Clinical standards for the management of adverse effects during treatment for TB

BACKGROUND: Adverse effects (AE) to TB treatment cause morbidity, mortality and treatment interruption. The aim of these clinical standards is to encourage best practise for the diagnosis and management of AE.METHODS: 65/81 invited experts participated in a Delphi process using a 5-point Likert scale to score draft standards.RESULTS: We identified eight clinical standards. Each person commencing treatment for TB should: Standard 1, be counselled regarding AE before and during treatment; Standard 2, be evaluated for factors that might increase AE risk with regular review to actively identify and manage these; Standard 3, when AE occur, carefully assessed and possible allergic or hypersensitivity reactions considered; Standard 4, receive appropriate care to minimise morbidity and mortality associated with AE; Standard 5, be restarted on TB drugs after a serious AE according to a standardised protocol that includes active drug safety monitoring. In addition: Standard 6, healthcare workers should be trained on AE including how to counsel people undertaking TB treatment, as well as active AE monitoring and management; Standard 7, there should be active AE monitoring and reporting for all new TB drugs and regimens; and Standard 8, knowledge gaps identified from active AE monitoring should be systematically addressed through clinical research.CONCLUSION: These standards provide a person-centred, consensus-based approach to minimise the impact of AE during TB treatment.CONTEXTE : Les effets indésirables (AE) du traitement de la TB sont une cause de morbidité, de mortalité et d’interruption du traitement. L’objectif de ces normes cliniques est d’encourager une meilleure pratique en matière de diagnostic et de prise en charge des AE. MÉTHODES : Ont participé 65/81 experts invités à un processus Delphi utilisant une échelle de Likert en 5 points pour évaluer des ébauches de normes. RÉSULTATS : Nous avons identifié huit normes cliniques. Chaque personne commençant un traitement antituberculeux devrait : Norme 1, être informée des AE avant et pendant le traitement ; Norme 2, être évaluée afin de détecter tout facteur susceptible d’augmenter le risque d’AE et faire l’objet d’un examen régulier afin d’identifier et de prendre en charge ces facteurs de manière proactive ; Norme 3, en cas d’AE, être évaluée avec soin et tenir compte d’éventuelles réactions allergiques ou d’hypersensibilité ; Norme 4, recevoir des soins appropriés pour minimiser la morbidité et la mortalité associées aux AE ; Norme 5, reprendre les médicaments antituberculeux après un AE grave selon un protocole standardisé avec une surveillance active de l’innocuité des médicaments ; Norme 6, les agents de santé doivent être formés aux AE, y compris à la manière de conseiller les personnes qui suivent un traitement antituberculeux, ainsi qu’à la surveillance et à la prise en charge actives des AE ; Norme 7 : tous les nouveaux médicaments et schémas antituberculeux doivent faire l’objet d’une surveillance active des AE et d’une notification ; et Norme 8 : les lacunes en matière de connaissances identifiées grâce à la surveillance active des AE doivent être systématiquement comblées par la recherche clinique. CONCLUSION : Ces normes fournissent une approche centrée sur la personne et fondée sur le consensus afin de minimiser l’impact des AE pendant le traitement de la TB

Diffusion equations and different spatial fractional derivatives

We investigate for the diffusion equation the differences manifested by the solutions when three different types of spatial differential operators of noninteger (or fractional) order are considered for a limited and unlimited region.  In all cases, we verify an anomalous spreading of the system, which can be connected to a rich class of anomalous diffusion processes

Integrating pharmacokinetics and pharmacodynamics in operational research to end tuberculosis

Tuberculosis (TB) elimination requires innovative approaches. The new Global Tuberculosis Network (GTN) aims to conduct research on key unmet therapeutic and diagnostic needs in the field of TB elimination using multidisciplinary, multisectorial approaches. The TB Pharmacology section within the new GTN aims to detect and study the current knowledge gaps, test potential solutions using human pharmacokinetics informed through preclinical infection systems, and return those findings to the bedside. Moreover, this approach would allow prospective identification and validation of optimal shorter therapeutic durations with new regimens. Optimized treatment using available and repurposed drugs may have an increased impact when prioritizing a personcentered approach and acknowledge the importance of age, gender, comorbidities, and both social and programmatic environments. In this viewpoint article, we present an in-depth discussion on how TB pharmacology and the related strategies will contribute to TB elimination

Effect of ω-conotoxin MVIIA and Phα1β on paclitaxel-induced acute and chronic pain

