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Dynamic treatment regimens

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https://www.readbyqxmd.com/read/29444453/efferocytosis-in-atherosclerotic-lesions-malfunctioning-regulatory-pathways-and-control-mechanisms
#1
REVIEW
Amir Tajbakhsh, Mehdi Rezaee, Petri T Kovanen, Amirhossein Sahebkar
Atherosclerosis is a dynamic and progressive inflammatory process in the intimal layer of large and medium-sized arteries, and it is the major contributor to the atherosclerotic cardiovascular disease (ACVD), the leading cause of death worldwide. In an atherosclerotic plaque, phagocytosis of apoptotic cells occurs through an intricate process designated efferocytosis. Defective efferocytosis has emerged as a causal factor in the etiopathogenesis of atherosclerosis and its progression into overt ACVD. Both specialized phagocytes (macrophages and dendritic cells) and non-specialized cells with phagocytic capabilities (smooth muscle and endothelial cells) are involved in the efferocytotic process...
February 11, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29424775/distribution-and-reduction-magnitude-of-hiv-dna-burden-in-cd4-t-cell-subsets-depend-on-art-initiation-timing
#2
Pierre Gantner, Cindy Barnig, Marialuisa Partisani, Guinevere Q Lee, Geneviève Beck-Wirth, Jean-Pierre Faller, Martin Martinot, Mahsa Mosheni-Zadeh, Christine Cheneau, Marie-Laure Batard, Patricia Fischer, Anne Fuchs, Béatrice Uring-Lambert, Siamak Bahram, David Rey, Samira Fafi-Kremer
OBJECTIVE: The aim of our study was to analyze the dynamics of HIV-DNA levels in CD4 T-cell subsets in individuals starting successful dolutegravir-based regimens. DESIGN: Twenty-seven individuals with acute infection (AI, n = 8) or chronic infection (CI, n = 5) and patients in virological success (VS, n = 10) or virological failure (VF, n = 4) on antiretroviral therapy (ART) who initiated a dolutegravir-based regimen were enrolled (NCT02557997)...
February 8, 2018: AIDS
https://www.readbyqxmd.com/read/29423521/efficacy-of-sym004-in-patients-with-metastatic-colorectal-cancer-with-acquired-resistance-to-anti-egfr-therapy-and-molecularly-selected-by-circulating-tumor-dna-analyses-a-phase-2-randomized-clinical-trial
#3
Clara Montagut, Guillem Argilés, Fortunato Ciardiello, Thomas T Poulsen, Rodrigo Dienstmann, Michael Kragh, Scott Kopetz, Trine Lindsted, Cliff Ding, Joana Vidal, Jenifer Clausell-Tormos, Giulia Siravegna, Francisco J Sánchez-Martín, Klaus Koefoed, Mikkel W Pedersen, Michael M Grandal, Mikhail Dvorkin, Lucjan Wyrwicz, Ana Rovira, Antonio Cubillo, Ramon Salazar, Françoise Desseigne, Cristina Nadal, Joan Albanell, Vittorina Zagonel, Salvatore Siena, Guglielmo Fumi, Giuseppe Rospo, Paul Nadler, Ivan D Horak, Alberto Bardelli, Josep Tabernero
Importance: Acquired resistance to anti-EGFR therapy (epidermal growth factor receptor) is frequently due to RAS and EGFR extracellular domain (ECD) mutations in metastatic colorectal cancer (mCRC). Some anti-EGFR-refractory patients retain tumor EGFR dependency potentially targetable by agents such as Sym004, which is a mixture of 2 nonoverlapping monoclonal antibodies targeting EGFR. Objective: To determine if continuous blockade of EGFR by Sym004 has survival benefit...
