Modelling the cost effectiveness of interferon beta and glatiramer acetate in the management of multiple sclerosis

OBJECTIVE: To evaluate the cost effectiveness of four disease modifying treatments (interferon betas and glatiramer acetate) for relapsing remitting and secondary progressive multiple sclerosis in the United Kingdom. DESIGN: Modelling cost effectiveness. SETTING: UK NHS. PARTICIPANTS: Patients with relapsing remitting multiple sclerosis and secondary progressive multiple sclerosis. MAIN OUTCOME MEASURES: Cost per quality adjusted life year gained. RESULTS: The base case cost per quality adjusted life year gained by using any of the four treatments ranged from £42 000 ($66 469; 61 630) to £98 000 based on efficacy information in the public domain. Uncertainty analysis suggests that the probability of any of these treatments having a cost effectiveness better than £20 000 at 20 years is below 20%. The key determinants of cost effectiveness were the time horizon, the progression of patients after stopping treatment, differential discount rates, and the price of the treatments. CONCLUSIONS: Cost effectiveness varied markedly between the interventions. Uncertainty around point estimates was substantial. This uncertainty could be reduced by conducting research on the true magnitude of the effect of these drugs, the progression of patients after stopping treatment, the costs of care, and the quality of life of the patients. Price was the key modifiable determinant of the cost effectiveness of these treatments

Estimating population cardinal health state valuation models from individual ordinal (rank) health state preference data

Ranking exercises have routinely been used as warm-up exercises within health state valuation surveys. Very little use has been made of the information obtained in this process. Instead, research has focussed upon the analysis of health state valuation data obtained using the visual analogue scale, standard gamble and time trade off methods. Thurstone’s law of comparative judgement postulates a stable relationship between ordinal and cardinal preferences, based upon the information provided by pairwise choices. McFadden proposed that this relationship could be modelled by estimating conditional logistic regression models where alternatives had been ranked. In this paper we report the estimation of such models for the Health Utilities Index Mark 2 and the SF-6D. The results are compared to the conventional regression models estimated from standard gamble data, and to the observed mean standard gamble health state valuations. For both the HUI2 and the SF-6D, the models estimated using rank data are broadly comparable to the models estimated on standard gamble data and the predictive performance of these models is close to that of the standard gamble models. Our research indicates that rank data has the potential to provide useful insights into community health state preferences. However, important questions remain

Estimating population cardinal health state valuation models from individual ordinal (rank) health state preference data

Ranking exercises have routinely been used as warm-up exercises within health state valuation surveys. Very little use has been made of the information obtained in this process. Instead, research has focussed upon the analysis of health state valuation data obtained using the visual analogue scale, standard gamble and time trade off methods. Thurstone’s law of comparative judgement postulates a stable relationship between ordinal and cardinal preferences, based upon the information provided by pairwise choices. McFadden proposed that this relationship could be modelled by estimating conditional logistic regression models where alternatives had been ranked. In this paper we report the estimation of such models for the Health Utilities Index Mark 2 and the SF-6D. The results are compared to the conventional regression models estimated from standard gamble data, and to the observed mean standard gamble health state valuations. For both the HUI2 and the SF-6D, the models estimated using rank data are broadly comparable to the models estimated on standard gamble data and the predictive performance of these models is close to that of the standard gamble models. Our research indicates that rank data has the potential to provide useful insights into community health state preferences. However, important questions remain.health state valuation; HUI-2; SF-6D

Estimating population cardinal health state valuation models from individual ordinal (rank) health state preference data

Ranking exercises have routinely been used as warm-up exercises within health state valuation surveys. Very little use has been made of the information obtained in this process. Instead, research has focussed upon the analysis of health state valuation data obtained using the visual analogue scale, standard gamble and time trade off methods. Thurstone’s law of comparative judgement postulates a stable relationship between ordinal and cardinal preferences, based upon the information provided by pairwise choices. McFadden proposed that this relationship could be modelled by estimating conditional logistic regression models where alternatives had been ranked. In this paper we report the estimation of such models for the Health Utilities Index Mark 2 and the SF-6D. The results are compared to the conventional regression models estimated from standard gamble data, and to the observed mean standard gamble health state valuations. For both the HUI2 and the SF-6D, the models estimated using rank data are broadly comparable to the models estimated on standard gamble data and the predictive performance of these models is close to that of the standard gamble models. Our research indicates that rank data has the potential to provide useful insights into community health state preferences. However, important questions remain

Effective patient–clinician interaction to improve treatment outcomes for patients with psychosis: a mixed-methods design

