Using stress testing to guide primary prevention of coronary heart disease among intermediate-risk patients: a cost-effectiveness analysis

Noninvasive stress testing might guide the use of aspirin and statins for primary prevention of coronary heart disease, but it is unclear if such a strategy would be cost effective.

Cost-effectiveness of pharmacogenetic testing to predict treatment response to angiotensin-converting enzyme inhibitor

OBJECTIVE: This study aimed to assess the potential cost-effectiveness of testing patients with nephropathies for the I/D polymorphism before starting angiotensin-converting enzyme (ACE) inhibitor therapy, using a 3-year time horizon and a healthcare perspective. METHODS: We used a combination of a decision analysis and Markov modeling technique to evaluate the potential economic value of this pharmacogenetic test by preventing unfavorable treatment in patients with nephropathies. The estimation of the predictive value of the I/D polymorphism is based on a systematic review showing that DD carriers tend to respond well to ACE inhibitors, while II carriers seem not to benefit adequately from this treatment. Data on the ACE inhibitor effectiveness in nephropathy were derived from the REIN (Ramipril Efficacy in Nephropathy) trial. We calculated the number of patients with end-stage renal disease (ESRD) prevented and the differences in the incremental costs and incremental effect expressed as life-years free of ESRD. A probabilistic sensitivity analysis was conducted to determine the robustness of the results. RESULTS: Compared with unselective treatment, testing patients for their ACE genotype could save 12 patients per 1000 from developing ESRD during the 3 years covered by the model. As the mean net cost savings was euro 356,000 per 1000 patient-years, and 9 life-years free of ESRD were gained, selective treatment seems to be dominant. CONCLUSION: The study suggests that genetic testing of the I/D polymorphism in patients with nephropathy before initiating ACE therapy will most likely be cost-effective, even if the risk for II carriers to develop ESRD when treated with ACE inhibitors is only 1.4% higher than for DD carriers. Further studies, however, are required to corroborate the difference in treatment response between ACE genotypes, before genetic testing can be justified in clinical practice.

Effectiveness and cost-effectiveness of traditional and new partner notification technologies for curable sexually transmitted infections: observational study, systematic reviews and mathematical modelling

BACKGROUND Partner notification is essential to the comprehensive case management of sexually transmitted infections. Systematic reviews and mathematical modelling can be used to synthesise information about the effects of new interventions to enhance the outcomes of partner notification. OBJECTIVE To study the effectiveness and cost-effectiveness of traditional and new partner notification technologies for curable sexually transmitted infections (STIs). DESIGN Secondary data analysis of clinical audit data; systematic reviews of randomised controlled trials (MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials) published from 1 January 1966 to 31 August 2012 and of studies of health-related quality of life (HRQL) [MEDLINE, EMBASE, ISI Web of Knowledge, NHS Economic Evaluation Database (NHS EED), Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA)] published from 1 January 1980 to 31 December 2011; static models of clinical effectiveness and cost-effectiveness; and dynamic modelling studies to improve parameter estimation and examine effectiveness. SETTING General population and genitourinary medicine clinic attenders. PARTICIPANTS Heterosexual women and men. INTERVENTIONS Traditional partner notification by patient or provider referral, and new partner notification by expedited partner therapy (EPT) or its UK equivalent, accelerated partner therapy (APT). MAIN OUTCOME MEASURES Population prevalence; index case reinfection; and partners treated per index case. RESULTS Enhanced partner therapy reduced reinfection in index cases with curable STIs more than simple patient referral [risk ratio (RR) 0.71; 95% confidence interval (CI) 0.56 to 0.89]. There are no randomised trials of APT. The median number of partners treated for chlamydia per index case in UK clinics was 0.60. The number of partners needed to treat to interrupt transmission of chlamydia was lower for casual than for regular partners. In dynamic model simulations, > 10% of partners are chlamydia positive with look-back periods of up to 18 months. In the presence of a chlamydia screening programme that reduces population prevalence, treatment of current partners achieves most of the additional reduction in prevalence attributable to partner notification. Dynamic model simulations show that cotesting and treatment for chlamydia and gonorrhoea reduce the prevalence of both STIs. APT has a limited additional effect on prevalence but reduces the rate of index case reinfection. Published quality-adjusted life-year (QALY) weights were of insufficient quality to be used in a cost-effectiveness study of partner notification in this project. Using an intermediate outcome of cost per infection diagnosed, doubling the efficacy of partner notification from 0.4 to 0.8 partners treated per index case was more cost-effective than increasing chlamydia screening coverage. CONCLUSIONS There is evidence to support the improved clinical effectiveness of EPT in reducing index case reinfection. In a general heterosexual population, partner notification identifies new infected cases but the impact on chlamydia prevalence is limited. Partner notification to notify casual partners might have a greater impact than for regular partners in genitourinary clinic populations. Recommendations for future research are (1) to conduct randomised controlled trials using biological outcomes of the effectiveness of APT and of methods to increase testing for human immunodeficiency virus (HIV) and STIs after APT; (2) collection of HRQL data should be a priority to determine QALYs associated with the sequelae of curable STIs; and (3) standardised parameter sets for curable STIs should be developed for mathematical models of STI transmission that are used for policy-making. FUNDING The National Institute for Health Research Health Technology Assessment programme.

