Effect of cementation level on performance of rubberized cement-stabilized aggregate mixtures

An investigation and comparison is made of the effect of cement content on the performance of rubberized cement-stabilized aggregate mixtures and on cement-stabilized aggregate mixtures containing no rubber (RCSAMs and CSAMs). These materials are intended to be used as a base course for pavement structures. Three cement contents (3%, 5%, and 7% by dry weight of aggregate) were investigated. Rubberized mixtures were manufactured by replacing 30% of one aggregate fraction that has a similar gradation of crumb rubber. Performance was evaluated under static and dynamic testing. The investigated properties are unconfined compressive strength, indirect tensile strength, indirect tensile static modulus, toughness, dynamic modulus of elasticity, dynamic modulus of rigidity and dynamic Poisson's ratio. Increasing cement content increases strength of both types of mixtures, especially in the CSAMs. It is found that using crumb rubber at low cement content is more feasible than with high cement contents. Stiffnesses increased for both types of mixture as cement content increased but decreased on incorporation of crumb rubber. Energy absorption capacity was inversely related to stiffness. Mesostructural investigation revealed that the cracks were propagated through the rubber particles for all cement contents

Using Parameter Constraints to Choose State Structures in Cost-Effectiveness Modelling.

BACKGROUND: This article addresses the choice of state structure in a cost-effectiveness multi-state model. Key model outputs, such as treatment recommendations and prioritisation of future research, may be sensitive to state structure choice. For example, it may be uncertain whether to consider similar disease severities or similar clinical events as the same state or as separate states. Standard statistical methods for comparing models require a common reference dataset but merging states in a model aggregates the data, rendering these methods invalid. METHODS: We propose a method that involves re-expressing a model with merged states as a model on the larger state space in which particular transition probabilities, costs and utilities are constrained to be equal between states. This produces a model that gives identical estimates of cost effectiveness to the model with merged states, while leaving the data unchanged. The comparison of state structures can be achieved by comparing maximised likelihoods or information criteria between constrained and unconstrained models. We can thus test whether the costs and/or health consequences for a patient in two states are the same, and hence if the states can be merged. We note that different structures can be used for rates, costs and utilities, as appropriate. APPLICATION: We illustrate our method with applications to two recent models evaluating the cost effectiveness of prescribing anti-depressant medications by depression severity and the cost effectiveness of diagnostic tests for coronary artery disease. CONCLUSIONS: State structures in cost-effectiveness models can be compared using standard methods to compare constrained and unconstrained models

Engaging community service or learning? Benchmarking community service in teacher education

The focus in this project has been on the extent of explicit commitment of teacher educators in universities to community service and community partnerships that find expression in the content and processes of programs. Such program expression reflects the reciprocity and mutual benefit of engagement with community in teacher education, albeit at a range of levels from superficial and isolated to complex and integrated. In teacher education, the focus is on community as a context for learning and in that sense the community provides significant benefit to the university and its students

Network Meta-analysis on Disconnected Evidence Networks When Only Aggregate Data Are Available:Modified Methods to Include Disconnected Trials and Single-Arm Studies while Minimizing Bias