February 8, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29392169/attenuation-of-maladaptive-responses-in-aortic-adventitial-fibroblasts-through-stimuli-triggered-sirna-release-from-lipid-polymer-nanocomplexes
#4
Chad T Greco, Robert E Akins, Thomas H Epps, Millicent O Sullivan
Lipid-siRNA assemblies are modified with photo-responsive polymers to enable spatiotemporally-controlled silencing of interleukin 1 beta (IL1β) and cadherin 11 (CDH11), two genes that are essential drivers of maladaptive responses in human aortic adventitial fibroblasts (AoAFs). These hybrid nanocomplexes address the critical challenge of locally mitigating fibrotic actions that lead to the high rates of vascular graft failures. In particular, the lipid-polymer formulations provide potent silencing of IL1β and CDH11 that is precisely modulated by a photo-release stimulus...
August 2017: Advanced Biosystems
https://www.readbyqxmd.com/read/29382708/spatial-heterogeneity-and-evolutionary-dynamics-modulate-time-to-recurrence-in-continuous-and-adaptive-cancer-therapies
#5
Jill Gallaher, Pedro M Enriquez-Navas, Kimberly A Luddy, Robert A Gatenby, Alexander Ra Anderson
Treatment of advanced cancers has benefited from new agents that supplement or bypass conventional therapies. However, even effective therapies fail as cancer cells deploy a wide range of resistance strategies. We propose that evolutionary dynamics ultimately determine survival and proliferation of resistant cells. Therefore, evolutionary strategies should be used with conventional therapies to delay or prevent resistance. Using an agent-based framework to model spatial competition among sensitive and resistant populations, we applied anti-proliferative drug treatments to varying ratios of sensitive and resistant cells...
January 30, 2018: Cancer Research
https://www.readbyqxmd.com/read/29375212/predictive-and-prognostic-value-of-serum-afp-level-and-its-dynamic-changes-in-advanced-gastric-cancer-patients-with-elevated-serum-afp
#6
Ya-Kun Wang, Lin Shen, Xi Jiao, Xiao-Tian Zhang
AIM: To investigate predictive and prognostic value of serum alpha-fetoprotein (AFP) level and its dynamic changes in patients with advanced gastric cancer with elevated serum AFP (AFPAGC). METHODS: One hundred and five patients with AFPAGC were enrolled in the study, and all of them underwent at least one cycle of systemic chemotherapy at our institute and had serum AFP ≥ 20 ng/mL at diagnosis or recurrence. Clinicopathologic features, serum AFP level at diagnosis and changes during treatment, first-line chemotherapy regimens, efficacy and toxicity, and survival information were collected...
January 14, 2018: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29371474/mutant-kras-circulating-tumor-dna-is-an-accurate-tool-for-pancreatic-cancer-monitoring
#7
Ruth Perets, Orli Greenberg, Talia Shentzer, Valeria Semenisty, Ron Epelbaum, Tova Bick, Shada Sarji, Ofer Ben-Izhak, Edmond Sabo, Dov Hershkovitz
BACKGROUND: Many new pancreatic cancer treatment combinations have been discovered in recent years, yet the prognosis of pancreatic ductal adenocarcinoma (PDAC) remains grim. The advent of new treatments highlights the need for better monitoring tools for treatment response, to allow a timely switch between different therapeutic regimens. Circulating tumor DNA (ctDNA) is a tool for cancer detection and characterization with growing clinical use. However, currently, ctDNA is not used for monitoring treatment response...
January 25, 2018: Oncologist
https://www.readbyqxmd.com/read/29358293/amikacin-pharmacokinetic-pharmacodynamic-pk-pd-analysis-in-pediatric-cancer-patients
#8
Ali A Alhadab, Mariam A Ahmed, Richard C Brundage
We performed PK-PD and simulation analyses to evaluate standard 15 mg/kg/day amikacin in children with cancer and to determine an optimal dosing strategy. A population pharmacokinetic model was developed from clinical data collected in 34 pediatric patients and used in a simulation study to predict the population probability of various dosing regimens to achieve accepted safety- (fCmin < 10 mg/L) and efficacy-linked (fCmax/MIC ≥ 8) targets. In addition, an adaptive resistance PD (ARPD) model of Pseudomonas aeruginosa was built based on literature time-kill curve data and linked to the PK model to perform PK-ARPD simulations and compare results with the probability approach...
