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Dynamic treatment regimens

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https://www.readbyqxmd.com/read/29244129/dolutegravir-reshapes-the-genetic-diversity-of-hiv-1-reservoirs
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
https://www.readbyqxmd.com/read/29096156/recurrence-dynamics-of-breast-cancer-according-to-baseline-body-mass-index
#10
Elia Biganzoli, Christine Desmedt, Marco Fornili, Evandro de Azambuja, Nathalie Cornez, Fernand Ries, Marie-Thérèse Closon-Dejardin, Joseph Kerger, Christian Focan, Angelo Di Leo, Jean-Marie Nogaret, Christos Sotiriou, Martine Piccart, Romano Demicheli
BACKGROUND: In cancer follow-up, in addition to the evaluation of survival probabilities, there is a fundamental need of assessing recurrence dynamics for optimal disease management. Although the time-dependent effect of the oestrogen receptor (ER) status of the tumour has already been described, so far no factor has proven to disentangle the multi-peak behaviour observed for breast cancer recurrences. Here, we aimed at investigating whether adiposity at diagnosis, reflected by increased patient's body mass index (BMI), could be associated with breast cancer recurrence patterns over time after primary cancer therapy...
October 30, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/29090407/pkpd-modeling-of-acquired-resistance-to-anti-cancer-drug-treatment
#11
Miro J Eigenmann, Nicolas Frances, Thierry Lavé, Antje-Christine Walz
Non-small cell lung cancer (NSCLC) patients greatly benefit from the treatment with tyrosine kinase inhibitors (TKIs) targeting the epidermal growth factor receptor (EGFR). However, emergence of acquired resistance inevitable occurs after long-term treatment in most patients and limits clinical improvement. In the present study, resistance to drug treatment in patient-derived NSCLC xenograft mice was assessed and modeling and simulation was applied to understand the dynamics of drug resistance as a basis to explore more beneficial drug regimen...
December 2017: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/29068286/dynamic-hiv-1-genetic-recombination-and-genotypic-drug-resistance-among-treatment-experienced-adults-in-northern-ghana
#12
Nicholas Israel Nii-Trebi, James Ashun Mensah Brandful, Shiro Ibe, Wataru Sugiura, Jacob Samson Barnor, Patrick Owiredu Bampoh, Shoji Yamaoka, Tetsuro Matano, Kazuhisa Yoshimura, Koichi Ishikawa, William Kwabena Ampofo
PURPOSE: There have been hardly any reports on the human immunodeficiency virus type 1 (HIV-1) drug-resistance profile from northern Ghana since antiretroviral therapy (ART) was introduced over a decade ago. This study investigated prevailing HIV-1 subtypes and examined the occurrence of drug resistance in ART-experienced patients in Tamale, the capital of the Northern Region of Ghana. METHODOLOGY: A cross-sectional study was carried out on HIV-infected adult patients receiving first-line ART...
November 2017: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/29048401/p53-dynamics-orchestrates-with-binding-affinity-to-target-genes-for-cell-fate-decision
#13
Mengqiu Wu, Hui Ye, Zhiyuan Tang, Chang Shao, Gaoyuan Lu, Baoqiang Chen, Yuyu Yang, Guangji Wang, Haiping Hao
Emerging evidence support that temporal dynamics is pivotal for signaling molecules in orchestrating smart responses to diverse stimuli. p53 is such a signaling molecule that employs temporal dynamics for the selective activation of downstream target genes and ultimately for cell fate decision. Yet how this fine-tuned p53 machinery is quantitatively decoded remains largely unclear. Here we report a quantitative mechanism defining how p53 dynamics orchestrates with binding affinity to target genes for cell fate decision...
October 19, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29029057/patient-specific-modelling-of-regional-tobramycin-concentration-levels-in-airways-of-patients-with-cystic-fibrosis-can-we-dose-once-daily
#14
Aukje C Bos, Johan W Mouton, Mireille van Westreenen, Eleni-Rosalina Andrinopoulou, Hettie M Janssens, Harm A W M Tiddens
Background: Inhaled tobramycin is important in the treatment of Pseudomonas aeruginosa (Pa) infections in cystic fibrosis (CF). However, despite its use it fails to attenuate the clinical progression of CF lung disease. The bactericidal efficacy of tobramycin is known to be concentration-dependent and hence changing the dosing regimen from a twice-daily (q12h) inhalation to a once-daily (q24h) inhaled double dose could improve treatment outcomes. Objectives: To predict local concentrations of nebulized tobramycin in the airways of patients with CF, delivered with the small airway-targeting Akita® system or standard PARI-LC® Plus system, with different inspiratory flow profiles...