Hide-and-seek in vegetation: time-to-detection is an efficient design for estimating detectability and occurrence

Ecology and conservation require reliable data on the occurrence of animals and plants. A major source of bias is imperfect detection, which, however, can be corrected for by estimation of detectability. In traditional occupancy models, this requires repeat or multi-observer surveys. Recently, time-to-detection models have been developed as a cost-effective alternative, which requires no repeat surveys and hence costs could be halved. We compared the efficiency and reliability of time-to-detection and traditional occupancy models under varying survey effort. Two observers independently searched for 17 plant species in 44100m(2) Swiss grassland quadrats and recorded the time-to-detection for each species, enabling detectability to be estimated with both time-to-detection and traditional occupancy models. In addition, we gauged the relative influence on detectability of species, observer, plant height and two measures of abundance (cover and frequency). Estimates of detectability and occupancy under both models were very similar. Rare species were more likely to be overlooked; detectability was strongly affected by abundance. As a measure of abundance, frequency outperformed cover in its predictive power. The two observers differed significantly in their detection ability. Time-to-detection models were as accurate as traditional occupancy models, but their data easier to obtain; thus they provide a cost-effective alternative to traditional occupancy models for detection-corrected estimation of occurrence.

The Cost-Effectiveness of Monitoring Strategies for Antiretroviral Therapy of HIV Infected Patients in Resource-Limited Settings: Software Tool.

BACKGROUND The cost-effectiveness of routine viral load (VL) monitoring of HIV-infected patients on antiretroviral therapy (ART) depends on various factors that differ between settings and across time. Low-cost point-of-care (POC) tests for VL are in development and may make routine VL monitoring affordable in resource-limited settings. We developed a software tool to study the cost-effectiveness of switching to second-line ART with different monitoring strategies, and focused on POC-VL monitoring. METHODS We used a mathematical model to simulate cohorts of patients from start of ART until death. We modeled 13 strategies (no 2nd-line, clinical, CD4 (with or without targeted VL), POC-VL, and laboratory-based VL monitoring, with different frequencies). We included a scenario with identical failure rates across strategies, and one in which routine VL monitoring reduces the risk of failure. We compared lifetime costs and averted disability-adjusted life-years (DALYs). We calculated incremental cost-effectiveness ratios (ICER). We developed an Excel tool to update the results of the model for varying unit costs and cohort characteristics, and conducted several sensitivity analyses varying the input costs. RESULTS Introducing 2nd-line ART had an ICER of US$1651-1766/DALY averted. Compared with clinical monitoring, the ICER of CD4 monitoring was US$1896-US$5488/DALY averted and VL monitoring US$951-US$5813/DALY averted. We found no difference between POC- and laboratory-based VL monitoring, except for the highest measurement frequency (every 6 months), where laboratory-based testing was more effective. Targeted VL monitoring was on the cost-effectiveness frontier only if the difference between 1st- and 2nd-line costs remained large, and if we assumed that routine VL monitoring does not prevent failure. CONCLUSION Compared with the less expensive strategies, the cost-effectiveness of routine VL monitoring essentially depends on the cost of 2nd-line ART. Our Excel tool is useful for determining optimal monitoring strategies for specific settings, with specific sex-and age-distributions and unit costs.

