Potential Economic Viability of Two Proposed Rifapentine-Based Regimens for Treatment of Latent Tuberculosis Infection

Rationale: Rifapentine-based regimens for treating latent tuberculosis infection (LTBI) are being considered for future clinical trials, but even if they prove effective, high drug costs may limit their economic viability. Objectives: To inform clinical trial design by estimating the potential costs and effectiveness of rifapentine-based regimens for treatment of latent tuberculosis infection (LTBI). Methods: We used a Markov model to estimate cost and societal benefits for three regimens for treating LTBI: Isoniazid/ rifapentine daily for one month, isoniazid/rifapentine weekly for three months (self-administered and directly-observed), and isoniazid daily for nine months; a strategy of ‘‘no treatment’ ’ used for comparison. Costs, quality-adjusted life-years gained, and instances of active tuberculosis averted were calculated for all arms. Results: Both daily isoniazid/rifapentine for one month and weekly isoniazid/rifapentine for three months were less expensive and more effective than other strategies under a wide variety of clinically plausibly parameter estimates. Daily isoniazid/rifapentine for one month was the least expensive and most effective regimen. Conclusions: Daily isoniazid/rifapentine for one month and weekly isoniazid/rifapentine for three months should be studied in a large-scale clinical trial for efficacy. Because both regimens performed well even if their efficacy is somewhat reduced

Skeletal Morphology of Opius dissitus and Biosteres carbonarius (Hymenoptera: Braconidae), with a Discussion of Terminology

The Braconidae, a family of parasitic wasps, constitute a major taxonomic challenge with an estimated diversity of 40,000 to 120,000 species worldwide, only 18,000 of which have been described to date. The skeletal morphology of braconids is still not adequately understood and the terminology is partly idiosyncratic, despite the fact that anatomical features form the basis for most taxonomic work on the group. To help address this problem, we describe the external skeletal morphology of Opius dissitus Muesebeck 1963 and Biosteres carbonarius Nees 1834, two diverse representatives of one of the least known and most diverse braconid subfamilies, the Opiinae. We review the terminology used to describe skeletal features in the Ichneumonoidea in general and the Opiinae in particular, and identify a list of recommend terms, which are linked to the online Hymenoptera Anatomy Ontology. The morphology of the studied species is illustrated with SEM-micrographs, photos and line drawings. Based on the examined species, we discuss intraspecific and interspecific morphological variation in the Opiinae and point out character complexes that merit further study

Comparative morphology of the forewing base articulationin Sternorrhyncha compared with a representative of Fulgoromorpha (Insecta, Hemiptera)

The forewing articulation of single species from each of the four subgroups of Sternorrhyncha (Aleyrodomorpha, Aphidomorpha, Coccomorpha, Psyllomorpha) was examined by optical and scanning electron microscopy. The species were compared with a species of Cixiidae (Fulgoromorpha), as an outgroup of Sternorrhyncha. We present the results of a comparative analysis of the forewing articulation in these five groups, propose a standardized terminology and compare our findings with those previously reported. The wing base of all examined species is composed of the following structures: anterior and posterior notal wing process, first, second, and third axillary sclerites, tegula, and axillary cord. The number of elements included in the wing base and the surrounding area is the greatest in Cacopsylla mali, the most complicated species from Sternorrhyncha. Based on the shape of axillary sclerites and the number of elements forming the wing base environment, Orthezia urticae (Coccomorpha) and Cixius nervosus (Fulgoromorpha) are the most similar. Among Sternorrhyncha, the most similar axillaries are those of Aphis fabae and Orthezia urticae, which is congruent with existing classifications. In this paper we show that the four groups from Sternorrhyncha exhibit their own distinct wing base morphology

Weather conditions and daily television use in the Netherlands, 1996–2005

This study examines the impact of daily atmospheric weather conditions on daily television use in the Netherlands for the period 1996–2005. The effects of the weather parameters are considered in the context of mood and mood management theory. It is proposed that inclement and uncomfortable weather conditions are associated with lower human mood, and that watching entertainment and avoiding informational programs may serve to repair such mood. We consequently hypothesize that people spend more time watching television if inclement and uncomfortable weather conditions (low temperatures, little sunshine, much precipitation, high wind velocity, less daylight) coincide with more airtime for entertainment programs, but that they view less if the same weather conditions coincide with more airtime devoted to information fare. We put this interaction thesis to a test using a time series analysis of daily television viewing data of the Dutch audience obtained from telemeters (T = 3,653), merged with meteorological weather station statistics and program broadcast figures, whilst controlling for a wide array of recurrent and one-time societal events. The results provide substantial support for the proposed interaction of program airtime and the weather parameters temperature and sunshine on aggregate television viewing time. Implications of the findings are discussed

Tuberculosis screening of travelers to higher-incidence countries: A cost-effectiveness analysis

