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

Disconnections in personal neglect

: Personal neglect is a disorder in the perception and representation of the body that causes the patients to behave as if the contralesional side of their body does not exist. This clinical condition has not been adequately investigated in the past as it has been considered a symptom of unilateral spatial neglect, which has mainly been studied with reference to extrapersonal space. Only a few studies with small samples have investigated the neuroanatomical correlates of personal neglect, and these have mainly focused on discrete cortical lesions and modular accounts, as well as being based on the hypothesis that this disorder is associated with somatosensory and spatial deficits. In the present study, we tested the novel hypothesis that personal neglect may be associated not only with discrete cortical and subcortical lesions, but also with disconnections of white matter tracts. We performed an advanced lesion analyses in a large sample of 104 right hemisphere damaged patients, 72 of whom were suffering from personal neglect. Results from the analyses of the grey and white matter were controlled for co-occurrent clinical variables such as extrapersonal neglect, anosognosia for hemiplegia and motor deficits, along with other lesion-related variables such as lesion size and the interval from the lesion onset to neuroimaging recordings. Our results reveal that personal neglect is associated with lesions in a medial network which involves the temporal cortex (Heschl's gyrus), the ventro-lateral nuclei of the thalamus and the fornix. This suggests that personal neglect involves a convergence between sensorimotor processes, spatial representation and the processing of self-referred information (episodic memory)

Respostas de enzimas antioxidantes a bioativador em plântulas de milho sob estresse hídrico.

Edição Especial contendo os Anais do XVIII Congresso Brasileiro de Sementes, Florianópolis, set. 2013

Classification of schizophrenia using feature-based morphometry

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Discrimination of meat produced by Bos taurus and Bos indicus finished under an intensive or extensive system

Research Areas: Agriculture ; Veterinary Sciences ; ZoologyMeat obtained under commercial conditions shows considerable variability, mostly due to genetic background and production system. In this study, meat physicochemical properties and fatty acid profiles were analysed to investigate the feasibility of using them as tools to discriminate between meats produced by different genetic groups and finishing systems. Samples of the Longissimus thoracis were collected from 160 commercial bulls of the B. taurus (n = 75) and B. indicus (n = 85) groups, finished either on pasture (n = 46) or with grain supplementation (n = 114) and analysed by standard procedures. Data were analysed by discriminant analysis using a stepwise procedure, to select the meat characteristics that better contribute to discriminate the various groups. Our results indicate that fatty acid profiles of meat had better discriminating ability than physicochemical properties, especially to identify meat from animals finished on grain or pasture. The overall discrimination of meat from different genetic groups was achieved with a slightly lower reliability. Nonetheless, our results show that reliability of allocation to genetic group can be improved if prior information on finishing system is considered. These results are of high importance because they can be incorporated as tools to assess the authenticity of beef, particularly in meat certification programs.info:eu-repo/semantics/publishedVersio

Pathogenic variants in EP300 and ANKRD11 in patients with phenotypes overlapping Cornelia de Lange syndrome

Cornelia de Lange syndrome (CdLS), Rubinstein–Taybi syndrome (RSTS), and KBG syndrome are three distinct developmental human disorders. Variants in seven genes belonging to the cohesin pathway, NIPBL, SMC1A, SMC3, HDAC8, RAD21, ANKRD11, and BRD4, were identified in about 80% of patients with CdLS, suggesting that additional causative genes remain to be discovered. Two genes, CREBBP and EP300, have been associated with RSTS, whereas KBG results from variants in ANKRD11. By exome sequencing, a genetic cause was elucidated in two patients with clinical diagnosis of CdLS but without variants in known CdLS genes. In particular, genetic variants in EP300 and ANKRD11 were identified in the two patients with CdLS. EP300 and ANKRD11 pathogenic variants caused the reduction of the respective proteins suggesting that their low levels contribute to CdLS-like phenotype. These findings highlight the clinical overlap between CdLS, RSTS, and KBG and support the notion that these rare disorders are linked to abnormal chromatin remodeling, which in turn affects the transcriptional machinery

Prediction of hyperaldosteronism subtypes when adrenal vein sampling is unilaterally successful

Objective: Adrenal venous sampling (AVS) is the gold standard to discriminate patients with unilateral primary aldosteronism (UPA) from bilateral disease (BPA). AVS is technically demanding and in cases of unsuccessful cannulation of adrenal veins, the results may not always be interpreted. The aim of our study was to develop diagnostic models to distinguish UPA from BPA, in cases of unilateral successful AVS and the presence of contralateral suppression of aldosterone secretion.Design: Retrospective evaluation of 158 patients referred to a tertiary hypertension unit who underwent AVS. We randomly assigned 110 patients to a training cohort and 48 patients to a validation cohort to develop and test the diagnostic models.Methods: Supervised machine learning algorithms and regression models were used to develop and validate two prediction models and a simple 19-point score system to stratify patients according to their subtype diagnosis.Results: Aldosterone levels at screening and after confirmatory testing, lowest potassium, ipsilateral and contralateral imaging findings at CT scanning, and contralateral ratio at AVS, were associated with a diagnosis of UPA and were included in the diagnostic models. Machine learning algorithms correctly classified the majority of patients both at training and validation (accuracy: 82.9-95.7%). The score system displayed a sensitivity/specificity of 95.2/96.9%, with an AUC of 0.971. A flow-chart integrating our score correctly managed all patients except 3 (98.1% accuracy), avoiding the potential repetition of 77.2% of AVS procedures.Conclusions: Our score could be integrated in clinical practice and guide surgical decision-making in patients with unilateral successful AVS and contralateral suppression

In vitro synergisms obtained by amphotericin B and voriconazole associated with non-antifungal agents against Fusarium spp

AbstractFusarium spp is an opportunistic fungal pathogen responsible for causing invasive hyalohyphomycosis in immunocompromised patients. Due to its susceptibility pattern with a remarkable resistance to antifungal agents the treatment failures and mortality rates are high. To overcome this situation, combination therapy may be considered which must be subjected to in vitro tests.In vitro activities of amphotericin B, itraconazole, and voriconazole associated with azithromycin, ciprofloxacin, fluvastatin, ibuprofen, metronidazole, and also the combination of amphotericin B plus rifampin against 23 strains of Fusarium spp. through the checkerboard technique based on M38-A2 [Clinical and Laboratory Standards Institute (2008). Reference method for broth dilution antifungal susceptibility testing of filamentous fungi; approved standard, 2nd ed. (CLSI document M38-A2) (ISBN 1-56238-668-9). Wayne, PA: CLSI] were evaluated.The best synergistic interactions with amphotericin B were with ibuprofen (43.5%) (FICI [fractional inhibitory concentration index] range = 0.25–2). Combinations with voriconazole showed synergism, mainly with ciprofloxacin (30.4%) (FICI range = 0.25–3) and metronidazole (30.4%) (FICI range = 0.1–4); however, all the combinations with itraconazole were indifferent. In general, antagonistic interactions were not registered.Our results showed that in vitro synergisms obtained by some combinations studied deserve attention since they were better than those showed by the antimycotic