Bairdhahn1577
Exosomes are extracellular vesicles secreted by cells with a particle size of 30-150 nm in diameter. Exosomes can be used as natural drug carriers. The treatment of cancer with drug-loaded exosomes is an area of high interest. This review introduces the composition, function, isolation and characterization of exosomes, and briefly describes the selection of exosome donor cells and methods for drug loading. Through studies on therapies with drug-loaded exosomes in gastric cancer, lung cancer, brain cancer and other cancers, the advantages and disadvantages of drug-loaded exosomes have been analyzed.
Although kinase inhibitors (KIs) are generally effective, their use has a large impact on the current health care budget. Dosing strategies to reduce treatment costs are warranted. Boosting pharmacokinetic exposure of KIs metabolized by cytochrome P450 (CYP)3A4 with ritonavir might result in lower doses needed and subsequently reduces treatment costs. This study is a proof-of-concept study to evaluate if the dose of erlotinib can be reduced by co-administration with ritonavir.
In this open-label, cross-over study, we compared the pharmacokinetics of monotherapy erlotinib 150mg once daily (QD) (control arm) with erlotinib 75mg QD plus ritonavir 200mg QD (intervention arm). Complete pharmacokinetic profiles at steady-state were taken up to 24h after erlotinib intake for both dosing strategies.
Nine patients were evaluable in this study. For the control arm, the systemic exposure over 24h, maximum plasma concentration and minimal plasma concentration of erlotinib were 29.3μg*h/mL (coefficient of variation ive therapies metabolized by CYP3A4.
Binary water - ethanol mixtures, by mimicking a clinically relevant medium's polarity-driven extraction strength, facilitate experimental modeling of patient exposure to chemicals which can potentially leach from a plastic material for pharmaceutical applications. Estimates of patient exposure could consequently benefit from a quantitative concept for tailoring the extraction strength of the simulating solvent mixture towards the one of the clinically relevant medium.
The hypothetical partition coefficient based upon the differential solubility between water-ethanol mixtures and water, [Formula see text], has been calculated by the log-linear model from Yalkowsky and coworkers and a cosolvency model based on Abraham-type linear solvation energy relationships (LSERs). Then, by applying a thermodynamic cycle using the partition coefficient LDPE/water, [Formula see text], partitioning between LDPE and the ethanol in water mixture was calculated and experimentally verified for a wide array of chemically diverent mixtures when input parameters from the clinically relevant medium are available. This approach can increase the reliability of patient exposure estimations and avoid overly complex extraction profiles, thus minimizing time and resources for chemical safety risk assessments on plastic materials used in pharmaceutical applications.
To review the factors contributing to underutilization of guideline-directed therapies, identify strategies to alleviate these factors, and apply these strategies for effective and timely dissemination of novel cardioprotective glucose-lowering agents.
Recent analyses demonstrate underutilization of cardioprotective glucose lowering agents despite guideline recommendations for their use. Major contributors to underutilization of guideline-directed therapies include therapeutic inertia, perceptions about side effects, and factors found at the level of the clinicians, patients, and the healthcare system. The recent emergence of several novel therapies, such as sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists, for use in cardiovascular disease provides a unique avenue to improve patient outcomes. To effectively utilize novel cardioprotective glucose lowering agents to improve cardiovascular outcomes, clinicians must recognize and learn from prior barriers to application of guideline-directed therapies. Further endeavors are prudent to ensure uptake of novel agents.
Recent analyses demonstrate underutilization of cardioprotective glucose lowering agents despite guideline recommendations for their use. Major contributors to underutilization of guideline-directed therapies include therapeutic inertia, perceptions about side effects, and factors found at the level of the clinicians, patients, and the healthcare system. The recent emergence of several novel therapies, such as sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists, for use in cardiovascular disease provides a unique avenue to improve patient outcomes. To effectively utilize novel cardioprotective glucose lowering agents to improve cardiovascular outcomes, clinicians must recognize and learn from prior barriers to application of guideline-directed therapies. Further endeavors are prudent to ensure uptake of novel agents.
Carbetocin, an oxytocin analog, given as a postpartum hemorrhage prophylaxis in elective Cesarean deliveries, frequently causes tachycardia and hypotension. Phenylephrine infusion has been shown to prevent spinal anesthesia-induced hypotension. The goal of this study was to evaluate if a slow infusion of carbetocin would reduce maternal heart rate variation and hemodynamic disturbances compared with a rapid bolus in parturients receiving a prophylactic phenylephrine infusion during elective Cesarean delivery.
In this double-blinded randomized controlled trial, 70 healthy parturients were allocated to either a bolus group or an infusion group. At cord clamping, participants in the bolus group received carbetocin 100 µg as a rapid intravenous bolus, while participants in the infusion group received carbetocin 100 µg over 10 min. The primary outcome was the variation in maternal heart rate from baseline during the 20 min following cord clamping. Secondary outcomes included blood pressure, cardiac output, and stroke volume variations during the study period, measured with the ClearSight™ hemodynamic monitor.
