The Long-Term Cost to the UK NHS and Social Services of Different Durations of IV Thiamine (Vitamin B1) for Chronic Alcohol Misusers with Symptoms of Wernicke's Encephalopathy Presenting at the Emergency Department.

BACKGROUND: Wernicke's encephalopathy (WE) is an acute neuropsychiatric condition caused by depleted intracellular thiamine, most commonly arising in chronic alcohol misusers, who may present to emergency departments (EDs) for a variety of reasons. Guidelines recommend a minimum 5-day course of intravenous (IV) thiamine in at-risk patients unless WE can be excluded. OBJECTIVE: To estimate the cost impact on the UK public sector (NHS and social services) of a 5-day course of IV thiamine, vs a 2- and 10-day course, in harmful or dependent drinkers presenting to EDs. METHODS: A Markov chain model compared expected prognosis of patients under alternative admission strategies over 35 years. Model inputs were derived from a prospective cohort study, expert opinion via structured elicitation and NHS costing databases. Costs (2012/2013 price year) were discounted at 3.5 %. RESULTS: Increasing treatment from 2 to 5 days increased acute care costs but reduced the probability of disease progression and thus reduced the expected net costs by GBP87,000 per patient (95 % confidence interval GBP19,300 to GBP172,300) over 35 years. CONCLUSIONS: Increasing length of stay to optimize IV thiamine replacement will place additional strain on acute care but has potential UK public sector cost savings. Social services and the NHS should explore collaborations to realise both the health benefits to patients and savings to the public purse.This study was funded by Archimedes UK Pharma Ltd, the manufacturer of Pabrinex®. Hayward Medical Communications provided editorial and writing support during manuscript development.This is the final version of the article. It was first available from Springer via http://dx.doi.org/10.1007/s40258-015-0214-

Efficient Research Design: Using Value-of-Information Analysis to Estimate the Optimal Mix of Top-down and Bottom-up Costing Approaches in an Economic Evaluation alongside a Clinical Trial.

In designing economic evaluations alongside clinical trials, analysts are frequently faced with alternative methods of collecting the same data, the extremes being top-down ("gross costing") and bottom-up ("micro-costing") approaches. A priori, bottom-up approaches may be considered superior to top-down approaches but are also more expensive to collect and analyze. In this article, we use value-of-information analysis to estimate the efficient mix of observations on each method in a proposed clinical trial. By assigning a prior bivariate distribution to the 2 data collection processes, the predicted posterior (i.e., preposterior) mean and variance of the superior process can be calculated from proposed samples using either process. This is then used to calculate the preposterior mean and variance of incremental net benefit and hence the expected net gain of sampling. We apply this method to a previously collected data set to estimate the value of conducting a further trial and identifying the optimal mix of observations on drug costs at 2 levels: by individual item (process A) and by drug class (process B). We find that substituting a number of observations on process A for process B leads to a modest £ 35,000 increase in expected net gain of sampling. Drivers of the results are the correlation between the 2 processes and their relative cost. This method has potential use following a pilot study to inform efficient data collection approaches for a subsequent full-scale trial. It provides a formal quantitative approach to inform trialists whether it is efficient to collect resource use data on all patients in a trial or on a subset of patients only or to collect limited data on most and detailed data on a subset.This is the author accepted manuscript. The final version is available from SAGE via http://dx.doi.org/10.1177/0272989X1562218

Planar chromatography - Current practice and future prospects

Planar chromatography, in the form of thin-layer or high-performance thin-layer chromatography (TLC, HPTLC), continues to provide a robust and widely used separation technique. It is unrivaled as a simple and rapid qualitative method for mixture analysis, or for finding bioactive components in mixtures. The format of TLC/HPTLC also provides a unique method for preserving the separation, enabling further investigation of components of interest (including quantification/structure determination) separated in both time and space from the original analysis. The current practice of planar chromatography and areas of development of the technology are reviewed and promising future directions in the use of TLC/HPTLC are outlined

Are brief interventions to increase physical activity cost-effective? A systematic review.

