Preventative interventions often demand that resources be consumed in the present in exchange for future benefits. Cost-effectiveness analysis is a tool to understand these trade-offs, and inform decision-making under resource constraints. Targeted testing and treatment (TTT) for latent tuberculosis infection (LTBI) consists in identifying people at high risk for LTBI for preventive treatment to decrease the risk of active tuberculosis disease (ATBD). The state of Tennessee began conducting TTT statewide in 2001. This study uses a decision tree to evaluate the cost and outcomes of TTT for LTBI in Tennessee, compared to passive ATBD case finding (PACF). Key probabilities were obtained from the Tennessee TTT program and the literature. Outcomes are measured in terms of Quality Adjusted Life Years (QALY). The cost-effectiveness threshold was $100,000/QALY saved. One-way sensitivity analyses around factors related to study design, the program’s environment, and program performance were conducted, as was probabilistic sensitivity analysis (PSA) which takes into account the uncertainty in multiple parameters simultaneously. The base case, with a 25-year analytic horizon and 3% discount rate, shows that TTT prevents 47 ATBD cases, and saves 31 QALYs per 100,000 patients screened at a societal cost of $12,579 per QALY saved. Sensitivity analyses identified value thresholds that would trigger a change in preferred policy. PSA shows that the likelihood that TTT would be cost-effective is low. Decision makers should carefully assess the characteristics of the local TB epidemic and expected program performance to determine whether TTT is preferable over PACF from a cost-effectiveness viewpoint.

An economic evaluation of the three interventions to conceive without the sexual transmission of HIV between heterosexual, HIV-discordant couples with positive male partners can inform policy decisions to subsidize pregnancy planning in this setting, as there is currently no coverage as such in Ontario. A decision tree and Markov model were designed to determine the short and long-term outcomes of unprotected intercourse restricted to timed ovulation (UIRTO), sperm washing with intrauterine insemination (SWIUI), and unprotected intercourse restricted to timed ovulation with pre-exposure prophylaxis (UIRTO-PrEP). In the short-term, UIRTO was the most cost-effective strategy. In the long-term, cases of negligible HIV transmission risk determined UIRTO-PrEP as the preferred option, while SWIUI was the choice method when this risk was high. There remains a viable risk of HIV transmission between discordant couples during attempts to conceive that require the concurrent and subsidized use of UIRTO-PrEP or SWIUI to protect against HIV infection.

An economic evaluation of the three interventions to conceive without the sexual transmission of HIV between heterosexual, HIV-discordant couples with positive male partners can inform policy decisions to subsidize pregnancy planning in this setting, as there is currently no coverage as such in Ontario. A decision tree and Markov model were designed to determine the short and long-term outcomes of unprotected intercourse restricted to timed ovulation (UIRTO), sperm washing with intrauterine insemination (SWIUI), and unprotected intercourse restricted to timed ovulation with pre-exposure prophylaxis (UIRTO-PrEP). In the short-term, UIRTO was the most cost-effective strategy. In the long-term, cases of negligible HIV transmission risk determined UIRTO-PrEP as the preferred option, while SWIUI was the choice method when this risk was high. There remains a viable risk of HIV transmission between discordant couples during attempts to conceive that require the concurrent and subsidized use of UIRTO-PrEP or SWIUI to protect against HIV infection.

In my thesis, in the theoretical part I deal with atrial fibrillation. I also deal with management of atrial fibrillation treatment. In the paper I explain the basic principles of pharmaco-economic evaluation in the Czech Republic, on the basis of which laws these pharmacological interventions are evaluated and who are in the Czech Republic. In the work I present cost breakdown and what are the most commonly used pharmaco-economic analyzes. In the practical part I will apply the theoretical knowledge. I have developed cost utility analysis based on available clinical evidence - randomized clinical trials ARISTOTLE (Granger, 2011), RE-LY (Connolly, 2009), ROCKET AF (Patel, 2011). I made an indirect comparison of the total benefits of NOACs. In the baseline scenario, I have calculated QALY to evaluate the benefits of effectiveness, safety and reduction of mortality. I have also dealt with a bleeding-related scenario. The ICER's greatest contribution to the public healthcare system has shown the active substance apixaban in both scenarios. I added the results and confirmed the clinical results of a recent, robust, retrospective study by Mayo Clinic (Yao, 2016).

