The available data support the evaluation of a drug combination in a larger population as a fixed-dose combination. Clinical Trials Registration. CTRI/2007/091/000031.
With the ever increasing demand for screening millions of prospective "novel coronavirus" or COVID-19 cases, and due to the emergence of high false negatives in the commonly used PCR tests, the necessity for probing an alternative simple screening mechanism of COVID-19 using radiological images (like chest X-Rays) assumes importance. In this scenario, machine learning (ML) and deep learning (DL) offer fast, automated, effective strategies to detect abnormalities and extract key features of the altered lung parenchyma, which may be related to specific signatures of the COVID-19 virus. However, the available COVID-19 datasets are inadequate to train deep neural networks. Therefore, we propose a new concept called domain extension transfer learning (DETL). We employ DETL, with pre-trained deep convolutional neural network, on a related large chest X-Ray dataset that is tuned for classifying between four classes viz. normal, other disease, pneumonia and Covid − 19. A 5fold cross validation is performed to estimate the feasibility of using chest X-Rays to diagnose COVID-19. The initial results show promise, with the possibility of replication on bigger and more diverse data sets. The overall accuracy was measured as 95.3% ± 0.02. In order to get an idea about the COVID-19 detection transparency, we employed the concept of Gradient Class Activation Map (Grad-CAM) for detecting the regions where the model paid more attention during the classification. This was found to strongly correlate with clinical findings, as validated by experts.
Arterolane (RBx 11160) maleate is a novel, rapidly acting synthetic trioxolane antimalarial compound being developed by Ranbaxy Research Laboratories (Haryana, India). It is presently under phase III in combination with piperaquine phosphate. The present work reports the relationship between pharmacokinetic (PK) parameter (AUC(0-8h) on day 0/day 6) and indices of pharmacodynamic (PD) response (50% parasite clearance [PC(50)], 90% parasite clearance [PC(90)], parasite clearance time [PCT], recrudescence) from a phase II, double-blind, multicenter, randomized, parallel-group, dose-ranging trial. Patients with acute uncomplicated P. falciparum malaria were randomized to 1 of 3 arterolane maleate (50, 100, and 200 mg) doses for 7 consecutive days. Plasma concentration data were available from 78, 76, and 75 patients receiving a 50-, 100-, and 200-mg dose, respectively. Based on PD modeling, its limitations and assumptions, minimum 150-mg dose arterolane maleate was recommended to optimize the probability of maximum therapeutic benefits for an adult. Doses higher than 100 mg are unlikely to reduce the probability of recrudescence. This study re-stresses the need of combining short and long-acting drugs to prevent resistance development and minimize recrudescence.
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