How to mathematically optimize drug regimens using optimal control

This article gives an overview of a technique calledoptimal control, which is used to optimize real-world quantities represented by mathematical models. I include background information about the historical development of the technique and applications in a variety of fields. The main focus here is the application to diseases and therapies, particularly the optimization of combination therapies, and I highlight several such examples. I also describe the basic theory of optimal control, and illustrate each of the steps with an example that optimizes the doses in a combination regimen for leukemia. References are provided for more complex cases. The article is aimed at modelers working in drug development, who have not used optimal control previously. My goal is to make this technique more accessible in the biopharma community.
Source: Journal of Pharmacokinetics and Pharmacodynamics - Category: Drugs & Pharmacology Source Type: research

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Publication date: Available online 18 January 2020Source: BiologicalsAuthor(s): David GervaisAbstractErwinia chrysanthemi l-asparaginase (ErA) has been used for the treatment of acute lymphoblastic leukaemia (ALL) for decades, and its safety and efficacy have been well demonstrated. ErA drug substance and drug product contain a small proportion of acidic isoforms, with a known mechanism of formation, which have been shown to be minor conformational variants retaining enzymatic activity and function. Specifications for these acidic isoforms were set with an extremely limited data set, and with further manufacturing experien...
Source: Biologicals - Category: Biology Source Type: research
Publication date: Available online 17 January 2020Source: The Lancet HaematologyAuthor(s): Irwin Walker, Tony Panzarella, Stephen Couban, Felix Couture, Gerald Devins, Mohamed Elemary, Geneviève Gallagher, Holly Kerr, John Kuruvilla, Stephanie J Lee, John Moore, Thomas Nevill, Gizelle Popradi, Jean Roy, Kirk R Schultz, David Szwajcer, Cynthia Toze, Ronan Foley, Cell Therapy Transplant CanadaSummaryBackgroundPrevious trials testing prevention strategies for chronic graft versus host disease (GVHD) have measured its cumulative incidence. In this trial of anti-thymocyte globulin, we measured treatment-independence at a...
Source: The Lancet Haematology - Category: Hematology Source Type: research
This study adds to the body of evidence in describing incidence and type of cardiac events experienced by an allogeneic and autologous HSCT population at one institution from 2012-2017. Sixty-five patients (9.8%) experienced cardiac events, including atrial arrhythmia (N = 39), acute heart failure (N = 9), acute coronary syndrome (N = 7), new onset hypertension (N = 9), with a few instances of bradycardia, ventricular arrhythmia, pericardial effusion, and pericarditis. Our multivariable regression analysis identified age (older), creatinine (higher) and history of coronary artery disease to significantly correlate with ris...
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research
No abstract available
Source: Oncology Times - Category: Cancer & Oncology Tags: News Source Type: research
No abstract available
Source: Oncology Times - Category: Cancer & Oncology Tags: News Source Type: research
ConclusionThese results highlight an anti-cancer activity of prazosin on AML by inhibiting the PI3K/Akt/mTOR pathway and targeting TNS1.
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research
Publication date: Available online 16 January 2020Source: Clinical Lymphoma Myeloma and LeukemiaAuthor(s): Bei Xiong, Mei Xue, Yalan Yu, Sanyun Wu, Xuelan ZuoAbstractTo investigate the clinical implications of SF3B1 mutation and ring sideroblasts in myelodysplastic syndrome-refractory cytopenia with multilineage dysplasia (MDS-RCMD), 238 consecutive MDS-RCMD patients were included in this study. Our results showed that SF3B1 mutation in MDS- RCMD patients identifies a distinct subgroup characterized by a high prevalence of erythroid dysplasia and a high proportion of ring sideroblasts, prolonged survival and reduced leukem...
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research
ConclusionThe present analysis identifies disparities in the initial management of older adults with FL owing to race and socioeconomic status. Future research should examine implications for subsequent treatment and health outcomes.
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research
AbstractSouth Africa (SA) has a high prevalence of human immunodeficiency virus (HIV) infection. People living with HIV are at markedly increased risk of developing Burkitt lymphoma (BL), which is characterized by theMYC translocation. There is a paucity of survival data of HIV-associated Burkitt lymphoma/leukaemia (HIV-BL) cases from SA, and the relationship between karyotype and outcomes has not been widely reported. Here we report the clinico-pathological characteristics of a cohort of cytogenetically confirmed HIV-BL cases. A retrospective, descriptive review was conducted of clinico-pathological features of HIV-BL pat...
Source: Annals of Hematology - Category: Hematology Source Type: research
In this study, 97 BMB samples of patients with acute leukemia and 30 iron-deficiency anemias (IDA) as control group were evaluated with immunohistochemistry. In comparison with controls, the counts of CD68+, CD163+, and CD206+macrophages were remarkably increased in BMB samples of acute leukemia (P 
Source: Annals of Hematology - Category: Hematology Source Type: research
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