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Dynamic treatment regimens

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https://www.readbyqxmd.com/read/28224315/modeling-of-free-fatty-acid-dynamics-insulin-and-nicotinic-acid-resistance-under-acute-and-chronic-treatments
#1
Robert Andersson, Tobias Kroon, Joachim Almquist, Mats Jirstrand, Nicholas D Oakes, Neil D Evans, Michael J Chappel, Johan Gabrielsson
Nicotinic acid (NiAc) is a potent inhibitor of adipose tissue lipolysis. Acute administration results in a rapid reduction of plasma free fatty acid (FFA) concentrations. Sustained NiAc exposure is associated with tolerance development (drug resistance) and complete adaptation (FFA returning to pretreatment levels). We conducted a meta-analysis on a rich pre-clinical data set of the NiAc-FFA interaction to establish the acute and chronic exposure-response relations from a macro perspective. The data were analyzed using a nonlinear mixed-effects framework...
February 21, 2017: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/28222681/the-need-for-treatment-scale-up-to-impact-hcv-transmission-in-people-who-inject-drugs-in-montr%C3%A3-al-canada-a-modelling-study
#2
Anthony Cousien, Pascale Leclerc, Carole Morissette, Julie Bruneau, Élise Roy, Viet Chi Tran, Yazdan Yazdanpanah, Joseph Cox
BACKGROUND: HCV transmission remains high in people who inject drugs (PWID) in Montréal. New direct-acting antivirals (DAAs), highly effective and more tolerable than previous regimens, make a "Treatment as Prevention" (TasP) strategy more feasible. This study assesses how improvements in the cascade of care could impact hepatitis C burden among PWID in Montréal. METHODS: We used a dynamic model to simulate HCV incidence and prevalence after 10 years, and cirrhosis complications after 10 and 40 years...
February 21, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28218209/clinical-study-of-acute-vasoreactivity-testing-in-patients-with-chronic-thromboembolic-pulmonary-hypertension
#3
Qi-Xia Xu, Yuan-Hua Yang, Jie Geng, Zhen-Guo Zhai, Juan-Ni Gong, Ji-Feng Li, Xiao Tang, Chen Wang
BACKGROUND: The clinical significance of acute vasoreactivity testing (AVT) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) remains unclear. We analyzed changes in hemodynamics and oxygenation dynamics indices after AVT in patients with CTEPH using patients with pulmonary arterial hypertension (PAH) as controls. METHODS: We analyzed retrospectively the results of AVT in 80 patients with PAH and 175 patients with CTEPH registered in the research database of Beijing Chao-Yang Hospital between October 2005 and August 2014...
2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28167544/nanoliposomal-buparvaquone-immunomodulates-leishmania-l-infantum-infected-macrophages-and-is-highly-effective-in-murine-model
#4
Thais Alves da Costa-Silva, Andrés Jimenez Galisteo, José Angelo Lauletta Lindoso, Leandro R S Barbosa, Andre Gustavo Tempone
Visceral leishmaniasis (VL) is a fatal parasitic neglected disease affecting 1.5 million people worldwide. Based on the drug repositioning approach, the aim of this work was to investigate the in vitro immunomodulatory potential of buparvaquone (BPQ) and to stablish a safe regimen to evaluate the in vivo efficacy of BPQ entrapped into negatively charged nanoliposomes (BPQ-LP) in Leishmania (L.) infantum infected hamsters. Small angle X-ray scattering (SAXS), dynamic light scattering (DLS) and ζ-potential were applied in order to study the influence of BPQ on the liposome structure...
February 6, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28152902/the-standardization-of-skin-cancer-treatment-recommendations-through-the-analysis-of-clinical-pathways-data-and-an-evidence-based-physician-driven-committee-process
#5
Amanda Barry, Hans Benson, Zach Lorinc, Kathleen Lokay
: 147 Background: Clinical pathways (CP) have the potential to improve the quality and safety of care and lead to more predictable outcomes and costs through standardization. Via Oncology's CP program aims to standardize care at radiation centers across its nationwide network. Created through an evidence-based, physician-driven committee process, CP recommend the best treatment plan for specific patient populations based on a hierarchy of efficacy, toxicity, and cost. In the absence of definitive data, reaching a consensus on the best treatment recommendation is difficult, particularly for disease states such as melanoma, squamous cell carcinoma, and basal cell carcinoma for which a wide range of radiation doses and schedules are considered effective and regional and institutional preferences may vary...
