The cost effectiveness of peginterferon alfa and ribavirin for the treatment of hepatitis C in children and young people

OBJECTIVES: To assess the cost-effectiveness of peginterferon ?-2a and peginterferon ?-2b in combination with ribavirin compared to best supportive care (BSC), for the treatment of chronic hepatitis C virus (HCV) in children and young people aged 3 to 17 years. METHODS: A Markov state-transition economic model of chronic HCV in children and young people was developed that extrapolated the impact of sustained virological response (SVR) on life expectancy, quality-adjusted life expectancy and lifetime costs. The model was adapted from one previously developed for adults. A systematic review was conducted of the clinical effectiveness of the treatments, and the health related quality of life for patients with hepatitis C. Uncertainty was explored through probabilistic and deterministic sensitivity analyses. RESULTS: Seven studies were identified that were relatively small and of generally poor quality. Estimates of SVR were similar for for peginterferon ?-2a (60%) and peginterferon ?-2b (58%) was similar, whilst the SVR for no treatment was assumed to be zero. From this model, peginterferon alfa (?-2a or ?-2b) in combination with ribavirin was more effective and cheaper than BSC. Sensitivity analyses suggest that the results were generally robust to all changes to the structural assumptions and input parameters. The model results were most sensitive to changes to the discount rate, time horizon, SVR and baseline fibrosis of the cohort. CONCLUSIONS: Treatment of children and young people with peginterferon alfa (?-2a or ?-2b) and ribavirin may be an effective therapy. Peginterferon alfa (?-2a or ?-2b) in combination with ribavirin is cost-effective compared with BSC. However, the available evidence is of poor quality. The views expressed in this paper are those of the authors and do not necessarily represent the views or policies of the UK HTA programme or Department of Health

Updating and amending systematic reviews and systematic maps in environmental management

Systematic reviews and systematic maps aim to provide an overview of the best available evidence to inform research, policy and practice. However, like any form of review, they will require updating periodically to ensure that the most recent evidence has been incorporated. Here we outline two types of review revisions as recognised in medicine: updates and amendments. Updates involve a search for new studies, expanding the evidence base through time. Any other change (e.g. in screening or synthesis) or correction to the original report is an amendment. Decisions as to whether/when it is appropriate to undertake an update or amendment must be made on a case-by-case basis, considering issues such as the reliability and scope of the existing review or map, likely volume of new evidence, resources available, and the likely value of including new information. Careful, consistent reporting is necessary to ensure transparency and repeatability, particularly where there are deviations from the original methods, and authors should highlight key advances relative to the original report. Updating environmental systematic reviews and maps will be an increasingly important activity as the numbers of both primary studies and synthetic reports in the literature continue to grow

Updating and amending systematic reviews and systematic maps in environmental management

Systematic reviews and systematic maps aim to provide an overview of the best available evidence to inform research, policy and practice. However, like any form of review, they will require updating periodically to ensure that the most recent evidence has been incorporated. Here we outline two types of review revisions as recognised in medicine: updates and amendments. Updates involve a search for new studies, expanding the evidence base through time. Any other change (e.g. in screening or synthesis) or correction to the original report is an amendment. Decisions as to whether/when it is appropriate to undertake an update or amendment must be made on a case-by-case basis, considering issues such as the reliability and scope of the existing review or map, likely volume of new evidence, resources available, and the likely value of including new information. Careful, consistent reporting is necessary to ensure transparency and repeatability, particularly where there are deviations from the original methods, and authors should highlight key advances relative to the original report. Updating environmental systematic reviews and maps will be an increasingly important activity as the numbers of both primary studies and synthetic reports in the literature continue to grow

Majorana Neutrino Masses from Anomalous U(1) Symmetries

We explore the possibility of interpreting the solar and atmospheric neutrino data within the context of the Minimal Supersymmetric Standard Model augmented by a single U(1) anomalous family symmetry spontaneously broken by non-zero vacuum expectation values of a pair of singlet fields. The symmetry retains a dimension-five operator which provides Majorana masses for left-handed neutrino states. Assuming symmetric lepton mass matrices, the model predicts inverse hierarchical neutrino mass spectrum, theta_{13}=0 and large mixing while at the same time it provides acceptable mass matrices for the charged fermions.Comment: 14 pages, no figure

Improved algebraic cryptanalysis of QUAD, Bivium and Trivium via graph partitioning on equation systems

We present a novel approach for preprocessing systems of polynomial equations via graph partitioning. The variable-sharing graph of a system of polynomial equations is defined. If such graph is disconnected, then the corresponding system of equations can be split into smaller ones that can be solved individually. This can provide a tremendous speed-up in computing the solution to the system, but is unlikely to occur either randomly or in applications. However, by deleting certain vertices on the graph, the variable-sharing graph could be disconnected in a balanced fashion, and in turn the system of polynomial equations would be separated into smaller systems of near-equal sizes. In graph theory terms, this process is equivalent to finding balanced vertex partitions with minimum-weight vertex separators. The techniques of finding these vertex partitions are discussed, and experiments are performed to evaluate its practicality for general graphs and systems of polynomial equations. Applications of this approach in algebraic cryptanalysis on symmetric ciphers are presented: For the QUAD family of stream ciphers, we show how a malicious party can manufacture conforming systems that can be easily broken. For the stream ciphers Bivium and Trivium, we nachieve significant speedups in algebraic attacks against them, mainly in a partial key guess scenario. In each of these cases, the systems of polynomial equations involved are well-suited to our graph partitioning method. These results may open a new avenue for evaluating the security of symmetric ciphers against algebraic attacks