Background and Objectives: Economic evaluation and decision analysis provide a framework to evaluate incremental costs and effects associated with alternative health interventions. These methods can also be used as a tool to evaluate alternative clinical behaviours or practice patterns. The objective of this thesis was to investigate the impact of current Canadian practices in human epidermal growth factor receptor-2 (HER2) testing to target trastuzumab in early-stage breast cancer (BC). Methods: Project 1: A systematic review of previous trastuzumab and HER2 testing economic analyses was conducted to identify methodological gaps and key lessons. Project 2: A population-level, retrospective cohort was studied to determine HER2 testing and trastuzumab treatment patterns in Ontario early-stage BC patients. Project 3: A cost-utility analysis of alternative test-treat strategies was conducted using a Markov model of BC calibrated to the Canadian setting, and incorporating Project 2 findings. Results: Project 1: Previous economic evaluations demonstrated that HER2 test accuracy and sequencing were key considerations when modelling the cost-effectiveness of trastuzumab treatment. Consideration of local testing and treatment practices was lacking. Project 2: HER2 testing and treatment practice differed from guidelines, where documentation was available. Only 88% of equivocal results were confirmed, while 57% of HER2 positive patients received trastuzumab. Project 3: Calibration of the BC model minimised gaps between trial-based survival and expected Canadian survival patterns. Deviations from guidelines in practice suggest that primary testing with fluorescence in situ hybridization (FISH) would produce greater health gains at a reduced cost vs. primary immunohistochemistry with FISH confirmation. This finding was more apparent as the prevalence of HER2 positive disease increased. Introduction of newer in situ hybridisation tests may be cost-effective as well. Conclusions: Practice deviations from guidelines are an important consideration when modelling the cost-effectiveness of trastuzumab therapy. Underlying local disease progression and prevalence can also significantly impact outcomes. / Dissertation / Doctor of Philosophy (PhD)

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Cost-utility analysis is one method of determining the cost effectiveness of nursing interventions. It is heralded by the World Health Organization as the measure to determine allocation of resources. This method of measurement includes calculation of both the cost of quality-adjusted life years (QALY) and the cost of disability-adjusted life years (DALY). The purpose of this article is to present cost-utility analysis as a relevant measure for describing the value of registered nurses. First the article will present a short overview of cost effectiveness, along with a discussion of two cost-effectiveness measures, cost-effective analysis and cost-utility analysis. Then the measurement of quality-adjusted life years and disability-adjusted life years will be presented. The article will conclude by challenging nurses to develop cost-utility analyses into a meaningful and useful methodology that can provide nursing with a process to measure the economic outcomes of our nursing interventions.

