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Dynamic treatment regimens

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https://www.readbyqxmd.com/read/28338827/strategies-for-halting-the-rise-of-multidrug-resistant-tb-epidemics-assessing-the-effect-of-early-case-detection-and-isolation
#1
Aquino L Espindola, Marie Varughese, Marek Laskowski, Affan Shoukat, Jane M Heffernan, Seyed M Moghadas
Background: The increasing rates of multidrug resistant TB (MDR-TB) have posed the question of whether control programs under enhanced directly observed treatment, short-course (DOTS-Plus) are sufficient or implemented optimally. Despite enhanced efforts on early case detection and improved treatment regimens, direct transmission of MDR-TB remains a major hurdle for global TB control. Methods: We developed an agent-based simulation model of TB dynamics to evaluate the effect of transmission reduction measures on the incidence of MDR-TB...
March 7, 2017: International Health
https://www.readbyqxmd.com/read/28329914/ginsenoside-rg3-restores-hepatitis-c-virus-induced-aberrant-mitochondrial-dynamics-and-inhibits-virus-propagation
#2
Seong-Jun Kim, Jae Young Jang, Eun-Jung Kim, Eun Kyung Cho, Dae Gyun Ahn, Chonsaeng Kim, Han Seul Park, Soung Won Jeong, Sae Hwan Lee, Sang Gyune Kim, Young Seok Kim, Hong Soo Kim, Boo Sung Kim, Ji-Hyung Lee, Aleem Siddiqui
Hepatitis C virus (HCV) alters mitochondrial dynamics associated with persistent viral infection and suppression of innate immunity. Mitochondrial dysfunction is also a pathologic feature of direct-acting antiviral (DAA) treatment. Despite the high efficacy of DAAs, their treatment of patients with chronic hepatitis C in interferon-sparing regimens occasionally produces undesirable side effects such as fatigue, migraine and other conditions, which may be linked to mitochondrial dysfunction. Here we show that clinically prescribed DAAs, including Sofosbuvir, affect mitochondrial dynamics...
March 22, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28303751/vasoactive-peptides-associate-with-treatment-outcome-ofbevacizumab-containing-therapy-in-metastatic-colorectal-cancer
#3
Helga Hagman, Pär-Ola Bendahl, Olle Melander, Jan Sundberg, Anders Johnsson, Mattias Belting
BACKGROUND: Hypertension is a common early adverse event of anti-angiogenic treatment of cancer and may associate with treatment response. However, blood pressure measurement as a surrogate response biomarker has methodological limitations, and predictive biomarkers of angiogenesis inhibitors are lacking. In disease associated with hypertension, vasoactive peptides have been linked to cardiovascular pressure load. Here, we have explored potential associations between circulating levels of vasoactive peptides and tumor response during bevacizumab-containing treatment of colorectal cancer...
March 17, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28273116/mdr-tb-treatment-as-prevention-the-projected-population-level-impact-of-expanded-treatment-for-multidrug-resistant-tuberculosis
#4
Emily A Kendall, Andrew S Azman, Frank G Cobelens, David W Dowdy
BACKGROUND: In 2013, approximately 480,000 people developed active multidrug-resistant tuberculosis (MDR-TB), while only 97,000 started MDR-TB treatment. We sought to estimate the impact of improving access to MDR-TB diagnosis and treatment, under multiple diagnostic algorithm and treatment regimen scenarios, on ten-year projections of MDR-TB incidence and mortality. METHODS: We constructed a dynamic transmission model of an MDR-TB epidemic in an illustrative East/Southeast Asian setting...
2017: PloS One
https://www.readbyqxmd.com/read/28235415/a-systematic-review-of-health-economic-models-of-opioid-agonist-therapies-in-maintenance-treatment-of-non-prescription-opioid-dependence
#5
Mersha Chetty, James J Kenworthy, Sue Langham, Andrew Walker, William C N Dunlop
BACKGROUND: Opioid dependence is a chronic condition with substantial health, economic and social costs. The study objective was to conduct a systematic review of published health-economic models of opioid agonist therapy for non-prescription opioid dependence, to review the different modelling approaches identified, and to inform future modelling studies. METHODS: Literature searches were conducted in March 2015 in eight electronic databases, supplemented by hand-searching reference lists and searches on six National Health Technology Assessment Agency websites...
February 24, 2017: Addiction Science & Clinical Practice
https://www.readbyqxmd.com/read/28224315/modeling-of-free-fatty-acid-dynamics-insulin-and-nicotinic-acid-resistance-under-acute-and-chronic-treatments
#6
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
#7
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
#8
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...
February 20, 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
#9
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
#10
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
#11
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
#12
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...
March 2017: HIV Clinical Trials
https://www.readbyqxmd.com/read/28110651/mass-spectrometry-imaging-for-the-investigation-of-intratumor-heterogeneity
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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...
April 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
#20
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
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