We conducted a quasi-experimental study to compare the response to meglumine antimoniate in patients with localized cutaneous leishmaniasis from two endemic areas of Brazil that were infected by two Leishmania species. Sixty-one were infected by Leishmania (Viannia) braziliensis (group B) and 57 by L. (V.) guyanensis (group G). All had a parasitologically proven diagnosis and were treated with 20 mg of pentavalent antimonial (Sb V)/kg/day given intravenously or intramuscularly for 20 days. Main outcomes were diagnosed using clinical criteria three months after treatment and patients were followed for six months. Intention-to-treat analysis showed a higher failure rate in group G (relative risk [RR] ϭ 1.5, 95% confidence interval [CI] ϭ 1.1-2.0, 2 ϭ 7.44, P ϭ 0.006). The analysis using an explanatory approach including 52 patients from group B and 49 from group G, who were regularly treated and followed for six months, showed a low cure rate (50. 8% in group B and 26.3% in group G) with a greater risk of failure in the latter group (RR ϭ 1.7, 95% CI ϭ 1.2-2.5, 2 ϭ 8.56, P ϭ 0.003). The effect of the etiologic agent remained significant after adjusting for age, disease duration, and site and number of lesions that were identified as predictors of failure in a logistic regression model. We concluded that Leishmania species constitute an important factor in predicting the outcome of cutaneous leishmaniasis treated with a pentavalent antimonial.
robust clinical studies on the safety and/or efficacy of chloroquine (CQ) and/or hydroxychloroquine (HCQ) for the treatment of COVID-19 during the recent 2020 pandemic.We searched PubMed and also MedRxiv.org (pre-print server for health sciences, without peer review), without any language restrictions and including Chinese publications, for studies published between Dec 2019 and April 5, 2020, using the search terms 'COVID-19, coronavirus, SARS-Cov-2'. We found three non-randomized studies with limited sample sizes in which (1) HCQ use led to a decrease in SARS-Cov-2 detected in respiratory secretions five days after treatment, together with azithromycin (France, 36 patients); (2) HCQ use shortened time to clinical recovery (China, 62 patients); and (3) CQ was superior to control treatment in inhibiting the exacerbation of pneumonia, improving lung imaging findings, and promoting virus-negative conversion and shortening the disease course (China, 100 patients). We found no published studies comparing different dosages of CQ/HCQ and their thorough safety assessment.
Added value of this studyIn a larger patient population, we found that a higher dosage of CQ for 10 days presented toxicity red flags, particularly affecting QTc prolongation. The limited sample size recruited so far does not allow to show any benefit regarding treatment efficacy, however the higher fatality associated with the higher dosage by day 13 of follow-up resulted in a premature halting of this arm. This is the first double-blinded, randomized clinical trial addressing different dosages of CQ for the treatment of severe patients with COVID-19 in the absence of a control group using placebo. Due to the impossibility of not using the drug recommended at the national level, we used historical data from the literature to infer comparisons for lethality endpoints. Follow-up until day 28 is ongoing with a larger sample size, in which long-term lethality will be better estimated.
Abstract. This paper presents the evolving objects library (EOlib), an object-oriented framework for evolutionary computation (EC) that aims to provide a flexible set of classes to build EC applications. EOlib design objective is to be able to evolve any object in which fitness makes sense. In order to do so, EO concentrates on interfaces; any object can evolve if it is endowed with an interface to do so. In this paper, we describe what features an object must have in order to evolve, and some examples of how EO has been put to practice evolving neural networks, solutions to the Mastermind game, and other novel applications.
Our retrospective review of patients with SBP suggests that serum bilirubin levels >4 mg and serum creatinine levels >1 mg/dl at the time of diagnosis represent significant risk factors for the clinical outcomes of patients with SBP. Patients without these risk factors may have a very low likelihood of death or renal failure.
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