Cost-effectiveness of noninvasive liver fibrosis tests for treatment decisions in patients with chronic hepatitis C

The cost-effectiveness of noninvasive tests (NITs) as alternatives to liver biopsy is unknown. We compared the cost-effectiveness of using NITs to inform treatment decisions in adult patients with chronic hepatitis C (CHC). We conducted a systematic review and meta-analysis to calculate the diagnostic accuracy of various NITs using a bivariate random-effects model. We constructed a probabilistic decision analytical model to estimate health care costs and outcomes (quality-adjusted life-years; QALYs) using data from the meta-analysis, literature, and national UK data. We compared the cost-effectiveness of four treatment strategies: testing with NITs and treating patients with fibrosis stage ≥F2; testing with liver biopsy and treating patients with ≥F2; treat none; and treat all irrespective of fibrosis. We compared all NITs and tested the cost-effectiveness using current triple therapy with boceprevir or telaprevir, but also modeled new, more-potent antivirals. Treating all patients without any previous NIT was the most effective strategy and had an incremental cost-effectiveness ratio (ICER) of £9,204 per additional QALY gained. The exploratory analysis of currently licensed sofosbuvir treatment regimens found that treat all was cost-effective, compared to using an NIT to decide on treatment, with an ICER of £16,028 per QALY gained. The exploratory analysis to assess the possible effect on results of new treatments, found that if SVR rates increased to >90% for genotypes 1-4, the incremental treatment cost threshold for the "treat all" strategy to remain the most cost-effective strategy would be £37,500. Above this threshold, the most cost-effective option would be noninvasive testing with magnetic resonance elastography (ICER=£9,189). Conclusions: Treating all adult patients with CHC, irrespective of fibrosis stage, is the most cost-effective strategy with currently available drugs in developed countries. © 2014 The Authors

EQ-5D in skin conditions: an assessment of validity and responsiveness

Aims and objectives This systematic literature review aims to assess the reliability, validity and responsiveness of three widely used generic preference-based measures of health-related quality of life (HRQL), i.e., EQ-5D, Health Utility Index 3 (HUI3) and SF-6D in patients with skin conditions. Methods A systematic search was conducted to identify studies reporting health state utility values obtained using EQ-5D, SF-6D, or HUI3 alongside other HRQL measures or clinical indices for patients with skin conditions. Data on test-retest analysis for reliability, known group differences or correlation and regression analyses for validity, and change over time or responsiveness indices analysis were extracted and reviewed. Results A total of 16 papers reporting EQ-5D utilities in people with skin conditions were included in the final review. No papers for SF-6D and HUI3 were found. Evidence of reliability was not found for any of these measures. The majority of studies included in the review (12 out of 16) examined patients with plaque psoriasis or psoriatic arthritis and the remaining four studies examined patients with either acne, hidradenitis suppurativa, hand eczema, or venous leg ulcers. The findings were generally positive in terms of performance of EQ-5D. Six studies showed that EQ-5D was able to reflect differences between severity groups and only one reported differences that were not statistically significant. Four studies found that EQ-5D detected differences between patients and the general population, and differences were statistically different for three of them. Further, moderate-to-strong correlation coefficients were found between EQ-5D and other skin-specific HRQL measures in four studies. Eight studies showed that EQ-5D was able to detect change in HRQL appropriately over time and the changes were statistically significant in seven studies. Conclusions Overall, the validity and responsiveness of the EQ-5D was found to be good in people with skin diseases, especially plaque psoriasis or psoriatic arthritis. No evidence on SF-6D and HUI3 was available to enable any judgments to be made on their performance

The deep distributions of helium isotopes, radiocarbon, and noble gases along the U.S. GEOTRACES East Pacific Zonal Transect (GP16)

