Multi-drug resistant tuberculosis in the Netherlands:Personalised treatment and outcome

Tuberculosis (TB) caused by bacilli that are resistant to the two major drugs, rifampicin and isoniazid is defined as Multi-Drug Resistant TB or MDRTB. MDRTB kills around 50% of people affected around the world. In contrast, treatment results of MDR-TB in the Netherlands (1985-2013) have consistently shown a high success rate (86%). This is comparable with worldwide WHO-targets for drug TB that is susceptible to 1st line TB drugs. Treatment of MDRTB was based on drug susceptibility testing (DST) and fast molecular genetic tests, while dosage was adjusted by pharmacokinetic measurements, by measuring drug concentrations in blood samples over time to estimate the total exposure of the drug and modeled these measurements to optimize dosing by maintaining efficacy while at the same time minimizing dose-dependent toxicity. We advocate a search for other antibiotics, not only new ones like bedaquiline and delamanid, but also antibiotics registered for other infections that may help treat TB. As such we describe ertapenem, not included in the WHO list of MDR-TB drugs. We argue that ertapenem is a promising drug for TB, with reasonable efficacy and limited side effects. Using aminoglycosides for MDR-TB, we applied individualized dosing based on the peak concentration divided by the minimal inhibitory concentration; we reduced the number of blood samples taken by comparing a limited sampling strategy with standard multiple blood sampling. The median dose was in our patients 400 mg, more than two-fold lower than the dose recommended by WHO, while outcome in our patients was favourable without failures or relapses. Concluding remarks. Molecular sensitivity testing combined with pharmacokinetic/pharmacodynamics may be an important weapon in the global fight against MDR-TB.In regard to aminoglycosides prospective PK/PD studies are necessary to confirm the efficacy of the lower dosage.Likewise, ertapenem needs further investigations as is seems to be a highly promising drug for the treatment of MDR-TB, parameters being efficacy and safety

Species Composition and Fire: Non-Additive Mixture Effects on Ground Fuel Flammability

Diversity effects on many aspects of ecosystem function have been well documented. However, fire is an exception: fire experiments have mainly included single species, bulk litter, or vegetation, and, as such, the role of diversity as a determinant of flammability, a crucial aspect of ecosystem function, is poorly understood. This study is the first to experimentally test whether flammability characteristics of two-species mixtures are non-additive, i.e., differ from expected flammability based on the component species in monospecific fuel. In standardized fire experiments on ground fuels, including monospecific fuels and mixtures of five contrasting subarctic plant fuel types in a controlled laboratory environment, we measured flame speed, flame duration, and maximum temperature. Broadly half of the mixture combinations showed non-additive effects for these flammability indicators; these were mainly enhanced dominance effects for temporal dynamics – fire speed and duration. Fuel types with the more flammable value for a characteristic determined the rate of fire speed and duration of the whole mixture; in contrast, maximum temperature of the fire was determined by the biomass-weighted mean of the mixture. These results suggest that ecological invasions by highly flammable species may have effects on ground-fire dynamics well out of proportion to their biomass

A Deep Proper-Motion Survey in Kapteyn Selected Areas: I. Survey Description and First Results for Stars in the Tidal Tail of Sagittarius and in the Monoceros Ring

We describe a high-precision, deep (to V ~ 19-21) absolute proper-motion survey that samples ~50 lines of sight in the Kapteyn Selected Areas along declination zones -15, 0 and 15 degrees. In many fields the astrometric baseline reaches nearly a century. We demonstrate that these data provide typical per star precisions between ~ 1 and 3 mas/yr to the above magnitude limits, with the absolute reference frame established by numerous extragalactic sources in each survey field. Combined with existing and ongoing photometric and radial velocity surveys in these fields, these astrometric data will enable, among other things, accurate, detailed dynamical modeling of satellite interactions with our Galaxy. In this contribution we describe the astrometric part of our survey and show preliminary results along the trailing tail of the Sagittarius dwarf galaxy, and in the Monoceros ring region.Comment: Accepter for publication in the Astronomical Journa

Weight loss during tuberculosis treatment is an important risk factor for drug-induced hepatotoxicity

The objective of this study was to determine the association between weight loss and drug-induced hepatotoxicity (DIH). A retrospective observational study of 192 active tuberculosis (TB) patients consecutively admitted in a tertiary referral TB centre in the Netherlands was conducted. The outcome measure for DIH was defined as hepatotoxicity necessitating interruption of anti-TB drugs. Multivariate logistic regression analysis on interruption of anti-TB drugs was performed, with age, sex, nutritional status, TB disease severity, drug resistance, comorbidity including baseline liver function tests, anti-TB drug regimen, co-medication and addictions as independent risk factors. Anti-TB drugs were interrupted in thirty-one patients (16.1 %). The most important risk factor was weight loss of 2 kg or more within 4 weeks during TB treatment (OR 211, 95% CI 36.0, 1232). Other independent risk factors were infection with hepatitis C (OR 19.6, 95% CI 2.4, 164), age over 60 years (OR 18.5, 95% CI 2.3, 151) and multi-drug-resistant TB (OR 8.2, 95% CI 1.3, 53.6). This study shows that weight loss during TB treatment was the most important risk factor for DIH necessitating interruption of anti-TB drugs. Causes of weight loss during TB treatment and the association between weight change and hepatotoxicity need further investigation

The Lithium Content of the Galactic Halo Stars

Thanks to the accurate determination of the baryon density of the universe by the recent cosmic microwave background experiments, updated predictions of the standard model of Big Bang nucleosynthesis now yield the initial abundance of the primordial light elements with an unprecedented precision. In the case of $^7$Li, the CMB+SBBN value is significantly higher than the generally reported abundances for Pop II stars along the so-called Spite plateau. In view of the crucial importance of this disagreement which has cosmological, galactic and stellar implications, we decided to tackle the most critical issues of the problem by revisiting a large sample of literature Li data in halo stars that we assembled following some strict selection criteria on the quality of the original analyses. [Abridged]Comment: 34 pages. Accepted for publication in A&A. Includes additional references and minor correction