Low Energy Thresholds and the Scalar Mass Spectrum in Minimal Supersymmetry

We discuss low energy threshold effects and calculate the sparticle masses in the context of the Minimal Supersymmetric Standard Model. We pay particular attention to the top squark and the Higgs mass parameters, and calculate the top Yukawa corrections, taking into account the successive decoupling of each particle at its threshold. We discuss the phenomenological implications in the context of the radiative symmetry breaking scenario.Comment: (CERN-TH.7411, Latex file, 12p, 1fig. not included

Testing the Nature of Kaluza-Klein Excitations at Future Lepton Colliders

With one extra dimension, current high precision electroweak data constrain the masses of the first Kaluza-Klein excitations of the Standard Model gauge fields to lie above $\simeq 4$ TeV. States with masses not much larger than this should be observable at the LHC. However, even for first excitation masses close to this lower bound, the second set of excitations will be too heavy to be produced thus eliminating the possibility of realizing the cleanest signature for KK scenarios. Previous studies of heavy $Z'$ and $W'$ production in this mass range at the LHC have demonstrated that very little information can be obtained about their couplings to the conventional fermions given the limited available statistics and imply that the LHC cannot distinguish an ordinary $Z'$ from the degenerate pair of the first KK excitations of the $\gamma$ and $Z$. In this paper we discuss the capability of lepton colliders with center of mass energies significantly below the excitation mass to resolve this ambiguity. In addition, we examine how direct measurements obtained on and near the top of the first excitation peak at lepton colliders can confirm these results. For more than one extra dimension we demonstrate that it is likely that the first KK excitation is too massive to be produced at the LHC.Comment: 38 pages, 10 Figs, LaTex, comments adde

The clinical effectiveness of diabetes education models for Type 2 diabetes: a systematic review

Objective: To examine the clinical effectiveness of patient education models for adults with Type 2 diabetes.Data sources: Electronic databases were searched from 2002 to January 2007.Review methods: A systematic review of the literature on educational interventions in diabetes was undertaken. This was an update of a previous systematic review.Results: Including studies identified in the previous systematic review, there were 13 published studies. Eight studies of education on multiple aspects of diabetes self-management were identified that provided education that was focused on a particular aspect of self-management. The quality of reporting and methodology of the studies was variable. Studies of multi-component educational interventions yielded mixed results. Some trials reported significant improvements on measures of diabetic control but others did not. Positive effects may be attributable to longer-term interventions with a shorter duration between the end of the intervention and the follow-up evaluation point. There may also be an effect of having a multi-professional team delivering the educational programme. Studies of focused educational interventions did not yield consistent results. Some effects were shown on measures of diabetic control in studies that focused on diet or exercise alone. Although the effects shown were generally small, those that were present did appear to be relatively long-lasting. This update review does not substantially alter the conclusions of the previous systematic review; for each outcome, the proportion of studies that demonstrated significant effects of education was similar.Conclusions: Based on the evidence, it would seem that education delivered by a team of educators, with some degree of reinforcement of that education made at additional points of contact, may provide the best opportunity for improvements in patient outcomes. Educators need to have time and resources to fulfil the needs of any structured educational programme. There is also a need for education to have a clear programme at the outset. From the evidence reported it is unclear what resources would need to be directed at the educators themselves to ensure that they can deliver programmes successfully. Any future research should consider patient education within the context of overall diabetes care and as such follow guidelines for the development and evaluation of complex interventions. Good-quality, longer-term studies would be desirable, but these would require careful consideration around the nature of any control group. Information is needed to clarify the sensitivity of diabetes education programmes to the performance of the diabetes educators, in order to ensure success and cost-effectiveness of education programmes.<br/

Collembola and macroarthropod community responses to carbamate, organophosphate and synthetic pyrethroid insecticides: direct and indirect effects

Non-target effects on terrestrial arthropod communities of the broad-spectrum insecticides chlorpyrifos and cypermethrin and the selective insecticide pirimicarb were investigated in winter wheat fields in summer. Effects of chlorpyrifos on arthropod abundance and taxonomic richness were consistently negative whereas effects of cypermethrin were negative for predatory arthropods but positive for soil surface Collembola. Pirimicarb effects were marginal, primarily on aphids and their antagonists, with no effect on the Collembola community. Collembola-predator ratios were significantly higher following cypermethrin treatment, suggesting that cypermethrin-induced increases in collembolan abundance represent a classical resurgence. Observations in other studies suggest Collembola resurgences may be typical after synthetic pyrethroid applications. Collembola responses to insecticides differed among species, both in terms of effect magnitude and persistence, suggesting that coarse taxonomic monitoring would not adequately detect pesticide risks. These findings have implications for pesticide risk assessments and for the selection of indicator species