Decision-analytic cost-effectiveness model to compare prostate cryotherapy to androgen deprivation therapy for treatment of radiation recurrent prostate cancer

Objective: To determine the cost-effectiveness of salvage cryotherapy (SC) in men with radiation recurrent prostate cancer (RRPC). Design: Cost-utility analysis using decision analytic modelling by a Markov model. Setting and methods: Compared SC and androgen deprivation therapy (ADT) in a cohort of patients with RRPC (biopsy proven local recurrence, no evidence of metastatic disease). A literature review captured published data to inform the decision model, and resource use data were from the Scottish Prostate Cryotherapy Service. The model was run in monthly cycles for RRPC men, mean age of 70 years. The model was run over the patient lifetime, to assess changes in patient health states and the associated quality of life, survival and cost impacts. Results are reported in terms of the discounted incremental costs and discounted incremental quality-adjusted life years (QALYs) gained between the 2 alternative interventions. Probabilistic sensitivity analysis used a 10 000 iteration Monte Carlo simulation. Results: SC has a high upfront treatment cost, but delays the ongoing monthly cost of ADT. SC is the dominant strategy over the patient lifetime; it is more effective with an incremental 0.56 QALY gain (95% CI 0.28 to 0.87), and less costly with a reduced lifetime cost of £29 719 (€37 619) (95% CI −51 985 to −9243). For a ceiling ratio of £30 000, SC has a 100% probability to be cost-effective. The cost neutral point was at 3.5 years, when the upfront cost of SC (plus any subsequent cumulative cost of side effects and ADT) equates the cumulative cost in the ADT arm. Limitations of our model may arise from its insensitivity to parameter or structural uncertainty. Conclusions: The platform for SC versus ADT cost-effective analysis can be employed to evaluate other treatment modalities or strategies in RRPC. SC is the dominant strategy, costing less over a patient's lifetime with improvements in QALYs

Estimation of Optimal Biomass Removal Rate Based on Tolerable Soil Erosion for Single-Pass Crop Grain and Biomass Harvesting System

As the demand for biomass feedstocks grows, it is likely that agricultural residue will be removed in a way that compromises soil sustainability due to increased soil erosion, depletion of organic matter, and deterioration of soil physical characteristics. Since soil erosion from agricultural fields depends on several factors including soil type, field terrain, and cropping practices, the amount of biomass that can be removed while maintaining soil tilth varies substantially over space and time. The RUSLE2 soil erosion model, which takes into account these spatio-temporal variations, was used to estimate tolerable agricultural biomass removal rates at field scales for a single-pass crop grain and biomass harvesting system. Soil type, field topography, climate data, management practices, and conservation practices were stored in individual databases on a state or county basis. Geographic position of the field was used as a spatial key to access the databases to select site-specific information such as soil, topography, and management related parameters. These parameters along with actual grain yield were provided as inputs to the RUSLE2 model to calculate yearly soil loss per unit area of the field. An iterative technique was then used to determine site-specific tolerable biomass removal rates that keep the soil loss below the soil loss thresholds (T) of the field. The tolerable removal rates varied substantially with field terrain, crop management practices, and soil type. At a location in a field in Winnebago county, Iowa, with ~1% slope and conventional tillage practices, up to 98% of the 11 Mg ha-1 total above-ground biomass was available for collection with negligible soil loss. There was no biomass available to remove with conventional tillage practices on steep slopes, as in a field in Crawford county, Iowa, with a 12.6% slope. If no-till crop practices were adopted, up to 70% of the total above-ground biomass could be collected at the same location with 12.6% slope. In the case of a soybean-corn rotation with no-till practices, about 98% of total biomass was available for removal at the locations in the Winnebago field with low slopes, whereas 77% of total biomass was available at a location in the Crawford field with a 7.5% slope. Tolerable removal rates varied substantially over an agricultural field, which showed the importance of site-specific removal rate estimation. These removal rates can be useful in developing recommended rates for producers to use during a single-pass crop grain and biomass harvesting operation. However, this study only considered the soil erosion tolerance level in estimating biomass removal rates. Before providing the final recommendation to end users, further investigations will be necessary to study the potential effects of continuous biomass removal on organic matter content and other biophysical properties of the soil

