Infrequent transition to direct oral anticoagulants in patients with cancer.

Introduction: Pharmacokinetic drug-drug interactions (DDIs) are challenging aspects of direct oral anticoagulant (DOAC) therapy in patients with cancer. We evaluated the prevalence of potential DOAC/antineoplastic agent DDIs and the one-year cumulative incidence of switching from low-molecular-weight heparin (LMWH) to a DOAC in patients with cancer.

Methods: Patients with cancer and an indication of LMWH were included from Herlev and Gentofte Hospital, Denmark, in the 2014-2019 period.

Prognosis of acute coronary syndrome stratified by cancer type and status - a nationwide cohort study.

Background: To investigated the prognosis of the most prevalent cancers (breast-, gastrointestinal-, and lung cancer), according to cancer status (i.e., active-, non-active-, history of-, and no cancer), following first-time of acute coronary syndrome (ACS).

Low-dose hydrocortisone in patients with COVID-19 and severe hypoxia: The COVID STEROID randomised, placebo-controlled trial.

Background: In the early phase of the pandemic, some guidelines recommended the use of corticosteroids for critically ill patients with COVID-19, whereas others recommended against the use despite lack of firm evidence of either benefit or harm. In the COVID STEROID trial, we aimed to assess the effects of low-dose hydrocortisone on patient-centred outcomes in adults with COVID-19 and severe hypoxia.

Methods: In this multicentre, parallel-group, placebo-controlled, blinded, centrally randomised, stratified clinical trial, we randomly assigned adults with confirmed COVID-19 and severe hypoxia (use of mechanical ventilation or supplementary oxygen with a flow of at least 10 L/min) to either hydrocortisone (200 mg/d) vs a matching placebo for 7 days or until hospital discharge.

Challenge and Impact of Quinidine Access in Sudden Death Syndromes: A National Experience.

Objectives: This study sought to determine the nature of quinidine use and accessibility in a national network of inherited arrhythmia clinics.

Background: Quinidine is an antiarrhythmic medication that has been shown to be beneficial in select patients with Brugada syndrome, early repolarization syndrome, and idiopathic ventricular fibrillation. Because of the low prevalence of these conditions and restricted access to quinidine through a single regulatory process, quinidine use is rare in Canada.

Reasons for hospitalization and risk of mortality in patients with atrial fibrillation treated with dabigatran or warfarin in the Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial.

Aims: Hospitalizations are common among patients with atrial fibrillation. This article aimed to analyse the causes and consequences of hospitalizations occurring during the Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial.

Methods And Results: The RE-LY database was used to evaluate predictors of hospitalization using multivariate regression modelling.

The Role of Manual Aspiration Thrombectomy in Patients Undergoing Primary Percutaneous Coronary Intervention for STEMI.

In STEMI, primary PCI restores macrovascular coronary blood flow effectively but microvascular perfusion remains a challenge. Thrombus has the potential to embolize to the microvasculature limiting effective coronary blood flow. Thrombus burden is associated with a higher mortality and manual aspiration thrombectomy has the potential to reduce thrombus burden.

Stroke in the TOTAL trial: a randomized trial of routine thrombectomy vs. percutaneous coronary intervention alone in ST elevation myocardial infarction.

Aims: TOTAL (N = 10 732), a randomized trial of routine manual thrombectomy vs. percutaneous coronary intervention alone in ST elevation myocardial infarction, showed no difference in the primary efficacy outcome but a significant increase in stroke. We sought to understand these findings.

A Meta-Analysis of Randomized Controlled Trials of Conventional Stenting Versus Direct Stenting in Patients With Acute Myocardial Infarction.

Background: Direct stenting (DS) is commonly used during percutaneous coronary intervention for acute myocardial infarction (AMI) to prevent distal embolization; however, no guideline recommendations exist regarding DS. We sought to compare DS with conventional stenting (CS) in patients presenting with AMI in a meta-analysis of randomized controlled trials.

Methods: Studies were identified from EMBASE, MEDLINE, and Cochrane databases.

ELISA microplate: a viable immunocapture platform over magnetic beads for immunoaffinity-LC-MS/MS quantitation of protein therapeutics?

Aim: Evaluate the performance of ELISA microplates versus commonly used magnetic beads for biological sample cleanup and/or enrichment in immunoaffinity-LC-MS/MS to reduce tedious beads washing procedures and a relatively high assay cost.

Materials & Methods: ELISA microplates were used as immunicapture platform and compared with magnetic beads for sample cleanup for LC-MS/MS quantitation of protein therapeutics.

Results: One unmodified and two surface-activated microplates provided comparable linear ranges and sensitivities for a therapeutic protein (mass 78 kDa) using a human serum sample of 100 µl with 1:1 dilution compared with Tosylactivated magnetic beads using 200 µl of human serum without sample dilution.

How to succeed in research during medical training: a qualitative study.

Purpose: The objective of this study was to examine the characteristics of the medical trainee (resident), the supervisor and the project that contribute to successful completion of resident-led research and publication in a peer-reviewed scientific journal.

Methods: Qualitative, interview-based study of Internal Medicine trainees and their supervisors. All interviewed trainees published at least one first-author research paper based on a project they completed during residency.

Guanidinated protein internal standard for immunoaffinity-liquid chromatography/tandem mass spectrometry quantitation of protein therapeutics.