BACKGROUND:At least 100,000 patients with schizophrenia receive care from community mental health teams (CMHTs) in England. These patients have regular meetings with clinicians, who assess them, engage them in treatment and co-ordinate care. As these routine meetings are not commonly guided by research evidence, a new intervention, DIALOG, was previously designed to structure consultations. Using a hand-held computer, clinicians asked patients to rate their satisfaction with eight life domains and three treatment aspects, and to indicate whether or not additional help was needed in each area, with responses being graphically displayed and compared with previous ratings. In a European multicentre trial, the intervention improved patients’ quality of life over a 1-year period. The current programme builds on this research by further developing DIALOG in the UK. RESEARCH QUESTIONS:(1) How can the practical procedure of the intervention be improved, including the software used and the design of the user interface? (2) How can elements of resource-oriented interventions be incorporated into a clinician manual and training programme for a new, more extensive ‘DIALOG+’ intervention? (3) How effective and cost-effective is the new DIALOG+ intervention in improving treatment outcomes for patients with schizophrenia or a related disorder? (4) What are the views of patients and clinicians regarding the new DIALOG+ intervention? METHODS:We produced new software on a tablet computer for CMHTs in the NHS, informed by analysis of videos of DIALOG sessions from the original trial and six focus groups with 18 patients with psychosis. We developed the new ‘DIALOG+’ intervention in consultation with experts, incorporating principles of solution-focused therapy when responding to patients’ ratings and specifying the procedure in a manual and training programme for clinicians. We conducted an exploratory cluster randomised controlled trial with 49 clinicians and 179 patients with psychosis in East London NHS Foundation Trust, comparing DIALOG+ with an active control. Clinicians working as care co-ordinators in CMHTs (along with their patients) were cluster randomised 1 : 1 to either DIALOG+ or treatment as usual plus an active control, to prevent contamination. Intervention and control were to be administered monthly for 6 months, with data collected at baseline and at 3, 6 and 12 months following randomisation. The primary outcome was subjective quality of life as measured on the Manchester Short Assessment of Quality of Life; secondary outcomes were also measured. We also established the cost-effectiveness of the DIALOG intervention using data from the Client Service Receipt Inventory, which records patients’ retrospective reports of using health- and social-care services, including hospital services, outpatient services and medication, in the 3 months prior to each time point. Data were supplemented by the clinical notes in patients’ medical records to improve accuracy. We conducted an exploratory thematic analysis of 16 video-recorded DIALOG+ sessions and measured adherence in these videos using a specially developed adherence scale. We conducted focus groups with patients (n = 19) and clinicians (n = 19) about their experiences of the intervention, and conducted thematic analyses. We disseminated the findings and made the application (app), manual and training freely available, as well as producing a protocol for a definitive trial. RESULTS:Patients receiving the new intervention showed more favourable quality of life in the DIALOG+ group after 3 months (effect size: Cohen’s d = 0.34), after 6 months (Cohen’s d = 0.29) and after 12 months (Cohen’s d = 0.34). An analysis of video-recorded DIALOG+ sessions showed inconsistent implementation, with adherence to the intervention being a little over half of the possible score. Patients and clinicians from the DIALOG+ arm of the trial reported many positive experiences with the intervention, including better self-expression and improved efficiency of meetings. Difficulties reported with the intervention were addressed by further refining the DIALOG+ manual and training. Cost-effectiveness analyses found a 72% likelihood that the intervention both improved outcomes and saved costs. LIMITATIONS:The research was conducted solely in urban east London, meaning that the results may not be broadly generalisable to other settings. CONCLUSIONS:(1) Although services might consider adopting DIALOG+ based on the existing evidence, a definitive trial appears warranted; (2) applying DIALOG+ to patient groups with other mental disorders may be considered, and to groups with physical health problems; (3) a more flexible use with variable intervals might help to make the intervention even more acceptable and effective; (4) more process evaluation is required to identify what mechanisms precisely are involved in the improvements seen in the intervention group in the trial; and (5) what appears to make DIALOG+ effective is that it is not a separate treatment and not a technology that is administered by a specialist; rather, it changes and utilises the existing therapeutic relationship between patients and clinicians in CMHTs to initiate positive change, helping the patients to improve their quality of life. FUTURE RESEARCH:Future studies should include a definitive trial on DIALOG+ and test the effectiveness of the intervention with other populations, such as people with depression. TRIAL REGISTRATION:Current Controlled Trials ISRCTN34757603. FUNDING:The National Institute for Health Research Programme Grants for Applied Research programme

Determination of 3D Trajectories of Knots in Solar Prominences Using MSDP Data

In this paper we present a new method of restoration of the true thee-dimensional trajectories of the prominence knots based on ground-based observations taken with a single telescope, which is equipped with a Multi-Channel Subtractive Double Pass imaging spectrograph. Our method allows to evaluate true three-dimensional trajectories of the prominence knots without any assumptions concerning the shape of the trajectories or dynamics of the motion. The reconstructed trajectories of several knots observed in three prominences are presented.Comment: 14 pages, 9 figures, accepted for publication in Solar Physic