BACKGROUND: Network meta-analysis (NMA) requires a connected network of randomized controlled trials (RCTs) and cannot include single-arm studies. Regulators or academics often have only aggregate data. Two aggregate data methods for analyzing disconnected networks are random effects on baseline and aggregate-level matching (ALM). ALM has been used only for single-arm studies, and both methods may bias effect estimates. METHODS: We modified random effects on baseline to separate RCTs connected to and disconnected from the reference and any single-arm studies, minimizing the introduction of bias. We term our modified method reference prediction. We similarly modified ALM and extended it to include RCTs disconnected from the reference. We tested these methods using constructed data and a simulation study. RESULTS: In simulations, bias for connected treatments for ALM ranged from −0.0158 to 0.051 and for reference prediction from −0.0107 to 0.083. These were low compared with the true mean effect of 0.5. Coverage ranged from 0.92 to 1.00. In disconnected treatments, bias of ALM ranged from −0.16 to 0.392 and of reference prediction from −0.102 to 0.40, whereas coverage of ALM ranged from 0.30 to 0.82 and of reference prediction from 0.64 to 0.94. Under fixed study effects for disconnected evidence, bias was similar, but coverage was 0.81 to 1.00 for reference prediction and 0.18 to 0.76 for ALM. Trends of similar bias but greater coverage for reference prediction with random study effects were repeated in constructed data. CONCLUSIONS: Both methods with random study effects seem to minimize bias in treatment connected to the reference. They can estimate treatment effects for disconnected treatments but may be biased. Reference prediction has greater coverage and may be recommended overall. HIGHLIGHTS: Two methods were modified for network meta-analysis on disconnected networks and for including single-arm observational or interventional studies in network meta-analysis using only aggregate data and for minimizing the bias of effect estimates for treatments only in trials connected to the reference. Reference prediction was developed as a modification of random effects on baseline that keeps analyses of trials connected to the reference separately from those disconnected from the reference and from single-arm studies. The method was further modified to account for correlation in trials with more than 2 arms and, under random study effects, to estimate variance in heterogeneity separately in connected and disconnected evidence. Aggregate-level matching was extended to include trials disconnected from the reference, rather than only single-arm studies. The method was further modified to separately estimate treatment effects and heterogeneity variance in the connected and disconnected evidence and to account for the correlation between arms in trials with more than 2 arms. Performance was assessed using a constructed data example and simulation study. The methods were found to have similar, and sometimes low, bias when estimating the relative effects for disconnected treatments, but reference prediction with random study effects had the greatest coverage. The use of reference prediction with random study effects for disconnected networks is recommended if no individual patient data or alternative real-world evidence is available

R You Still Using Excel? The Advantages of Modern Software Tools for Health Technology Assessment

The Professional Society for Health Economics and Outcomes Research Economic models are used in health technology assessments (HTAs) to evaluate the cost-effectiveness of competing medical technologies and inform the efficient use of health care resources. Historically, these models have been developed with specialized commercial software (such as TreeAge) or more commonly with spreadsheet software (almost always Microsoft Excel). Although these tools may be sufficient for relatively simple analyses, they put unnecessary constraints on the analysis that may ultimately limit its credibility and relevance. In contrast, modern programming languages such as R, Python, Matlab, and Julia facilitate the development of models that are (i) clinically realistic, (ii) capable of quantifying decision uncertainty, (iii) transparent and reproducible, and (iv) reusable and adaptable. An HTA environment that encourages use of modern software can therefore help ensure that coverage and pricing decisions confer greatest possible benefit and capture all scientific uncertainty, thus enabling correct prioritization of future research

Secukinumab versus adalimumab for psoriatic arthritis: comparative effectiveness up to 48 weeks using a matching-adjusted indirect comparison

Secukinumab and adalimumab are approved for adults with active psoriatic arthritis (PsA). In the absence of direct randomized controlled trial (RCT) data, matching-adjusted indirect comparison can estimate the comparative effectiveness in anti-tumor necrosis factor (TNF)-naïve populations. Individual patient data from the FUTURE 2 RCT (secukinumab vs. placebo; N = 299) were adjusted to match baseline characteristics of the ADEPT RCT (adalimumab vs. placebo; N = 313). Logistic regression determined adjustment weights for age, body weight, sex, race, methotrexate use, psoriasis affecting ≥ 3% of body surface area, Psoriasis Area and Severity Index score, Health Assessment Questionnaire Disability Index score, presence of dactylitis and enthesitis, and previous anti-TNF therapy. Recalculated secukinumab outcomes were compared with adalimumab outcomes at weeks 12 (placebo-adjusted), 16, 24, and 48 (nonplacebo-adjusted). After matching, the effective sample size for FUTURE 2 was 101. Week 12 American College of Rheumatology (ACR) response rates were not significantly different between secukinumab and adalimumab. Week 16 ACR 20 and 50 response rates were higher for secukinumab 150 mg than for adalimumab (P = 0.017, P = 0.033), as was ACR 50 for secukinumab 300 mg (P = 0.030). Week 24 ACR 20 and 50 were higher for secukinumab 150 mg than for adalimumab (P = 0.001, P = 0.019), as was ACR 20 for secukinumab 300 mg (P = 0.048). Week 48 ACR 20 was higher for secukinumab 150 and 300 mg than for adalimumab (P = 0.002, P = 0.027), as was ACR 50 for secukinumab 300 mg (P = 0.032). In our analysis, patients with PsA receiving secukinumab were more likely to achieve higher ACR responses through 1 year (weeks 16-48) than those treated with adalimumab. Although informative, these observations rely on a subgroup of patients from FUTURE 2 and thus should be considered interim until the ongoing head-to-head RCT EXCEED can validate these findings. Novartis Pharma AG