Author Posting. © The Author(s), 2017. This is the author's version of the work. It is posted here under a nonexclusive, irrevocable, paid-up, worldwide license granted to WHOI. It is made available for personal use, not for redistribution. The definitive version was published in Marine Chemistry 201 (2018): 167-182, doi:10.1016/j.marchem.2017.03.009.We report the deep distributions of noble gases, helium isotopes, and radiocarbon measured during the U.S. GEOTRACES GP16 East Pacific Zonal Transect between 152 and 77°W at 12- 15°S in the South Pacific. The dominant feature is an intense tongue of hydrothermal effluent that extends more than 4,000 km westward from the East Pacific Rise (EPR) at ~2500m depth. The patterns reveal significant “downstream” variations in water mass structure, advection, and mixing that belie the simple perception of a continuous plume extending westward from the EPR. For example, one feature observed at 120°W, 14°S has tracer signatures that are consistent with a water mass originating from an area as much as 2,000 km south of this section, suggesting a quasi-permanent northward flow on the western flank of the EPR. Helium isotope variations in the plume show a uniquely high 3He/4He source in the tongue compared with typical mid-ocean ridge basalts (MORB), consistent with the anomalously high ratios observed in MORB glasses from the EPR segment just south of this transect. The water column data also reveal that the background 3He/4He east of the EPR is significantly lower than values characteristic of MORB, suggesting an additional, more geographically distributed radiogenic 4He flux of order 107 mol/y into the deep Pacific. In the western end of the section, incoming bottom waters have relatively less hydrothermal hydrothermal helium, more radiocarbon, and more oxygen, as well as negative saturation anomalies for the heavy noble gases (Ar, Kr, and Xe). During the basin-scale upwelling of this water, diapycnal mixing serves to erase these negative anomalies. The relative magnitudes of the increases for the heavy noble gases (Ar, Kr, and Xe) are quantitatively consistent with this process. This leads us to estimate the relatively smaller effects on He and Ne saturations, which range from near zero to 0.2% and 0.3% respectively. With this information, we are able to refine our estimates of the magnitude of 3He and 4He excesses and the absolute 3He/4He ratio of non-atmospheric helium introduced into deep Pacific waters.The work was funded under National Science Foundation grant number OCE-1232991 for WJJ and OCE-1130870 for CRG

Exploring what lies behind public preferences for avoiding health losses caused by lapses in healthcare safety and patient lifestyle choices

© 2013 Singh et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.This article has been made available through the Brunel Open Access Publishing Fund.Background: Although many studies have identified public preferences for prioritising health care interventions based on characteristics of recipient or care, very few of them have examined the reasons for the stated preferences. We conducted an on-line person trade-off (PTO) study (N=1030) to investigate whether the public attach a premium to the avoidance of ill health associated with alternative types of responsibilities: lapses in healthcare safety, those caused by individual action or lifestyle choice; or genetic conditions. We found that the public gave higher priority to prevention of harm in a hospital setting such as preventing hospital associated infections than genetic disorder but drug administration errors were valued similar to genetic disorders. Prevention of staff injuries, lifestyle diseases and sports injuries, were given lower priority. In this paper we aim to understand the reasoning behind the responses by analysing comments provided by respondents to the PTO questions. Method: A majority of the respondents who participated in the survey provided brief comments explaining preferences in free text responses following PTO questions. This qualitative data was transformed into explicit codes conveying similar meanings. An overall coding framework was developed and a reliability test was carried out. Recurrent patterns were identified in each preference group. Comments which challenged the assumptions of hypothetical scenarios were also investigated. Results: NHS causation of illness and a duty of care were the most cited reasons to prioritise lapses in healthcare safety. Personal responsibility dominated responses for lifestyle related contexts, and many respondents mentioned that health loss was the result of the individual’s choice to engage in risky behaviour. A small proportion of responses questioned the assumptions underlying the PTO questions. However excluding these from the main analysis did not affect the conclusions. Conclusion: Although some responses indicated misunderstanding or rejection of assumptions we put forward, the results were still robust. The reasons put forward for responses differed between comparisons but responsibility was the most frequently cited. Most preference elicitation studies only focus on eliciting numerical valuations but allowing for qualitative data can augment understanding of preferences as well as verifying results.EPSRC through the MATCH programme(EP/F063822/1 and EP/G012393/1) and HERG within Brunel University

Contextual factors among indiscriminate or larger attacks on food or water supplies, 1946-2015

This research updates previous inventories of malicious attacks on food and water to include data from 1946 through mid-2015. A systematic search of news reports, databases and previous inventories of poisoning events was undertaken. Incidents that threatened or were intended to achieve direct harm to humans, and that were either relatively large (number of victims > 4 or indiscriminate in intent or realisation were included. Agents could be chemical, biological or radio-nuclear. Reports of candidate incidents were subjected to systematic inclusion and exclusion criteria as well as validity analysis (not always clearly undertaken in previous inventories of such attacks). We summarise contextual aspects of the attacks that may be important for scenario prioritisation, modelling and defensive preparedness. Opportunity is key to most realised attacks, particularly access to dangerous agents. The most common motives and relative success rate in causing harm were very different between food and water attacks. The likelihood that people were made ill or died also varied by food/water mode, and according to motive and opportunity for delivery of the hazardous agent. Deaths and illness associated with attacks during food manufacture and prior to sale have been fewer than those in some other contexts. Valuable opportunities for food defence improvements are identified in other contexts, especially food prepared in private or community settings

