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Both tacrolimus (TAC) and fentanyl are frequently used in patients receiving allogeneic hematopoietic stem cell transplantation (HSCT). A recently published report demonstrated that fentanyl can reduce the total body clearance of TAC; however, most patients in this study were administered concomitantly with azole antifungal agents, which are known to be strong inhibitors of CYP3A. Hence, the exact effect of fentanyl on TAC pharmacokinetics was unclear. In the current study, the authors retrospectively investigated the pharmacokinetic interaction between TAC and fentanyl in patients who were not concomitantly administered drugs that affect TAC metabolism.
Patients with continuous infusion of TAC and fentanyl after HSCT at the Tokyo Medical and Dental University between January 2014 and December 2018 were enrolled. The total body clearance of TAC was compared before and after the initiation or discontinuation of fentanyl.
Thirty patients (24 male and 6 female; median age, 11 years) were screened for their eligibility. Twenty-eight patients were enrolled for evaluating the effects of the fentanyl initiation on TAC pharmacokinetics; two patients were excluded because of the absence of data related to the TAC blood concentrations or the concomitant use of azole antifungals. Twenty patients were enrolled for investigating the effects of fentanyl discontinuation on TAC pharmacokinetics, whereas ten patients were excluded because of the absence of data related to the blood concentration of TAC or the additional administration of azole antifungals. Further, the total body clearance of TAC was not significantly affected by the initiation or discontinuation of fentanyl, although there were large inter-individual variations. In addition, the results remained the same even when the analysis was performed independently for adults and children.
Intravenous infusion of fentanyl does not affect the pharmacokinetics of TAC.
Intravenous infusion of fentanyl does not affect the pharmacokinetics of TAC.
Heterogeneity in scrolling behavior of Descemet membrane endothelial keratoplasty (DMEK) grafts complicates DMEK surgery. This prospective observational study assessed scrolling axes of DMEK grafts relative to the donor's eye.
The eye bank randomly marked the rim of corneoscleral donor buttons during trephination and recorded the position relative to the donor's axis. Surgeons were masked to the absolute position of the eye bank marking and recorded the scrolling axis relative to the eye bank marking and DMEK upside-down orientation. The scrolling axis was categorized as vertical (0 to 30 degrees and 150 to 180 degrees), oblique (>30 to 60 degrees and 120 to <150 degrees), and horizontal (>60 to <120 degrees). Scrolling patterns of corneas from the same donor were assessed.
Scrolling patterns of 202 donor corneas from 149 donors were determined. The donor graft scrolled predominantly vertically to the donor's cornea [75%; 95% confidence interval (CI), 68%-80%]. this website Horizontal axes (11%) and oblique axes (14%) were less common. The median deviation in scrolling axes after unfolding the grafts was 0 degrees from the original scrolling axis (interquartile range, 0-15), indicating that scrolling axes were stable. Fellow eyes of 46 donors had 3.55 times higher odds of a nonvertical scrolling pattern if the first eye had a nonvertical scrolling pattern (95% CI, 1.37-9.20), suggesting that donor factors influencing both eyes could contribute to scrolling patterns.
DMEK grafts have a natural and stable scrolling tendency at vertical axis of donor's cornea. Anticipating scrolling axes might help improve preparation techniques for DMEK grafts and outcomes.
DMEK grafts have a natural and stable scrolling tendency at vertical axis of donor's cornea. Anticipating scrolling axes might help improve preparation techniques for DMEK grafts and outcomes.
Lipoprotein(a) [Lp(a)] is a cardiovascular factor, for which there is no approved specific lowering treatment. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to have lowering effects on Lp(a). Aim of this systematic review is to synthesize the current literature and quantify the effects of PCSK9 inhibitors on the serum Lp(a) levels in human subjects. Double-blind, phase 2 or 3, randomized-controlled trials comparing PCSK9 inhibitors (alirocumab or evolocumab) to placebo and/or ezetimibe and/or other lipid-lowering therapy were deemed eligible for inclusion. We searched MEDLINE (via PubMed), CENTRAL, Scopus, and Web of Science as of 17 June 2020. Quality assessment was performed using the Revised Cochrane risk-of-bias tool for randomized trials. Forty-three studies were identified (64,107 patients randomized) and 41 studies were included in the quantitative analysis. PCSK9 inhibitors reduced Lp(a) levels by -26.7% (95% CI, -29.5% to -23.9%) with a significant heterogeneity waseline low-density lipoprotein cholesterol due to the intervention is significantly associated with the effect size difference (P less then 0.0001). PCSK9 inhibitors reduced low-density lipoprotein cholesterol by -54% (95% CI -57.6% to -50.6%). There is substantial efficacy of the currently approved PCSK9 inhibitors in the lowering of Lp(a) levels. Dedicated randomized controlled trials are needed to establish the benefit of this intervention.
Despite sacubitril/valsartan being on the market since 2015, clinicians are still determining the best way to initiate therapy to optimize outcomes and minimize potential for side effects. The purpose of this study is to investigate real-world outpatient experience of prescribing sacubitril/valsartan therapy based on appropriate patient selection, dosing conversion, and tolerability. This retrospective cohort study evaluated patients' prescribed sacubitril/valsartan therapy in cardiology clinics associated with an academic institution between February 1, 2016, and August 30, 2018. Patients were excluded if they were less than 18 years of age, enrolled in a clinical trial involving sacubitril/valsartan, or had insufficient data. The primary outcome was to determine how many heart failure patients initiated on sacubitril/valsartan were performed so appropriately based on guideline and package insert recommendations. Select secondary outcomes included rates of adverse events and need for adjustment of concomitant heart failure medications.
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