OBJECTIVE: To determine whether brief interventions promoting physical activity are cost-effective in primary care or community settings. DESIGN: Systematic review of economic evaluations. METHODS AND DATA SOURCES: We searched MEDLINE, EMBASE, PsycINFO, CINAHL, EconLit, SPORTDiscus, PEDro, the Cochrane library, National Health Service Economic Evaluation Database and the Cost-Effectiveness Analysis Registry up to 20 August 2014. Web of Knowledge was used for cross-reference search. We included studies investigating the cost-effectiveness of brief interventions, as defined by National Institute for Health and Care Excellence, promoting physical activity in primary care or the community. Methodological quality was assessed using Drummond's checklist for economic evaluations. Data were extracted from individual studies fulfilling selection criteria using a standardised pro forma. Comparisons of cost-effectiveness and cost-utility ratios were made between studies. RESULTS: Of 1840 identified publications, 13 studies fulfilled the inclusion criteria describing 14 brief interventions. Studies varied widely in the methods used, such as the perspective of economic analysis, intervention effects and outcome measures. The incremental cost of moving an inactive person to an active state, estimated for eight studies, ranged from £96 to £986. The cost-utility was estimated in nine studies compared with usual care and varied from £57 to £14 002 per quality-adjusted life year; dominant to £6500 per disability-adjusted life year; and £15 873 per life years gained. CONCLUSIONS: Brief interventions promoting physical activity in primary care and the community are likely to be inexpensive compared with usual care. Given the commonly accepted thresholds, they appear to be cost-effective on the whole, although there is notable variation between studies.This paper presents independent research funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (Grant Reference Number RP-PG-0608-10079).This is the final version of the article. It first appeared from BMJ via http://dx.doi.org/10.1136/bjsports-2015-09465

The effects of maintenance schedules following pulmonary rehabilitation in patients with chronic obstructive pulmonary disease: a randomised controlled trial.

OBJECTIVES: Pulmonary rehabilitation (PR) provides benefit for patients with chronic obstructive pulmonary disease (COPD) in terms of quality of life (QoL) and exercise capacity; however, the effects diminish over time. Our aim was to evaluate a maintenance programme for patients who had completed PR. SETTING: Primary and secondary care PR programmes in Norfolk. PARTICIPANTS: 148 patients with COPD who had completed at least 60% of a standard PR programme were randomised and data are available for 110 patients. Patients had greater than 20 pack year smoking history and less than 80% predicted forced expiratory volume in 1 s but no other significant disease or recent respiratory tract infection. INTERVENTIONS: Patients were randomised to receive a maintenance programme or standard care. The maintenance programme consisted of 2 h (1 h individually tailored exercise training and 1 h education programme) every 3 months for 1 year. PRIMARY AND SECONDARY OUTCOME MEASURES: The Chronic Respiratory Questionnaire (CRQ) (primary outcome), endurance shuttle walk test (ESWT), EuroQol (EQ5D), hospital anxiety and depression score (HADS), body mass index (BMI), body fat, activity levels (overall score and activity diary) and exacerbations were assessed before and after 12 months. RESULTS: There was no statistically significant difference between the groups for the change in CRQ dyspnoea score (primary end point) at 12 months which amounted to 0.19 (-0.26 to 0.64) units or other domains of the CRQ. There was no difference in the ESWT duration (-10.06 (-191.16 to 171.03) seconds), BMI, body fat, EQ5D, MET-minutes, activity rating, HADS, exacerbations or admissions. CONCLUSIONS: A maintenance programme of three monthly 2 h sessions does not improve outcomes in patients with COPD after 12 months. We do not recommend that our maintenance programme is adopted. Other methods of sustaining the benefits of PR are required. TRIAL REGISTRATION NUMBER: NCT00925171.This paper presents independent research funded by the National Institute for Health Research (NIHR) under its Research for Patient Benefit (RfPB) Programme (Grant Reference Number PB-PG-0408-16225). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.This is the final published version. It first appeared at http://bmjopen.bmj.com/content/5/3/e005921.full?g=w_thorax_open_tab

Transport theory yields renormalization group equations

We show that dissipative transport and renormalization can be described in a single theoretical framework. The appropriate mathematical tool is the Nakajima-Zwanzig projection technique. We illustrate our result in the case of interacting quantum gases, where we use the Nakajima-Zwanzig approach to investigate the renormalization group flow of the effective two-body interaction.Comment: 11 pages REVTeX, twocolumn, no figures; revised version with additional examples, to appear in Phys. Rev.