Drosophila Condensin II subunit Chromosome-associated protein D3 regulates cell fate determination through non-cell-autonomous signaling

Citation: Klebanow, L. R., Peshel, E. C., Schuster, A. T., De, K., Sarvepalli, K., Lemieux, M. E., . . . Longworth, M. S. (2016). Drosophila Condensin II subunit Chromosome-associated protein D3 regulates cell fate determination through non-cell-autonomous signaling. Development, 143(15), 2791-2802. doi:10.1242/dev.133686The pattern of the Drosophila melanogaster adult wing is heavily influenced by the expression of proteins that dictate cell fate decisions between intervein and vein during development. dSRF (Blistered) expression in specific regions of the larval wing disc promotes intervein cell fate, whereas EGFR activity promotes vein cell fate. Here, we report that the chromatin-organizing protein CAP-D3 acts to dampen dSRF levels at the anterior/posterior boundary in the larval wing disc, promoting differentiation of cells into the anterior crossvein. CAP-D3 represses KNOT expression in cells immediately adjacent to the anterior/posterior boundary, thus blocking KNOT-mediated repression of EGFR activity and preventing cell death. Maintenance of EGFR activity in these cells depresses dSRF levels in the neighboring anterior crossvein progenitor cells, allowing them to differentiate into vein cells. These findings uncover a novel transcriptional regulatory network influencing Drosophila wing vein development, and are the first to identify a Condensin II subunit as an important regulator of EGFR activity and cell fate determination in vivo

A high-performance 14C accelerator mass spectrometry system

Author Posting. © Arizona Board of Regents on behalf of the University of Arizona, 2010. This article is posted here by permission of Dept. of Geosciences, University of Arizona for personal use, not for redistribution. The definitive version was published in Radiocarbon 52 (2010): 228-235.A new and unique radiocarbon accelerator mass spectrometry (AMS) facility has been constructed at the Woods Hole Oceanographic Institution. The defining characteristic of the new system is its large-gap optical elements that provide a larger-than-standard beam acceptance. Such a system is ideally suited for high-throughput, high-precision measurements of 14C. Details and performance of the new system are presented

Cost-effectiveness of noninvasive liver fibrosis tests for treatment decisions in patients with chronic hepatitis B in the UK: systematic review and economic evaluation

The copyright line for this article was changed on 18 November 2016 after original online publication. Abbreviations: CEAF cost-effectiveness frontier. CHB chronic hepatitis B. CI confidence intervals. FN false negative. FP false positive. HBV hepatitis B virus. HCC hepatocellular carcinoma. ICER incremental cost-effectiveness ratio. NITs noninvasive tests. QUADAS Quality Assessment of Diagnostic Accuracy Studies. QUALYs quality-adjusted-life-years. TN true negative. TP true positive.Copyright © 2015 The Authors. We compared the cost-effectiveness of various noninvasive tests (NITs) in patients with chronic hepatitis B and elevated transaminases and/or viral load who would normally undergo liver biopsy to inform treatment decisions. We searched various databases until April 2012. We conducted a systematic review and meta-analysis to calculate the diagnostic accuracy of various NITs using a bivariate random-effects model. We constructed a probabilistic decision analytical model to estimate health care costs and outcomes quality-adjusted-life-years (QALYs) using data from the meta-analysis, literature, and national UK data. We compared the cost-effectiveness of four decision-making strategies: testing with NITs and treating patients with fibrosis stage ≥F2, testing with liver biopsy and treating patients with ≥F2, treat none (watchful waiting) and treat all irrespective of fibrosis. Treating all patients without prior fibrosis assessment had an incremental cost-effectiveness ratio (ICER) of £28 137 per additional QALY gained for HBeAg-negative patients. For HBeAg-positive patients, using Fibroscan was the most cost-effective option with an ICER of £23 345. The base case results remained robust in the majority of sensitivity analyses, but were sensitive to changes in the ≥F2 prevalence and the benefit of treatment in patients with F0–F1. For HBeAg-negative patients, strategies excluding NITs were the most cost-effective: treating all patients regardless of fibrosis level if the high cost-effectiveness threshold of £30 000 is accepted; watchful waiting if not. For HBeAg-positive patients, using Fibroscan to identify and treat those with ≥F2 was the most cost-effective option.The analysis for Hepatitis B was part of a larger project funded by The National Institute for Health Research Health Technology Assessment (HTA project 09/114/02) and will be published in full in the Health Technology Assessment journal series. Visit the HTA programme website for more details www.hta.ac.uk/link to project page