AbstractThe treatment with the chemotherapeutic agent paclitaxel produces a painful peripheral neuropathy, and is associated with an acute pain syndrome in a clinically significant number of patients. However, no standard therapy has been established to manage the acute pain or the chronic neuropathic pain related to paclitaxel. In the present study, we evaluated the analgesic potential of two N-type voltage-gated calcium channel (VGCC) blockers, ω-conotoxin MVIIA and Phα1β, on acute and chronic pain induced by paclitaxel. Adult male rats were treated with four intraperitoneal injections of paclitaxel (1+1+1+1mg/kg, in alternate days) and the development of mechanical hyperalgesia was evaluated 24h (acute painful stage) or 15days (chronic painful stage) after the first paclitaxel injection. Not all animals showed mechanical hyperalgesia 24h after the first paclitaxel injection, but those that showed developed a more intense mechanical hyperalgesia at the chronic painful stage. Intrathecal administration (i.t.) of ω-conotoxin MVIIA (3–300pmol/site) or Phα1β (10–300pmol/site) reduced the mechanical hyperalgesia either at the acute or at the chronic painful stage induced by paclitaxel. When administered at the acute painful stage, ω-conotoxin MVIIA (300pmol/site, i.t.) and Phα1β (300pmol/site, i.t.) prevented the worsening of chronic mechanical hyperalgesia. Furthermore, Phα1β (30-300pmol/site, i.t.) elicited less adverse effects than ω-conotoxin MVIIA (10-300 pmol/site, i.t.). Taken together, our data evidence the involvement of N-type VGCC in pain sensitization induced by paclitaxel and point out the potential of Phα1β as a safer alternative than ω-conotoxin MVIIA to treat the pain related to paclitaxel

Root growth and nitrate uptake of three different catch crops in deep soil layers

Catch crops can reduce NO3 losses from leaching, but little is known about the importance of deep rooting for the efficiency of NO3 depletion. In a field experiment, we investigated the N uptake and root growth of three types of catch crops using minirhizotrons (glass tubes of 70-mm o.d.) reaching 2.4 m. Our purpose was to evaluate minirhizotron methodology and the importance of deep rooting in the ability of catch crops to take up NO3 from deep soil layers. Nitrogen uptake was studied over a 6-d period at the end of October by injection of 15NO3 at four depths in the ranges: 0.4 to 1, 0.5 to 1.4, and 1 to 2.5 m under Italian ryegrass (Lolium multiflorum Lam.), winter rye (Secale cereale L.), and fodder radish (Raphanus sativus L. var. oleiformis Pers.), respectively. The root depth of the three species were 0.6, 1.1, and more than 2.4 m, respectively. No 15N was taken up from placements below root depth, and linear relationships were found between root density and 15N uptake from different depths. Residual soil NO3 of 18, 59, and 87 kg N ha−1 was left under fodder radish, winter rye, and ryegrass, respectively. The measurements obtained with the minirhizotron method were highly relevant for evaluating N uptake from different soil layers, and root depths of the catch crops were important for N depletion. Knowledge about root growth and N uptake in deep soil layers may be utilized when designing crop rotations with improved N use efficiency. Where N has been left by a preceding crop and leached to deeper soil layers, it may be recycled by deep-rooted catch crops

Estradiol inhibits the effects of extracellular ATP in human sperm by a non genomic mechanism of action

Steroid hormones, beside their classical genomic mechanism of action, exert rapid, non genomic effects in different cell types. These effects are mediated by still poorly characterized plasma membrane receptors that appear to be distinct from the classic intracellular receptors. In the present study we evaluated the non genomic effects of estradiol (17βE2) in human sperm and its effects on sperm stimulation by extracellular ATP, a potent activator of sperm acrosome reaction. In human sperm 17βE2 induced a rapid increase of intracellular calcium (Ca2+) concentrations dependent on an influx of Ca2+ from the extracellular medium. The monitoring of the plasma membrane potential variations induced by 17βE2 showed that this steroid induces a rapid plasma membrane hyperpolarization that was dependent on the presence of Ca2+ in the extracellular medium since it was absent in Ca2+ free-medium. When sperm were pre-incubated in the presence of the K+ channel inhibitor tetra-ethylammonium, the 17βE2 induced plasma membrane hyperpolarization was blunted suggesting the involvement of K+ channels in the hyperpolarizing effects of 17βE2. Extracellular ATP induced a rapid plasma membrane depolarization followed by acrosome reaction. Sperm pre-incubation with 17βE2 inhibited the effects of extracellular ATP on sperm plasma membrane potential variations and acrosome reaction. The effects of 17βE2 were specific since its inactive steroisomer 17αE2 was inactive. Furthermore the effects of 17βE2 were not inhibited by tamoxifen, an antagonist of the classic 17βE2 intracellular receptor

MAGIC observations of very high energy gamma-rays from HESS J1813-178

Recently, the HESS collaboration has reported the detection of gamma-ray emission above a few hundred GeV from eight new sources located close to the Galactic Plane. The source HESS J1813-178 has sparked particular interest, as subsequent radio observations imply an association with SNR G12.82-0.02. Triggered by the detection in VHE gamma-rays, a positionally coincident source has also been found in INTEGRAL and ASCA data. In this Letter we present MAGIC observations of HESS J1813-178, resulting in the detection of a differential gamma-ray flux consistent with a hard-slope power law, described as dN/(dA dt dE) = (3.3+/-0.5)*10^{-12} (E/TeV)^{-2.1+/-0.2} cm^(-2)s^(-1)TeV^(-1). We briefly discuss the observational technique used, the procedure implemented for the data analysis, and put this detection in the perspective of multifrequency observations.Comment: Accepted by ApJ Letter