January 22, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29330466/target-engagement-imaging-of-parp-inhibitors-in-small-cell-lung-cancer
#9
Brandon Carney, Susanne Kossatz, Benjamin H Lok, Valentina Schneeberger, Kishore K Gangangari, Naga Vara Kishore Pillarsetty, Wolfgang A Weber, Charles M Rudin, John T Poirier, Thomas Reiner
Insufficient chemotherapy response and rapid disease progression remain concerns for small-cell lung cancer (SCLC). Oncologists rely on serial CT scanning to guide treatment decisions, but this cannot assess in vivo target engagement of therapeutic agents. Biomarker assessments in biopsy material do not assess contemporaneous target expression, intratumoral drug exposure, or drug-target engagement. Here, we report the use of PARP1/2-targeted imaging to measure target engagement of PARP inhibitors in vivo. Using a panel of clinical PARP inhibitors, we show that PARP imaging can quantify target engagement of chemically diverse small molecule inhibitors in vitro and in vivo...
January 12, 2018: Nature Communications
https://www.readbyqxmd.com/read/29275595/-clinical-efficacy-of-rivaroxaban-in-prevention-and-treatment-of-postoperative-deep-vein-thrombosis-for-severe-traumatic-brain-injury
#10
Z L Zhang, W M Liu, Y Zhang, G H Wang, C Yan, H Q Wang, Q B Huang
Objective: To explore the clinical efficacy of rivaroxaban in the prevention and treatment of postoperative deep vein thrombosis (DVT) for severe traumatic brain injury (sTBI). Methods: Patients with sTBI who met the inclusion criteria were enrolled in this study, including 119 males (75.8%) and 38 females (24.2%), aged (38.75 ± 11.98) years old. DVT was prevented and treated according to the DVT screening and anticoagulation regimen. Intermittent venous compression was used on all of the patients to prevent DVT, and D-dimer dynamic monitoring and regular ultrasound were performed to screen for DVT...
December 5, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/29249480/emergence-of-drug-resistance-in-patients-with-tuberculosis-cared-for-by-the-indian-health-care-system-a-dynamic-modelling-study
#11
Stephanie Law, Amy S Piatek, Cheri Vincent, Olivia Oxlade, Dick Menzies
BACKGROUND: India has the highest number of patients with tuberculosis and multidrug-resistant tuberculosis in the world. We used a transmission model to project the emergence of drug resistance in India due to incorrect tuberculosis management practices in multiple sectors, including public and private providers, chemists, and non-allopathic practitioners. METHODS: We constructed a dynamic Markov model to represent India's tuberculosis epidemic, including a probabilistic framework reflecting complex treatment-seeking pathways...
January 2017: Lancet. Public Health
https://www.readbyqxmd.com/read/29244129/dolutegravir-reshapes-the-genetic-diversity-of-hiv-1-reservoirs
#12
Pierre Gantner, Guinevere Q Lee, David Rey, Thibault Mesplede, Marialuisa Partisani, Christine Cheneau, Geneviève Beck-Wirth, Jean-Pierre Faller, Mahsa Mohseni-Zadeh, Martin Martinot, Mark A Wainberg, Samira Fafi-Kremer
Objectives: Better understanding of the dynamics of HIV reservoirs under ART is a critical step to achieve a functional HIV cure. Our objective was to assess the genetic diversity of archived HIV-1 DNA over 48 weeks in blood cells of individuals starting treatment with a dolutegravir-based regimen. Methods: Eighty blood samples were prospectively and longitudinally collected from 20 individuals (NCT02557997) including: acutely (n = 5) and chronically (n = 5) infected treatment-naive individuals, as well as treatment-experienced individuals who switched to a dolutegravir-based regimen and were either virologically suppressed (n = 5) or had experienced treatment failure (n = 5)...