The energy consumption that arises from the utilisation of information processing systems adds a significant contribution to environmental pollution and has a big share of operation costs. This entails that we need to find ways to reduce the energy consumption of such systems. When trying to save energy it is important to ensure that the utility (e.g., user experience) of a system is not unnecessarily degraded, requiring a careful trade-off analysis between the consumed energy and the resulting utility. Therefore, research on energy efficiency has become a very active and important research topic that concerns many different scientific areas, and is as well of interest for industrial companies. The concept of quantiles is already well-known in mathematical statistics, but its benefits for the formal quantitative analysis of probabilistic systems have been noticed only recently. For instance, with the help of quantiles it is possible to reason about the minimal energy that is required to obtain a desired system behaviour in a satisfactory manner, e.g., a required user experience will be achieved with a sufficient probability. Quantiles also allow the determination of the maximal utility that can be achieved with a reasonable probability while staying within a given energy budget. As those examples illustrate important measures that are of interest when analysing energy-aware systems, it is clear that it is beneficial to extend formal analysis-methods with possibilities for the calculation of quantiles. In this monograph, we will see how we can take advantage of those quantiles as an instrument for analysing the trade-off between energy and utility in the field of probabilistic model checking. Therefore, we present algorithms for their computation over Markovian models. We will further investigate different techniques in order to improve the computational performance of implementations of those algorithms. The main feature that enables those improvements takes advantage of the specific characteristics of the linear programs that need to be solved for the computation of quantiles. Those improved algorithms have been implemented and integrated into the well-known probabilistic model checker PRISM. The performance of this implementation is then demonstrated by means of different protocols with an emphasis on the trade-off between the consumed energy and the resulting utility. Since the introduced methods are not restricted to the case of an energy-utility analysis only, the proposed framework can be used for analysing the interplay of cost and its resulting benefit in general.:1 Introduction 1.1 Related work 1.2 Contribution and outline 2 Preliminaries 3 Reward-bounded reachability properties and quantiles 3.1 Essentials 3.2 Dualities 3.3 Upper-reward bounded quantiles 3.3.1 Precomputation 3.3.2 Computation scheme 3.3.3 Qualitative quantiles 3.4 Lower-reward bounded quantiles 3.4.1 Precomputation 3.4.2 Computation scheme 3.5 Energy-utility quantiles 3.6 Quantiles under side conditions 3.6.1 Upper reward bounds 3.6.2 Lower reward bounds 3.6.2.1 Maximal reachability probabilities 3.6.2.2 Minimal reachability probabilities 3.7 Reachability quantiles and continuous time 3.7.1 Dualities 4 Expectation Quantiles 4.1 Computation scheme 4.2 Arbitrary models 4.2.1 Existential expectation quantiles 4.2.2 Universal expectation quantiles 5 Implementation 5.1 Computation optimisations 5.1.1 Back propagation 5.1.2 Reward window 5.1.3 Topological sorting of zero-reward sub-MDPs 5.1.4 Parallel computations 5.1.5 Multi-thresholds 5.1.6 Multi-state solution methods 5.1.7 Storage for integer sets 5.1.8 Elimination of zero-reward self-loops 5.2 Integration in Prism 5.2.1 Computation of reward-bounded reachability probabilities 5.2.2 Computation of quantiles in CTMCs 6 Analysed Protocols 6.1 Prism Benchmark Suite 6.1.1 Self-Stabilising Protocol 6.1.2 Leader-Election Protocol 6.1.3 Randomised Consensus Shared Coin Protocol 6.2 Energy-Aware Protocols 6.2.1 Energy-Aware Job-Scheduling Protocol 6.2.1.1 Energy-Aware Job-Scheduling Protocol with side conditions 6.2.1.2 Energy-Aware Job-Scheduling Protocol and expectation quantiles 6.2.1.3 Multiple shared resources 6.2.2 Energy-Aware Bonding Network Device (eBond) 6.2.3 HAECubie Demonstrator 6.2.3.1 Operational behaviour of the protocol 6.2.3.2 Formal analysis 7 Conclusion 7.1 Classification 7.2 Future prospects Bibliography List of Figures List of Tables

Cost-utility analysis is one method of determining the cost effectiveness of nursing interventions. It is heralded by the World Health Organization as the measure to determine allocation of resources. This method of measurement includes calculation of both the cost of quality-adjusted life years (QALY) and the cost of disability-adjusted life years (DALY). The purpose of this article is to present cost-utility analysis as a relevant measure for describing the value of registered nurses. First the article will present a short overview of cost effectiveness, along with a discussion of two cost-effectiveness measures, cost-effective analysis and cost-utility analysis. Then the measurement of quality-adjusted life years and disability-adjusted life years will be presented. The article will conclude by challenging nurses to develop cost-utility analyses into a meaningful and useful methodology that can provide nursing with a process to measure the economic outcomes of our nursing interventions.