mean reduction in cost was £2759 per patient. TIPS was especially cost-effective in patients requiring between 6 and 12 drains per year with a mean saving of £9204 per patient. CONCLUSIONS: TIPS is both a clinically effective and economically advantageous therapeutic option for selected patients with refractory ascites.

A comparison of the reproducibility of the parameters of the ¹³C-aminopyrine breath test for the assessment of hepatic function.

This study determined the within-subject and between-subject variability of different ways of expressing the results of the (13)C-aminopyrine breath test ((13)C-ABT) and the effect of shortening the test duration. The (13)C-ABT was conducted on three separate occasions in 10 healthy volunteers and on a single occasion in 22 patients with established liver cirrhosis. The within-subject variability of cumulative percentage dose recovered (cPDR), using measured CO(2) production rate (VCO(2)), in the reference group over three trials was 15% over 120 min. Higher within-subject variability in cPDR would have been evident if the test was terminated at either 30 or 60 min. Substitution of predicted VCO(2) to calculate cPDR yielded comparable values at all time points. Significant differences between cirrhotics and reference group were evident after just 10 min using PDR/h, cPDR or enrichment (all P<0.05). The ABT demonstrates clinically acceptable reproducibility. Shortening of the duration may make the test more acceptable clinically, but it is associated with increasing imprecision.

Estimated progression rates in three United Kingdom hepatitis C cohorts differed according to method of recruitment.

OBJECTIVES: To estimate hepatitis C virus (HCV) progression rates between disease stages prior to cirrhosis, using data from liver biopsies in three observational cohorts. To demonstrate how the method of cohort recruitment can influence the estimation of HCV-progression rates. STUDY DESIGN AND SETTING: Data came from three United Kingdom observational cohorts, assembled from different referral sources. In total, 987 HCV-infected patients with an estimated (or known) date of infection and at least one histologically scored liver biopsy were eligible for inclusion in the analysis. Liver biopsy scores were used to determine the stage of HCV-related liver disease. A three-state continuous time Markov model was used to estimate covariate-specific average probabilities of progression of disease. RESULTS: After adjusting for confounders, considerably different rates of disease progression were estimated in the three cohorts. For a group of patients with the same demographics, the estimated 20-year probability of progression to cirrhosis was 12% (95% confidence interval CI = 6-22) in a hospital-based cohort, 6% (95% CI = 3-13) in a posttransfusion cohort, and 23% (95% CI = 14-37) in a cohort recruited from a tertiary referral center. CONCLUSION: Researchers using estimates of disease progression should be aware that the method of cohort recruitment has considerable influence on the progression rates that are derived.

Quantitative versus morphological assessment of liver fibrosis: semi-quantitative scores are more robust than digital image fibrosis area estimation.

BACKGROUND/AIM: Digital image analysis (DIA) allows quantitative assessment of fibrosis on liver biopsy. Accurate determination of a threshold greyscale level representing fibrous tissue is critical. This method has not been fully evaluated in clinical practice. METHODS: Digital images of stained liver biopsy sections were captured by microscopy and converted to greyscale. A novel method of determining the threshold greyscale value at which to measure fibrosis area was developed (peak proportion area change (PPAC)). Reproducibility was tested in comparison with standard interactive thresholding and with semi-quantitative scoring using the Histological activity index (HAI) system by a histopathologist. Fibrosis areas for different sections from the same biopsy core were also compared by each method. RESULTS: Comparison between PPAC and interactive thresholding method demonstrated superior reproducibility of the PPAC method: r > 0.7, P < 0.001 compared with r = 0.19-0.64 (not all reaching significance). On a single section, reproducibility was similar for PPAC and the modified HAI system. When different sections from the same core were compared, the HAI system was more robust. CONCLUSIONS: The PPAC method is superior to standard interactive thresholding. However, variability in DIA scores between sections invalidates the technique for clinical use and semi-quantitative scoring systems remain the gold standard for fibrosis assessment.

Demand, appropriateness and prescribing of 'lifestyle drugs': a consultation survey in general practice.

BACKGROUND: The simultaneous launch of orlistat and sildenafil in 1998 provoked much media attention, particularly around the role of lifestyle drugs and their potential costs if controls were not established. Fears were also expressed that primary care would be overwhelmed by demand, and little information was available about the attitude of GPs to their new role as prescribers of lifestlye drugs. Partly in response to these concerns, tight prescribing guidelines and licensed indications, for sildenafil and orlistat, respectively, were issued. OBJECTIVE: Our aim was to describe levels of demand for orlistat and sildenafil in general practice, whether this demand was translated into a prescription, adherence to prescribing guidelines/licensed indications and the GP perception of appropriateness of an NHS prescription for either of these drugs. METHOD: We carried out an observational study in primary care conducted over a 6-week period during 1999. Twenty-seven GPs were recruited, each from a different practice. All GP consultations were recorded for the study period and the GP completed a structured questionnaire each time sildenafil or orlistat were discussed in a consultation. RESULTS: Sildenafil was discussed in 0.5% (68/13 394) of consultations and orlistat in 0.3% (42/13 394). GPs thought that a corresponding NHS prescription would be highly appropriate in 57 and 74% of cases, respectively, although for both lifestyle drugs, nearly 20% of GPs thought such prescriptions were inappropriate. An NHS prescription was issued in 43% of consultations in which sildenafil had been discussed and 33% in which orlistat had been discussed. Five out of 29 NHS sildenafil prescriptions were issued to patients failing to fulfil the requirements of prescribing guidelines; similarly, one out of 14 orlistat prescriptions fell outside licensed indications. There were four examples of NHS prescriptions for sildenafil which were given even when the GP thought the drug to be inappropriate, whereas orlistat was never given when the GP thought it inappropriate. CONCLUSIONS: Levels of demand for the two lifestyle drugs, sildenafil and orlistat, were modest when compared with earlier media predictions. Neither was there evidence that GP was pitted against patient in their negotiation concerning a lifestyle drug NHS prescription since most GPs agreed with their patients that such a prescription was appropriate. Prescribing guidelines and licensed indications were generally adhered to, but the modest level of demand raises questions about expanding the guidelines for sildenafil.