Game theory of mind

This paper introduces a model of ‘theory of mind’, namely, how we represent the intentions and goals of others to optimise our mutual interactions. We draw on ideas from optimum control and game theory to provide a ‘game theory of mind’. First, we consider the representations of goals in terms of value functions that are prescribed by utility or rewards. Critically, the joint value functions and ensuing behaviour are optimised recursively, under the assumption that I represent your value function, your representation of mine, your representation of my representation of yours, and so on ad infinitum. However, if we assume that the degree of recursion is bounded, then players need to estimate the opponent's degree of recursion (i.e., sophistication) to respond optimally. This induces a problem of inferring the opponent's sophistication, given behavioural exchanges. We show it is possible to deduce whether players make inferences about each other and quantify their sophistication on the basis of choices in sequential games. This rests on comparing generative models of choices with, and without, inference. Model comparison is demonstrated using simulated and real data from a ‘stag-hunt’. Finally, we note that exactly the same sophisticated behaviour can be achieved by optimising the utility function itself (through prosocial utility), producing unsophisticated but apparently altruistic agents. This may be relevant ethologically in hierarchal game theory and coevolution

Developing a prioritisation framework in an English Primary Care Trust.

BACKGROUND: In the English NHS, Primary Care Trusts (PCTs) are required to commission health services, to maximise the well-being of the population, subject to the available budget. There are numerous techniques employed to make decisions, some more rational and transparent than others. A weighted benefit score can be used to rank options but this does not take into account value for money from investments. METHODS: We developed a weighted benefit score framework for use in an English PCT which ranked options in order of 'cost-value' or 'cost per point of benefit'. Our method differs from existing techniques by explicitly combining cost and a composite weighted benefit score into the cost-value ratio. RESULTS: The technique proved readily workable, and was able to accommodate a wide variety of data and competing criteria. Participants felt able to assign scores to proposed services, and generate a ranked list, which provides a solid starting point for the PCT Board to discuss and make funding decisions. Limitations included potential for criteria to be neither exhaustive nor mutually exclusive and the lack of an interval property in the benefit score limiting the usefulness of a cost-value ratio. CONCLUSION: A technical approach to decision making is insufficient for making prioritisation decisions, however our technique provides a very valuable, structured and informed starting point for PCT decision making

A proteomics study of rheumatoid arthritis patients on etanercept identifies putative biomarkers associated with clinical outcome measures

\ua9 The Author(s) 2023. Objectives: Biologic DMARDs (bDMARDs) are widely used in patients with RA, but response to bDMARDs is heterogeneous. The objective of this work was to identify pretreatment proteomic biomarkers associated with RA clinical outcome measures in patients starting bDMARDs. Methods: Sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS) was used to generate spectral maps of sera from patients with RA before and after 3 months of treatment with the bDMARD etanercept. Protein levels were regressed against RA clinical outcome measures, i.e. 28-joint DAS (DAS28) and its subcomponents and DAS28 <2.6 (i.e. remission). The proteins with the strongest evidence for association were analysed in an independent, replication dataset. Finally, subnetwork analysis was carried out using the Disease Module Detection algorithm and biological plausibility of identified proteins was assessed by enrichment analysis. Results: A total of 180 patients with RA were included in the discovery dataset and 58 in the validation dataset from a UK-based prospective multicentre study. Ten individual proteins were found to be significantly associated with RA clinical outcome measures. The association of T-complex protein 1 subunit g with DAS28 remission was replicated in an independent cohort. Subnetwork analysis of the 10 proteins from the regression analysis identified the ontological theme, with the strongest associations being with acute phase and acute inflammatory responses. Conclusion: This longitudinal study of 180 patients with RA commencing etanercept has identified several putative protein biomarkers of treatment response to this drug, one of which was replicated in an independent cohort