March 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28138980/dynamic-population-pharmacokinetic-pharmacodynamic-modelling-and-simulation-supports-similar-efficacy-in-glycosylated-haemoglobin-response-with-once-or-twice-daily-dosing-of-canagliflozin
#6
Willem de Winter, Adrian Dunne, Xavier Woot de Trixhe, Damayanthi Devineni, Chyi-Hung Hsu, Jose Pinheiro, David Polidori
AIM: Canagliflozin is an SGLT2 inhibitor approved for the treatment of type-2 diabetes. A dynamic population pharmacokinetic-pharmacodynamic (PK/PD) model relating 24-h canagliflozin exposure profiles to effects on glycosylated haemoglobin was developed to compare the efficacy of once-daily and twice-daily dosing. METHODS: Data from two clinical studies, one with once-daily, and the other with twice-daily dosing of canagliflozin as add-on to metformin were used (n = 1347)...
November 7, 2016: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28134057/hiv-viral-kinetics-and-t-cell-dynamics-in-antiretroviral-na%C3%A3-ve-persons-starting-an-integrase-strand-transfer-inhibitor-and-protease-inhibitor-regimen
#7
Maile Y Karris, Sonia Jain, Tyler R C Day, Josué Pérez-Santiago, Miguel Goicoechea, Michael P Dubé, Xiaoying Sun, Celsa Spina, Eric S Daar, Richard H Haubrich, Sheldon Morris
BACKGROUND: Nucleos(t)ide reverse transcriptase inhibitor (NRTI)-sparing regimens may potentially minimize antiretroviral (ART) toxicities, but demonstrate mixed efficacy and toxicity results. The impact of an integrase strand transfer inhibitor (INSTI) and protease inhibitor (PI) regimen on HIV viral dynamics and T cell kinetics remains underdescribed. OBJECTIVE: To compare the effect of raltegravir + ritonavir boosted lopinavir (RAL + LPV/r) to efavirenz/tenofovir disoproxil fumarate/emtricitabine (EFV/TDF/FTC) on HIV kinetics and T cell dynamics...
January 30, 2017: HIV Clinical Trials
https://www.readbyqxmd.com/read/28110651/mass-spectrometry-imaging-for-the-investigation-of-intratumor-heterogeneity
#8
B Balluff, M Hanselmann, R M A Heeren
One of the big clinical challenges in the treatment of cancer is the different behavior of cancer patients under guideline therapy. An important determinant for this phenomenon has been identified as inter- and intratumor heterogeneity. While intertumor heterogeneity refers to the differences in cancer characteristics between patients, intratumor heterogeneity refers to the clonal and nongenetic molecular diversity within a patient. The deciphering of intratumor heterogeneity is recognized as key to the development of novel therapeutics or treatment regimens...
2017: Advances in Cancer Research
https://www.readbyqxmd.com/read/28109869/outcomes-infectiousness-and-transmission-dynamics-of-patients-with-extensively-drug-resistant-tuberculosis-and-home-discharged-patients-with-programmatically-incurable-tuberculosis-a-prospective-cohort-study
#9
Keertan Dheda, Jason D Limberis, Elize Pietersen, Jody Phelan, Aliasgar Esmail, Maia Lesosky, Kevin P Fennelly, Julian Te Riele, Barbara Mastrapa, Elizabeth M Streicher, Tania Dolby, Abdallah M Abdallah, Fathia Ben-Rached, John Simpson, Liezel Smith, Tawanda Gumbo, Paul van Helden, Frederick A Sirgel, Ruth McNerney, Grant Theron, Arnab Pain, Taane G Clark, Robin M Warren
BACKGROUND: The emergence of programmatically incurable tuberculosis threatens to destabilise control efforts. The aim of this study was to collect prospective patient-level data to inform treatment and containment strategies. METHODS: In a prospective cohort study, 273 South African patients with extensively drug-resistant tuberculosis, or resistance beyond extensively drug-resistant tuberculosis, were followed up over a period of 6 years. Transmission dynamics, infectiousness, and drug susceptibility were analysed in a subset of patients from the Western Cape using whole-genome sequencing (WGS; n=149), a cough aerosol sampling system (CASS; n=26), and phenotypic testing for 18 drugs (n=179)...