December 13, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29218008/improving-the-adherence-to-antiretroviral-therapy-a-difficult-but-essential-task-for-a-successful-hiv-treatment-clinical-points-of-view-and-practical-considerations
#13
REVIEW
Simona A Iacob, Diana G Iacob, Gheorghita Jugulete
HIV infection is responsible for one the most devastating human pandemics. The advent of antiretroviral therapy has changed the course of the pandemic and saved millions of lives. Complex therapeutic regimens have been introduced since 1996 and have contributed to the transformation of HIV infection into a treatable chronic diseases. New types of potent antiretrovirals and their combinations, including "once daily" treatment, have simplified the regimens and diminished side effects. Nevertheless the adherence to antiretroviral therapy remains unsatisfactory and varies between 27 and 80% across different population in various studies, compared with the required level of 95%...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29193852/frequency-domain-response-analysis-for-quantitative-systems-pharmacology-models
#14
Pascal Schulthess, Teun M Post, James Yates, Piet H van der Graaf
Drug dosing regimen can significantly impact drug effect and, thus, the success of treatments. Nevertheless, trial and error is still the most commonly used method by conventional pharmacometric approaches to optimize dosing regimen. In this tutorial, we utilize four distinct classes of quantitative systems pharmacology models to introduce frequency-domain response analysis, a method widely used in electrical and control engineering that allows the analytical optimization of drug treatment regimen from the dynamics of the model...
November 28, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/29165413/-ophthalmoferon-efficacy-in-the-treatment-of-children-with-chronic-blepharoconjunctivitis
#15
L P Prozornaya, V V Brzheskiy
AIM: To study possibilities of using the medication Ophthalmoferon in the treatment of children with chronic allergic and Demodex blepharoconjunctivitis. MATERIAL AND METHODS: We examined 40 children (80 eyes) aged 3 to 17 years with chronic allergic (group I) and Demodex (group II) blepharoconjunctivitis. Each group was divided into two subgroups ('A' and 'B') respectively based on the treatment regimen used. Subgroup 'A' patients received Ophtalmoferon instillations (four times per day for four weeks) in addition to the standard therapy, whereas subgroup 'B' patients got only basic treatment of blepharoconjunctivitis...
2017: Vestnik Oftalmologii
https://www.readbyqxmd.com/read/29145397/post-kala-azar-dermal-leishmaniasis-in-the-indian-subcontinent-a-threat-to-the-south-east-asia-region-kala-azar-elimination-programme
#16
REVIEW
Eduard E Zijlstra, Fabiana Alves, Suman Rijal, Byron Arana, Jorge Alvar
BACKGROUND: The South-East Asia Region Kala-azar Elimination Programme (KAEP) is expected to enter the consolidation phase in 2017, which focuses on case detection, vector control, and identifying potential sources of infection. Post-kala-azar dermal leishmaniasis (PKDL) is thought to play a role in the recurrence of visceral leishmaniasis (VL)/kala-azar outbreaks, and control of PKDL is among the priorities of the KAEP. METHODOLOGY AND PRINCIPAL FINDING: We reviewed the literature with regard to PKDL in Asia and interpreted the findings in relation to current intervention methods in the KAEP in order to make recommendations...