Rationale: A protein internal standard (IS) is essential and superior to a peptide IS to achieve reproducible results in the quantitation of protein therapeutics using immunoaffinity-liquid chromatography/tandem mass spectrometry (LC/MS/MS). Guanidination has been used as a protein post-modification technique for more than half a century. A decade ago, the modification was applied to lysine-ending peptides to enhance their MALDI responses and peptide sequencing coverage.

Apparent anti-Woodward-Hoffmann addition to a nickel bis(dithiolene) complex: the reaction mechanism involves reduced, dimetallic intermediates.

Nickel dithiolene complexes have been proposed as electrocatalysts for alkene purification. Recent studies of the ligand-based reactions of Ni(tfd)2 (tfd = S2C2(CF3)2) and its anion [Ni(tfd)2](-) with alkenes (ethylene and 1-hexene) showed that in the absence of the anion, the reaction proceeds most rapidly to form the intraligand adduct, which decomposes by releasing a substituted dihydrodithiin. However, the presence of the anion increases the rate of formation of the stable cis-interligand adduct, and decreases the rate of dihydrodithiin formation and decomposition.

The mechanism of alkene addition to a nickel bis(dithiolene) complex: the role of the reduced metal complex.

The binding of an alkene by Ni(tfd)(2) [tfd = S(2)C(2)(CF(3))(2)] is one of the most intriguing ligand-based reactions. In the presence of the anionic, reduced metal complex, the primary product is an interligand adduct, while in the absence of the anion, dihydrodithiins and metal complex decomposition products are preferred. New kinetic (global analysis) and computational (DFT) data explain the crucial role of the anion in suppressing decomposition and catalyzing the formation of the interligand product through a dimetallic complex that appears to catalyze alkene addition across the Ni-S bond, leading to a lower barrier for the interligand adduct.

Disposition and mass balance of [14C]vernakalant after single intravenous and oral doses in healthy volunteers.

Vernakalant hydrochloride is a novel antiarrhythmic drug for the rapid conversion of atrial fibrillation to sinus rhythm and prevention of relapse. In this open-label, parallel design study, 8 healthy men received single 240-mg doses of [(14)C]vernakalant hydrochloride, given as a 10-minute intravenous (IV) infusion on day 1, and as an oral gel capsule on day 22. Plasma, urine, and fecal samples were collected for 7 days after dosing to measure vernakalant and its metabolites and to estimate mass balance of total [(14)C] recovery.

Variations in the management of pneumonia in pediatric emergency departments: compliance with the guidelines.

Objective: We sought to assess compliance with evidence-based guidelines for the management of pediatric pneumonia, including the variations in tests ordered and antimicrobials prescribed. Our primary hypothesis was that compliance with the treatment recommendations from the most current guidelines would be low for antimicrobial prescriptions.

Methods: We conducted a chart review at the Children's Hospital in London, Ont.

Steady-state pharmacokinetics of micafungin and voriconazole after separate and concomitant dosing in healthy adults.

We assessed the pharmacokinetics and interactions of steady-state micafungin (Mycamine) or placebo with steady-state voriconazole in 35 volunteers. The 90% confidence intervals around the least-squares mean ratios for micafungin pharmacokinetic parameters and placebo-corrected voriconazole pharmacokinetic parameters were within the 80%-to-125% limits, indicating an absence of drug interaction.

Comparative tacrolimus pharmacokinetics: normal versus mildly hepatically impaired subjects.

Tacrolimus (FK506, Prograf), marketed for the prophylaxis of organ rejection following allogenic liver or kidney transplantation, is virtually completely metabolized. The major metabolic pathways are P450 3A4-mediated hydroxylation and demethylation. Since P450 hepatic drug-metabolizing enzymes may be impaired in hepatic dysfunction, a study was conducted to characterize oral and intravenous tacrolimus pharmacokinetics in 6 patients with mild hepatic dysfunction and compared with parameters to those from normal subjects obtained in a separate study.

Coadministration of tacrolimus and mycophenolate mofetil in stable kidney transplant patients: pharmacokinetics and tolerability.

The tolerance and pharmacokinetics (PK) of tacrolimus (T) by the addition of mycophenolate mofetil (MMF) in stable kidney transplant patients (6/group) on long-term tacrolimus-based therapy were investigated. Patients received combination T and MMF therapy at three MMF doses: 1, 1.5, and 2 g/day administered twice daily.

Safety, tolerance, and pharmacokinetics of a small unilamellar liposomal formulation of amphotericin B (AmBisome) in neutropenic patients.

The safety, tolerance, and pharmacokinetics of a small unilamellar liposomal formulation of amphotericin B (AmBisome) administered for empirical antifungal therapy were evaluated for 36 persistently febrile neutropenic adults receiving cancer chemotherapy and bone marrow transplantation. The protocol was an open-label, sequential-dose-escalation, multidose pharmacokinetic study which enrolled a total of 8 to 12 patients in each of the four dosage cohorts. Each cohort received daily doses of either 1.

An HPLC/MS/MS assay for tacrolimus in patient blood samples. Correlation with results of an ELISA assay.

An HPLC/MS/MS assay for tacrolimus in whole blood using FR900520 as an internal standard was validated over the standard curve range of 0.100-10.040 ng ml-1.

Measurement of tacrolimus (FK506) and its metabolites: a review of assay development and application in therapeutic drug monitoring and pharmacokinetic studies.

Tacrolimus (FK506, Prograf) is a macrolide immunosuppressant used for the prevention of organ rejection after transplantation. Tacrolimus demonstrates considerable interindividual variation in its pharmacokinetic profile. This has caused difficulty in defining the optimum regimen and has highlighted the need for therapeutic drug monitoring.