Abstract Background Travelers to countries with high tuberculosis incidence can acquire infection during travel. We sought to compare four screening interventions for travelers from low-incidence countries, who visit countries with varying tuberculosis incidence. Methods Decision analysis model: We considered hypothetical cohorts of 1,000 travelers, 21 years old, visiting Mexico, the Dominican Republic, or Haiti for three months. Travelers departed from and returned to the United States or Canada; they were born in the United States, Canada, or the destination countries. The time horizon was 20 years, with 3% annual discounting of future costs and outcomes. The analysis was conducted from the health care system perspective. Screening involved tuberculin skin testing (post-travel in three strategies, with baseline pre-travel tests in two), or chest radiography post-travel (one strategy). Returning travelers with tuberculin conversion (one strategy) or other evidence of latent tuberculosis (three strategies) were offered treatment. The main outcome was cost (in 2005 US dollars) per tuberculosis case prevented. Results For all travelers, a single post-trip tuberculin test was most cost-effective. The associated cost estimate per case prevented ranged from $21,406 for Haitian-born travelers to Haiti, to$161,196 for US-born travelers to Mexico. In all sensitivity analyses, the single post-trip tuberculin test remained most cost-effective. For US-born travelers to Haiti, this strategy was associated with cost savings for trips over 22 months. Screening was more cost-effective with increasing trip duration and infection risk, and less so with poorer treatment adherence. Conclusion A single post-trip tuberculin skin test was the most cost-effective strategy considered, for travelers from the United States or Canada. The analysis did not evaluate the use of interferon-gamma release assays, which would be most relevant for travelers who received BCG vaccination after infancy, as in many European countries. Screening decisions should reflect duration of travel, tuberculosis incidence, and commitment to treat latent infection.</p

Strategies for Treating Latent Multiple-Drug Resistant Tuberculosis: A Decision Analysis

BACKGROUND: The optimal treatment for latent multiple-drug resistant tuberculosis infection remains unclear. In anticipation of future clinical trials, we modeled the expected performance of six potential regimens for treatment of latent multiple-drug resistant tuberculosis. METHODS: A computerized Markov model to analyze the total cost of treatment for six different regimens: Pyrazinamide/ethambutol, moxifloxacin monotherapy, moxifloxacin/pyrazinamide, moxifloxacin/ethambutol, moxifloxacin/ethionamide, and moxifloxacin/PA-824. Efficacy estimates were extrapolated from mouse models and examined over a wide range of assumptions. RESULTS: In the base-case, moxifloxacin monotherapy was the lowest cost strategy, but moxifloxacin/ethambutol was cost-effective at an incremental cost-effectiveness ratio of $21,252 per quality-adjusted life-year. Both pyrazinamide-containing regimens were dominated due to their toxicity. A hypothetical regimen of low toxicity and even modest efficacy was cost-effective compared to "no treatment." CONCLUSION: In our model, moxifloxacin/ethambutol was the preferred treatment strategy under a wide range of assumptions; pyrazinamide-containing regimens fared poorly because of high rates of toxicity. Although more data are needed on efficacy of treatments for latent MDR-TB infection, data on toxicity and treatment discontinuation, which are easier to obtain, could have a substantial impact on public health practice

Impact of DOTS expansion on tuberculosis related outcomes and costs in Haiti

BACKGROUND: Implementation of the World Health Organization's DOTS strategy (Directly Observed Treatment Short-course therapy) can result in significant reduction in tuberculosis incidence. We estimated potential costs and benefits of DOTS expansion in Haiti from the government, and societal perspectives. METHODS: Using decision analysis incorporating multiple Markov processes (Markov modelling), we compared expected tuberculosis morbidity, mortality and costs in Haiti with DOTS expansion to reach all of the country, and achieve WHO benchmarks, or if the current situation did not change. Probabilities of tuberculosis related outcomes were derived from the published literature. Government health expenditures, patient and family costs were measured in direct surveys in Haiti and expressed in 2003 US$. RESULTS: Starting in 2003, DOTS expansion in Haiti is anticipated to cost$4.2 million and result in 63,080 fewer tuberculosis cases, 53,120 fewer tuberculosis deaths, and net societal savings of $131 million, over 20 years. Current government spending for tuberculosis is high, relative to the per capita income, and would be only slightly lower with DOTS. Societal savings would begin within 4 years, and would be substantial in all scenarios considered, including higher HIV seroprevalence or drug resistance, unchanged incidence following DOTS expansion, or doubling of initial and ongoing costs for DOTS expansion. CONCLUSION: A modest investment for DOTS expansion in Haiti would provide considerable humanitarian benefit by reducing tuberculosis-related morbidity, mortality and costs for patients and their families. These benefits, together with projected minimal Haitian government savings, argue strongly for donor support for DOTS expansion

QTL detection by multi-parent linkage mapping in oil palm (Elaeis guineensis Jacq.)

A quantitative trait locus (QTL) analysis designed for a multi-parent population was carried out and tested in oil palm (Elaeis guineensis Jacq.), which is a diploid cross-fertilising perennial species. A new extension of the MCQTL package was especially designed for crosses between heterozygous parents. The algorithm, which is now available for any allogamous species, was used to perform and compare two types of QTL search for small size families, within-family analysis and across-family analysis, using data from a 2 × 2 complete factorial mating experiment involving four parents from three selected gene pools. A consensus genetic map of the factorial design was produced using 251 microsatellite loci, the locus of the Sh major gene controlling fruit shell presence, and an AFLP marker of that gene. A set of 76 QTLs involved in 24 quantitative phenotypic traits was identified. A comparison of the QTL detection results showed that the across-family analysis proved to be efficient due to the interconnected families, but the family size issue is just partially solved. The identification of QTL markers for small progeny numbers and for marker-assisted selection strategies is discussed