Stress Tensor from the Trace Anomaly in Reissner-Nordstrom Spacetimes

The effective action associated with the trace anomaly provides a general algorithm for approximating the expectation value of the stress tensor of conformal matter fields in arbitrary curved spacetimes. In static, spherically symmetric spacetimes, the algorithm involves solving a fourth order linear differential equation in the radial coordinate r for the two scalar auxiliary fields appearing in the anomaly action, and its corresponding stress tensor. By appropriate choice of the homogeneous solutions of the auxiliary field equations, we show that it is possible to obtain finite stress tensors on all Reissner-Nordstrom event horizons, including the extreme Q=M case. We compare these finite results to previous analytic approximation methods, which yield invariably an infinite stress-energy on charged black hole horizons, as well as with detailed numerical calculations that indicate the contrary. The approximation scheme based on the auxiliary field effective action reproduces all physically allowed behaviors of the quantum stress tensor, in a variety of quantum states, for fields of any spin, in the vicinity of the entire family (0 le Q le M) of RN horizons.Comment: 43 pages, 12 figure

Haemodynamic changes with paracetamol in critically-ill children.

PURPOSE: Paracetamol has been associated with a reduction in blood pressure, especially in febrile, critically-ill adults. We hypothesised that blood pressure would fall following administration of paracetamol in critically-ill children and this effect would be greater during fever and among children with a high body surface area to weight ratio. METHODS: A 12-month prospective observational study of children (0-16years) admitted to paediatric intensive care, who underwent pulse contour analysis and received paracetamol concurrently. RESULTS: Mean arterial blood pressure decreased significantly by 4.7% from baseline (95% CI 1.75-8.07%) in 31 children following 148 doses of paracetamol. The nadir was 2-hour post-dose. The effect was pronounced in children with fever at baseline (6.4%, 95% CI 2.8-10%), although this was not statistically significant. There was no simple relationship between this effect and body surface area to weight ratio. The association between a change in blood pressure and changes in heart rate or measured stroke volume was poor; therefore it was likely that a change in the systemic vascular resistance contributes most to this effect. CONCLUSION: There is a significant but modest reduction in blood pressure post-paracetamol in critically-ill children. This is likely related to a change in systemic vascular resistance

Joint modelling of serological and hospitalization data reveals that high levels of pre-existing immunity and school holidays shaped the influenza A pandemic of 2009 in the Netherlands.

Obtaining a quantitative understanding of the transmission dynamics of influenza A is important for predicting healthcare demand and assessing the likely impact of intervention measures. The pandemic of 2009 provides an ideal platform for developing integrative analyses as it has been studied intensively, and a wealth of data sources is available. Here, we analyse two complementary datasets in a disease transmission framework: cross-sectional serological surveys providing data on infection attack rates, and hospitalization data that convey information on the timing and duration of the pandemic. We estimate key epidemic determinants such as infection and hospitalization rates, and the impact of a school holiday. In contrast to previous approaches, our novel modelling of serological data with mixture distributions provides a probabilistic classification of individual samples (susceptible, immune and infected), propagating classification uncertainties to the transmission model and enabling serological classifications to be informed by hospitalization data. The analyses show that high levels of immunity among persons 20 years and older provide a consistent explanation of the skewed attack rates observed during the pandemic and yield precise estimates of the probability of hospitalization per infection (1-4 years: 0.00096 (95%CrI: 0.00078-0.0012); 5-19 years: 0.00036 (0.00031-0.0044); 20-64 years: 0.0015 (0.00091-0.0020); 65+ years: 0.0084 (0.0028-0.016)). The analyses suggest that in The Netherlands, the school holiday period reduced the number of infectious contacts between 5- and 9-year-old children substantially (estimated reduction: 54%; 95%CrI: 29-82%), thereby delaying the unfolding of the pandemic in The Netherlands by approximately a week

Penrose Diagram for a Transient Black Hole

A Penrose diagram is constructed for a spatially coherent black hole that smoothly begins an accretion, then excretes symmetrically as measured by a distant observer, with the initial and final states described by a metric of Minkowski form. Coordinate curves on the diagram are computationally derived. Causal relationships between space-time regions are briefly discussed. The life cycle of the black hole demonstrably leaves asymptotic observers in an unaltered Minkowski space-time of uniform conformal scale.Comment: 14 pages, 9 figures, spelling correction

Evidence Synthesis for Stochastic Epidemic Models.

In recent years, the role of epidemic models in informing public health policies has progressively grown. Models have become increasingly realistic and more complex, requiring the use of multiple data sources to estimate all quantities of interest. This review summarises the different types of stochastic epidemic models that use evidence synthesis and highlights current challenges