Niemanncantu9497

FDA has approved iron oxide nanoparticles (IONs) coated with organic compounds as a safe material with less toxic effects compared with the naked metal ions and nanoparticles. In this study, the biological and physicochemical characteristics of a nanostructured iron-polysaccharide complexes (Nano-IPC) biosynthesized by Enterobacter sp. were evaluated. Furthermore, the serum biochemical parameters, tissue iron level, red blood cell parameters, and organ ferritin of rats were measured for investigating the effect of the Nano-IPCs in comparison with FeSO4 as a supplement for iron deficiency. The biosafety data demonstrated 35% increment of viability in Hep-G2 hepatocarcinoma cell lines when treated with nanoparticles (500 μg/mL) for 24 h. Besides, iron concentration in serum and tissue as well as the expression of ferritin L subunit in animals treated with the Nano-IPCs supplement were meaningfully higher than the FeSO4-supplemented and negative control animals. Moreover, the expression level of ferritin H subunit and biochemical factors remained similar to the negative control animals in the Nano-IPC-supplemented group. These results indicated that Nano-IPCs can be considered as a nontoxic supplement for patients carrying iron-deficiency anemia (IDA).BACKGROUND A randomized phase III trial comparing whole-brain radiotherapy (WBRT) to observation following definitive local treatment of intracranial melanoma metastases with neurosurgery and/or stereotactic surgery (SRS) is underway. OBJECTIVE We sought to assess the pre-trial cost-effectiveness of WBRT, hippocampal-avoidant WBRT (HA-WBRT), and observation (SRS or surgery alone) for this population to guide trial data collection efforts and reduce decision uncertainty.  METHODS A time-dependent Markov model followed patients treated with neurosurgery or SRS who received subsequent WBRT, HA-WBRT or observation over a 5-year time horizon. Model inputs were sourced from published literature and results tested for robustness using probabilistic sensitivity analysis. Value of information (VOI) analysis was undertaken to guide data collection for the randomized trial. RESULTS Over 5 years, the WBRT strategy produced 1.74 QALYs (2.38 life-years) at a mean cost of $40,128 (costs in 2017 Australian dollars); HA-WBRT produced 1.88 QALYs (2.38 life-years) and cost $42,977; and SRS/surgery alone produced 1.65 QALYs (2.13 life-years) at a cost of $46,281. Probabilistic sensitivity analysis showed HA-WBRT was the preferred strategy in 77% of simulations. Cost-effectiveness results were most sensitive to utilities of the controlled-disease health state in the WBRT group, and costs of HA-WBRT. The EVPI for a randomized trial was estimated at $6,888 per person. CONCLUSIONS HA-WBRT may be cost-effective for the treatment of melanoma brain metastases. The results predicted in our model can be validated with prospective trial data when available.A large body of evidence suggests that not only direct anticoagulant effects but also major bleeding events and stroke prevention depend on plasma concentrations of direct oral anticoagulants (DOACs). Concomitant drugs that cause drug-drug interactions (DDIs) alter DOAC exposure by increasing or decreasing DOAC bioavailability and/or clearance; hence, they might affect the efficacy and safety of DOAC therapy. Patients with renal impairment already receive smaller DOAC maintenance doses because avoidance of elevated DOAC exposure might prevent serious bleeding events. For other causes of increased exposure such as DDIs, management is often less well-defined. Considering that DOAC patients are often older and have multiple co-morbidities, polypharmacy is highly prevalent. However, the effect of multiple drugs on DOAC exposure, and especially the impact of DDIs when concurring with drug-disease interactions as observed in renal impairment, has not been thoroughly elucidated. In order to provide effective and safe anticoagulation with DOACs, understanding the mechanisms and magnitude of DDIs appears relevant. Instead of avoiding drug combinations with DOACs, more DDI trials should be conducted and new strategies such as dose adjustments based on therapeutic drug monitoring should be investigated. However, dose adjustments based on concentration measurements cannot currently be recommended because evidence-based data are missing.BACKGROUND Busulfan therapeutic drug monitoring (TDM) is necessary to better achieve the target exposure in children before hematopoietic stem cell transplantation (HSCT). However, TDM-based dosing may be challenging if intra-individual pharmacokinetic variability (also denoted inter-occasion variability [IOV]) occurs during therapy. OBJECTIVES The objectives of this study were to describe and quantify busulfan IOV in children, and to investigate its potential determinants. METHODS We performed a new analysis of published data from children who received intravenous busulfan over 4 days before HSCT. We calculated individual pharmacokinetic parameters on each day of therapy using a published population pharmacokinetic model of busulfan and analyzed their changes. Population estimation of IOV was also performed with non-linear mixed effects (NLME) modeling. Potential predictors of significant decrease in busulfan clearance (CL) were assessed by using machine learning approaches. Selleck BLZ945 RESULTS IOV could be assessed in 136 children. Between day (D) 1 and D2, most patients (80%) experienced a decrease in busulfan CL, with a median change of - 7.9%. However, both large decreases (minimum, -  48.5%) and increases in CL (maximum, + 44%) were observed. Over D1-D3 of therapy, mean CL significantly decreased (-  15%), with a decrease of ≥ 20% in 22% of patients. Some patients also showed unstable CL from day to day. NLME modeling of IOV provided a coefficient of variation of 10.6% and 13.1% for volume of distribution (Vd) and CL, respectively. Some determinants of significant decreases in busulfan CL were identified, but predictive performance of the models was limited. CONCLUSIONS Significant busulfan intra-individual variability may occur in children who receive a HSCT and is hardly predictable. The main risk is busulfan overexposure. Performing TDM repeatedly over therapy appears to be the best way to accurately estimate busulfan exposure and perform precision dosing.