December 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28993326/a-dynamic-stress-model-explains-the-delayed-drug-effect-in-artemisinin-treatment-of-plasmodium-falciparum
#15
Pengxing Cao, Nectarios Klonis, Sophie Zaloumis, Con Dogovski, Stanley C Xie, Sompob Saralamba, Lisa J White, Freya J I Fowkes, Leann Tilley, Julie A Simpson, James M McCaw
Artemisinin resistance constitutes a major threat to the continued success of control programs for malaria, particularly in light of developing resistance to partner drugs. Improving our understanding of how artemisinin-based drugs act and how resistance manifests is essential for the optimisation of dosing regimens and the development of strategies to prolong the lifespan of current first-line treatment options. Recent short drug-pulse in vitro experiments have shown that the parasite killing rate depends not only on drug concentration but also the exposure time, challenging the standard pharmacokinetic-pharmacodynamic(PK-PD) paradigm in which the killing rate depends only on drug concentration...
October 9, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28991889/trends-in-drug-resistance-prevalence-hiv-1-variants-and-clinical-status-in-hiv-1-infected-pediatric-population-in-madrid-1993-2015-analysis
#16
Patricia Rojas Sánchez, Sara Domínguez, Santiago Jiménez De Ory, Luis Prieto, Pablo Rojo, Pepa Mellado, Marisa Navarro, Rafael Delgado, José Tomas Ramos, África Holguín
BACKGROUND: The expanded use of long-term antiretroviral treatments in infected children may exacerbate the problem of drug resistance mutations (HIVDR) selection, which can compromise treatment efficiency. OBJECTIVE: We describe the temporal trends of HIVDR and the HIV-1 variants during 23 years (1993-March 2016) in the Madrid cohort of HIV-infected children and adolescents. METHODS: We selected patients with at least one available HIV-1 pol sequence/genotypic resistance profile, establishing different groups according to the sampling year of first resistance data...
October 6, 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/28982739/discovery-of-methylated-circulating-dna-biomarkers-for-comprehensive-non-invasive-monitoring-of-treatment-response-in-metastatic-colorectal-cancer
#17
Ludovic Barault, Alessio Amatu, Giulia Siravegna, Agostino Ponzetti, Sebastian Moran, Andrea Cassingena, Benedetta Mussolin, Chiara Falcomatà, Alexandra M Binder, Carmen Cristiano, Daniele Oddo, Simonetta Guarrera, Carlotta Cancelliere, Sara Bustreo, Katia Bencardino, Sean Maden, Alice Vanzati, Patrizia Zavattari, Giuseppe Matullo, Mauro Truini, William M Grady, Patrizia Racca, Karin B Michels, Salvatore Siena, Manel Esteller, Alberto Bardelli, Andrea Sartore-Bianchi, Federica Di Nicolantonio
OBJECTIVE: Mutations in cell-free circulating DNA (cfDNA) have been studied for tracking disease relapse in colorectal cancer (CRC). This approach requires personalised assay design due to the lack of universally mutated genes. In contrast, early methylation alterations are restricted to defined genomic loci allowing comprehensive assay design for population studies. Our objective was to identify cancer-specific methylated biomarkers which could be measured longitudinally in cfDNA (liquid biopsy) to monitor therapeutic outcome in patients with metastatic CRC (mCRC)...
October 5, 2017: Gut
https://www.readbyqxmd.com/read/28977932/inhibitor-of-h3k27-demethylase-jmjd3-utx-gsk-j4-is-a-potential-therapeutic-option-for-castration-resistant-prostate-cancer
#18
Viacheslav M Morozov, Ying Li, Matthew M Clowers, Alexander M Ishov
Androgen receptor (AR) mediates initiation and progression of prostate cancer (PCa); AR-driven transcription is activated by binding of androgens to the ligand-binding domain (LBD) of AR. Androgen ablation therapy offers only a temporary relief of locally advanced and metastatic PCa, and the disease eventually recurs as a lethal castration-resistant PCa (CRPC) as there is no effective treatment for CRPC patients. Thus, it is critical to identify novel targeted and combinatorial regimens for clinical management of CRPC...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28970735/arterioportal-shunt-incidental-to-treatment-with-oxaliplatin-that-mimics-recurrent-gastric-cancer
#19
Hong-Beum Kim, Sang-Gon Park
Arterioportal shunt (APS) is an organic communication between the hepatic arterial system and the portal venous system. The APS is one of the major causes of transient hepatic attenuation differences on dynamic computed tomography (CT) or magnetic resonance imaging (MRI). This condition is usually associated with trauma, liver cirrhosis, and malignancies of the liver. However, there has been no report about oxaliplatin-induced APS. A 41-year-old male was diagnosed with Stage IIIB gastric cancer. The patient initially underwent neoadjuvant chemotherapy with capecitabine and oxaliplatin After 3 cycles of therapy, the mass had markedly decreased, and a total gastrectomy with splenectomy was performed...
September 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28969664/perspective-on-the-dynamics-of-cancer
#20
REVIEW
Youcef Derbal
BACKGROUND: The genetic diversity of cancer and the dynamic interactions between heterogeneous tumor cells, the stroma and immune cells present daunting challenges to the development of effective cancer therapies. Although cancer biology is more understood than ever, this has not translated into therapies that overcome drug resistance, cancer recurrence and metastasis. The future development of effective therapies will require more understanding of the dynamics of homeostatic dysregulation that drives cancer growth and progression...
October 3, 2017: Theoretical Biology & Medical Modelling
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