Estimating the prevalence of comorbid conditions and their effect on health care costs in patients with diabetes mellitus in Switzerland.

BACKGROUND Estimating the prevalence of comorbidities and their associated costs in patients with diabetes is fundamental to optimizing health care management. This study assesses the prevalence and health care costs of comorbid conditions among patients with diabetes compared with patients without diabetes. Distinguishing potentially diabetes- and nondiabetes-related comorbidities in patients with diabetes, we also determined the most frequent chronic conditions and estimated their effect on costs across different health care settings in Switzerland. METHODS Using health care claims data from 2011, we calculated the prevalence and average health care costs of comorbidities among patients with and without diabetes in inpatient and outpatient settings. Patients with diabetes and comorbid conditions were identified using pharmacy-based cost groups. Generalized linear models with negative binomial distribution were used to analyze the effect of comorbidities on health care costs. RESULTS A total of 932,612 persons, including 50,751 patients with diabetes, were enrolled. The most frequent potentially diabetes- and nondiabetes-related comorbidities in patients older than 64 years were cardiovascular diseases (91%), rheumatologic conditions (55%), and hyperlipidemia (53%). The mean total health care costs for diabetes patients varied substantially by comorbidity status (US$3,203-$14,223). Patients with diabetes and more than two comorbidities incurred US$10,584 higher total costs than patients without comorbidity. Costs were significantly higher in patients with diabetes and comorbid cardiovascular disease (US$4,788), hyperlipidemia (US$2,163), hyperacidity disorders (US$8,753), and pain (US$8,324) compared with in those without the given disease. CONCLUSION Comorbidities in patients with diabetes are highly prevalent and have substantial consequences for medical expenditures. Interestingly, hyperacidity disorders and pain were the most costly conditions. Our findings highlight the importance of developing strategies that meet the needs of patients with diabetes and comorbidities. Integrated diabetes care such as used in the Chronic Care Model may represent a useful strategy.

Associating optical measurements and estimating orbits of geocentric objects through population-based meta-heuristic methods

Currently several thousands of objects are being tracked in the MEO and GEO regions through optical means. The problem faced in this framework is that of Multiple Target Tracking (MTT). In this context both, the correct associations among the observations and the orbits of the objects have to be determined. The complexity of the MTT problem is defined by its dimension S. The number S corresponds to the number of fences involved in the problem. Each fence consists of a set of observations where each observation belongs to a different object. The S ≥ 3 MTT problem is an NP-hard combinatorial optimization problem. There are two general ways to solve this. One way is to seek the optimum solution, this can be achieved by applying a branch-and- bound algorithm. When using these algorithms the problem has to be greatly simplified to keep the computational cost at a reasonable level. Another option is to approximate the solution by using meta-heuristic methods. These methods aim to efficiently explore the different possible combinations so that a reasonable result can be obtained with a reasonable computational effort. To this end several population-based meta-heuristic methods are implemented and tested on simulated optical measurements. With the advent of improved sensors and a heightened interest in the problem of space debris, it is expected that the number of tracked objects will grow by an order of magnitude in the near future. This research aims to provide a method that can treat the correlation and orbit determination problems simultaneously, and is able to efficiently process large data sets with minimal manual intervention.

Low-cost disposable ALT electrochemical microsensors for in-vitro hepatotoxic assessment

Liver-on-chip systems are widely seen as having the potential to replace animal testing for long-term liver toxicity assessments. However, such systems necessitate solutions, such as electrochemical microsensors, to provide information about the cells exposed to chemical compounds in a confined space. This study describes the development of microsensors for the detection of alanine-aminotransferase (ALT), an intracellular enzyme found in hepatocytes, for monitoring the viability of in-vitro hepatic cell cultures. The electrochemical sensors were developed by using screen printed electrodes functionalized by drop-casting. These technologies are intended to produce disposable and low-cost sensors that can easily be exchanged once their performance is degraded. The sensors are capable of measuring ALT in a microfluidic environment through the detection of changes in glutamate concentration. The microsensors were found to be stable for more than 60 days and were successfully tested using hepatocellular lysates to assess their capability to quantify ALT activity in a hepatic cell culture. These results open the way to their integration in liver bioreactors to assess hepatocellular toxicity in-vitro.