November 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29133558/pharmacokinetics-and-drug-drug-interactions-of-lopinavir-ritonavir-administered-with-first-and-second-line-antituberculosis-drugs-in-hiv-infected-children-treated-for-multidrug-resistant-tuberculosis
#17
Louvina E van der Laan, Anthony J Garcia-Prats, H Simon Schaaf, Tjokosela Tikiso, Lubbe Wiesner, Mine de Kock, Jana Winckler, Jennifer Norman, Helen McIlleron, Paolo Denti, Anneke C Hesseling
Background Lopinavir/ritonavir forms the backbone of current first-line antiretroviral regimens in young HIV-infected children. As multidrug-resistant (MDR) tuberculosis (TB) frequently occurs in young children in high-burden TB settings, it is important to identify potential interactions between MDR-TB treatment and lopinavir/ritonavir. We describe the pharmacokinetics of and potential drug-drug interactions between lopinavir/ritonavir and routine drugs used for MDR-TB treatment in HIV-infected children.Methods A combined population pharmacokinetic model was developed to jointly describe the pharmacokinetics of lopinavir and ritonavir in 32 HIV-infected children (16 on MDR-TB treatment with combinations of high-dose isoniazid, pyrazinamide, ethambutol, ethionamide, terizidone, a fluoroquinolone, and amikacin: and 16 without TB), who were established on a lopinavir/ritonavir-containing antiretroviral regimen...
November 13, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29127049/predicting-mutant-selection-in-competition-experiments-with-ciprofloxacin-exposed-escherichia-coli
#18
David D Khan, Pernilla Lagerbäck, Christer Malmberg, Anders N Kristoffersson, Erik Gullberg, Cao Sha, Otto Cars, Dan I Andersson, Diarmaid Hughes, Elisabet I Nielsen, Lena E Friberg
Predicting competition between antibiotic susceptible wild-type and less susceptible mutant bacteria is valuable for understanding how drug concentrations influence emergence of resistance. Pharmacokinetic-pharmacodynamic (PKPD) models predicting the rate and extent of takeover of resistant bacteria during different antibiotic pressures can thereby be a valuable tool in improving treatment regimens. The aim of this study was to evaluate a previously developed mechanism-based PKPD model for its ability to predict in vitro mixed-population experiments with competition between E...
November 7, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/29104515/simcausal-r-package-conducting-transparent-and-reproducible-simulation-studies-of-causal-effect-estimation-with-complex-longitudinal-data
#19
Oleg Sofrygin, Mark J van der Laan, Romain Neugebauer
The simcausal R package is a tool for specification and simulation of complex longitudinal data structures that are based on non-parametric structural equation models. The package aims to provide a flexible tool for simplifying the conduct of transparent and reproducible simulation studies, with a particular emphasis on the types of data and interventions frequently encountered in real-world causal inference problems, such as, observational data with time-dependent confounding, selection bias, and random monitoring processes...
2017: Journal of Statistical Software
https://www.readbyqxmd.com/read/29100193/phase-ii-multicentre-randomised-trial-of-eribulin-plus-gemcitabine-versus-paclitaxel-plus-gemcitabine-as-first-line-chemotherapy-in-patients-with-her2-negative-metastatic-breast-cancer
#20
RANDOMIZED CONTROLLED TRIAL
Yeon Hee Park, Seock-Ah Im, Sung-Bae Kim, Joo Hyuk Sohn, Keun Seok Lee, Yee Soo Chae, Ki Hyeong Lee, Jee Hyun Kim, Young-Hyuck Im, Ji-Yeon Kim, Tae-Yong Kim, Kyung-Hun Lee, Jin-Hee Ahn, Gun Min Kim, In Hae Park, Soo Jung Lee, Hye Sook Han, Se Hyun Kim, Kyung Hae Jung
BACKGROUND: Paclitaxel plus gemcitabine (PG) combination chemotherapy is a preferred chemotherapeutic regimen for patients with metastatic breast cancer (MBC). Eribulin mesylate is a halichondrin non-taxane inhibitor of microtubule dynamics. A recent pooled analysis with eribulin showed improved overall survival (OS) in various MBC patient subgroups pretreated with anthracycline and taxane. Furthermore, eribulin may have less neurotoxicity than paclitaxel. PATIENTS AND METHODS: This study was a prospective randomised phase II, open-label, two-arm, multicentre study comparing eribulin plus gemcitabine (EG) with PG chemotherapy as a first-line treatment for patients with human epidermal growth factor receptor 2-negative MBC...
November 2017: European Journal of Cancer
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