Unique pharmacological properties of etrasimod among S1P receptor modulators.

Etrasimod (ADP334) is an oral, once-daily, selective sphingosine 1-phosphate (S1P) receptor modulator for the treatment of moderately to severely active ulcerative colitis and in development for the treatment of immune-mediated inflammatory diseases. Interaction between S1P and its five receptor subtypes (S1P-S1P) plays a role in several physiologic systems, including the cardiovascular and immune systems. Since differences in S1PR binding and downstream intracellular signaling could contribute to distinct profiles of drug efficacy and safety, we directly compared the S1P selectivity profile of etrasimod to three marketed S1PR modulators: fingolimod, ozanimod, and siponimod.

The Association Between Intradialytic Symptom Clusters and Recovery Time in Patients Undergoing Maintenance Hemodialysis: An Exploratory Analysis.

Background: Individuals receiving hemodialysis often experience concurrent symptoms during treatment and frequently report feeling unwell after dialysis. The degree to which intradialytic symptoms are related, and which specific symptoms may impair health-related quality of life (HRQoL) is uncertain.

Objectives: To explore intradialytic symptoms clusters, and the relationship between intradialytic symptom clusters with dialysis treatment recovery time and HRQoL.

Pyoderma Gangrenosum After Insertion of a Hemodialysis Catheter: Koebner Phenomenon, Systemic Inflammatory Response Syndrome, and a Delay in Diagnosis.

Rationale: Pyoderma gangrenosum is a rare neutrophilic dermatosis. Misdiagnosis of pyoderma gangrenosum as an infection is not uncommon. Pyoderma gangrenosum can be associated with Koebner phenomenon and rarely results in systemic inflammatory response syndrome and shock.

Infection rates and tolerability of three different immunoglobulin administration modalities in patients with primary immunodeficiency diseases.

This analysis evaluated the efficacy and overall tolerability of immunoglobulin (Ig) treatment modalities (intravenous Ig [iv.Ig], subcutaneous Ig [sc.Ig] and facilitated sc.

Comparing Renal Replacement Therapy Modalities in Critically Ill Patients With Acute Kidney Injury: A Systematic Review and Network Meta-Analysis.

Objectives: To compare different modalities of renal replacement therapy in critically ill adults with acute kidney injury.

Data Sources: We searched Medline, PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from inception to 25 May, 2020.

A New, Quick, and Simple Protocol to Evaluate Microalgae Polysaccharide Composition.

In this work, a new methodological approach, relying on the high specificity of enzymes in a complex mixture, was developed to estimate the composition of bioactive polysaccharides produced by microalgae, directly in algal cultures. The objective was to set up a protocol to target oligomers commonly known to be associated with exopolysaccharides' (EPS) nutraceutical and pharmaceutical activities (i.e.

The DIalysis Symptom COntrol-Restless Legs Syndrome (DISCO-RLS) Trial: A Protocol for a Randomized, Crossover, Placebo-Controlled Blinded Trial.

Background: Restless legs syndrome (RLS) affects approximately 30% of patients with end-stage kidney disease and is associated with impaired sleep and health-related quality of life. Medications used to treat RLS in patients receiving dialysis may have an increased risk of adverse events with dose titration, and residual RLS symptoms are common despite the use of effective treatments. Randomized controlled trials of monotherapy and combination pharmacologic therapy for RLS in hemodialysis are needed.

Nephrologist Views Regarding Cannabinoid Use in Advanced Chronic Kidney Disease and Dialysis: A Survey.

Context: The efficacy and safety of cannabinoids to treat symptoms in individuals with kidney disease is uncertain.

Objectives: We sought to elicit Canadian nephrologists' views regarding the use and study of cannabinoids in patients with kidney disease in an Internet-based survey of Canadian of Society of Nephrology members treating adult patients with kidney disease including dialysis.

Methods: The degree to which respondents supported the use or study of cannabinoids for symptoms common in kidney disease was assessed using a modified Likert scale ranging from 1 to 7 (anchored at 1-definitely would not and 7-being definitely would).

Screening questions for the diagnosis of restless legs syndrome in hemodialysis.

Background: Restless legs syndrome (RLS) is common in end-stage renal disease and is associated with reduced health-related quality of life. Simple and accurate screening instruments are needed since RLS is underdiagnosed and treatable. We examined the operating characteristics of screening questions and a disease-specific measurement tool for the diagnosis of RLS in hemodialysis.

Tolerability of Ig20Gly during onboarding in patients with primary immunodeficiency diseases.

Background: The subcutaneous immune globulin (SCIG) 20% product, Ig20Gly, was shown to be efficacious and well tolerated in 2 phase 2/3 North American and European studies at infusion volumes up to 60 mL/site and rates up to 60 mL/h/site in patients with primary immunodeficiency diseases.

Objective: To assess patient experience after switching to Ig20Gly with fast infusion rates and large infusion volumes/site in the North American study.

Methods: In this analysis of the open-label phase 2/3 study in which patients aged ≥2 years received weekly Ig20Gly infusions for up to approximately 1.

Attitudes and Opinions of Canadian Nephrologists Toward Continuous Quality Improvement Options.

Background And Objectives: A shift to holding individual physicians accountable for patient outcomes, rather than facilities, is intuitively attractive to policy makers and to the public. We were interested in nephrologists' attitudes to, and awareness of, quality metrics and how nephrologists would view a potential switch from the current model of facility-based quality measurement and reporting to publically available reports at the individual physician level.