Practical long-distance quantum key distribution system using decoy levels

Quantum key distribution (QKD) has the potential for widespread real-world applications. To date no secure long-distance experiment has demonstrated the truly practical operation needed to move QKD from the laboratory to the real world due largely to limitations in synchronization and poor detector performance. Here we report results obtained using a fully automated, robust QKD system based on the Bennett Brassard 1984 protocol (BB84) with low-noise superconducting nanowire single-photon detectors (SNSPDs) and decoy levels. Secret key is produced with unconditional security over a record 144.3 km of optical fibre, an increase of more than a factor of five compared to the previous record for unconditionally secure key generation in a practical QKD system.Comment: 9 page

An investigation into the fertilizer potential of slaughterhouse cattle paunch

In Australia, the red meat processing industry actively seeks approaches to improve the management of solid waste from processing operations and enhance the environmental performance. Recycling of paunch waste to farmland could be a cost-effective and practicable environmental option. However, little is known about the agronomic value of fresh and composted paunch, and the associated requirements for land application. Therefore, a short-term experimental work was undertaken to assess potential risks due to weed seed contamination and determine the agronomic response of ryegrass (Lolium perenne L.) to soil incorporation of paunch. The risk of weed contamination from soil application of paunch appeared to be low; however, methods that account for viability of seeds may be required to fully discard such a risk. Soil application of paunch at field equivalent rates of 150-300 kg ha-1 of N increased dry matter yield by ≈30% on average compared with untreated grass, but was approximately 35% lower than a mineral fertilizer treatment applied at the same rates. Dry matter yield of paunch-treated grass was between 2000 and 3000 kg per ha over four consecutive cuts at 25-day intervals. Nitrogen use-efficiency of paunch was approximately 10% (range: 3% to 20%, depending on paunch type), and total N in harvested plant material showed values, which were between 2% and 3%. Overall, there appears to be potential for paunch-derived products to be used as a source of carbon and nutrients in crop production. Areas that merit a research priority within this space are also outlined in this paper. Such work is required to inform soil-, climate- and crop-specific land application rates, optimize agronomic performance, and minimize environmental concerns. There is also a requirement for the value proposition to industry to be determined, including reduced cost of disposal of material via gate fees and fertilizer replacement value

Development Length Criteria: Bars Without Transverse Reinforcement

An expression that accurately represents development and splice strength as a function of concrete cover and bar spacing is developed and used to establish and evaluate modifications to the bond and development provisions of the ACI Building Code (ACI 318-89) for bars without transverse reinforcement The expression for development and splice strength is similar in form to expressions developed by Orangun, Jirsa, and Breen (1975, 1977), but is obtained using techniques that limit the effects of unintentional bias in the test data. The resulting expression provides a more accurate representation of development and splice strength than do the earlier expressions, and provides better guidance when there is a significant difference between the concrete cover and one-half of the clear spacing between bars. The expression for development and splice strength is used to establish new criteria that follow the format of ACI 318-89 and to evaluate design criteria that are currently under review by ACI Subcommittee 318-B. The new criteria that follow the format of ACI 318-89 are generally conservative and economical. The provisions under study by Subcommittee 318-B are unconservative for No. 6 bars and smaller with minimum covers and close spacings, and are overconservative for most bars with higher covers and wider spacings. Modifications are recommended that increase both the safety and the economy provided by the provisions under study by ACI Subcommittee 318-B

Dryland ecohydrology and climate change: critical issues and technical advances

Drylands cover about 40% of the terrestrial land surface and account for approximately 40% of global net primary productivity. Water is fundamental to the biophysical processes that sustain ecosystem function and food production, particularly in drylands where a tight coupling exists between ecosystem productivity, surface energy balance, biogeochemical cycles, and water resource availability. Currently, drylands support at least 2 billion people and comprise both natural and managed ecosystems. In this synthesis, we identify some current critical issues in the understanding of dryland systems and discuss how arid and semiarid environments are responding to the changes in climate and land use. The issues range from societal aspects such as rapid population growth, the resulting food and water security, and development issues, to natural aspects such as ecohydrological consequences of bush encroachment and the causes of desertification. To improve current understanding and inform upon the needed research efforts to address these critical issues, we identify some recent technical advances in terms of monitoring dryland water dynamics, water budget and vegetation water use, with a focus on the use of stable isotopes and remote sensing. These technological advances provide new tools that assist in addressing critical issues in dryland ecohydrology under climate change