Maximum heart rate variation was not different between the groups bolus group, mean (standard deviation) 29.8 (25.2)% vs infusion group, 27.2 (23.3)%; P = 0.67. The increase in heart rate occurred significantly earlier in the bolus group than in the infusion group (median [interquartile range] time, 105 [69-570] sec vs 485 [255-762] sec; P = 0.02; group × time interaction two-way repeated measures ANOVA, P = 0.04). There was no significant difference in maximum variations for the other hemodynamic parameters between the groups.
Carbetocin infused over ten minutes did not reduce the magnitude of maternal heart rate variation but delayed its occurrence. This finding could be relevant to the anesthesiologist caring for parturients in whom a slight increase in maternal heart rate is clinically undesirable.
www.
gov (NCT03404544); registered 19 January 2018.
gov (NCT03404544); registered 19 January 2018.
Cannabis' effect on seizure activity is an emerging topic that remains without consensus and merits further investigation. We therefore performed a scoping review to identify the available evidence and knowledge gaps within the existing literature on cannabis product exposures as a potential cause of seizures in humans.
A scoping review was conducted in accordance with the PRISMA Extension for Scoping Reviews guidelines. Cpd 20m molecular weight The PubMed and Scopus databases were searched over a 20-year period from the date of the database query (12/21/2020). Inclusion criteria were (1) English language original research articles, (2) inclusion of human subjects, and (3) either investigation of seizures as a part of recreational cannabinoid use OR of exogenous cannabinoids as a cause of seizures.
A total of 3104 unique articles were screened, of which 68 underwent full-text review, and 13 met inclusion/exclusion criteria. Ten of 11 studies evaluating acute cannabis exposures reported a higher seizure incidence than would be e9 tetrahydrocannabinol (THC) may be the causative xenobiotic for this phenomenon.Despite the high prevalence and adverse clinical outcomes of severe tricuspid regurgitation (TR), conventional treatment options, surgical or pharmacological, are limited. Surgery is associated with a high peri-operative risk and medical treatment has not clearly resulted in clinical improvements. Therefore, there is a high unmet need to reduce morbidity and mortality in patients with severe TR. During recent years, several transcatheter solutions have been studied. This review focuses on the transcatheter edge-to-edge repair of TR (TTVR) with respect to patient selection, the procedure, pre- and peri-procedural echocardiographic assessments and clinical outcomes. Furthermore, we highlight the current status of TTVR in the Netherlands and provide data from our initial experience at the University Medical Centre Groningen.
Data on the impact of the cumulative percutaneous left atrial appendage closure (LAAC) caseload on cardiovascular outpatient and hospitalisation costs are limited.
The present single-institution analysis includes patients treated consecutively from the beginning of our LAAC experience in January 2012 until December 2016. Pre- and post-LAAC costs for hospitalisation and ambulatory visits were included.
Atotal of 676patients underwent percutaneous LAAC (using the Watchman device) 49(2012), 78(2013), 211 (2014), 210 (2015), and 129 (2016). LAAC procedural costs were stable over the years (overall median €9639; 2012 €9630; 2013 €10,003; 2014 €9841; 2015 €9394; 2016 €9530; p = 0.8) and there was no correlation between cumulative caseload and procedural costs (p = 0.9). Although annualised cardiovascular management costs after LAAC were lower than before LAAC (median difference between pre-LAAC and post-LAAC yearly costs €727; 2012 €235; 2013 €1187; 2014 €716; 2015 €527; 2016 €1052; p = 0.5 among years analysed) from the beginning of the cumulative procedural experience, asignificant reduction in costs was observed only from 2014 onwards. Institutional cumulative LAAC caseload and year of procedure were not related to the amount of reduction in the costs for cardiovascular care.
LAAC led to cost-of-care savings from the beginning of our institutional procedural experience.
LAAC led to cost-of-care savings from the beginning of our institutional procedural experience.
Dysfunctional cerebral autoregulation often precedes delayed cerebral ischemia (DCI). Currently, there are no data-driven techniques that leverage this information to predict DCI in real time. Our hypothesis is that information using continuous updated analyses of multimodal neuromonitoring and cerebral autoregulation can be deployed to predict DCI.
Time series values of intracranial pressure, brain tissue oxygenation, cerebral perfusion pressure (CPP), optimal CPP (CPPOpt), ΔCPP (CPP - CPPOpt), mean arterial pressure, and pressure reactivity index were combined and summarized as vectors. A validated temporal signal angle measurement was modified into a classification algorithm that incorporates hourly data. The time-varying temporal signal angle measurement (TTSAM) algorithm classifies DCI at varying time points by vectorizing and computing the angle between the test and reference time signals. The patient is classified as DCI+ if the error between the time-varying test vector and DCI+ reference vector is smaller than that between the time-varying test vector and DCI- reference vector.