Design Setting Participants And Measurements: The study was conducted using a web-based survey instrument (Online Appendix 1).

Two phosphAte taRGets in End-stage renal disease Trial (TARGET): A Randomized Controlled Trial.

Background And Objectives: Hyperphosphatemia is common among recipients of maintenance dialysis and is associated with a higher risk of mortality and cardiovascular events. A large randomized trial is needed to determine whether lowering phosphate concentrations with binders improves patient-important outcomes. To inform such an effort we conducted a pilot randomized controlled trial.

A Novel Targeted Screening Tool for Hypogammaglobulinemia: Measurement of Serum Immunoglobulin (IgG, IgM, IgA) Levels from Dried Blood Spots (Ig-DBS Assay).

Purpose: To develop an assay to quantify serum immunoglobulin (IgG, IgM, IgA) levels using dried blood spots (DBS) obtained on collection cards to be used as a tool for targeted screening for hypogammaglobulinemia.

Methods: DBS samples, along with simultaneous serum samples, were collected from 107 healthy individuals (11 months to 57 years of age). After eluting proteins from DBS, IgG, IgM, and IgA were quantified by an enzyme-linked immunosorbent assay (ELISA).

Coronary artery calcification, cardiovascular events, and death: a prospective cohort study of incident patients on hemodialysis.

Background: Coronary calcification in patients with end-stage renal disease (ESRD) is associated with an increased risk of cardiovascular outcomes and death from all causes. Previous evidence has been limited by short follow-up periods and inclusion of a heterogeneous cluster of events in the primary analyses.

Objective: To describe coronary calcification in patients incident to ESRD, and to identify whether calcification predicts vascular events or death.

The Safety of Eplerenone in Hemodialysis Patients: A Noninferiority Randomized Controlled Trial.

Background And Objectives: Mineralocorticoid receptor antagonism reduces morbidity and mortality in patients with heart failure, but the safety of these drugs in patients receiving dialysis is unclear. This study evaluated whether hyperkalemia and/or hypotension limited the use of eplerenone, a selective mineralocorticoid receptor antagonist, in hemodialysis patients.

Design, Setting, Participants, & Measurements: This was a randomized controlled trial of prevalent patients receiving hemodialysis at five Canadian centers.

Risk factors and impact of major bleeding in critically ill patients receiving heparin thromboprophylaxis.

Purpose: Bleeding frequently complicates critical illness and may have serious consequences. Our objectives are to describe the predictors of major bleeding and the association between bleeding and mortality in medical-surgical critically ill patients receiving heparin thromboprophylaxis.

Methods: We prospectively studied patients from 67 intensive care units and six countries enrolled in a thromboprophylaxis trial (NCT00182143) comparing dalteparin with unfractionated heparin.

Adjudication of bleeding outcomes in an international thromboprophylaxis trial in critical illness.

Introduction: Measuring bleeding in critical care trials is challenging. We determined the reliability of adjudicated bleeding assessments in a large thromboprophylaxis trial in the intensive care unit (ICU).

Materials And Methods: PROphylaxis for ThromboEmbolism in Critical Care Trial (PROTECT) was an international randomized controlled trial that compared dalteparin to unfractionated heparin for the prevention of deep vein thrombosis in the ICU.

Red blood cell transfusion and increased length of storage are not associated with deep vein thrombosis in medical and surgical critically ill patients: a prospective observational cohort study.

Introduction: With prolonged storage times, cell membranes of red blood cells (RBCs) undergo morphologic and biochemical changes, termed 'RBC storage lesions'. Storage lesions may promote inflammation and thrombophilia when transfused. In trauma patients, RBC transfusion was an independent risk factor for deep vein thrombosis (DVT), specifically when RBC units were stored > 21 days or when 5 or more units were transfused.

Impact of haemoglobin and erythropoietin dose changes on mortality: a secondary analysis of results from a randomized anaemia management trial.

Background: Anaemia is a common complication of chronic kidney disease. A number of studies have identified an adverse association between haemoglobin (Hgb) variability and mortality. To date, no study has evaluated the impact of Hgb variability on mortality in the setting of a uniform Hgb target and erythropoiesis-stimulating agents (ESA) dosing strategy.

The 4Ts scoring system for heparin-induced thrombocytopenia in medical-surgical intensive care unit patients.

Background: Heparin-induced thrombocytopenia (HIT) is commonly considered but rarely confirmed in critically ill patients. The 4Ts score (Thrombocytopenia, Timing of thrombocytopenia, Thrombosis, and oTher reason) might identify individual patients at risk of having this disorder.

Objective: The aim of the study was to evaluate the value of the 4Ts HIT score in comparison with the serotonin-release assay (SRA) in critically ill patients.

Event adjudication and data monitoring in an intensive care unit observational study of thromboprophylaxis.

Background: The objective of this report is to describe the roles, responsibilities and recommendations of a 3-member Event Adjudication Committee (EAC) and a 5-member data monitoring committee (DMC) for a prospective multicenter observational study of critically ill patients with renal insufficiency examining the bioaccumulation and bleeding risk associated with dalteparin thromboprophylaxis.

Methods: The EAC reviewed bleeding events to adjudicate whether they were major or minor and whether they were related to dalteparin (uncertain, unlikely, or likely). The DMC reviewed all bleeds deemed by the EAC as uncertain or likely due to dalteparin then recommended either to continue or suspend enrolment pending review by the steering committee, or requested more information.