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Capsule Networks Showed Excellent Performance in the Classification of hERG Blockers/Nonblockers.
Front Pharmacol. 2019;10:1631
Authors: Wang Y, Huang L, Jiang S, Wang Y, Zou J, Fu H, Yang S
Abstract
Capsule networks (CapsNets), a new class of deep neural network architectures proposed recently by Hinton et al., have shown a great performance in many fields, particularly in image recognition and natural language processing. However, CapsNets have not yet been applied to drug discovery-related studies. As the first attempt, we in this investigation adopted CapsNets to develop classification models of hERG blockers/nonblockers; drugs with hERG blockade activity are thought to have a potential risk of cardiotoxicity. Two capsule network architectures were established: convolution-capsule network (Conv-CapsNet) and restricted Boltzmann machine-capsule networks (RBM-CapsNet), in which convolution and a restricted Boltzmann machine (RBM) were used as feature extractors, respectively. Two prediction models of hERG blockers/nonblockers were then developed by Conv-CapsNet and RBM-CapsNet with the Doddareddy's training set composed of 2,389 compounds. The established models showed excellent performance in an independent test set comprising 255 compounds, with prediction accuracies of 91.8 and 92.2% for Conv-CapsNet and RBM-CapsNet models, respectively. Various comparisons were also made between our models and those developed by other machine learning methods including deep belief network (DBN), convolutional neural network (CNN), multilayer perceptron (MLP), support vector machine (SVM), k-nearest neighbors (kNN), logistic regression (LR), and LightGBM, and with different training sets. All the results showed that the models by Conv-CapsNet and RBM-CapsNet are among the best classification models. Overall, the excellent performance of capsule networks achieved in this investigation highlights their potential in drug discovery-related studies.
PMID: 32063849 [PubMed]
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Evaluation of the cost-effectiveness of dexrazoxane for the prevention of anthracycline-related cardiotoxicity in children with sarcoma and haematologic malignancies: a European perspective.
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Evaluation of the cost-effectiveness of dexrazoxane for the prevention of anthracycline-related cardiotoxicity in children with sarcoma and haematologic malignancies: a European perspective.
Cost Eff Resour Alloc. 2020;18:7
Authors: Dewilde S, Carroll K, Nivelle E, Sawyer J
Abstract
Background: Anthracycline-treated childhood cancer survivors are at higher risk of cardiotoxicity, especially with cumulative doses received above 250 mg/m2. Dexrazoxane is the only option recommended for cardiotoxicity prevention in high-risk patients supported by randomised trials but its cost-effectiveness in paediatric cancer patients has not been established.
Methods: A cost-effectiveness model applicable to different national healthcare system perspectives, which simulates 10,000 patients with either sarcoma or haematologic malignancies, based upon baseline characteristics including gender, age at diagnosis, cumulative anthracycline dose and exposure to chest irradiation. Risk equations for developing congestive heart failure and death from recurrence of the original cancer, secondary malignant neoplasms, cardiac death, pulmonary death, and death from other causes were derived from published literature. These are applied to the individual simulated patients and time until development of these events was determined. The treatment effect of dexrazoxane on the risk of CHF or death was based upon a meta-analysis of randomised and non-randomised dexrazoxane studies in each tumour type. The model includes country specific data for drug and administration costs, all aspects of heart failure diagnosis and management, and death due to different causes for each of the five countries considered; France, Germany, the UK, Italy, and Spain.
Results: Dexrazoxane treatment resulted in a mean QALY benefit across the five countries ranging from 0.530 to 0.683 per dexrazoxane-treated patient. Dexrazoxane was cost-effective for paediatric patients receiving anthracycline treatment for sarcoma and for haematologic malignancies, irrespective of the cumulative anthracycline dose received. The Incremental Cost Effectiveness Ratio (ICER) was favourable in all countries irrespective of anthracycline dose for both sarcoma and haematological malignancies (range: dominant to €2196). Individual ICER varied considerably according to country with dominance demonstrated for dexrazoxane in Spain and Italy and ratios approximately double the European average in the UK and Germany.
Conclusions: Dexrazoxane is a highly cost-effective therapy for the prevention of anthracycline cardiotoxicity in paediatric patients with sarcoma or haematological malignancies in Europe, irrespective of the healthcare system in which they receive treatment. These benefits persist when patients who receive doses of anthracycline > 250 mg/m2 are included in the model.
PMID: 32063753 [PubMed]
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Protective strategies to prevent trastuzumab-induced cardiotoxicity - Authors' reply.
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Protective strategies to prevent trastuzumab-induced cardiotoxicity - Authors' reply.
Lancet. 2020 Feb 15;395(10223):492-493
Authors: Earl HM, Hiller L, Plummer C, Miles D, Wardley AM, Cameron DA, Dunn JA
PMID: 32061290 [PubMed - in process]
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Fluoropyrimidine-Associated Cardiotoxicity.
//www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif //www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--www3.us.elsevierhealth.com-extractor-graphics-pubmed-clinicslogo.gif Related Articles
Fluoropyrimidine-Associated Cardiotoxicity.
Cardiol Clin. 2019 Nov;37(4):399-405
Authors: Kanduri J, More LA, Godishala A, Asnani A
Abstract
Fluoropyrimidines are chemotherapeutic agents that confer great benefit to many patients with solid tumors, but their use is often limited by cardiotoxicity. The incidence and precise mechanisms of cardiotoxicity remain uncertain. Clinical presentations of fluoropyrimidine toxicity are varied and include chest pain, myocardial infarction, acute cardiomyopathy, arrhythmia, cardiogenic shock, and sudden cardiac death. Proposed mechanisms include coronary vasospasm, coronary endothelial dysfunction, direct myocardial toxicity, myocarditis, and Takotsubo cardiomyopathy. Therapeutic and prophylactic interventions primarily target coronary vasospasm as the underlying cause. Prospective studies are needed to develop evidence-based approaches to cardioprotection in patients receiving fluoropyrimidines.
PMID: 31587781 [PubMed - indexed for MEDLINE]
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Cardiotoxicity of Immune Therapy.
//www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif //www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--www3.us.elsevierhealth.com-extractor-graphics-pubmed-clinicslogo.gif Related Articles
Cardiotoxicity of Immune Therapy.
Cardiol Clin. 2019 Nov;37(4):385-397
Authors: Ganatra S, Parikh R, Neilan TG
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