Cost-effectiveness of initial stress cardiovascular MR, stress SPECT or stress echocardiography as a gate-keeper test, compared with upfront invasive coronary angiography in the investigation and management of patients with stable chest pain: Mid-term outcomes from the CECaT randomised controlled trial

Objectives: To compare outcomes and cost-effectiveness of various initial imaging strategies in the management of stable chest pain in a long-term prospective randomised trial. Setting: Regional cardiothoracic referral centre in the east of England. Participants: 898 patients (69% man) entered the study with 869 alive at 2 years of follow-up. Patients were included if they presented for assessment of stable chest pain with a positive exercise test and no prior history of ischaemic heart disease. Exclusion criteria were recent infarction, unstable symptoms or any contraindication to stress MRI. Primary outcome measures: The primary outcomes of this follow-up study were survival up to a minimum of 2 years post-treatment, quality-adjusted survival and cost-utility of each strategy. Results: 898 patients were randomised. Compared with angiography, mortality was marginally higher in the groups randomised to cardiac MR (HR 2.6, 95% CI 1.1 to 6.2), but similar in the single photon emission CT-methoxyisobutylisonitrile (SPECT-MIBI; HR 1.0, 95% CI 0.4 to 2.9) and ECHO groups (HR 1.6, 95% CI 0.6 to 4.0). Although SPECT-MIBI was marginally superior to other non-invasive tests there were no other significant differences between the groups in mortality, quality-adjusted survival or costs. Conclusions: Non-invasive cardiac imaging can be used safely as the initial diagnostic test to diagnose coronary artery disease without adverse effects on patient outcomes or increased costs, relative to angiography. These results should be interpreted in the context of recent advances in imaging technology. Trial registration: ISRCTN 47108462, UKCRN 3696

Cost-effectiveness and value of information analysis of a low-friction environment following skin graft in patients with burn injury

Background Patients with burn injuries may receive a skin graft to achieve healing in a timely manner. However, in around 7% of cases, the skin graft is lost (fails to attach to the wound site) and a re-grafting procedure is necessary. It has been hypothesised that low-friction (smooth, more slippery) bedding may reduce the risk of skin-graft loss. A before and after feasibility study comparing low-friction with standard bedding in skin-grafted patients was conducted in order to collect proof of concept data. The resulting relative risk on the primary outcome (number of patients with skin graft failure) for the non-randomised study provided no evidence of effect but had a large standard error. The aim of this study is to see if an appropriately powered randomised control trial would be worthwhile. Methods A probabilistic decision-analytic model was constructed to compare low-friction bedding to standard care in a population of burn patients who have undergone skin grafting. Results from the before and after study were used as model inputs. The sensitivity of results to bias in the relative risk of graft loss was conducted. Low-friction bedding is considered optimal if expected incremental net benefit (INB) is positive. Uncertainty is assessed using cost-effectiveness acceptability curves. Expected Value of Perfect Partial Information (EVPPI) provides an upper bound for the potential net health benefits of new research for given model input. Results At a willingness to pay threshold of £20,000 per QALY, INB = £151 (95% Credible Interval (CrI) −142 to 814), marginally favouring low-friction bedding but with high uncertainty (probability of being cost-effective 70.5%). Expected value of perfect information (EVPI) per patient was £20.29, which results in a population EVPI of £174,765 over a 10-year lifetime for the technology (based on 1000 patients per year who would benefit from the intervention). The parameter contributing most to the uncertainty was the inpatient care cost, i.e. information that could be obtained from the audit of practice and without an expensive trial. These findings were robust to a wide-range of assumptions about the potential bias due to the observational nature of the comparative evidence. Conclusions Our study results suggest that an RCT (randomised controlled trial) is unlikely to be worthwhile, but there may be value in a study to estimate the re-graft rates and associated costs in this population