January 18, 2017: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/28102485/-18-f-fet-pet-prior-to-recurrent-high-grade-glioma-re-irradiation-additional-prognostic-value-of-dynamic-time-to-peak-analysis-and-early-static-summation-images
#10
Daniel F Fleischmann, Marcus Unterrainer, Peter Bartenstein, Claus Belka, Nathalie L Albert, Maximilian Niyazi
Most high-grade gliomas (HGG) recur after initial multimodal therapy and re-irradiation (Re-RT) has been shown to be a valuable re-treatment option in selected patients. We evaluated the prognostic value of dynamic time-to-peak analysis and early static summation images in O-(2-(18)F-fluoroethyl)-l-tyrosine ((18)F-FET) PET for patients treated with Re-RT ± concomitant bevacizumab. We retrospectively analyzed 72 patients suffering from recurrent HGG with (18)F-FET PET prior to Re-RT. PET analysis revealed the maximal tumor-to-background-ratio (TBRmax), the biological tumor volume, the number of PET-foci and pattern of time-activity-curves (TACs; increasing vs...
January 19, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28101809/sequential-exposure-of-bortezomib-and-vorinostat-is-synergistic-in-multiple-myeloma-cells
#11
Charvi Nanavati, Donald E Mager
PURPOSE: To examine the combination of bortezomib and vorinostat in multiple myeloma cells (U266) and xenografts, and to assess the nature of their potential interactions with semi-mechanistic pharmacodynamic models and biomarkers. METHODS: U266 proliferation was examined for a range of bortezomib and vorinostat exposure times and concentrations (alone and in combination). A non-competitive interaction model was used with interaction parameters that reflect the nature of drug interactions after simultaneous and sequential exposures...
January 18, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28100241/personalized-life-expectancy-and-treatment-benefit-index-of-antiretroviral-therapy
#12
Yanni Xiao, Xiaodan Sun, Sanyi Tang, Yicang Zhou, Zhihang Peng, Jianhong Wu, Ning Wang
BACKGROUND: The progression of Human Immunodeficiency Virus (HIV) within host includes typical stages and the Antiretroviral Therapy (ART) is shown to be effective in slowing down this progression. There are great challenges in describing the entire HIV disease progression and evaluating comprehensive effects of ART on life expectancy for HIV infected individuals on ART. METHODS: We develop a novel summative treatment benefit index (TBI), based on an HIV viral dynamics model and linking the infection and viral production rates to the Weibull function...
January 18, 2017: Theoretical Biology & Medical Modelling
https://www.readbyqxmd.com/read/28091752/management-of-secondary-hyperparathyroidism-practice-patterns-and-outcomes-of-cinacalcet-treatment-with-or-without-active-vitamin%C3%A2-d-in-austria-and-switzerland-the-observational-transit-study
#13
Wolfgang Pronai, Alexander R Rosenkranz, Andreas Bock, Renate Klauser-Braun, Christine Jäger, Gunther Pendl, Margit Hemetsberger, Karl Lhotta
Secondary hyperparathyroidism is a complex disorder requiring an individualized multicomponent treatment approach. This study was conducted to identify treatment combinations used in clinical practice in Austria and Switzerland and the potential to control this disorder. A total of 333 adult hemodialysis and peritoneal dialysis patients were analyzed. All patients received conventional care prior to initiation of a cinacalcet-based regimen. During the study, treatment components, e.g. cinacalcet, active vitamin D analogues and phosphate binders, were adapted to individual patient requirements and treatment dynamics were documented...
January 13, 2017: Wiener Klinische Wochenschrift
https://www.readbyqxmd.com/read/28089562/sequential-multiple-assignment-randomized-trials-an-opportunity-for-improved-design-of-stroke-reperfusion-trials
#14
William J Meurer, Nicholas J Seewald, Kelley Kidwell
BACKGROUND: Modern clinical trials in stroke reperfusion fall into 2 categories: alternative systemic pharmacological regimens to alteplase and "rescue" endovascular approaches using targeted thrombectomy devices and/or medications delivered directly for persistently occluded vessels. Clinical trials in stroke have not evaluated how initial pharmacological thrombolytic management might influence subsequent rescue strategy. A sequential multiple assignment randomized trial (SMART) is a novel trial design that can test these dynamic treatment regimens and lead to treatment guidelines that more closely mimic practice...
January 12, 2017: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/28077142/steroid-withdrawal-after-renal-transplantation-a-retrospective-cohort-study
#15
Maria C Haller, Michael Kammer, Alexander Kainz, Heather J Baer, Georg Heinze, Rainer Oberbauer
BACKGROUND: Immunosuppressive regimens in renal transplantation frequently contain corticosteroids, but many centers withdraw steroids as a consequence of unwanted side effects of steroids. The optimal timing to withdraw steroids after transplantation, however, remains unclear. The aim of this study was to determine an optimal time point following kidney transplantation that is associated with reduced mortality without jeopardizing the allograft to allow safe discontinuation of steroids...
