Burnettefoldager2873

Transporter-mediated drug-drug interactions are one of the major mechanisms in pharmacokinetic-based drug interactions and correspondingly affecting drugs' safety and efficacy. Regulatory bodies underlined the importance of the evaluation of transporter-mediated interactions as a part of the drug development process. The liver is responsible for the elimination of a wide range of endogenous and exogenous compounds via metabolism and biliary excretion. Therefore, hepatic uptake transporters, expressed on the sinusoidal membranes of hepatocytes, and efflux transporters mediating the transport from hepatocytes to the bile are determinant factors for pharmacokinetics of drugs, and hence, drug-drug interactions. In parallel with the growing research interest in this area, regulatory guidances have been updated with detailed assay models and criteria. According to well-established preclinical results, observed or expected hepatic transporter-mediated drug-drug interactions can be taken into account for clinical studies. In this paper, various methods including in vitro, in situ, in vivo, in silico approaches, and combinational concepts and several clinical studies on the assessment of transporter-mediated drug-drug interactions were reviewed. Informative and effective evaluation by preclinical tools together with the integration of pharmacokinetic modeling and simulation can reduce unexpected clinical outcomes and enhance the success rate in drug development.

To evaluate the effects of a quality improvement initiative regarding the administration of antibiotics at the time of obstetric anal sphincter injury (OASIS) repair.

At University of Michigan-a tertiary care center in Ann Arbor, MI, USA, we implemented a quality improvement intervention aimed at administering a single dose of broad-spectrum antibiotics at the time of OASIS repair. Best practice recommendations and reminders were presented to the department. Cefazolin plus metronidazole or clindamycin plus gentamycin were the recommended antibiotics. The effects of this intervention were assessed based on a chart review of deliveries between January 4, 2014 and February 13, 2019, which included patient data both pre-initiative and post-initiative to compare the prevalence of antibiotic use at the time of OASIS repair.

Recommended antibiotic use increased from 0.3% (1/372) pre-initiative to 75.7% (106/140) post-initiative (P<0.001), and any antibiotic use increased from 6.5% (24/372) to 82.9% (116/140, P<0.001). The proportion of cases complicated by wound infection/breakdown decreased by 55% after the quality improvement intervention (3.2% pre-intervention vs 1.4% post-intervention, P=0.22).

Following a departmental quality improvement intervention aimed at increasing antibiotic administration at the time of OASIS repair, antibiotic use increased 13-fold. Although underpowered to detect a significant difference in wound complications, our study showed a clinically meaningful decrease in wound infection/breakdown with antibiotic administration.

Following a departmental quality improvement intervention aimed at increasing antibiotic administration at the time of OASIS repair, antibiotic use increased 13-fold. Although underpowered to detect a significant difference in wound complications, our study showed a clinically meaningful decrease in wound infection/breakdown with antibiotic administration.

This study aims to assess the prevalence of post-stroke cognitive impairment, and to evaluate the correlation of ASPECTS with impaired cognition.

150 patients presenting with acute middle cerebral artery territory ischaemic stroke were included in this study. Risk factors of ischaemic stroke and the initial NIHSS were determined. An initial and a follow-up non-contrast CT brain were carried out after seven days which were assessed by ASPECTS. The prevalence of cognitive impairment was determined by MoCA during the follow up of patients after three months. Correlations of ASPECTS, NIHSS and MoCA were done by Spearman correlation. Multivariate logistic regression analysis was carried out for the independent variables of cognitive impairment.

The prevalence of post-stroke cognitive impairment in this study, according to the threshold for cognitive impairment with a MoCA score of 25 or less, was 25.3% (38 patients). Significant positive correlations between ASPECTS and total MoCA test domains were found (r = 0.73 and P = 0.002). Logistic regression analysis demonstrated that the independent factors associated with cognitive impairment were older age, certain domains of the MoCA test like executive functions, memory, attention, language, NIHSS, HTN, and ASPECTS.

There is a prevalence of cognitive impairment in about 25% of patients after three months of follow-up in cases with acute ischaemic stroke. ASPECTS is directly correlated with cognitive impairment, and may be considered as a biomarker of post-stroke cognitive impairment.

There is a prevalence of cognitive impairment in about 25% of patients after three months of follow-up in cases with acute ischaemic stroke. Metabolism modulator ASPECTS is directly correlated with cognitive impairment, and may be considered as a biomarker of post-stroke cognitive impairment.Negative immunofixation electrophoresis (IFE) of serum and/or urine is a diagnostic marker for determining a complete response (CR) after immunotherapy for multiple myeloma (MM). However, residual therapeutic antibodies such as elotuzumab (IgG-κ), can compromise IFE evaluation when the affected immunoglobulins belong to the same IgG-κ subclass. We thus sought to develop a simple and rapid method to treat patient serum before IFE to distinguish the residual elotuzumab. Serum samples from patients receiving elotuzumab were treated with a predetermined amount of soluble signaling lymphocyte activation molecule F7 (SLAMF7) protein and then subjected to conventional IFE testing. We tested our method in samples from 12 patients. The IgG-κ band in IFE disappeared or shifted after elotuzumab treatment in four patients with no bone marrow minimal residual disease and normalized free light chain, whereas seven patients with any sign of residual MM showed a remaining IgG-κ band after treatment. One-hour incubation of samples with 6-9 molar excess soluble SLAMF7 before IFE was sufficient to distinguish residual elotuzumab in 11 of 12 samples.