January 12, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28066805/evaluation-of-soft-tissue-sarcoma-response-to-preoperative-chemoradiotherapy-using-dynamic-contrast-enhanced-magnetic-resonance-imaging
#16
Wei Huang, Brooke R Beckett, Alina Tudorica, Janelle M Meyer, Aneela Afzal, Yiyi Chen, Atiya Mansoor, James B Hayden, Yee-Cheen Doung, Arthur Y Hung, Megan L Holtorf, Torrie J Aston, Christopher W Ryan
This study aims to assess the utility of quantitative dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) parameters in comparison with imaging tumor size for early prediction and evaluation of soft tissue sarcoma response to preoperative chemoradiotherapy. In total, 20 patients with intermediate- to high-grade soft tissue sarcomas received either a phase I trial regimen of sorafenib + chemoradiotherapy (n = 8) or chemoradiotherapy only (n = 12), and underwent DCE-MRI at baseline, after 2 weeks of treatment with sorafenib or after the first chemotherapy cycle, and after therapy completion...
December 2016: Tomography: a Journal for Imaging Research
https://www.readbyqxmd.com/read/28063990/efficient-tuning-of-sirna-dose-response-by-combining-mixed-polymer-nanocarriers-with-simple-kinetic-modeling
#17
Chad T Greco, Victoria G Muir, Thomas H Epps, Millicent O Sullivan
: Two of the most prominent challenges that limit the clinical success of siRNA therapies are a lack of control over cargo release from the delivery vehicle and an incomplete understanding of the link between gene silencing dynamics and siRNA dosing. Herein, we address these challenges through the formulation of siRNA polyplexes containing light-responsive polymer mixtures, whose varied compositions and triggered release behavior provide enhanced gene silencing and controlled dose responses that can be predicted by simple kinetic models...
March 1, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28045934/priority-setting-for-novel-drug-regimens-to-treat-tuberculosis-an-epidemiologic-model
#18
Emily A Kendall, Sourya Shrestha, Ted Cohen, Eric Nuermberger, Kelly E Dooley, Lice Gonzalez-Angulo, Gavin J Churchyard, Payam Nahid, Michael L Rich, Cathy Bansbach, Thomas Forissier, Christian Lienhardt, David W Dowdy
BACKGROUND: Novel drug regimens are needed for tuberculosis (TB) treatment. New regimens aim to improve on characteristics such as duration, efficacy, and safety profile, but no single regimen is likely to be ideal in all respects. By linking these regimen characteristics to a novel regimen's ability to reduce TB incidence and mortality, we sought to prioritize regimen characteristics from a population-level perspective. METHODS AND FINDINGS: We developed a dynamic transmission model of multi-strain TB epidemics in hypothetical populations reflective of the epidemiological situations in India (primary analysis), South Africa, the Philippines, and Brazil...
January 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28043418/the-effectiveness-of-patient-tailored-treatment-for-acute-organophosphate-poisoning
#19
Chih-Chuan Lin, Dong-Zong Hung, Hsien-Yi Chen, Kuang-Hung Hsu
BACKGROUND: To determine a new pralidoxime (PAM) treatment guideline based on the severity of acute organophosphate intoxication patients, APACHE II score, and dynamic changes in serum butyrylcholinesterase (BuChE) activity. METHODS: This is a randomization trial. All patients received supportive care measurements and atropinization. Each enrolled patient was treated with 2 gm PAM intravenously as the loading dose. The control group was treated according to the WHO's recommended PAM regimen, and the experimental group was treated according to their APACHE II scores and dynamic changes in BuChE activity...
December 2016: Biomedical Journal
https://www.readbyqxmd.com/read/28043170/impact-of-disease-drug-and-patient-adherence-on-the-effectiveness-of-antiviral-therapy-in-pediatric-hiv
#20
Chiara Piana, Meindert Danhof, Oscar Della Pasqua
Maintaining effective antiretroviral treatment for life is a major problem, in both resource-limited and resource-rich countries. Despite the progress observed in paediatric antiretroviral therapy, approximately 12% of children still experience treatment failure due to drug resistance, inadequate dosing and poor adherence. We explore the current status of antiretroviral therapy in children with focus on the interaction between disease, drug pharmacokinetics and patient behavior, all of which are strongly interconnected and determine treatment outcome...
January 3, 2017: Expert Opinion on Drug Metabolism & Toxicology
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